Products of Aldol Addition and Related Reactions Notation for their Prediction Stephen 0. ~waukwal' Purdue University, West Lafayette, IN 47907 Crossed aldol addition and related reactions often give rise to many products ( l , 2 ) .This usually is the case when each of the reacting molecules has an a-hydrogen atom. In many cases it is difficult to identify all the possible products of such reactions. Arelatively simple case can be seen in the reaction between butanal, A, and propanal, B, where four products are obtained. Products 3 and 4 arise from the self additions of ethanal and propanal molecules, respectively. Product 1 results from the addition of ethanal and propanal but with the propaual providing the electrophilic carbon. Product 2 results when ethanal provides the electrophilic carbon. When the reaction between two unsymmetrical ketones are considered in a similar way, it becomes difficultto predict all the possible products arising from the reaction. For instance, the aldol addition reaction between hutanone and 2-pentanone gives 8 products which may not be easy to predict. A simple method that can be used to predict products of aldol and aldol-type addition reactions is hereby reported. The method utilizes two notations designated by C,' and Cn- where the former represents the nth carbon atom having the electrophilic center, (carbonyl m u p in this case) and the later represents the nth carbon atom having an acidic hydrogen (a-carbon in this case). This notation also uses a continuous numbering system in which each carbon atom in the reactant molecule is assigned a number. Examples of the use of this notation are demonstrated in Tables 1and 2. I t should be noted from Table 1that C ; and C$ represent the electrophilic carbons 1 and 3 while C< and C p represent the nucleophilic carbons 2 and 4, respectively. I t also should be noted that the numbers appended in the product molecules serve only to identify each carbon atom as i t appears in the reactant molecule. These numbers, therefore, are not to be used in naming the molecules. 'Visiting Faculty. Permanent Address-Chemistry Department, Ondo State University, Ado-Ekiti, Nigeria.
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Numbering System The following numbering system is adopted in this paper for the prediction of aldol addition products. Table 1. Generation of Aldol Products for the Reaction of Ethanal with Propanal
#
Notation
New Bond
1
Ci-Cz
2 3 4
c1-c4
+Ci) + c4-)
1
(Cit
2
('21'
3 4
(c$ + c2-) (C$
Structure
+ c4-)
c3-c2 C3-C4
(1) One reactant molecule is numbered first following the IUPAC rules. Then the second reactant molecule is num-
bered starting with the number immediately following the largest number used in the numbering of the first re(2) When two aliphatic aldehydes are involved, numbering starts from the aldehyde having the least number of ear-
bon atoms. (3) In a reaction involving an aldehyde and a ketone, the aldehyde is numbered first regardless of its carbon length. (4) When two ketones are involved, the one with the shortest
chain is numbered first. ( 5 ) When the reaction involves an aromatic and an aliphatic aldehyde or ketone, numbering starts fmm the aliphatic compound. In general, the priority in the order of number-
ing is: aldehyde>ketone> ester>cyanide > alkyb halide> aromatic.
A simple method tu arrive at these product notations is to list all the electro~hiliccarbons in the two reactine molecules on one side of a bar while all the carbons caving
Table 2. Generation of Aldol Roducts for the Reaction of Butanone and 2-Wntanone
L4& +
I
Notational Analysis
3
Prod No.
dl
Products
5
Product Notation
acidic hydrogens are listed on the other side of the bar using the above notations. Each carbon on the left is then combined with each carbon on the right which gives rise to a specific product. This is shown above for the previously discussed reaction. Other Applications
Products of malonic ester synthesis of carboxylic acids or the acetoacetic ester synthesis of ketones can be character-
Product structure
New Bond
ized equally using this method. An example of this is shown for the malonic ester synthesis of pentanoic acid. Cyclization Reactions
This notational analysis can be used equally for the prediction of ~roductsarisine from intramolecular cvclization reactions i3-5). For example, base treatment of compound C will give rise to 8 possible products using this notational analysis (Table 3). Product 17 is the predominant one due to its stability followed by product 16. Volume 70 Number 8 August 1993
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Products 15 and 18 will each give a fourmembered ring compound which may not be stable. Products 13, 14, 19, and 20 cannot be formed for obvious reasons. No new bonds can form in the areas indicated. It can be seen from all the analysis above that this method of prediction of carbanion reaction products will be useful to students in particular for a better understanding of aldol condensation and related reactions.
Table 3. Notation for the Rediction of Cyclization Products
Substrate
Acknowledgment I wish to express my gratitude to Harry Morrison for his useful suggestions. Literature Cited 1. Stepanov,A.Y;ShchulrinaM. J. Russ. Phys4hPm. Soe 1926.58
84C. 2 . Gottwalt. F:Wiedemann. O.Ann. 1934,513,25. 3. Smtt, J. W.: Banner, B.L.:Saucy, G. J. Or#. Chem. 1973,37,16M. 4. Stork, G.; Canem, B. J. Am. Chem. Soe. 1W8.95.6152. 5 . Marshall. J. A,: Fsnta, W.I . J. O z . Chpm 1964,29,2501.
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Journal of Chemical ~ducati'on
Notational Analysis
c6+
c
Generated Pmducts
