Cannizzaro Chlorides

Reacts slowly on heating without evolution of gas. Esters some acid chlorides and anhydrides benzaldehyde (undergoes Cannizzaro s reaction, p. 342). 

Hydroxyalkylthiazoles are also obtained by cyclization or from alkoxyalkyl-thiazoles by hydrolysis (36, 44, 45, 52, 55-57) and by lithium aluminium hydride reduction of the esters of thiazolecarboxylic acids (58-60) or of the thiazoleacetic adds. The Cannizzaro reaction of 4-thiazolealdehyde gives 4-(hydroxymethyl)-thiazole (53). The main reactions of hydroxyalkyl thiazoles are the synthesis of halogenated derivatives by the action of hydrobroraic acid (55, 61-63), thionyl chloride (44, 45, 63-66), phosphoryl chloride (52, 62, 67), phosphorus penta-chloride (58), tribromide (38, 68), esterification (58, 68-71), and elimination that leads to the alkenylthiazoles (49, 72). 

Hydroxjrmethylbenzof Jthiophenes are most conveniently prepared by reduction with lithium aluminum hydride of the corresponding carboxylic acid78,100 S37 485,486,521,528,540 or ester.77,87,336,337, 52i, 526 Lesg frequently, they are prepared by reduction of the corresponding aldehyde 100,487 or acid chloride,618 with sodium boro-hydride, or, in the case of 2-hydroxymethylbenzo[6]thiophenes, by reaction of the 2-lithium derivative with formaldehyde.90,628 3-Hydroxymethylbenzo[6]thiophene has been prepared from the corresponding aldehyde by means of a crossed Cannizzaro reaction... 

The aldehyde was typically aromatic it gave the hydramide in its reaction with ammonia, and underwent the Cannizzaro reaction. CTM was phos-phorylated by PCI, in the presence of aluminium chloride to give... 

Investigation of the mechanism of these reactions has suggested ways in which the yields can be improved. Acidic conditions (pH 2) will prevent Cannizzaro rearrangement of any glyoxal-type species and also serve to hydrolyse any Schiff bases which result from side reactions of aldehyde and amine. Conditions should be adjusted so that the rate of hydrolysis of linear products is equal to the rate of cyclocondensation, allowing accumulation of the imidazole products. From glyoxal, formaldehyde and ammonium chloride the yield of imidazole can be inereased to 85% by careful control of the conditions. With an appropriate alkylammonium chloride, 1-substituted imidazoles are also accessible (e.g. 1-methyl (56%), 1-isopropyl (46%), 1-cyclohexyl (49%), 1-n-butyl (55%), 1-t-butyl (25%)). The process may have some applications, but yields drop off with branched alkyl compounds [22 j. Imidazolium salts are also available under similar conditions when two molar equivalents of a primary alkylamine are used [23]. 

Benzyl chloride was prepared in 1853 by Cannizzaro by acting on benzyl alcohol with hydrochloric acid. It is particularly well known for its use in organic synthesis. It was used as a war gas in the war of 1914-18, but only for a short time. To-day its importance is as a raw material for the preparation of bromobenzyl cyanide. 

This substance, which has well-known lachrymatory properties, may be obtained according to Cannizzaro by the action of phosphorus iodide with benzyl alcohol or by the action of potassium iodide on benzyl chloride or bromide. 

Benzyl alcohol is prepared commercially by the distillation of benzyl chloride with potassium or sodium carbonate. It may also be prepared by the Cannizzaro reaction of benzaldehyde and potassium hydroxide. 

Derivation (a) By hydrolysis of benzyl chloride (b) from benzaldehyde by catalytic reduction or Cannizzaro reaction. 

Derivation (a) By a Cannizzaro reaction from benzaldehyde, (b) by esterifying benzyl alcohol with benzoic acid, (c) by treating sodium benzoate with benzyl chloride. 

CK hydrolyzes to form HCI and HOCl only slowly. However, the hydrolysis rate (Bailey and Bishop, 1973) increases in the presence of bases, such as sodium hydroxide. Although cyanogen chloride can be prepared by reacting cyanide with chlorine water, CICN reacts with hypochlorite at pH 7-8 (Price et al., 1947). Complete hydrolysis (aqueous sodium hydroxide/heat) of cyanogen chloride produces ammonia, and the detection of this ammonia was the basis for an early, nonspecific test for CICN. Ammonolysis of CICN using ethanohc ammonia produces cyanamide, NH2CN (Cloez and Cannizzaro, 1851) ... 

Vanillin subjected to Cannizzaro Reaction with KOH/NaOH at 200°C yields vanillic acid which upon treatment with acetic anhydride and diethyl carbamoyl chloride gives rise to acetylated ethamivan. This subsequently on deacetylation in aqueous NaOH yields the official compoimd. 

Benzyl alcohol is the second most important product from benzyl chloride. Stanislao Cannizzaro deduced its structure in 1853 from the reaction of benzaldehyde with potassium hydroxide. 

Stanislao Cannizzaro (Palermo, Sicily, 1826-Rome, 10 May 1910) studied in Palermo and Naples. In 1847 he took part in the Rebellion. In 1850 he became Piria s assistant in Paris and in 1851 published his first research, on cyanogen chloride and cyanamide, done jointly with Cloez in Chevreul s laboratory. In 1852 he was appointed in Alessandria and in 1853 published an important researdi on the action of caustic potash on benzaldehyde, obtaining potassium benzoate and benzyl alcohol ( Cannizzaro s reaction ) 2C,H5CHO+KOH=C.HsCOOK+C,H8CH,OH. In 1855 he became professor in G noa, where at fimt there was no laboratory, and there he wrote his famous pamphlet. In i860 he joined Garibaldi at Palermo. In 1861 he became professor in Palermo and in 1870 in Rome, where he was created senator. ... 

---