Propionic acid chloride, hydrolysis

Similar aggressive reaction conditions characterize the hydrolysis of acid chlorides, in particular when using short-chain alkyl-substituted acid chlorides such as propionic acid chloride. This fast reaction serves well as a model reaction for micro channel processing, especially for IR monitoring owing to the strong changes in the carbonyl peak absorption by reaction [21]. 

Ibuprofen Ibuprofen, 2-(4-iTo-butylphenyl)propionic acid (3.2.23), can be synthesized by various methods [88-98]. The simplest way to synthesize ibuprofen is by the acylation of Mo-butylbenzol by acetyl chloride. The resulting iTo-butylbenzophenone (3.2.21) is reacted with sodium cyanide, giving oxynitrile (3.2.22), which upon reaction with hydroiodic acid in the presence of phosphorus is converted into 2-(4-iTo-butylphenyl)pro-pionic acid (3.2.23), which subsequently undergoes phases of dehydration, reduction, and hydrolysis. 

Later Gronowitz and Maltesson reported the extension of this method to the preparation of thieno[2,3-6]thiophene (1) derivatives. A mixture of 3-(3-thienyl)acrylic acid, thionyl chloride, and pyridine was heated for 24 hours. 2-Chloro-3-(3-thienyl)-acrylic acid (4.5%), 3,5-dichlorothieno[2,3-6]thiophene-2-carbonyl chloride (99) (9.5%), 3-chlorothieno[2,3-Z)]thiophene-2-carbonyl chloride (100) (79.1%), and other compounds were detected by GLC among the reaction products [Eq. (31)]. Hydrolysis of the reaction mixture gave 3-chlorothieno[2,3-Z>]thiophene-2-carboxylic acid in 63% yield dechlorination of the latter by copper in propionic acid converted it into thieno[2,3-6]thiophene-2-carboxylic acid. 

The presence of the propionamide fragment in the stmcture of the anti-inflammatory agent broperamole (125-1) is reminiscent of the heterocycle-based NSAID propionic acids. The activity of this agent may trace back to the acid that would result on hydrolysis of the amide. Tetrazoles are virtually always prepared by reaction of a nitrile with hydrazoic acid or, more commonly, sodium azide in the presence of acid in a reaction very analogous to a 1,3-dipolar cycloaddition. A more recent (and safer) version of the reaction noted later (see losartan, 77-4) uses tributyltin azide. In the case at hand, reaction of the anion of mefa-bromobenzonitrile (125-1) with sodium azide and an acid affords the tetrazole (125-2). Condensation of the anion from that intermediate with ethyl acrylate leads to the product from Michael addition saponiflcation gives the corresponding carboxylic acid (125-3). This is then converted to the acid chloride reaction with piperidine affords broperamole (125-4) [136]. 

Carbonation of benzo[6]thienylmethylmagnesium chlorides usually gives only a low yield of the required acetic acid (Section VI,D,4).485,517,526,528 a- Hydroxy - a-(3-benzo[6]thienyl)propionic acid (306) is formed by hydrolysis of the product of the reaction between 3-benzo[6]thienylmagnesium bromide and ethyl pyruvate.207... 

A wide variety of A2B monomers, such as 2,2-dimethyl propionic acid, 3,5-diacetoxybenzoic acid, 3,5-6is(trimethylsiloxy)benzoyl chloride, 3,5-dihydroxy-benzoic acid, and 5-acetoxyisophthalic acid have been used for the synthesis of hyperbranched polymers. A majority of the polymers are synthesized via step-wise polymerizations where A B monomers are bulk-polymerized in the presence of a suitable catalyst, typically an acid or a transesterification agent. To achieve satisfactory conversion, the low-molecular-weighf condensation product (e.g. H2O, CH3OH) formed during the reaction has to be removed. This is most often accomplished by passing an inert gas or by reducing the pressure in the reaction vessel. A drawback of polycondensation polymers is that they are prone to depolymerization by hydrolysis, which might restrict their use. 

Amino cyanides are obtained by the action of ammonia and hydrocyanic acid, or of ammonium chloride and sodium cyanide, on aldehydes, or alternatively from cyanohydrins and ammonia. They are best hydrolysed by concentrated hydrochloric acid, the resulting amino acids being then obtained as hydrochlorides, whence the free amino acids can be liberated by means of lead monoxide, ammonia, or pyridine. For a critical consideration of the hydrolysis of amino cyanides see Cocker and Lapworth.632 The synthesis of DL-alanine has been detailed twice.780 633 That of racemic ac-amino-ac-phenyl-propionic acid from acetophenone, sodium cyanide, and ammonium chloride by way of the amino cyanide was worked out by Steiger.634 /9-Alanine is obtained in 85-90% yield when 3-aminopropionitrile is added to aqueous barium hydroxide at 90-95° during 40 min and kept at that temperature for a further 40 min.635... 

A useful route to cyclized 2-thienyl ketones has been found by Gol dfarb and co-workers. Starting from 2,5-dichlorothiophen, they obtained the keto-acids (78) by conventional Friedel-Crafts reaction with ester chlorides of succinic and glutaric acid followed by hydrolysis. By treatment with copper in refluxing propionic acid the 2-chlorine could selectively be reduced and Wolff-Kishner reduction then yielded (78a), which in turn could be ring-closed to (78b) by conventional means. Some other dechlorination methods have also been used. ... 

Poly(vinyl acetate) dispersions form lightfast, dry, hard, brittle films. Plasticizers therefore have to be used (external plasticization), which are, however, volatile and lead to embrittlement of the films after a relatively short time. Internally plasticized dispersions of copolymers of vinyl acetate with vinyl laurate, butyl maleate, Versatic Acid esters, or ethylene form permanently flexible, nonaging films that are not, however, always sufficiently resistant to hydrolysis. Terpolymer (vinyl acetate-ethylene-vinyl chloride) dispersions form films that are more resistant to hydrolysis than homopolymer and copolymer dispersions. The films also have a higher mechanical strength and lower flammability. The glass transition temperature of the terpolymer can be varied within wide limits and properties can be matched to requirements by using a suitable choice of comonomers. The same is true of vinyl propionate copolymer dispersions. 

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