Carboxylic acids, from diazoketones

Carboxylic acids from diazoketones via carboxylic acid amides... 

Carboxylic acids from r -diazoketones Ring contraction... 

Carboxylic acids from oc-diazoketones Horner-Wolff rearrangement... 

Irradiation (s. a. under iVaA Og) Carboxylic acids from a-diazoketones... 

At the present time, most of the positive photoresists used in the manufacture of microcircuits consist of a low molecular weight phenolic resin and a photoactive dissolution inhibitor. This composite system is not readily soluble in aqueous base but becomes so upon irradiation with ultraviolet light. When this resist is exposed, the dissolution inhibitor, a diazoketone, undergoes a Wolff rearrangement followed by reaction with ambient water to produce a substituted indene carboxylic acid. This photoinduced transformation of the photoactive compound from a hydrophobic molecule to a hydrophillic carboxylic acid allows the resin to be rapidly dissolved by the developer. (L2,3)... 

The formation of a-diazoketones from carboxylic acids (via the acyl chloride or an anhydride) and the subsequent Wolff Rearrangement in the presence of nucleophiles results in a one-carbon homologation of carboxylic acids. This reaction sequence. 

Fig. 14.29. Preparation of an a-diazoketone (compound E) from a ketone (A) and subsequent Wolff rearrangement of the a-diazoketone. Initially, A is transformed to give the enolate B of its a-formyl derivative. In a Regitz diazo group transfer reaction, this will then be converted into the a-diazoketone E. Ring contraction via Wolff rearrangement occurs and the 10-membered cyclic diazoketone C rearranges in aqueous media to give the nine-membered ring carboxylic acid E via the ketene D.

A further reaction which appears to involve the formation of 1 5-, 2 3-, and 3 4-bonds is the reaction of a-chloro-a-phenylmercapto-ketones (8) (prepared from the corresponding a-diazoketones) with liquid carboxylic acids and ammonia.74 The course of the reaction is not clearly understood, but shows similarities to the reaction of... 

A reaction which is applicable to the synthesis of imidazoles substituted at C-4 by sulfur substituents is the interaction of a-chloro-a-phenyl thioketones (prepared from the corresponding diazoketones) with ammonia and carboxylic acids. Although the detailed reaction course is yet uncertain, it bears a close resemblance to the reactions of a-chloro ketones with amides. The method has been used to prepare 2-ethyl-4-methyl-5-phenylthioimidazole (145) using ammonia, propanoic acid and 1-chloro-l-phenylthiopropanone (Scheme 82). 

A number of miscellaneous methods which involve multibond formation are included here for completeness in spite of the fact that their synthetic utilities do not appear to be great. A reaction which closely resembles the a-halogenokeione-amide method is the cyclization of an a-chloro-a-phenylthioketone (prepared from the diazoketone) with ammonia and a carboxylic acid. It has been used to prepare 2-ethyl-4-methyl-5-phenylthioimidazole in 32% yield [68]. 

Illustrating the versatility of C-cyanoglycoside nitrile derivatives, Myers, et ai.,15 formed a diazoketone from the peracetylated C-cyanoglucoside shown. The reaction sequence, illustrated in Scheme 2.2.20, involved the initial hydrolysis of the nitrile to the corresponding primary amide. Subsequent hydrolysis afforded the carboxylic acid. On conversion of the acid to a mixed carbonic anhydride followed by treatment with diazomethane, the desired diazoketone was obtained. 

Carboxylic acid amides from diazoketones COCHNs —v CHjCONH ... 

Carboxylic acid esters from a-diazoketones COCHNg —CH2COOR s. 4, 220... 

Diazoketones such as 307 can be formed from acid chlorides by reaction with diazomethane. Subsequent treatment with aqueous Ag20 leads to the Wolff rearrangement and formation of a carboxylic acid of one carbon more than the starting acid chloride. This sequence is known as the Arndt-Eistert synthesis.252 a synthetic example using this is taken from Weinreb s studies toward the synthesis of cylindrospermopsin,253 iu which 315 was treated with (1) oxalyl chloride, (2) CH2N2 and (3) Ag20, MeOH to give a mixture of products 22% of 316 and 39% of 317. 

Photfrfysis of a-Diazo Carbonyl Compounds - Some recent advances in the matrix photochemistry of diazoketones, including some heterocyclic species, have been reviewed. Flash photolysis of 10-diazo-9(10//)-phenanthrenone (35) in aqueous solution led to the detection of two transient species on the pathway to the final product, fluorene-9-carboxylic acid. These were identified, from solvent isotope effects and the nature of the observed acid-base catalysis, as fluorenylideneketene (36, X = CO) and the enol of fluorene-9-carboxylic acid (36, X = C(0H)2), formed by hydration of the ketene. In related studies, fluorenylideneketene was found to react with amines to give ylides as intermediates on the route to the amide final products. The product distribution from the photochemical reactions of 2-diazo-3-oxo-5,10,15,20-tetraphenylchlorins with alcohols strongly depends on the central metal ion of the irradiated diazoketones. ... 

If the ketene was produced via a Wolff rearrangement at low temperature then the carboxylic acid c.ster. should certainly form as a result of the room temperature exposure. In view of this we conclude that the mechanism for the vacuum electron beam exposure docs not involve a Wolff rearrangement. Instead we propose that-a carbene formed by loss of Aj from the diazoketone plays a central role in the chemistry that ensues after electron beam exposure. The propo.sed mechanism for the electron beam induced chemistry discu.ssed thus far is summarized in the scheme below. 

Carboxylic acid amides from a-diazoketones COCHNo CHoCON <... 

---