Acid halides aliphatic

Cyclization of cyanohydrins with aliphatic acid anhydrides in the presence of strong acids (pAT < 1) or aromatic acids halides in the presence of SnCl4. 

Other examples are acetoacetates alkylamines and alkylhalides/acid halides ethers esters chloroformates ketones lactames lactones malonates mercaptanes and orthoesters in aliphatics catechol/hydroquinone/resorcinol, cresidines haloaromatics in aromatics and coumarines, cyanuric chloride, picolines, quinolines, and thiazoles in heterocylics. 

In sulfamation, also termed IV-sulfonation, compounds of the general structure I NSC H are formed as well as their corresponding salts, acid halides, and esters. The reagents are sulfamic acid (amido—sulfuric acid), SO3—pyridine complex, S03—tertiary amine complexes, aliphatic amine—S03 adducts, and chlorine isocyanate—S03 complexes (3). 

This chapter deals with the kinetics and mechanisms of the hydrolysis of carboxylic acid derivatives of general formula RCOX. These include carboxylic acid halides, amides, and anhydrides with small sections on carboxylic acid cyanides etc. Many recent developments in this field have been made with acid derivatives in which R is not an aliphatic or aromatic group, for example, carbamic acid derivatives, and these are reported where relevant, as are reactions such as ethanolysis, aminolysis, etc. where they throw light on the mechanisms of hydrolysis. 

A simpler nonphosgene process for the manufacture of isocyanates consists of the reaction of amines with carbon dioxide in the presence of an aprotic organic solvent and a nitrogeneous base. The corresponding ammonium carbamate is treated with a dehydrating agent. This concept has been applied to the synthesis of aromatic and aliphatic isocyanates. The process relies on the facile formation of amine—carbon dioxide salts using acid halides such as phosphoryl chloride [10025-87-3] and thionyl chloride [7719-09-7] (30). 

General methods for the preparation of acid halides from aliphatic carboxylic acids are described in Section 5.12.1, p. 692. Phosphorus pentachloride is the preferred chlorinating agent for aromatic acids which contain electron-withdrawing substituents, and which do not react readily with thionyl chloride. The preparation of both p-nitrobenzoyl chloride and 3,5-dinitrobenzoyl chloride is described in Expt 6.161. These particular acid chlorides are valuable reagents for the characterisation of aliphatic alcohols and simple phenols, with which they form crystalline esters (see Section 9.6.4, p. 1241 and Section 9.6.6, p. 1248). 

Treatment of acyl halides (3) with Sml2 provides 1,2-diketones (4) via the coupling of acyl radicals, which are sp2 carbon-centered radicals (eq. 2.2). Generally, aromatic acid halides are more reactive than aliphatic acid halides. 

The simpler examples are readily hydrolysed in aqueous solution, and therefore react with sodium hydrogen carbonate and also give the ester test they may be confirmed by applying the hydroxamic ester test (Section 9.5.3, p. 1222). Carbonyl adsorption is apparent in the infrared spectrum at about 1820 cm-1 and at about 1760cm-1. It should be noted that aromatic anhydrides and higher aliphatic anhydrides are not readily hydrolysed with water and are therefore effectively neutral (Section 9.5.3, p. 1218). The final characterisation of the acid anhydride is achieved by conversion into a crystalline carboxylic acid derivative as for acid halides. 

Synthesis of Phenyl Ethers A phenol (aromatic alcohol) can be used as the alkoxide fragment, but not the halide fragment, for the Williamson ether synthesis. Phenols are more acidic than aliphatic alcohols (Section 10-6), and sodium hydroxide is sufficiently basic to form the phenoxide ion. As with other alkoxides, the electrophile should have an unhindered primary alkyl group and a good leaving group. 

Modified phosphorus halides, which allow more controlled reaction conditions, have been developed more recently. Thus 2,2,2-tribromo- and 2,2,2-trichloro-1,3,2-benzodioxaphospholes (la) and (lb), "" as well as dichloro- and dibromo-phosphoranes (2a) and (2b)" have been used successfully in the preparation of a number of aromatic and aliphatic acid halides. These reactions can be carried out at room temperature or slightly above and convert carboxylic acids or anhydrides in good yield to the acid halides. Also, unsaturated acids tolerate these reaction conditions. In many cases products can be isolated by distilling the acid halide directly from the reaction mixture. An advantage of these reagents is their... 

More recent approaches which avoid acidic conditions are based on the application of trimethylsilyl bromide or iodide (equation 12). With aliphatic acid halides a high reactivity (often the reaction is exothermic) is observed. The isolation of the products can be effected immediately after the addition of trimethylsilyl halide is complete. With aromatic halides heating is sometimes required. Easy woilc-up is possible, because only the low boiling trimethylsilyl chloride has to be removed before the product is isolated by distillation. Table 5 gives some examples. 

Activation of carboxylic acids by phosphoms acid halides in the form of different derivatives (3-7) has been used extensively in more recent years. These methods have been tested not only for saturated aliphatic or aromatic carboxylic acids but also for functionalized derivatives. In Table 6 some examples are collected where (3) and (4) were applied successfully. The reactions are carried out at room temperature in acetone or dichloromethane by treatment of the carboxylic acid with 1 equiv. of triethylamine or A -ethylpiperidine and 0.5 equiv. of the reagent (equation 25). The anhydrides are either collected by filtration or recovered by evaporation of the solvent after washing with water. 

Thallium(I) cyanide was introduced by Taylor and McKillop as a reagent. Aromatic and heteroaromatic acyl cyanides are produced in go yield, whereas aliphatic acid halides lead under these conditions mainly to dimerization products. 18-Crown-6 is a good catalyst for the preparation of cyanoformate in methylene chloride with potassium cyanide and chloroformates. Similarly, tetraethylammonium cyanide gives cyanoformates in high yield under very mild conditions. Aroyl cyanides are generated easily by phase transfer catalysis with tetra-n-butylammonium bromide. Tri- -butyltin cyanide proved successful only with aromatic acid halides, leading to dimerization products with aliphatic compounds. ... 

A general method for the preparation of a-cyano ketones from acid halides was developed recently (equation 43).i57.i58 trimethylsilyl cyanide as reagent a great number of acyl cyanides can be prepared under mild conditions in high yield. In particular the synthetically useful aliphatic derivatives have become accessible by this reaction. Table 13 lists examples for aliphatic, a, -unsaturated and benzylic acyl cyanides. The procedure is very simple in that trimethylsilyl cyanide and acid chloride are mixed and kept without solvent. The reaction is followed by IR spectroscopy. As soon as all of the trimethylsilyl cyanide is consumed, the product can be isolated, normally by distillation, or directly used for fruther reactions. 

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