provide a way to temporarily modify a carbonyl group so that the carbon atom behaves as a nucleophile (electron-rich site reactive to positive species) in displacement and addition reactions. Among the reactions are alleviation, reaction with 1,2-oxides to form mercaptals of /^-hydroxy ketones or aldehydes, reaction with ketones and aldehydes to give mercaptals of a-hydroxy aldehydes and ketones, and oxidation (and then hydrolysis) to form carboxylic acids. Dr. Corey and Dr. Seebach also find that the carbanions are useful starting materials for making 1,2-, 1,3-, and other dicarbonyl derivatives. The Harvard chemists prepare the carbanions by reacting 1,3-dithianes with n-butyllithium. They have made a variety of carbanions including those in which the group attached at the C-2 position is primary, secondary, or tertiary alkyl; allyl; benzyl; aryl; or an oxygen-containing group such as CH-CHL,(OC,H5)2. The anion in which hydrogen is attached at the C-2 position can be alkylated in 70 to 90% yield with a wide variety of alkyl halides, Dr. Corey and Dr. Seebach find. Good yields are also obtained in introducing a second alkyl group. For example, they have obtained a 70 % yield of the 2,2-diisopropyldithiane by two successive alkylations with isopropyl iodide in one reaction vessel. The carbanions react readily with 1,2-oxides to form mercaptals of /?hydroxy ketones or aldehydes. For example, the reaction of the 2-methyldithiane carbanion with styrene oxide gives a 70% yield of product. The product yields benzylideneacetone after hydrolysis and dehydration, the Harvard chemists find. Ketones and aldehydes combine with the carbanions to give good yields of mercaptals of a-hydroxy aldehydes and ketones. When the dithiane carbanion is added to ketones, the products can be dehydrated to give ketene mercaptals. The carbanions also add to imines. For example, the 2-methyldithiane carbanion reacts with benzylideneaniline to give a 70% yield of an adduct. In addition, the carbanions react with oxygen to give carboxylic acids after subsequent hydrolysis. Dicarbonyls. Dr. Corey and Dr. Seeback have used the carbanions to synthesize a variety of dicarbonyl derivatives. Carbon dioxide reacts with the anions to give mercaptals of a36
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keto carboxylic acids (70 to 7 5 % yield). A large excess of ethyl chloroformate (instead of carbon dioxide) gives ethyl carboxylates which can be saponified to the dithianecarboxylic acids. Monomercaptals of 1,2-diketones can be made from the carbanions and carboxylic acid derivatives. Esters can sometimes be used as starting materials. For example, the 2-methyldithiane carbanion reacts with ethyl cyclohexanecarboxylate to give a 60% yield of the monomercaptal. By contrast, the anion reacts with ethyl benzoate to give the dimercaptal in 9 5 % yield. The reaction of nitriles with the carbanions produces monomercaptals. For example, the reaction of the 2methyldithiane anion with benzonitrile gives an 80% yield of the monomercaptal. Dr. Corey and Dr. Seebach find that 1,2-addition rather than 1,4-addition occurs in the reaction of the carbanions with a,/?-unsaturated carbonyl compounds. For example, the reaction of the dithiane carbanion with ethyl cinnamate gives a mixture containing the monomercaptal and an adduct formed from a 2:1 molar ratio of anion to ethyl cinnamate. Alkylation of the carbanions by ketals of aand /?-halo carbonyl compounds— XCH 2 CH (OR) o, for example—represents an approach to 1,3- and 1,4-dicarbonyl structures, they note. Alkylation reactions furnish another route to derivatives of dicarbonyl compounds, the Harvard chemists point out. Reaction of the carbanions with 1,4-dibromobutane gives the 1,6-diketone derivatives in over 80% yields. Reaction of the dithiane carbanion with 1,3-dibromopropane gives a 66% yield of the 1,5-diketone derivative. The carbanions couple when treated with oxidizing agents to produce 1,2-carbonyl derivatives. Among the oxidizing agents that Dr. Corey and Dr. Seebach have used are 1,2dibromomethane, copper ( I I ) , and iodine. As a result of the work with 1,3dithiane-derived carbanions, there are now several good procedures available for selective hydrolysis of various types of dithianes to carbonyl compounds at mild conditions, the Harvard pair points out. One significant result of the work will be the simplifying of complex syntheses by revealing new, alternate routes, they note.
Water Spurs Carbonium Ion Rearrangement Carbonium ions generated in a nonprotonating medium rearrange less readily than do those generated in an aqueous medium, according to Dr. Lester Friedman and his associates at Case Institute of Technology, Cleveland, Ohio. They have shown that nonprotonating solvents, such as chloroform, benzene, and cyclohexane, enhance hydrocarbon yields, minimize skeletal rearrangements and double bond migrations, and increase cyclopropane formation [/. Am. Chem. Soc, 87, 5788, 5790 (1965)]. Working with Dr. Friedman were J. H. Bayless, A. T. Jurewicz, and F. D. Mendicino. By generating carbonium ions by diazotizing amine salts, the Case chemists find that, in chloroform, isobutylamine gives a 30% yield of hydrocarbons—70% isobutene, 15% methylcyclopropane, and 15% rearranged butenes. In protic medium, 50% aqueous acetic acid, the hydrocarbon yield drops to 12%—40% isobutene, 2.5% methylcyclopropane, and 57%? rearranged butenes. Aqueous systems stabilize a carbonium ion by solvating it. This allows it to rearrange to a thermodynamically more stable structure. Since an aprotic medium cannot solvate as effectively, stabilization is decreased, and the products are derived from kinetic rather than thermodynamic factors. Counter-ion-derived products (esters and alcohols) also are rearranged less in nonprotonating solvents, again indicating kinetic control. When carbonium ions are generated in benzene, toluene, or anisole, a small amount (1%) of aromatic substitution occurs. Dr. Friedman finds that the isopropyl cation alkylates toluene to give all three cymene isomers: 42% ortho, 24% meta, and 34% para. This agrees with results from comparable experiments done by Dr. Donald E. Pearson at Vanderbilt University, Nashville, Tenn. The Case group also finds that alkylating benzene with the carbonium ion from n-propylamine gives 97% unrearranged n-propylbenzene, and 3 % isopropylbenzene. The Vanderbilt workers reported 4 5 % n-propylbenzene and 55% isopropylbenzene. Competition experiments by Dr. Friedman indicate that toluene is 1.7 to 2.8 times as reactive as benzene toward the isopropyl cation.,
