Talk:Aldol reaction

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Former featured article Aldol reaction is a former featured article. Please see the links under Article milestones below for its original nomination page (for older articles, check the nomination archive) and why it was removed.
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Archive 1 ( - Feb 2006)

Revisions[edit]

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)

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[edit]

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[edit]

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):

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[edit]

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[edit]

"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[edit]

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[edit]

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[edit]

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[edit]

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?[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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?[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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 ...[edit]

... 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 ...[edit]

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[edit]

  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 [when?] 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 (talkcontribs) 10:10, 8 March 2015 (UTC)