Talk:Aldol reaction/Archive 1

Archive 1

Quality of Article

This article is terrible. It needs a lot of work. The aldol reaction isn't very useful?!? Eugene Kwan 07:27, 15 December 2005 (UTC)

I agree that this article is terrible and needs tons of work. I'll help out fixing it. ~K 15:47, 15 December 2005 (UTC)

• to state that the article is terrible is not a nice gesture the 15 or so editors who have contributed thus far. the article does need serious work: improve link density, most recent additions do not have any links at all, improve pics, contribute references. V8rik 16:50, 15 December 2005 (UTC)

Fair enough, I should have used more diplomatic language. But this article is not up to the good standards Wikipedia deserves yet. I'll be adding some completely new schemes soon. --Eugene Kwan

Crossed aldol section

I caught some errors in section entitled Crossed aldol reaction. I've reworked it and entitled the section Enolate formation. Please double check my work. ~K 04:41, 16 December 2005 (UTC)

You should check out http://www.courses.fas.harvard.edu/~chem206/Fall_2005/Lectures_and_Handouts/ There's a lot of information available there. I have a few points: - you only get crossed products if there's more than one set of enolizable protons - perhaps a less colloquial word than "preformed" might be appropriate? - strictly speaking, you also need the retroaldol reaction to be slow for it to be under kinetic control. but I think that you're basically correct. - there are other ways to form magnesium enolates. wouldn't using a grignard run the risk of adding to the carbonyl? common conditions use MgBr2 OEt2 with some amine base. - it's probably worth mentioning E vs Z enolates and the effect of HMPA - good work! Eugene Kwan 06:27, 16 December 2005 (UTC)

Thanks for the tips, and good point about the MeMgBr. I remember it being more basic than nucleophilic, but I think I should remove that statement just to be sure. And, of course, there is tons more to write. You're clearly the expert on this subject. Why don't you write a little? ~K 07:36, 16 December 2005 (UTC)

I'm still working on this page...only about half done here. Please feel free to chime in... I'd appreciate any comments. Eugene Kwan 09:01, 17 December 2005 (UTC)

• Hi Eugene, you are doing a great job, I have made a new edit: re-introduced the original introduction by user ~K, I think all articles should have such type of intro. Provided links as well. Modified the references, the part on Stereoselectivity still has too much jargon, many reactions in the See also section are captured in the aldol condensation. V8rik 16:54, 17 December 2005 (UTC)

Original references

Can someone please find the original 1872 references from Wurtz and Borodin? I can't seem to find them. ~K 18:18, 17 December 2005 (UTC)

I found the Wurtz reference. Still looking for the Borodin reference. ~K 23:48, 17 December 2005 (UTC)

Work in Progress

I've left in some empty sections to organize myself...I plan to work on this again soon. I hope this isn't against the rules... Anyone think we can get this page into the Featured Articles? That'd be so cool. Of course, it needs a ton of work before it's ready for that. Eugene Kwan 00:02, 18 December 2005 (UTC)

I was also thinking that this would be a good first chemical reaction featured article. It's a long road to a FA, but if we stick with it we can do it. When we are finished with the page, we'll submit it for peer review, and after that we'll submit it for FA status. ~K 00:28, 18 December 2005 (UTC)

Just to piggyback on here, where there's a decent chance of finding a chemist (!) we have an iodine clock reaction and Old Nassau reaction article but no general article on clock reactions. I'm hoping someone here might be inspired, once you're done with this article, of course! - Nunh-huh 00:31, 18 December 2005 (UTC)

Make this request to the Wikiproject Chemistry. I'm sure someone there can help you with this. ~K 00:45, 18 December 2005 (UTC)

Wow! I didn't know we had one! Thanks. - Nunh-huh 02:21, 18 December 2005 (UTC)

Comments

I've added lots in the stereoselectivity section...any comments? Maybe someone can do the thermo vs. kinetic enolate bit in the previous section. Eugene Kwan 03:29, 19 December 2005 (UTC)

Nature errors to correct

Nature disputes the accuracy of this article; see http://www.nature.com/news/2005/051212/multimedia/438900a_m1.html and Wikipedia:External_peer_review#Nature. We're hoping they will provide a list of the alleged errors soon. —Steven G. Johnson 01:46, 15 December 2005 (UTC)

So will someone be checking this article again, or can we take down the externally reviewed tag? I urge people to check the article thoroughly for errors. Eugene Kwan 03:30, 19 December 2005 (UTC)

Nature will shortly be releasing a list of errors (or something equivalent). I think that the idea is we'll wait till then, make sure we've addressed any valid points, and then take the tag down. - Nunh-huh 03:54, 20 December 2005 (UTC)

The results of what exactly Nature suggested should be corrected is out... -- user:zanimum

• The mechanisms of base and acid catalysed aldol reactions should have every step as an equilibrium process
• The acid catalysed process should include the dehydration step, which occurs spontaneously under acid conditions and, being effectively irreversible, pulls the equilibrium through to product.
• The statement that LDA is avoided at all possible as it is difficult to handle is rubbish. Organic chemists routinely use this reagent – which they either make as required or use commercially available material.

• • See link details, assuming this is the version that Nature examined: version point 1: granted, all steps should have been equilibria. point 2: not granted, condensations are covered in aldol condensation and it is clearly stated that acid conditions will lead to dehydration. point 3 not granted: Wiki states that use of LDA is cumbersome because of low temperature required 200 K not every lab has access to liquid nitrogen or dry ice. Not the use of LDA itself is questioned. V8rik 20:04, 22 December 2005 (UTC)

I agree with all three criticisms. If they haven't already been corrected, they will be corrected this weekend. ~K 01:16, 23 December 2005 (UTC)

I believe the errors found by Nature have been corrected. Could someone please verify this? ~K 03:28, 23 December 2005 (UTC)

Hi guys...here's my take:

1. I believe the equilibria problem is mostly fixed. I take the opinion that if you form an enolate using a stoichiometric amount of strong base, then that's irreversible. With soft enolization conditions, you may or may not be forming the enolate quantitatively. With boron enolates, I think you form the enolate completely. As with hydrolysis of the metal alkoxide, I think that's reasonably irreversible. So only step 3 in scheme 1 should have an equilibrium arrow. As for the enol/enolate modes scheme I drew, I guess I should have drawn an equilibrium arrow for the bottom right arrow showing addition of the enolate to the aldehyde. I can fix that later. And acid-dehydration is irreversible. I think this whole point is kind of a minor point anyways...I hardly think it's a big deal.

2. The acid-catalyzed (enol mode) mechanism indeed shows irreversible dehydration now.

3. LDA: In our group, we make our own LDA all the time. I personally find it irritating, as it might add an hour to my setup time, but I wouldn't call it "cumbersome". Heck, I wouldn't even call having to put on a chiral auxillary all that cumbersome, and that adds at least one "loading" step and one cleavage step. I'd say that the use of LDA is extremely common. At any rate, I removed the offending remark, which I guess I didn't really agree with, a long time ago.

Btw, liquid nitrogen is probably cheaper than milk most places. And dry ice is really cheap too...I mean, if they throw it on stage during various performances then it isn't too valuable. When I was in high school, I bought a huge sack of it for twenty bucks. I think that means both fall under "easily accessible".

In my opinion, the bother in making LDA (or LiHMDS) isn't really adding the BuLi to the amine, but really the annoyance of having to titrate the BuLi frequently. That means you have to dry another set of glassware, have various dry reagents, syringes, etc. etc. As the LDA article points out, you don't even need -78C to make LDA. I've certainly made it at say, -20C. The trouble is the enolate might not be stable above -78C or the aldol might not work properly.

I'll be adding more stuff soon...just busy with Christmas now. There's a lot of new material...I'd appreciate it if people would go through and check it all, since there's a lot of places where I could have messed up. I think the article no longer deserves the "errors" tag though. Merry Christmas, everyone. Eugene Kwan 22:19, 23 December 2005 (UTC)

Agree with Eugene above. LDA is not really that hard to handle and liquid N2 is dirty cheap. I think the article looks quite impresive now. After those empty sections are filled I think it would easily pass FAC. -- Rune Welsh | ταλκ | Esperanza 13:44, 25 December 2005 (UTC)

I completely agree with the Nature reviewer on all counts. Under the traditional aldol conditions of NaOR in ROH as base all steps are reversible (the dehydration step is much less so). Our page should show that, this type of method is still widely used. Indeed the standard lab prep of dibenzalacetone from acetone and benzaldehyde (see Williamson's lab text) is done in water with NaOH as catalyst – clearly the enolate is formed reversibly. I agree that low temperature LDA work is "avoided" is wrong; I was involved in making a 400 L batch of LDA in 1983 (we made an enolate at well above -78 C), and my old company (after 1987) had a plant capable of running -78 C reactions routinely on 400 L scale and larger. Dry ice is routinely used in many chemistry labs. Walkerma 20:57, 28 December 2005 (UTC)

I agree with the above statement about the traditional base-catalyzed aldol conditions: all the intermediates and products are in equilibrium. However, when using "kinetic conditions" with preformed enolates there is no (or very little) equilibrium. We should mention this. (P.S. The thought of working with 400L of LDA scares me. :) ) ~K 02:52, 29 December 2005 (UTC)

Stereochemical Models

Would someone mind checking over the stereochemical models I've put in...you know, for absolute stereochemistry, consistency, and general sense? I think it's all correct, but with so many stereocenters... I'm debating how to do the rest of the article...any sections that should be added/deleted/expanded? Eugene Kwan 22:16, 25 December 2005 (UTC)

What remains is basically a section on kinetic vs thermodynamic enolates, the Evans methodology, and an example or two from total synthesis. Also, it'd be good if we updated the links, references, and had people proofread it... I've updated the control section and restructured some of the article. Eugene Kwan 08:17, 28 December 2005 (UTC)

Eugene, your doing a great job. Keep on going! When you're done, alot of people will probably rewrite alot of what you've written, but you shouldn't take that the wrong way. We're all chipping in to make the article better. Right now, you're our "resident expert", and you've given the article much needed direction and content. I look forward to what comes next. ~K 02:41, 29 December 2005 (UTC)

Let me second that. When this is done it will be better than Britannica by far! I won't review the stereochemistry till I get home and can check things in March etc. Walkerma 03:08, 29 December 2005 (UTC)

The "new look" article - lacking basic material?

I think a lot of fantastic material has been added to this article, thanks to all who worked on that. If I had been the Nature reviewer, I would have also asked why the asymmetric aldol is not covered, and possibly the Mukaiyama aldol too, and now we have a good section on the asymmetric aldol at least. However I do have one serious criticism; the article now reads like a section from "Carey and Sundberg," i.e., it is much too advanced for the average reader. I know that my undergrads, even chem majors, would have a hard time following this article. I firmly believe that the article should provide both the basics for beginners and some more advanced and topical info for grad students and the like. I think a lot could be done with simple reorganisation; for example the base-catalysed mechanism is inextricably merged in with the diastereoselectivity, these should be separated. Does anyone mind if I do a rewrite once Eugene is finished? Walkerma 21:11, 28 December 2005 (UTC)

I agree with the criticism that there is not enough for the average reader. However, I strongly believe that Wikipedia needs to incorporate advanced content such as this to really become a world-class encyclopedia. My suggestion is that we should ADD content that would satisfy the average reader, but not remove content that would satisfy the advanced reader. ~K 02:37, 29 December 2005 (UTC)

Absolutely! I wan't being polite when I used the word fantastic! We should add to this, not take away. Walkerma 03:06, 29 December 2005 (UTC)

After re-reading this article after the recent edits I realized why I hate Org Chem so much... Maybe we could move the more technically complex sections to their own subarticles? -- Rune Welsh | ταλκ | Esperanza 03:09, 29 December 2005 (UTC)

My initial reaction to the thought of subarticles is one of horror. However, I'm willing to be convinced it may work. ~K 03:27, 29 December 2005 (UTC)

I think we can structure the article in such a way that the beginner mainly sees what they want, but the more advanced reader will look at the TOC and click to the appropriate (more advanced) piece. I would like to have a go at this after New Year if people are OK with that, perhaps we can see if it is necessary after that? It is certainly possible that large subtopics like the Mukaiyama might have their own page in time, but I think it'd be a shame to split up the core sections. Walkerma 04:17, 29 December 2005 (UTC)

Hi everyone, and thank you for the input. I'd like to address some of your comments, and tender some suggestions. Certainly, there is a lot of advanced material here. There has been a lot of work done on the aldol reaction the last thirty or so years, and what you see here is really just the tip of the iceberg. I agree that the article could perhaps be restructured to be more inviting to the average reader; however, I wonder if people might suggest, more specifically, what more basic material ought to be in the article? I didn't include some of the standard sophomore stuff like the intramolecular aldol stuff...

As for sub-articles, I must say I oppose such an idea. I don't really see the advantage of that, and some logical flow could be lost. A prior discussion of enolate geometry is essential to a discussion of aldol stereocontrol. The diastereoselectivity of the aldol will lead naturally into a discussion of the Evans' auxiliary method. Now, the article may become quite long, but perhaps this will not be such a big problem if everything is sectioned properly and if the most basic information can be summarized at the beginning.

As far as extra topics to be included, I felt that discussions of the Mukaiyama aldol would really lengthen the article, and frankly, be a lot of work. One might feel forced to cover the methods of generating silyl enol ethers, and then the geometry of said ethers, and then move on to other "aldol surrogates" like metalloenamines, which are a whole topic on their own. We should probably decide to limit the discussion somehow...

I suppose any discussion of the aldol reaction, beyond the basic points, is necessarily technical. I appreciate that Wikipedia is not a technical manual, but I really think what we've covered here is not terribly beyond what a typical Ph.D. organic chemist knows. And I see no reason why a junior or senior major in chemistry couldn't use what's here to write an in-depth report or something. I think it's nice to have a relatively simplified view of the aldol reaction condensed in one place. Eugene Kwan 07:02, 29 December 2005 (UTC)

• • I restate my comment that the article contains too much jargon and is too technical. This should not mean that material gets thrown out. In my view Wiki articles cannot be too technical if the underlying principles are worked out. The current article lacks many links.

1. Links to concepts that should be included: Nucleophilic addition
2. concepts mentioned in the text but not linked: antiperiplanar chair conformation chemical equilibrium diethyl malonate benzaldehyde methylene malonate sodium ethoxide Stereoselective olefin hyperconjugation Stoichiometry bond length diastereoselectivity chirality stereocenter epimer Pentane interference rotamer links to these articles will really help the average reader
3. concepts mentioned in text but not explained pi* orbital triphenylmethyllithium 9-BBN-Cl, DIPEA, Cy2BCl 1,3-diaxial interaction allylic 1,3-strain diastereoface polyketide stereoarray

Also many Aldol variations are already contained in separate articles (5 other variations branch of in the aldol condensation reaction alone) so I have no problem with subarticles for variations. V8rik 20:03, 29 December 2005 (UTC)

Sure, there are many links missing. But I thought it prudent to leave them out until much of the text is fleshed out. I think it's rather unreasonable to expect every concept to be explained, at least within the aldol article. There's really no reason to discuss what a pi* orbital is or what allylic strain is. Perhaps Wikipedia ought to have stuff on it, but at any rate, anyone interested in the more advanced sections has surely heard of those. Also, I don't think reagents like 9-BBN-Cl are really "concepts". If they are mentioned in the text, they're in some sort of example... Who is this "average reader"? How much chemistry background does one expect him or her to have? I'm sort of new to this. Eugene Kwan 20:24, 29 December 2005 (UTC)

Just a few points:

1) Don't worry about the missing links. They will get filled in.

2) Don't worry about explaining every concept. They will get explained eventually.

3) Don't worry about explaining every reagent. Once again, they will get their own pages eventually.

4) The page is so far geared towards the "average organic chemist with a PhD". I like it that way. We must also include the "average undergrad" who has just learned in O-chem class what the aldol reaction is. We will work on that. Walkerma has said he has some ideas. I wouldn't worry about this.

5) My advice: Just write the page how you think it should be written. If it's the truth then it will stick.

This is shaping up to be a fantastic article. I look forward to seeing it's completion. ~K 01:16, 30 December 2005 (UTC)

Hey, thanks. That is reassuring. I do strive for accuracy, but it is a complicated topic... Eugene Kwan 06:21, 30 December 2005 (UTC)

K is absolutely right, I couldn't have put it better. Keep up the good work! Walkerma 16:47, 30 December 2005 (UTC)

Evans Aldol

I've added a lot of stuff on the Evan's aldol. I'm going to add some stuff on the catalytic, asymmetric methods available, and give an example or two in total synthesis, and then that'll probably be the bulk of my contributions... As always, your feedback is appreciated. Eugene Kwan 23:55, 1 January 2006 (UTC)

Common Format

Hi everyone, not to be a bother or anything, but do you think we might stick to a common chemical structure format? I've been using the ACS template with no explicit hydrogens unless necessary... Also, do you think the intro scheme and the enol/enolate scheme I put in are sort of similar? Eugene Kwan 05:22, 5 January 2006 (UTC)

Hi Eugene. Yes, your scheme and mine are quite similar, I plagiarised yours shamelessly! I hope that on Friday to post a rewrite of that section so the duplication will disappear, but I don't think it's a serious problem for a temporary situation as there are significant differences. I wanted to get the intro up fairly quickly. As for format, I think your format is the right one for the bulk of the article, but for the intro I think it's better to include hydrogens. Many undergraduates have a hard time understanding line-angle formula; for this reason most textbooks (such as Wade that I cite) show hydrogens explicitly when explaining the basics, but they use line-angle in many questions & examples. Is it a problem to do our schemes like in Wade? I think the only other scheme I plan to revise is the mechanism scheme, which I plan to break into two parts as I want to describe the mechanisms explicitly. By the way, I loved your definition of the aldol; I struggled with this for a while for the intro, then noticed yours in the text that followed, better than anything I could think of! Walkerma 06:28, 5 January 2006 (UTC)

Well, I guess that's OK. The hydrogens reduce some of the aesthetics of the introduction, that's all. Maybe we could have a nice looking scheme for the "teaser" bit of the article, and then a more detailed one for the introduction, which is presumably targeted at say, the "uninformed undergraduate". Eugene Kwan 02:27, 6 January 2006 (UTC)

Now that the errors have been fixed, should we update the external peer review/nature errors page? I'm not sure how to do that. Eugene Kwan 02:29, 6 January 2006 (UTC)

I did that a while ago. ~K 04:24, 6 January 2006 (UTC)

Question on example used

I am working on mechanism schemes (offline, in ACS format Eugene!), trying to tie things in with the later article. We show propiophenone and acetophenone reacting to give an aldol product, but based on what I know of ketone equilibria and aldol thermodynamics this reaction is unlikely to go to any significant extent. Am I wrong (maybe because of the aryl group)? Or should we consider having two aldehydes for the crossed aldol example? Wade uses acetaldehyde and propionaldehyde, this example is often used I think. Please let me know your thoughts, thanks, Walkerma 07:04, 6 January 2006 (UTC) By the way I fixed a couple of things in the intro scheme. Walkerma 07:18, 6 January 2006 (UTC)

Well, to be honest, I just made up that reaction. It's not really a reaction you'd want to try, anyways. I only meant to use that to illustrate the problem of multiple products. I suppose we could find a real example... Eugene Kwan 07:41, 6 January 2006 (UTC)

Evans' chiral oxazolidone edit

I removed part of the end of 5.1 Evans' Oxazolidone Chemistry which discusses stereoselective β-hydroxyketone reduction. It was off-topic, and as the section was getting longish, it seemed a good way to trim the article. However, if others feel I'm wrong, the text is still in the database and can easily be put back in the article. ~K 21:22, 7 January 2006 (UTC)

Perhaps I should have made this clear, but I think it's pretty important, because if you don't reduce the imide aldol adduct, and you try to cleave the auxiliary, then you lose a stereocenter. I should probably have mentioned that allylic strain is what preserves all these stereocenters under such basic conditions. Also, these imide aldol adducts allow you to get what amounts to anti aldol adducts without actually doing an anti aldol. Eugene Kwan 03:41, 8 January 2006 (UTC)

I see what you're saying. I think if you put that clarification in the article, then knuckleheads like me would follow you better. ~K 05:43, 8 January 2006 (UTC)

No, no, it's my fault, it wasn't clear at all. Eugene Kwan 05:56, 8 January 2006 (UTC)

Direction for Article

Hi guys, Sorry I haven't had time to work on the article. I was just wondering where we want to take article from here? As I mentioned before, it'd be cool if we could get it up to "featured article" standards... Eugene Kwan 22:21, 20 January 2006 (UTC)

Here's what I think.

1. We finish the article.
2. We get other chemists from WP:Chemistry to evaluate the article.
3. We submit the article for Peer Review.
4. We submit the article to Featured Article Candidates.
5. We bask in the glory of a featured article.

~K 03:21, 21 January 2006 (UTC)

I agree with ~K, though before we do any basking we need to agree on what is needed for #1. Obviously there are the two empty sections at the end. I can also accept Eugene's comment about keeping the Mukaiyama aldol on a separate page, though IMHO we should have a short page on it before making the main aldol an FAC. For myself, I would also like to do a bit of clarification on the crossed aldol problem, and I think we need to make clear the main selectivity issues:

• • Chemoselectivity (the crossed aldol- which C=O reacts as the electrophile?)
  • Regioselectivity (where will the enolate form? kinetic vs thermodynamic etc.)
  • Diastereoselectivity (E vs Z enolates)
  • Enantioselectivity (Evans and other methods)

Any thoughts? Other things we need to do? Walkerma 04:22, 21 January 2006 (UTC)

I still need to fix up the end of the Evans' aldol section, add a bit on catalytic, enantioselective methods, and put in a bit on practical applications in total synthesis. I could add a little on the Mukaiyama aldol too. I'd welcome any clarification on the selectivity issues, although I'm unclear as to what exactly needs clarification... Perhaps to get a featured article, we need a snazzy picture? I'm not sure what such a picture would be, however. Eugene Kwan 05:21, 21 January 2006 (UTC)

I think the reaction schemes help break up the text somewhat, but one or two photos would spice it up nicely. Could you take a picture of an aldol rxn going on in a (tidy) fume hood - perhaps syringing in something into a stirred rb flask? I'm not likely to be running an aldol any time soon, at least not until August. Also, it would be really nice if we could get a nice picture of David A. Evans, but only if he's amenable to such a thing. Walkerma 06:20, 21 January 2006 (UTC)

NPOV

"The aldol reaction is an important carbon-carbon bond forming reaction in organic chemistry[1][2]"

Importance is inherently subjective. If the cited articles claim that the reaction is important, the article should make it more clear that the opinion (as well as the fact that the reaction is a carbon-carbon bond forming reaction in organic chemistry) comes from the articles. However, I suspect it would be far better to rework the sentence/paragraph to show that the reaction is important, rather than saying that the reaction is important. --Dfeuer 02:11, 25 January 2006 (UTC)

I'm not sure how the policy applies to this situation, but this is a widely regarded opinion. Would it be improper to say that nuclear fission is an important way of generating power, or that applying paint to canvas is an important way of making art? If you want to make C-C bonds in organic chemistry, this is a really important way of doing it. Oh, and apologies for the continuing delay...things are ridiculously busy in the lab now. Eugene Kwan 03:28, 25 January 2006 (UTC)

I think it would be equally improper to say that nuclear fission is an important way of generating power or that applying paint to canvas is an important way of making art. An anti-nuclear activist would likely dispute your assertion that nuclear fission is important. Paint on canvas is an important form of art for many people, but it is unimportant to blind people and people whose cultures emphasize other art forms or even lack works of paint and canvas altogether. Importance always requires context. Dfeuer 07:00, 25 January 2006 (UTC)

Even a nuclear activist would agree that nuclear power is an important method of generating power, if not a prudent one. It doesn't matter that some people can't or won't appreciate paintings as art; since most people do, paintings qualify as an important form of art. The context is implicit here: organic synthesis. Any reasonable, informed person would agree that the reaction is an important way of making C-C bonds. I don't think there's much "opinion" to it.

In terms of the spirit of the policy, no one is advocating the use of the aldol reaction here, and nor is it biased in favor of it (e.g. the aldol reaction is a better C-C bond forming reaction than alkylation). This is like saying "cars are an important form of transportation"--nothing is being said for or against cars. It is left up to the reader to decide, for example, what is a good reaction and what is not. Eugene Kwan 20:11, 25 January 2006 (UTC)

"Since most people [appreciate paintings as art], paintings qualify as an important form of art." Painting is considered an important form of art in western culture. In large parts of the world, it is insignificant. Dfeuer 03:35, 28 January 2006 (UTC)

This is not simply an opinion! One can check the references, which confirm that the reaction is indeed important, based on the fact that at both the basic level (Wade) and the more advanced level (March) a lengthy description is given for the reaction and its uses (March gives 58 references). Moreover, this type of introduction is a standard style used in chemistry. Finally, the fact that Nature chose to review this topic is also an indication of its importance. Walkerma 20:33, 25 January 2006 (UTC)

The only reason I can see for claiming that the reaction is important is to convince someone to read the article about it. While this is very common in textbooks and scientific articles, it is not good style. If someone looks up Aldol reaction in Wikipedia, they do so because they already think it's important enough to learn something about. I would venture a guess that it would be just as sensible to have nearly every article in Wikipedia claim that its topic is important. Dfeuer 03:23, 28 January 2006 (UTC)

I say "important" because there are reactions of various levels of importance. I would say the aldol reaction is very important, whereas the Eglington coupling (two terminal alkynes, copper) is of marginal importance. However, I wouldn't object if someone took out "important". Eugene Kwan 06:07, 28 November 2006 (UTC)

Errors in the 'Matched/Mismatched' section

The 'matched case' and 'mismatched case' show the same aldehyde, though the transition states are drawn with their enantiomers. (Presumably, the enantiomer of the 'matched case' aldehyde should be shown.) The referenced JACS article (1995, 117, 9073) does not contain the reaction in the image, although it is similar.

Yes, I thought I had explained that, but I think I might have left it out. The real reaction done is with the same aldehyde, but to show the model more clearly, I drew the enantiomer of the aldehyde. As for where the reaction came from, I got it from the Chem 206 notes (www.courses.fas.harvard.edu/~chem206; Aldol lecture 2), and I just put in the reference that was given. I'm a little puzzled as to where that example is from now. Suggestions? Eugene Kwan 01:04, 22 February 2006 (UTC)

New Picture

I took a picture today of my aldol reaction. I'm not sure how you make it smaller, so please, reformat, reformat! Thanks. Eugene Kwan 20:13, 28 February 2006 (UTC)

OK, someone helpfully resized it. How do I move the caption? It's now stuck in the middle of the text. Eugene Kwan 20:45, 28 February 2006 (UTC)

Sorry I missed the caption. I have moved it now. There's quite a bit of whitespace right now (at least in my browser) so maybe things need to be shuffled around a bit. Edgar181 20:53, 28 February 2006 (UTC)

Revisions

Hey guys, I have a little time to work on this article again...I'm open for suggestions. I was going to add a bit on the newer organocatalytic and catalytic, asymmetric methods, plus some stuff on thiazolodinethione auxiliaries. Any ideas? It's a pretty big article already. What do we need to do to get it to "featured article" level? Eugene Kwan 16:30, 24 November 2006 (UTC)

• Hi Eugene, welcome back, I haven't changed my view on this article since the last time (see my notes somewhere in the text above) but the article should be considered for featured article as it is. I am having some problems though with your use of syn and anti with respect to linear aliphatic chains in the text V8rik 17:39, 24 November 2006 (UTC)

OK, sure...thanks. What problems are you referring to? Are they mentioned above? Eugene Kwan 04:33, 25 November 2006 (UTC)

• • they are in this part. There was some unfinished discussion on what the average Wiki reader is and I maintain that you cannot expect the average reader to have any knowledge on the Aldol reaction. On the other hand you can simply direct to other articles when thing are unclear. One example: if the reader is unfamiliar with nucleophilic addition you simple link it in the text as nucleophilic addition, a reader already familiar with nucleophilic addition can skip it and read on. If you go for FA status non-chemists will review the article and I am sure you will get questions on unclear technical terms. I have already taken care of stereoinduction and allylic strain but other unexplained terms remain V8rik 18:25, 25 November 2006 (UTC)

• This reaction is a standard part of the second-semester syllabus in most US introductory undergraduate organic chem courses, so probably many thousands of students check this page (mostly around April, when it is usually taught). These students should know the basics of organic chemistry, including basic carbonyl chemistry, but many will probably be unfamiliar with terms like regiochemistry, stereoselectivity, asymmetric induction, kinetic vs. thermodynamic products. They should hear in class about use LDA and alkoxide bases (no others!), dehydration, and the problem of control in crossed aldols. In the UK it's probably similar, but may go a little deeper (e.g. kinetic vs thermodynamic enolates). I also cover the reaction in more detail in my advanced organic class - a much smaller number of students take this - and for that course the more advanced coverage in this article (E/Z enolates, Evans, etc.) is excellent. I hope this provides some guidance on what I'd guess the "average" reader of this page could be expected to know. Walkerma 06:22, 26 November 2006 (UTC)

OK, I'll tell you what. I'll let you guys figure out what sort of editing to do, and I'll just add some more material. I am a bit concerned about the length of this article, however. Any thoughts? Eugene Kwan 22:29, 26 November 2006 (UTC)

I've added a lot of new material, and am still in the process of finishing it. Please let me know what you think. Eugene Kwan 23:22, 27 November 2006 (UTC)

• Best continue discussion at Wikipedia:Featured article candidates/Aldol reaction at this stage...V8rik 17:40, 29 November 2006 (UTC)

1. This article could easily be MUCH longer given what's known about aldols. 2. The carreira Cu enolate aldol under header "Mukaiyama aldol reaction" is an enolate mechanism, and therefore NOT a Mukaiyama aldol, and it should be moved or made into a new category.

Introduction

I would vote for

The aldol reaction is an important method for forming carbon-carbon bonds

instead of "constructing". One constructs the skeleton of a molecule, or perhaps even the stereochemistry around a particularly difficult center, but a simple carbon-carbon bond is just "formed".

Also, I'm not really in favor or "naturally occurring molecules". "Natural products" is what the total synthesis folks synthesize, and using any other word is imprecise language and talking down to the readership. They deserve better. Dr Zak 22:09, 7 December 2006 (UTC)

It should also be pointed out that two stereocenters are set up in one reaction step, it's a salient feature. Dr Zak 22:28, 7 December 2006 (UTC)

I agree, especially with using forming instead of constructing. These are always called bond formation reactions in my experience. Maybe the idea was to avoid the funny-sounding "for forming", but that could be avoided by rephrasing. Maybe "The aldol reaction is an important carbon-carbon bond formation reaction", or "The aldol reaction is an important method for the formation of carbon-carbon bonds". Itub 23:34, 7 December 2006 (UTC)

OK, agreed. I just thought the ordinary person would not have the terms "natural product" or "bond formation" in their vocabulary. It's a tough job. What's the FA status? Will it just sit on the FA nominees list forever? Also, I felt thalidomide was a bad example, since the enantiomers interconvert in the body. Eugene Kwan 03:36, 8 December 2006 (UTC)

Amen, brother, on the thalidomide. Plus it's not an aldol adduct either. By the way, shouldn't it read "multigram-scale quantities of the drug" near the end of the first paragraph? Dr Zak 03:43, 8 December 2006 (UTC)

Yes, that works too. Eugene Kwan 00:06, 9 December 2006 (UTC)

Hey, this is great! Good work, everyone! A note about chemistry images: PNG looks fine, but there's a big problem with getting all the images to look the same size. It looks really weird with all the structures being different sizes. So I don't like PNG for the structures. Anyways, if you guys see any more errors, please, let me know! Eugene Kwan 05:57, 9 December 2006 (UTC)

Level of contributor

I have a question: what would you estimate is the average contributor's level for this article? My personal estimate is 3rd year undergraduate Chemistry major. Does that sound reasonable? The reason I ask is because the average contributor is W is much lower than that and I would love it if guys are your level could help to reconcile these two things (essays? whatever):

• Wikipedia:100,000 feature-quality articles
• Wikipedia:Expert retention

BTW: My own qualifications are B.S. in Chem. Eng., RPI '83. -- 64.9.234.5 02:42, 26 January 2007 (UTC)

Actually, I think most of the contributors are Ph.D. level. I'm a 3rd year Ph.D. student. Eugene Kwan 17:10, 26 January 2007 (UTC)

Thanks. I have noted that in the WP:100K project. I hope that they authors of that article set some realistic goals. IMHO, it seems like 5K FA by the end of 2007 would be something close to miraculous. To be honest, even 2K FA by the end of 2007 seems a tad aggressive to me, but I am for aiming high. Still, 100K seems to be a goal declared by the unrealisitic. I say: aim for 5K (or less if you think failure is discouraging) and pray for a miracle. -- 199.33.32.40 22:37, 26 January 2007 (UTC)

I am thinking of recommending that we maybe need to protect the feelings and the work of a scare resource: hard-science experts (HSE) who are active within the project. The WikiProject efforts are a step in that direction, but active HSE's are a scarce resource that require special protection. There are templates like {{ExpertChemistry}}, but they protect articles, not users. In a psychological way, maybe this article can be used, sort of as an ornate mace, to cow into submission any trolls who would otherwise interfere with and drive away true HSE's who are still willing to contribute to the project. But, I am getting ahead of myself. We need a small, gentle solution first. Maybe we should make a user template to the effect:

HSE This user is a hard-science expert. Please defer to their credentials, accomplishments and experience.

Let's not tie it to whatever Hard science artilce defines unless that article reaches a high level of stability and we can live with that definition. Now, let's think about what hard-science does not include: Humanities (maybe they can get their own user template), fiction writers, even hard-science science fiction writers. Math (again, get their own template), Technology. In other words, in terms of the top-level groups on the Main Page, we are talking about Science and Geography. I would love to include Math and Technology, but I would think that we would need a special requirement of "must be at M.S. or PhD level". I would love to include History and Economy (which is also single out by the Nobel Prize process) and that is about it. Anyway, I just cannot stand to see what it happening with WP:QUIT. I really miss Jnc and KimvdLinde and those guys. There were very nice and they became discouraged because the community did not give them support when they, in an emotional way, needed that support. I think that we can use this kind of article as a threshold without drawing too much attention to it (lest it become a target for disgruntled sub-experts). In other words, if they cannot get themselves through this article, then they probably are not a HSE in anything. I say that because while Math obviously touches every hard science, I tend to think that every true HSE has enough knowledge of chemistry to get through this article also. If we cannot develop the MediaWiki software technology in a timely fashion to give HSE's some clout and comfort, then we must do so within the less formal community process. What do you guys think? -- 70.231.154.13 17:55, 30 January 2007 (UTC)

Let's also recognize that this article has a good clean "threashold tool" because, unlike biology and cosmology, it has no obvious social or religious implications and so it does not tend to attract trolls. See the paragraph about technology in Dehumanization#Other topics for a deeper understanding of the "technology vs. religion" problem, which seems to be writ large here at Wikipedia. But with the advent of biotechology, there is no question that there is a pool of biology experts, again, KimvdLinde being among them, who need defending from determined trolls, under-educated know-it-alls, creationists, and whatnot. -- 70.231.154.13 19:40, 30 January 2007 (UTC)

Organocatalysis

The following sentence appears in the Organocatalysis section: "A more recent[when?] development is the use of chiral secondary amine catalysts. These secondary amines form transient enamines when exposed to ketones, which may react enantioselectively[48] with suitable aldehyde electrophiles." The question [when?] was asked correctly by someone, and it has not been answered as yet (1.10.2014). Ref.48 points to a contribution by Carreira, E.M. et al. in the year 2006. Is it possible that this [2006] is the answer? Only the contributor adding the above lines can help. Zghajos User:Zghajos From Wikipedia, the free encyclopedia Jump to: navigation, search Remarks to the Wikipedia Organocatalytic aldol reactions

Zoltan G. Hajos zghajos(AT)t-online.hu

The reaction scheme (a) as shown in the Wikipedia Organocatalytic aldol reactions page has only been described in the Hajos, Parrish Patent (b) and the Hajos, Parrish paper (c).

Since Hajos and Parrish worked at ambient temperature using a catalytic amount (3% molar equiv.) of (S)-(-)-proline they could isolate the optically active intermediate bicyclic ketols a prerequisite of elucidating the reaction mechanism. This was most likely the reason for Professor Claude Agami to call the reaction the Hajos-Parrish reaction in his paper in J.Chem.Soc., Chemical Commun., 1985, 441-442 (d).

The Hajos, Parrish Patent (b) also described the Asymmetric synthesis utilizing (S)-(-)-proline even in the absence of added solvent.

The last few lines of the Hajos, Parrish 1974 paper read: "We believe our results may be considered an example of a simplified model of a biological system in which (S)-(-)-proline plays the role of an enzyme." This has been referred in a publication by Mohammad Movassaghi and Eric N. Jacobsen of the Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA: The Simplest "Enzyme" Science, 6 December 2002, Vol. 298, 1904-1905 (e).

The above is also described in the Benjamin List Tetrahedron report number 613 in 2002 (f). This Tetrahedron report shows that the Schering group executed the reaction under non biological conditions using (S)-Proline (47 mol%), 1N perchloric acid, in acetonitrile at 80 degrees C. Hence, they could not isolate the Hajos, Parrish intermediate bicyclic ketols. The original 1985 naming of the reaction by Claude Agami (d) has been expanded in this 2002 paper (f) by adding three more names of the Schering group.

References to the Zoltan G. Hajos Remarks. a.http://upload.wikimedia.org/wikipedia/commons/d/de/Organocatalytic1.gif]

b. Hajos, Z, G.; Parrish, D. R. Asymmetric Synthesis of Optically Active Polycyclic Organic Compunds. German Patent DE 2102623, July 29, 1971.

c. Hajos, Z. G.; Parrish, D. R. J. Org. Chem. 1974,39,1615.

d. Agami, C.; Levisalles, J.; Puchot, C. J. Chem. Soc., Chem. Commun. 1985, 8, 441-442. doi:10.1039/C39850000441

e. Movassaghi, M.; Jacobsen, E. N., Science, 2002, 298, 1904-1905. doi:10.1126/science.1076547

f. List, B, Tetrahedron 2002, 58, 5573-5590 doi:10.1016/S0040-4020(02)00516-1 references 12 doi:10.1021/jo00925a003 and 13 doi:10.1002/anie.197104961

The above was posted by User:Zghajos (15:55 UTC, 5 February 2007) and moved here later that day by User:Walkerma, for discussion. Walkerma 16:49, 5 February 2007 (UTC)

I'm not sure I understand what's being said here...what is the proposed modification? When people talk about the "Hajos-Parrish reaction", they refer to the example I provided. I haven't investigated the history behind the reaction closely. Eugene Kwan 16:56, 5 February 2007 (UTC)

(Edit conflict) OK, I'm at work so can't comment more, but how should we incorporate this information into the article? Dr. Hajos has graciously given us some helpful refs on the reaction that bears his name, I suggest we try to review this to decide how best to incorporate the key parts of it in an "encyclopedic" way. Eugene, K, and others, what do you think? (I see Eugene has already commented!) Walkerma 16:59, 5 February 2007 (UTC)

Dr. Hajos has privately proposed to me that we simply call it the "Hajos-Parrish" reaction. Knowing nothing about the history behind the reaction, I have no opinion. If it turns out he reported the reaction first, then I don't object. If both groups reported the reactions at the same time, then both should be given credit, even if the conditions were harsher for one group. Eugene Kwan 14:47, 8 February 2007 (UTC)

This article may shed some light on the history - which is obviously important for the naming. I plan to order the Angewandte article so I can look at it; U. Eder, G. Sauer, R. Wiechert, Angew. Chem. Int. Ed. 1971, 10, 496. DOI. Since both works (the other being the Hajos patent) came out in 1971, we need to look more closely at this, I think. Walkerma 16:13, 8 February 2007 (UTC)

I don't know the history, but I believe that the current version of the article is correct in saying "This is commonly referred to as the Hajos-Parrish-Eder-Sauer-Wiechert reaction", because that is the only way I've seen people refer to this reaction. Itub 16:24, 8 February 2007 (UTC)

Please comment on my more neutral statement. Eugene Kwan 22:48, 9 February 2007 (UTC)

Hello Dr.Kwan: Thank you for making the changes in the text below the reaction equation leading to the bicyclic ketol or aldol, if you wish. The fact remains that, one cannot synthesize this compound under the "harsher" Schering reaction conditions which bypass this compound and lead to the optically active bicyclic dione. The reaction scheme as it is shown in the article has only been reported by us (ZGH and DRP); the Schering group has not reported it. Thanks again and greetings, Zoltan (March 2, 2008) 84.2.146.123 (talk) 08:19, 2 March 2008 (UTC)

Comment from OTRS

"In the section of "the Stereoselectivity: Alpha stereocenter on the enolate," there are figures for Z and E enolates right underneath the description "In the case of an E enolate, the dominant control element is allylic 1,3-strain whereas in the case of a Z enolate, the dominant control element is the avoidance of 1,3-diaxial interactions. The general model is presented below:" I believe the structure for Z enolate is correct, but I think your E enolate structure is false, as you notice both of your E and Z are the same. Please let me know, because it doesn't really make sense otherwise."

Well above my head, please review and fix if necessary. Thanks, Guy (Help!) 17:56, 5 May 2007 (UTC)

My apologies. You see the enolate structures are correct above, but not below. I have made the appropriate correction. Eugene Kwan 01:03, 6 May 2007 (UTC)

Complex articles and introduction articles - input requested

As the editors of this article have produced an example of what I would say can fairly be called a complex article, could I ask for input on the issues of complex articles and "introduction to" articles at Wikipedia talk:Featured article candidates/Introduction to general relativity? I mention this article down near the bottom of that talk page, and list a series of "introduction to" articles. Thanks. Carcharoth 00:23, 15 July 2007 (UTC)

• The editors of this page have made sure that the introduction is easy to understand. If the introduction is still too technical changes should be made to the introduction. A introduction to page will not help. The general relativity page is a disaster, it should be trimmed down to 15% of its current size and the details should be left to the satellite pages (there are 13 Main article links!). There should be no need for a intro page there also. V8rik 19:41, 15 July 2007 (UTC)

"Made sure"? Line 2 of this article is "In its usual form, it involves the nucleophilic addition of a ketone enolate to an aldehyde to form a β-hydroxy ketone, or "aldol" (aldehyde + alcohol), a structural unit found in many naturally occurring molecules and pharmaceuticals." Tempshill (talk) 23:32, 13 February 2009 (UTC)

I sympathize with you, but it's simply impossible to explain this topic in an understandable way to someone who has no chemistry background, much like it would be impossible to describe how to, say, repair a car to a caveman who has never heard of electricity, gasoline, or metal working. I must ask you to simply accept my assurance that, given say, a semester of organic chemistry at the sophomore level, the article should be eminently comprehensible. Eugene Kwan (talk) 02:15, 14 February 2009 (UTC)

I have updated line 2 with relevant links. Basically you need to have an understanding of chemical reaction, carbon-carbon bond nucleophilic addition, ketone, aldehyde and enolate before you can fully appreciate this article V8rik (talk) 21:01, 14 February 2009 (UTC)

I wasn't complaining, merely pointing out that to a layman, the article is baffling and incomprehensible; let's not have any illusions that this article is otherwise. It's unfortunate but I'll shrug and believe you when you say it's impossible to write anything on the subject that is understandable to the layman. I do think it goes overboard and ought to be half the current size, but then I'm just skimming it. Tempshill (talk) 01:34, 15 February 2009 (UTC)

Footnote lecture

How to add a footnote:

NOTE: Footnotes in this article use names, not numbers. Please see Wikipedia:Footnotes for details.

1. Assign your footnote a unique name, for example TheSun_Dec9.
2. Add the macro^[1] to the body of the article, where you want the new footnote.
3. Take note of the name of the footnote that immediately precedes yours in the article body.
4. Add #^ to the footnote numbered-list, immediately below the footnote you noted in step 3. No need to re-number anything!
5. Multiple footnotes to the same reference: see Wikipedia:Footnotes for a how-to, if you do not succeed by simply following the pattern.

Does this apply to old-style footnotes?--SallyForth123 20:31, 30 July 2007 (UTC)

Sorry changed your eddit to make it better readable--Stone (talk) 12:06, 2 March 2008 (UTC)

RACEMIC (+/-) mixture

hi,

how about adding a comment stating that the SYN or ANTI diastereoselectivity involve RACEMIC product mixtures?

see: http://www.chem.usyd.edu.au/~mcerlean/CHEM3115Lecture4.pdf

I think this keyword is key for making this article more "complete", or helpful.

--Koala Paw (talk) 17:52, 11 March 2008 (UTC)

e.g.: draw two Zimmerman-Traxler 6-membered-chair transition states as mirror images: get two enantiomeric transition-states which are equal in energy...

can also point out that one enolate adds to the "Si"-face, the other to the "Re"-face, according to CIP rules / nomenclature, etc.

--Koala Paw (talk) 18:10, 11 March 2008 (UTC)

• Sounds interesting, by all means make the edits you think will expand / improve this article V8rik (talk)

and last, maybe not, but anyway not least: IF you have an "alpha"-chiral aldehyde, one can PREDICT (by making use of the Felkin-Ahn model, for instance) whether the enolate attacks the "Si"- or "Re"-face of the "alpha"-chiral aldehyde...

note though that NOW the two 'enantiomers' are no longer equal in energy... (if they were, we'd get a RACEMIC mixture, once again!)

--Koala Paw (talk) 22:15, 11 March 2008 (UTC)

By all means reword it if you think it will make it more clear, but I think the term diastereoselectivity speaks for itself. You do get a racemic mixture if you start with an achiral enolate and achiral aldehyde, but you might well not if either is optically active. I think doubling each Z-T transition state would just confuse things. Eugene Kwan (talk) 01:29, 12 March 2008 (UTC)

doubling (mirroring) it _once_ would do, to make the ORIGIN of my argument clearer. and I don't intend to change the main page... I'll leave that up to the wiki formatting experts...

on a different note, as long as what is written is written lucidly and intelligibly and most importantly coherently (!) that's fine. but this ALDOL page is getting quite long (many 15" screens to scroll down...) - a well placed "tautology" (which I would argue racemic & diastereomeric, as it were, is not) IMHO would help, rather than confuse any old reader...

--Koala Paw (talk) 11:04, 12 March 2008 (UTC)

boron enolate

hi.

What is good:

• The two key examples / reactions for cis & trans boron enolates are given.

• The antiperiplanarity drawing.

I would add:

• Deprotonation is _NOT_ through a chair transition-state.

• elucidate the transition-state further, eg with two supplemental drawings for two said reactions:
  • free rotation about (CO)-CH2Me bond, and the orientation of the methyl DEPENDS on whether the base OR the boron ligand is the BULKY candidate...

--Koala Paw (talk) 23:06, 16 March 2008 (UTC)

Hi Koala, I appreciate the comments, but I'm really not sure what you're getting at. It's certainly probable that deprotonation does not conform to the Ireland model; I merely mentioned it for historical reasons. That's why I mention that its validity is questionable. Which reactions are you referring to? Eugene Kwan (talk) 03:08, 19 March 2008 (UTC)

Oh, the Ireland model is fine for LDA, but I wasn't referring to that "type of" enolisation:

The above was explicitly and only referring to BORON ENOLATES and their formation.

That they are formed differently (than, say, Li+ enolates), viz _not_ via an Ireland chair and that we have tools / other models / rationalizations to predict E vs Z / trans vs cis enolate outcomes is important to note and know, I think.

Bene?

--Koala Paw (talk) 20:05, 19 March 2008 (UTC)

possible typo?

Or maybe I am just ignorant. My question is at Image_talk:Typicalaldol2.gif. Any advice / comments (or: answers!) will be appreciated. Mike Schwartz (talk) 20:31, 15 August 2008 (UTC)

Concerning Wikipedia policy

User Eugene Kwan as well as I use our real names, and use our expertise in our discussions. Could it not be made mandatory for contributors of Wikipedia to reveal their real names and qualifications the way Dr. Kwan and myself have done? To be more explicit: what gives the right to a person associated with Wikipedia to delete an article unless it is a hoax or it is offensive to a person or to a group of people? Does an administrator working for Wikipedia have the same positive feeling that Dr.Kwan or myself had when we accomplished something in the laboratory? In other words: it is always easier to destroy than to create. Zoltan G. Hajos.Zghajos (talk) 03:48, 3 October 2008 (UTC)

I don' know what this has to do specifically with the Aldol reaction article and it sounds like it involves issues far larger than just this page. On its face, it looks like User:Zghajos's concern about his edits, so let's take it to User talk:Zghajos. DMacks (talk) 05:24, 3 October 2008 (UTC)

Agreed, except that you shouldn't call me "Dr." Not yet, anyways. Eugene Kwan (talk) 05:36, 3 October 2008 (UTC)

Lead

This article does not have a proper separation of the lead from the body of the article. Many things mentioned in the lead such as the history of its discovery are not mentioned again. It would not be rated GA under current standards.--Grahame (talk) 03:23, 15 February 2009 (UTC)

I don't understand your first comment; the lead is separated from the rest of the article by the table of contents, as it is in all of the recent featured articles on the main page. This lead is long, but if I recall correctly, that was because of requests made at FAC. I agree, though, that a short history section in the main body would be a good idea. Thanks, Walkerma (talk) 03:32, 15 February 2009 (UTC)

I'm just saying that the lead should be a short concise summary of the article, not separate material: "Significant information should not appear in the lead if it is not covered in the remainder of the article, although specific facts, such as birthdates, titles, or scientific designations will often appear in the lead only, as may certain quotations. This should not be taken to exclude information from the lead, but to include it in both the lead and body: in a well-constructed article, the relative emphasis given to information in the lead will be reflected in the rest of the text." (Wikipedia:Lead section#Relative emphasis).--Grahame (talk) 03:42, 15 February 2009 (UTC)

Tehcnical detail

Hello,

I realise that this is a highly technical article, but this is not really accessible to anyone without a bachelors in organic chemistry (or equivalent). Even the first few sentences are tough work:

In its usual form, it involves the nucleophilic addition of a ketone enolate to an aldehyde to form a β-hydroxy ketone, or
"aldol"  (aldehyde + alcohol), a structural unit found in many naturally occurring molecules and pharmaceuticals.[4][5][6] 
Sometimes, the aldol addition product loses a molecule of water during the reaction to form an α,β-unsaturated ketone. 

I am not averse to technical content but as a featured article it should represent something that is, at least in the lede, accessible to the reader who is not familiar with the entire topic area. Obviously this is far more difficult a task than for music, video games, sports and other non-technical articles. User A1 (talk) 06:05, 15 February 2009 (UTC)

Hi, I'm a high school student, and this article is readily accessible to me. I believe that this is a very well written article, and serves as a useful technical resource. 59.92.94.245 (talk) 07:07, 15 February 2009 (UTC)

Instructional aids

Clearly this subject can be difficult for the uninitiated - I think that organic chemistry is probably one of the more fearsome courses of the undergraduate curriculum. Still, there are some things that might be done to make this article a little clearer to the novice.

• Omitted hydrogens. The first reaction on the page does not show the hydrogens on the carbon atoms in the product, but does show them in the reactants (where they occur on a double bond and as an aldehyde). This is undeniably the standard representation, but you're showing people a reaction that appears to create one single product, in an article that eventually is going to spend a great deal of time on enantiomers and stereoselectivity. I can picture a novice staring at the reaction and thinking that H₂ is eliminated when the new bond is formed. It would be best to clarify this graphical issue at the beginning, though it may be difficult to do so concisely.

• Animation. It would be some work, but it shouldn't be extraordinarily difficult to produce an animation sequence showing how the reaction progresses. (see RasMol and Cn3D for example, though prettier results can be obtained with proprietary programs) But if someone has such a graphic already made, all Wikipedia would greatly appreciate the donation... especially since I'd worry that even if I did prepare a crude sequence myself it would be ruled out as "WP:original research", since I might (not implausibly) have inaccurately portrayed some aspect of the mechanism.

• "Typical" reaction. While some of the later graphics show more general reactions, the article starts off using a "typical" reaction that includes some distracting features (Ph, Li). The newcomer then has to figure out which parts of the reaction are important and which to ignore.

• Better introduction of stereoselectivity. The section on stereoselectivity begins by introducing syn and anti, (E) and (Z). But these are issues of notation not directly relevant to this article. Later on it is explained that "Modern organic syntheses now require the synthesis of compounds in enantiopure form. Since the aldol addition reaction creates two new stereocenters, up to four stereoisomers may result." - but this is under the "Evans' oxazolidinone chemistry" subheading, later in the article. Nowhere do we explain to the novice that a stereocenter (for practical purposes) is just a carbon with four ligands no two of which are identical, because any fewer can lie in a flat plane and be a mirror image of themselves, and any identical groups can be swapped to form a mirror image. I think we should have the marking of the stereocenters all the way up in the first graphic in the lead, and the lead should summarize a little bit of the stereochemistry. For simplicity we should stick to just one way of describing the chirality and use it consistently throughout this article, noting only that a different notation exists as described in another article. (Also note that the first quoted sentence is technically unsourced, though it isn't hard to find references e.g. [2],[3])

• Antibonding. The pi* orbital is mentioned, but not Wikilinked, and the role of antibonding orbitals in the transition is not explained. There is a simpler way to describe that orientation - when a double bond forms, the ligands at either end need to be lined up in a plane rather than being twisted at some angle (which double bonds don't do). If the antibonding orbital is mentioned at all, it should be described in more detail.

Despite these comments I don't mean to be critical of anyone for putting together this article, which really is very instructive. Many great chemists have written organic chemistry textbooks, but has anyone written one that can easily be understood? Still, Wikipedia is not paper, and it should be determined by experiment whether the hypertext format makes it possible to teach difficult topics more effectively than printed source. Mike Serfas (talk) 09:37, 15 February 2009 (UTC)

If there's one thing I've learned from the editorial process (peer review), it's that you can't please everyone. But a lot of these are good suggestions. Here are some opinions:

omitted hydrogens, explaining chirality, E/Z, syn/anti: if you can't understand these things, then I doubt you're going understand the stereoselectivity of the reaction, which, after all, is a huge part of the article. That's basically why people care about this reaction. It's not just under the Evans auxiliary...Ireland model, E vs. Z enolates, etc.

antibonding: that's a good way of describing it, and I agree there should be a link. But it's beyond the scope of the article to describe the general role of antibonding; it's a basic concept that is assumed.

typical reaction: I don't consider "Ph" and "Li" as "distractions." If you find those novel, then everything is going to be rather confusing, no matter how it's written.

animation: It sounds like a good idea, and I'm not opposed to having a link for it, but I have never been convinced that they're terribly useful for understanding a reaction. I think the first thing to help someone understand a reaction is to draw them a picture of which bonds are formed and which ones are broken. The motion in animations can be an enormous distraction. Also, I am not sure the approach trajectories of organic reactions are understood well enough in most cases to make these things valid.

Thanks for the input. Eugene Kwan (talk) 12:16, 16 February 2009 (UTC)

Another thing about omitted hydrogens: putting them in can be really confusing. It substantially increases the visual complexity of a scheme without really adding any actual information. Nobody who's even been to the first class of organic chemistry should think that H2 has been eliminated. Eugene Kwan (talk) 12:21, 16 February 2009 (UTC)

first picture missing description

See headline. --87.78.34.91 (talk) 14:51, 15 February 2009 (UTC)

First picture needs lots of things...removal of some descriptive text (along with adding description in a caption), converting to a better format (higher-resolution png or even better svg), removal of redundant parts (the second line can just redraw the aldol-reaction product from the first line instead of redoing that chemical step). I'm headed out, but can work on it in a few hours. DMacks (talk) 15:55, 15 February 2009 (UTC)

That's not a picture, that's a reaction scheme, so it doesn't need, and shouldn't have, a caption. The second line is not redundant; the purpose is to show the difference between an aldol addition and an aldol condensation. I'm not sure about what file formats people like, but it looks fine to me. Eugene Kwan (talk) 12:19, 16 February 2009 (UTC)

Notice that only the second step of the second line is called the condensation. That's another problem:) But "step 1 is called A, step 1+2 is called B" could still be written without repeating step 1...just say what each thing is and more clearly illustrating how one name is just the first step of a two-step (with different overall name) rather than two distinct things. Like the "ENOL mode" of the first diagram of the Mechanism section. DMacks (talk) 18:25, 16 February 2009 (UTC)

What program is used to create all those beautiful illustrations?

I initially thought the illustrations of chemical reactions were created through as some sort of wiki markup similar to <math></math>, so I was surprised to find out they are actually uploaded images. So I was wondering how were these actually created! Thanks in advance, Do U(knome)? ^yes..._{or no} 10:11, 17 February 2009 (UTC)

Using a molecule editor, possibly ChemDraw.

Ben (talk) 10:48, 17 February 2009 (UTC)

I used ChemDraw 7. Eugene Kwan (talk) 12:55, 17 February 2009 (UTC)

Ahh, I see. Thanks to both! Do U(knome)? ^yes..._{or no} 13:03, 17 February 2009 (UTC)

Biological Aldol Reactions

This new section is a good idea, but there doesn't seem to be very much actual information there. Perhaps it should wait until an expert can come along and write something more detailed. Eugene Kwan (talk) 00:50, 5 March 2009 (UTC)

lead

I thought the lead was disorganized and people complained it didn't make a lot of sense before, so I took another stab at it. Fire away. It's probably still too technical, but I don't have a good sense for what needs to be expanded on, and what needs to be linked to.Eugene Kwan (talk) 04:41, 5 July 2009 (UTC)

Stereoselectivity: Merged model for stereoinduction

Dear Mr (Dr yet?) Kwan, in the above mentioned section I can look as long as I want to, but I can't see a difference between the 2 aldehydes in the matched and the mismatched cases. Both seem to have the methyle group in (S)-configuration, yet the mismatched case shows a transition state with (R)-config. As I believe that the TS shows it correctly, you maybe want to correct the drawing in the reaction equation. If I'm wrong, please point it out to me where i got on the wrong track. Thank you.

Schmid —Preceding unsigned comment added by 85.216.71.39 (talk) 20:54, 27 October 2009 (UTC)

Ah, shoot, you're right. Actually, I looked in the original paper, and I noticed that the scheme shown is for some related TBS system. The paper has a PMB there, with slightly different selectivities. So the aldehyde and the products need to be fixed in the mismatched case. That figure took quite a while to draw, and I don't have the original ChemDraw handy anymore, so maybe somebody could take care of this? Everything is from line 1 and line 4 in ref. 27. Sorry about the mistake. I think I took it from the Chem 206 notes originally, and I probably made a mistake when copying it or drawing it out. I'm working on the "Dr." thing still, but it should be soon. Eugene Kwan (talk) 22:16, 27 October 2009 (UTC)

Oh, I'm relieved now that it wasn't me. I was about to go crazy about that. But alas, I'm not Wiki-expert. Perhaps someone could take the .gif and correct the bonds of the aforementioned methylgroup to "wedged"? Just color them black ;). Best wishes. Schmid —Preceding unsigned comment added by 85.216.71.39 (talk) 22:59, 27 October 2009 (UTC)

A non-WPexpert opinion on the Aldol Reaction article

An in-depth coverage of the subject would inevitably stir-up a good part of Organic Chemistry and all its underlying concepts : multistep equilibrations,kinetics,chemo-,regio- and stereoselectivity,notation,mechanisms,catalysis, synthetic methodology,variants of the reaction and more.So it would have to be long and technical.But,
1. Does it really need to go to such lengths and 2.if the answer is yes, should it not make some effort to offer something to the chemically innocent visitor ALSO?
On account 1.I don't see any reason why WP should not try to expand readership among Chemistry students preparing for exams or even qualified chemists but in a different field etc.Even supplying material in the style of an academic review article may not be a bad idea.Making such an approach an appraised prototype though ,may be taken to imply that this is how things should be done ,which I don't agree with because of 2.It seems to me that the layered approach of editing would be in everybody's interest.First the overall picture,set the frame of what is to follow,define the basics, example ,importance history ,a photo or a drawing (an informative one, I mean)in one word the encyclopaedic material and all this with minimal technicalities and minimal linking.Clear concise captivating should the target at this first layer.Other layers to follow AFTER THIS FIRST one can cater to completeness verifiability and the rest of the scientific stuff. All of the above ,although self evident, do not seem to apply in this present case.I do not mean to belittle the work done by the authors as they have produced an excellent assay on the subject .I understand that I am allowed ,in principle,to make my proposal but this is no trivial matter at such level of quality.I would have preferred the original editors doing it.Cleanthis (talk) 16:51, 17 August 2010 (UTC)

Thanks for your comments. I wrote a lot of the article, and was certainly aware of such considerations. I think the truth is the layman is not going to get much out of the aldol reaction--there are too many missing prerequisites. To some extent, the layered approach you suggest is taken care of by the "lead"--the first section. But there are limits...can you be more specific about how you think things should be changed? I'm not really sure I understand what you're suggesting. I (we) have written it so that someone who's taken a sophomore course on organic chemistry can learn a lot of the important stuff about the aldol reaction. And while some of it is fairly sophisticated, a lot of it is just stuff that organic chemists should know. Eugene Kwan (talk) 01:38, 18 August 2010 (UTC)

Image comment

I have removed the following comment from the article text, which seems to be referring to File:Mergedmodel.gif: "The S stereochemistry of the alpha methyl on the mismatched aldehyde should be R, (out of the plane), simmilar to the correctly drawn transition state". I can't figure out exactly which structure is being referred to. Can anyone help out? -- Ed (Edgar181) 16:44, 13 December 2010 (UTC)

To be honest, all this stuff is pretty complicated, and I already know there are some errors in the stereochemistry in the diagrams somewhere. But I'd have to sit down for several hours to sort it all out...seems like the diagram you're referring to stands on its own anyways. Sorry to be useless...I think at this point the best thing would be for another synthetic organic chemist to go through all the diagrams very carefully. It's hard to see your own mistakes. They're easy to get in there too--all it takes is an epimerized stereocenter. Eugene Kwan (talk) 05:49, 14 December 2010 (UTC)

FAR

This article was promoted in 2006, and doesn't appear to meet current FA standards. See also should be pruned and items incorporated in the text, there are multiple WP:MSH issues, there are WP:MOSBOLD issues throughout, we find an undefined terms in the first paragraph (dimerization, INN), and there is vague prose throughout (One common solution is to form the enolate of one partner first, and then add the other partner under kinetic control.[16] Kinetic control means that the forward aldol addition reaction must be significantly faster than the reverse retro-aldol reaction). Please work on these issues, so a featured article review will not be needed. SandyGeorgia (Talk) 15:37, 15 February 2011 (UTC)

• "INN" is out, and "dimerization" (as part of a sentence that was nearly half cut'n'paste from another in same paragraph) removed also. DMacks (talk) 16:08, 15 February 2011 (UTC)
• WP:MOSBOLD resolved. DMacks (talk) 08:07, 16 February 2011 (UTC)
• WP:MSH resolved as much as possible. DMacks (talk) 11:53, 20 February 2011 (UTC)

image in lead section

I can see that there was a desire to fill in the blank space to the right of the TOC, but I sorta wonder about what is there now.

1. I really don't think the blank space to the right of TOCs bothers readers. They can skip to the article pretty fast. Not like they need that white space filled in. It's like your house. Not every room needs filling. Can have some margin there

2. If we do keep it, seems like the caption should be worked on and made more lead worthy. Like definitely simplify it (too "hard" now). The specific chemicals tell us nothing important (they're just liquids, I have to take you on faith anyhow, could be water for all I know). Better to explain what each flask does and the tubing and all. And give a generality (enolate in one side, other is for products, or whatever).

3. What about putting it up high in normal position? At least it's a photograph and kinda attracts people. But I would skinny the caption way down. All that explaining can be done in article, but maybe just saying "laboratory setup for an Aldol reaction" would be enough. After all, there is plenty of text in the lead anyhow.

TCO (talk) 01:56, 18 February 2011 (UTC)

I hear you. When I was writing the article, I felt it needed a picture, and I happened to be doing the reaction, so I just took a picture of it. Many people have said that the lead is "too technical." All I can say is that it's a technical article that cannot be simplified to the level of a chemistry-naive audience. That said, Wikipedia is not "Wikipedia for Dummies" and I think there are a lot of people who have taken some organic chemistry who will end up reading articles like this one. I disagree--knowing what the reagents are in the flask *is* useful. Most liquids in organic chemistry are clear and colorless. In contrast, people who have done some organic chemistry know what the tubes and flasks are for. It's like showing a picture of the UN and explaining what the chairs and the podium are for. No, I want to know who's talking to whom!

What happened to the scheme in the lead? It's the same scheme I drew, but the settings are all weird now. Eugene Kwan (talk) 14:29, 18 February 2011 (UTC)

This change to the scheme? One I removed had different weird settings (low resolution, pixelation from gif compression artifacts) and some bonds appeared to be colored incorrectly. I've been gradually working on updating chem diagrams to current MOS standards in chemistry articles...lots of .gif here could be cleaned up in various ways (not flagged by the FAR questioner above, but one of my personal wiki-chem-gnome crusades:). DMacks (talk) 14:57, 18 February 2011 (UTC)

No sweat, but how about moving it down in article? And discussing the setup a bit more (mass transfer, etc.) TCO (talk) 16:27, 18 February 2011 (UTC)

I think having a typical scheme for the reaction is appropriate in the lead. Can you be more specific about what you mean by "discussing the setup"? Eugene Kwan (talk) 16:38, 18 February 2011 (UTC)

I could go along with something other than a reaction-scheme for lede image. A chemist might appreciate the specific details of it (what makes it Aldol and what makes Aldol interesting), chemists and students would be able to interpret it at all (what all the lines mean in the structures), but I think a photo of an experimental setup (especially one that includes the some of the special equipment often needed) also helps draw in other lay readers rather than scaring them off right away. An alternative might be a diagram of an important product molecule that can be made by the reaction (ideally a complex molecule where multiple aldol reactions are used to build it efficiently)--"hey, this reaction might be interesting because it makes a complicated thing I may have heard of so easily!". All the structural details are critical to (and support the chemical importance of) the reaction, but there are at least some aspects that are accessible and maybe interesting to people who don't know much about any of that. I agree with others who have (essentially) said that we shouldn't hide the advanced details, but also that if possible we should include something for lower level readers--being a general-use encyclopedia, not a graduate-level text. DMacks (talk) 16:42, 18 February 2011 (UTC)

Separately from the "what image in lede", I like the idea of dDiscussing the setup in more detail...somewhere. In the enolate-control sections, the ideas of amount (by extension, order-of-addition), temperature, and reactivity of reagents are discussed, so an intro paragraph describing the experimental setup (dry-ice bath, cannula transfer, etc.) would fit well. DMacks (talk) 16:42, 18 February 2011 (UTC)

Kwan: You have a lot of chemical examples, so spending the time on the specific aldehydes that happened to be in that flask is not the most crucial way to use the image. Nothing "bad" about it. But if instead, you used that caption (or even had a section) to discuss how to run the reaction, that would be better. You have two flasks and some sort of tube running between them (although I can't be clear if it's just a tube at RT between two chilled flasks? Is one flask for products and one for reactants? Is it a two-step reaction process? IOW, use that image to help us understand how the reaction is really performed. This is nothing anti chemistry. But you really have lots of example reactions which carry the weight of explaining the aldehyde-alcohol linking. Let's use this one for explaining the process.TCO (talk) 16:56, 18 February 2011 (UTC)

I respectfully disagree. The article is about the aldol reaction, not how to run reactions under an inert atmosphere, which I assume you already know something about or can look up. To clarify, there is no tube connecting both flasks. The two lines are just coming from a manifold to keep the enolate under nitrogen. The tubes are at room temperature, but the dry ice/acetone bath is enough to keep the contents of the pear-shaped round-bottomed flasks at -78 C. As it says in the caption, one flask contains LDA, which is added to tert-butyl propionate to form the enolate, which is one of the reactants. I've already done it there, so the flask of LDA is now superfluous--it just contains the LDA I didn't use up. One then adds aldehyde to the enolate. This is why it's crucial for the caption to contain descriptions of what's in the flasks. Also, it's erroneous to think that this is an "aldehyde-alcohol linking," as that implies that the reactants are an aldehyde and an alcohol. No, the product is a beta-hydroxyl carbonyl compound. The reactants are two carbonyl compounds. I hope this clears things up. Eugene Kwan (talk) 12:58, 22 February 2011 (UTC)

Image in beginning of article

I find the image at the beginning of the article difficult to look at because of the colors. Could we please change it to black and white ? Thank you. --129.67.115.252 (talk) 20:24, 21 November 2013 (UTC)

For the sake of the regular editors here, can you state the specific problem? Is it red-green colour-blindness? It is unlikely that anything can change quickly, but if the real issue is not made clear, you can be sure nothing will change. (WIth clarity, one could expect only slow change in the direction you suggest, because quick and easy changes like dropping colour-content would negatively impact the vast majority of readers, and/or create an impractical image redesign task for the editors.)

In any case, there is a old-fashioned solution to this that is available immediately: Create a hardcopy print-out of the pages you wish to read. With some tinkering with printer/copier contrast, I am sure you can find a setting where all bonds, atoms, arrows, and annotations are legible. This allows you to proceed immediately as you need, and does not hinder others who can make good use of the colour content. Cheers, LeProf — Preceding unsigned comment added by 50.179.92.36 (talk) 21:26, 5 December 2013 (UTC)

Brava, bravo, ladies and gentlemen, brava, bravo

This is truly an outstanding modern synthetic chemistry article, and as one that spends a great deal of time editing chem articles here, it's a pleasure to see one executed and maintained so well (and with such collegiality). Unusually, I have nothing specific to offer or suggest, vis-a-vis changes, but will keep looking in at History to see its evolution going forward. Besides new reviews and research work coming out—realize, here, the expectation is for secondary, and not primary sources to predominate—I would look to the Chem 206 and other Boger/Evans-type lecture notes online, to see content directions being used in good programs that are less research-oriented and more pedagogic/encyclopedic. (And every once in a while the online graduate research presentations now very common at good programs—Harvard, Illinois, Caltech, etc—will also shed some light on the perspectives of important leaders in the field; if a Denmark student at UIUC prepares a presentation for a graduate course on the current status of Lewis base-mediated ... well, you get what I mean.)

Otherwise, I will (with your forbearance) begin to bring other chemistry needs to your attention here, to perhaps inspire some further excellent work. I prepare content, but often cannot take time to create (or solicit from best source) the needed images to make an article complete. As we all know—and Roald Hoffmann nicely reminded us (http://onlinelibrary.wiley.com/doi/10.1002/anie.199100013/abstract, http://www.roaldhoffmann.com/other)—the images are central, and nearly all, sometimes. For instance, I am finishing a rewrite of the stub on David Evans, and there are few extant images I would feel good about being put up in his article. E.g., vancomycin aglycone would be a nice image to feature, but all the ones in WikiMedia are atrocious. Would never do that to him. Cheers, and look for another mssg soon. LeProf (see LeProf_7272). — Preceding unsigned comment added by 50.179.92.36 (talk) 21:15, 5 December 2013 (UTC)

New lead written, as start of re-write of Natural product article ...

... and I would invite the contributors to the aldol reaction article to:

• make overall suggestions to revise the lead of the Natural product article, and
• make any suggestions, in Talk, as to what might be a strong outline for a full rewrite of this important, currently weak related article. Cheers. LeProf — Preceding unsigned comment added by 50.179.92.36 (talk) 05:38, 7 December 2013 (UTC)

Ignore this. The new lead I wrote was reverted by two cannot-change-status-quo editors that appear to be stalking me. If you wish to see the lead I wrote, and comment on the quality of the existing versus alternative leads, what I wrote now appears in talk. LeProf

Draft related to possible more widely understandable article opening ...

Per earlier discussion regarding a simplified opening, here is a quick draft with a de.wikiedia figure. Use of this could be done by giving the existing opening a new "General introduction" section heading (to limit effort required). The figure could also be rejiggered to save space. Comments, action welcome. Cheers. LeProf

" The aldol reaction is a chemical reaction that is important both in nature, where it is central to all of biochemistry taking place in living organisms (e.g., in aldolase enzymes), and in human endeavors in organic chemistry, where it has found great utility to make molecules in the pharmaceutical industry and to allow first academic synthesis of molecules from nature (natural products). Discovered concurrently in the 19th century by Alsatian and Russian chemists, the reaction forms new bonds between carbon atoms (carbon–carbon bonds), by combining at its simplest, a two carbon fragment and a one carbon fragment to create a new three carbon product; in practice, each piece is much larger, because the reaction accommodates further substituents being attached to each fragment. The reaction is distinct in its using a carbon-carbon double bond, drawn C=C, for the two carbon fragment, where one carbon bears a partial negative charge; this is the nucleophile. It is generated as an isomeric form of a ketone such as the common solvent acetone, or the fragrance precursor acetophenone. The isomer is called an enol; under basic conditions it is negatively charged, and so an enolate. For the one carbon fragment (though essentially always bigger than one carbon), the reaction can use the carbon-oxygen double bond, drawn C=O, of an aldehyde such as formaldehyde, acetaldehyde (a relative of acetic acid in vinegar, found in ripe fruits), or benzaldehyde (from bitter almond oil). Notably, as explained further below, a second ketone could also be used to provide the second fragment. The C=O unit of these bears a partial positive charge on its carbon atom; i.e, it is an electrophile. Under carefully controlled conditions, reaction of this pair of nucleophile and electrophile results in a new bond between the atoms bearing the opposite charges, a new carbon-carbon bond. A base-mediated aldol reaction is illustrated below in "line-angle" form, where intersections of multiple lines imply a further carbon atom.

Aldol reaction between acetone in black, and acetaldehyde in blue, under basic conditions, using lithium diisopropylamide, LDA at very low (dry ice) temperatures, and quenching with water to general the aldol product, 4-hydroxypentan-2-one, which is a β-hydroxyketone.

The ketone, acetone, shown in black at left, is isomerized in the complete absence of water at very low temperature, and is given its negative charge to provide the needed enolate (by deprotonation with the base LDA, see figure legend and below). In this case, it is a lithium enolate, because of the lithium (Li⁺) counterion from the LDA. While the negative charge is shown on the oxygen, it actually resides significantly on the terminal (end) carbon of the C=C shown. This negative charge (electron density) "attacks" the partial positive charge of the C=O of acetaldehyde shown in blue. The reaction combines the two fragments, giving the newly formed bond in red. This is termed a condensation reaction for its "condensing" two smaller ones into one larger one. The intermediate formed is called an alkoxide, which is an anionic form of an alcohol, here a lithium alkoxide, given the Li⁺ counterion present. When the reaction is quenched with water (H₂O, as shown), or when an enzyme shuttles in what's needed, the alkoxide is converted to the final product (with LiOH as byproduct). The product, an alcohol (akin to the isopropanol of rubbing alcohol), is also termed an aldol, an anachonism combining the words aldehyde and alcohol. The reaction can be performed in a variety of ways that combine of C=C and C=O units (including where a single ketone serves both roles, a reaction called a self-condensation). The resulting aldol has both carbonyl and hydroxyl functional groups (see figure legend), and is extraordinarily common; one example is fructose 1,6-bisphosphate, an intermediate in central metabolism (gluconeogenesis and glycolysis) that is three steps from glucose, and another is the cholesterol-lowering statin drug atorvastatin calcium (Lipitor®). Finally, it is critically noteworthy that the reaction results in the formation of up to two new chiral/stereogenic centers—as in both of these examples—and creating such centers selectively, with only the desired "handedness" present, is both necessary for modern chemistry applications in industry, and tremendously challenging in its practice. It is estimated that the aldol reaction was reported upon XX times in the scientific literature since its discovery, and it is used every second of every day by living systems, and many times daily in laboratory chemistry operations around the world. " — Preceding unsigned comment added by 50.179.92.36 (talk) 09:17, 7 December 2013 (UTC)

Hi there, thanks for thinking about this. I do think we need a shorter and more focused lead. I think this is a good start, but it erases some of the good stuff in the original lead. It is still too long and has some specific issues, which I comment on below:

" >The aldol reaction is a chemical reaction that is important both in nature, where it is central to all of >biochemistry taking place in living organisms (e.g., in aldolase enzymes), and in human endeavors in >organic chemistry, where it has found great utility to make molecules in the pharmaceutical industry and to allow >first academic synthesis of molecules from nature (natural products).

This long description could apply to lots of reactions. Is there support for the claim that it allowed "first academic total synthesis"?

> Discovered concurrently in the 19th century by Alsatian and Russian chemists, the reaction forms new bonds

This is less specific than before. I would prefer that we mention the scientists by name.

>between carbon atoms (carbon–carbon bonds), by combining at its simplest, a two carbon fragment and a one carbon fragment >to create a new three carbon product; in practice, each piece is much larger, because the reaction accommodates further >substituents being attached to each fragment.

I would suggest that our focus should be to give the retron, not explain fragment coupling.

> The reaction is distinct in its using a carbon-carbon double bond, drawn C=C, for the two carbon fragment, where one >carbon bears a partial negative charge; this is the nucleophile.

I'm not sure the fact that the reaction uses an olefin is distinct. In fact, reactions where there is little polarization are the hardest!

> It is generated as an isomeric form of a >ketone such as the common solvent acetone, or the fragrance precursor acetophenone. The isomer is called an >enol; under basic conditions it is negatively charged, and so an enolate.

The fact that acetone is a common solvent and acetophenone is a fragrance are irrelevant. Perhaps saying "readily available precursors such as acetone or acetophenone" would be more accurate?

>For the one carbon fragment (though essentially always bigger than one carbon), the reaction can use the carbon-oxygen >double bond, drawn C=O, of an aldehyde such as formaldehyde, acetaldehyde (a relative of acetic acid in >vinegar, found in ripe fruits), or benzaldehyde (from bitter almond oil).

Same comment as above.

> Notably, as explained further below, a second ketone could also be used to provide the second fragment. The C=O unit

It seems like we're embarking on a complicated explanation that would best be relegated to a new section called "reaction scope" or something similar. I would propose that the lead merely explain a very typical aldol reaction and that we leave the specifics to later sections, on the basis that these specifics would not be interesting to the casual reader.

>of these bears a partial positive charge on its carbon atom; i.e, it is an electrophile. Under carefully controlled >conditions, reaction of this pair of nucleophile and electrophile results in a new bond between the atoms bearing the

Describing it as a polar reaction is useful. But what do you mean by "carefully controlled"? Are some reactions less carefully controlled than others? I'm not sure this needs emphasis either. In the original lead, I said in the first sentence that a carbon-carbon bond was formed. That seems more economical to me.

>opposite charges, a new carbon-carbon bond. A base-mediated aldol reaction is illustrated below in "line-angle" form, >where intersections of multiple lines imply a further carbon atom.

Are we really required to explain the structures?

> [reaction scheme]

The new scheme is simpler, but we've lost the distinction between addition and condensation. We've also lost nomenclature for alpha and beta. Also, can we stick to a standard ACS settings or European equivalent? These settings look strange to me.

>The ketone, acetone, shown in black at left, is isomerized in the complete absence of water at very low >temperature, and is given its negative charge to provide the needed enolate (by deprotonation with the base LDA,

I'd suggest that this is more commonly called a deprotonation.

>see figure legend and below). In this case, it is a lithium enolate, because of the lithium (Li⁺) >counterion from the LDA. While the negative charge is shown on the oxygen, it actually resides significantly on the >terminal (end) carbon of the C=C shown. This negative charge (electron density) "attacks" the partial positive charge

But it is still more on the oxygen than the carbon. Would it make sense to show a resonance structure?

>of the C=O of acetaldehyde shown in blue. The reaction combines the two fragments, giving the newly formed bond in red. >This is termed a condensation reaction for its "condensing" two smaller ones into one larger one. The intermediate

This is incorrect. Condensation refers to the loss of water. This is merely aldol addition.

>formed is called an alkoxide, which is an anionic form of an alcohol, here a lithium alkoxide, given the >Li⁺ counterion present. When the reaction is quenched with water (H₂O, as shown), or when an >enzyme shuttles in what's needed, the alkoxide is converted to the final product (with LiOH as byproduct). The product,

What does "when an enzyme shuttles in what's needed" mean? Perhaps we should say that "upon protonation with water"?

>an alcohol (akin to the isopropanol of rubbing alcohol), is also termed an aldol, an anachonism combining

As before, rubbing alcohol is irrelevant, and it's not our job to describe what the alcohol functional group is in this article.

>the words aldehyde and alcohol. The reaction can be performed in a variety of ways that combine of C=C and C=O >units (including where a single ketone serves both roles, a reaction called a self-condensation). The resulting aldol

Should these distinctions be in the lead? I had them there before, but I'm not sure about this.

>has both carbonyl and hydroxyl functional groups (see figure legend), and is extraordinarily common; one >example is fructose 1,6-bisphosphate, an intermediate in central metabolism (gluconeogenesis and >glycolysis) that is three steps from glucose, and another is the cholesterol-lowering statin drug >atorvastatin calcium (Lipitor®). Finally, it is critically noteworthy that the reaction results in the formation of

This is all nice, but what about the other examples I had before?

>up to two new chiral/stereogenic centers—as in both of these examples—and creating >such centers selectively, with only the desired "handedness" present, is both necessary for modern

Why can't we just say chirality? Also, nothing in the foregoing discussion has to do with chirality, so we should probably say something about the fact that intrinsically, there's no control over chirality, but modern methods now allow us to do so.

>chemistry applications in industry, and tremendously challenging in its practice. It is estimated that the aldol reaction

What do you mean by "tremendously challenging"? Isn't this at odds with the rest of this section?

>was reported upon XX times in the scientific literature since its discovery, and it is used >every second of every day by living systems, and many times daily in laboratory chemistry operations around the world.

This seems excessive to me. I mean, the aldol reaction is important, but it's not the most important thing in the entire world...

"

If I had to make a list of things that should go into the lead for a reaction, it would be:

- what does the reaction do? i.e., what are the starting materials and products? - what is its synthetic importance? what is its retron and what important commodities or iconic natural products has it been used to make? - what is the mechanism, in simplistic terms?

I like the new lead in that it's simpler, speaks to a more general science audience in terms of basic concepts, and gets at all three of these points. I think it could use some more focused writing, become shorter, and emphasize the broader importance of the reaction in a more specific and less ostentatious way. I have a lot to do right now, but if you take another shot at it, I could make more edits later?

Eugene Kwan (talk) 16:03, 8 December 2013 (UTC)

Sorry to be so long in getting back to you. I failed to mark this talk page to watch, and assumed, not seeing a ping at my Talk page, that you dismissed me as a crazy, and did not reply. In any case, now seeing your careful review of the proposed lede, I will attend further to it. See also the note, left today, vis-a-vis the Natural Products page. Cheers, Le Prof Leprof 7272 (talk) 20:00, 3 June 2014 (UTC)

Possible FAR

1. sections like "Biological aldol reactions", "Acidity", "Enolate mechanism", "Enol mechanism" have no footnotes, lot sections like "Crossed-aldol reactant control" needs additional footnotes;
2. There's 3 template needs to be clarify;
3. Some sentences sounds ... textbook... I mean just like a teacher in classroom: "The problem of "control" in the aldol addition is best demonstrated by an example. Consider the outcome of this hypothetical reaction:" with a big formula below, and then "In this reaction ......". But this is not, and shouldn't be a textbook.
4. Such a big picture for lead section, feels inappropriate and unnecessary, specially when there's another big image right after. I also feel that third section for the lead, start with "For example, stereogenic aldol units are especially common...", for lead section, this feels kind over detail.

--Jarodalien (talk) 14:20, 21 February 2015 (UTC)

I replaced the {{more footnotes}} (all the references were already in-line therefore this tag is not appropriate) with a more appropriate {{refimprove}} tag (because some paragraphs are unsupported). I also note that the ratio of citations to prose is actually slightly higher in the current version than when this article was promoted to FA:

• Current version: article Prose size (text only): 26 kB (3993 words) "readable prose size", 58 citations, 58/3993 = 0.0145 citations/word
• Version when promoted to FA Prose size (text only): 22 kB (3379 words) "readable prose size" 41 citations, 41/3379 = 0.0121 citations/word

Furthermore there were many unsupported paragraphs when the article was promoted. Rather than saying this article no longer meets FA standards, it would be more accurate to say that current FA standards are higher than when this article was promoted. Boghog (talk) 16:10, 7 March 2015 (UTC)

I translated this artical to chinese version around three years ago and found a few mistakes in the pictures:

1. Crimmins thiazolidinethione aldol section: A nitrogen atom was missed in the structure of sapateine.

2. Picture after this sentence "Many methods are available for the cleavage of the auxiliary:", the base of hydrolysis reaction is lithium hydroxide (LiOH), not (LiOOH). Merphisto (talk • contribs) 10:10, 8 March 2015 (UTC)