Alcoholysis, acyl chlorides

Alcoholysis of 1 -chloro-2-acyl-1,1,2-trifluoroethane, available from trifluoro-ethylene, an acyl chloride, and aluminum chloride, leads to 1-fluoro- 1-acylacetates [/] (equation 1) It is surpnsing that the remaining carbon-tluorine bond resists hydrolysis. 

Investigations into the mechanism of hydrolysis and alcoholysis of acyl halides have been largely concerned with acyl chlorides and in particular with benzoyl chloride and the related aromatic acid chlorides. This was a result of the relatively slow rate of hydrolysis of benzoyl chloride compared with acetyl chloride (although their alcoholysis rates are easily measurable) and it is only comparatively recently90 that stop-flow techniques have been used to measure the faster rate of hydrolysis. However, in spite of this limitation, considerable progress has been made towards elucidation of the mechanism or mechanisms of hydrolysis and alcoholysis of these halides. 

The effect of substitution in the benzene ring on reactivity of the acyl chloride group was investigated by a series of workers, using hydrolysis and alcoholysis. Data from these workers are compiled in Table 15 for mono-substituted benzoyl chlorides. 

E) Alcoholysis of Acyl Chlorides. Add 5 drops of acetyl chloride to 1 ml of ethanol. What is the product resulting from this reaction Can this test be used for detection of the hydroxyl group If so, try it with a less reactive hydroxy compound. 

Keto esters. Meldrum s acid (1) reacts with acyl chlorides in CH2CI2 in the presence of pyridine to form an acyl Meldrum s acid (2) in almost quantitative yield. These derivatives undergo alcoholysis readily to form )5-keto esters (3). ... 

The relative reactivities toward nucleophilic addition-elimination are acyl chlorides > acid anhydrides > esters carboxylic acids > amides > carboxylate ions. Hydrolysis, alcoholysis, and aminolysis are reactions in which water, alcohols, and amines, respectively, convert one compound into two compounds. 

Treatment of [2- C]malonic acid with acetone in the presence of acetic anhydride and catalytic amounts of concentrated sulfuric acids provides [5- C]Meldrum s acid (419). one of the most versatile low molecular weight building blocks . As summarized in Figure 6.124, its reactivity at C2 is analogous with that of the malonate diesters already discussed. However, the reactivity of the initial adducts differs. For example, hydrolysis or alcoholysis (including tert-BuOH) of the initial adducts with alkyl halides , aldehydes and acyl chlorides gives directly the [2- C]carboxylic acids/esters, a,/3-unsaturated acids/esters and /3-keto acids/esters, respectively, with simultaneous elimination of acetone and In contrast, the 2-(alkoxymethylene)[2- C]malonate... 

Because of the particular structural features of compound 4, pointed out in Section I, the D-glucofuranosyluronic halide anomers not only have inverse thermodynamic stabilities with respect to those of D-glucopyranosyl halides but also show a different behavior towards alcohols. For instance, 2,5-di-O-acyl-a-D-gluco-furanosylurono-6,3-lactone halides, which are difficult to prepare, do not react with alcohols, inasmuch as an endo approach of the reagent is inhibited.14 The /3-bromides and -chlorides, however, just like /3-D-glucopyranosyl chlorides, are subject to alcoholysis, with formation of /3-D-glucofuranosidurono-6,3-lactones.16... 

Ethyl 3-oxoalkanoates when not commercially available can be prepared by the acylation of tert-butyl ethyl malonate with an appropriate acid chloride by way of the magnesium enolate derivative. Hydrolysis and decarboxylation in acid solution yields the desired 3-oxo esters [59]. 3-Keto esters can also be prepared in excellent yields either from 2-alkanone by condensation with ethyl chloroformate by means of lithium diisopropylamide (LDA) [60] or from ethyl hydrogen malonate and alkanoyl chloride usingbutyllithium [61]. Alternatively P-keto esters have also been prepared by the alcoholysis of 5-acylated Mel-drum s acid (2,2-dimethyl-l,3-dioxane-4,6-dione). The latter are prepared in almost quantitative yield by the condensation of Meldrum s acid either with an appropriate fatty acid in the presence of DCCI and DMAP [62] or with an acid chloride in the presence of pyridine [62] (Scheme 7). 

Fig. 13.65. Acylation of various malonic diester or malonic half-ester enolates with carboxylic acid chlorides. Spontaneous decarboxylation of the acylation products to furnish /3-ketoesters (see variants 1 and 2) and transformation of the acylation products into /3-ketoesters by way of alcoholysis/decarboxylation (see variant 3).

C-7 Side-Chain Cleavage. 7-ACA (1), the key intermediate for the synthesis of a large number of the clinical cephalosporins, cannot be made by fermentation, nor can it be readily obtained by enzymatic removal (187) of the aminoadipic acid side chain from cephalosporin C. Because substantial quantities of 7-ACA are used, an efficient method for the chemical cleavage of the acyl side chain of cephalosporin C was sought. The first efficient method involved diazotization using nitrosyl chloride, followed by hydrolysis or alcoholysis, and gave 7-ACA in 50% yield (22,23,87,188). The reaction proceeds via the formation of the cyclic imino ether (57) which is easily hydrolyzed under very mild conditions. 

Diacyl monosulfides are cleaved analogously to acylsulfur chlorides, which with thiols form l-acyl-2-alkyldisulfanes, whence alcoholysis affords alkyl-... 

Acylation of the bis-enamines (196) by acid chlorides followed by acidic alcoholysis leads to a wide variety of yields (highest in the absence of an a-H in the chloride) of 6-keto-esters (197) in an alternative to the direct Claisen method. The intermediate acylated enamines can also be converted into 6-keto-amides 185... 

Alcoholysis of the acyl organyl sulfides RC(0)SxR (R, R =alkyl, aryl x=2, 3) in the presence of hydrogen chloride gives the organyl hydrodi- and hydrotrisulfides RSxH (x=2,3) in good yield [20,21,65,176,282]. Acyl alkyl disulfides react with thiols to yield asymmetrical disulfides [200]. Selenium bis(thiocar-... 

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