Chloroacetonitrile, reactions with chloride

The SN2 identity exchange reaction of chloride with chloroacetonitrile (equation 23) was studied in an FT-ICR spectrometer and also theoretically by means of statistical theories (RRKM with the microcanonical variational transition state) and high-level ab initio calculations238. 

CHLOROACETONITRILE or o-CHLOROACETONITRILE or 2-CHLOROACETONITRILE (107-14-2) ClCHjCN Forms explosive mixture with air (flash point 133°F/56°C Fire Rating 2). Contact with water, steam, or strong acid, or acid fumes produce toxic hydrogen cyanide gas. Violent reaction with strong oxidizers. Incompatible with sodium nitrate, lithium alanate. Thermal decomposition releases toxic hydrogen cyanide and hydrogen chloride gas. On small fires, use dry... 

For the reaction of a cyanoalkyl compound more drastic conditions are required. A solution of resorcinol monomethyl ether, chloroacetonitrile and aluminium chloride in dichloroethane added with stirring to an ice-cold solution of boron trichloride and reaction at ambient temperature during 20 hours followed by acidification produced an 81% yield of 2-hydroxy-4-methoxychloroacetophenone (ref.133). 

Synthesis of Thiophens by Ring-closure Reactions.—The reaction of dipotassium nitroethylenedithiolate and a-chlorocarbonyl derivatives, followed by oxidation with iodine, gave (1). Treatment of pentane-2,4-dione with carbon disulphide in the presence of potassium hydroxide, followed by treatment with ethyl bromoacetate, methyl iodide, and alkali, gave (2). Compounds of type (3) were formed in the reaction of 1-cyanomethylpyridinium chloride with carbon disulphide and alkylating agents such as chloroacetonitrile, ethyl bromoacetate, phenacyl bromide, or chloroacetamide in the presence of alkali, and intramolecularly cyclized to (4). After 5-methylation, the pyridine ring could be cleaved by reaction with phenylsulphonylacetonitrile and alkali in DMSO... 

The formation of cyclopropanes from 7C-deficient alkenes via an initial Michael-type reaction followed by nucleophilic ring closure of the intermediate anion (Scheme 6.26, see also Section 7.3), is catalysed by the addition of quaternary ammonium phase-transfer catalysts [46,47] which affect the stereochemistry of the ring closure (see Chapter 12). For example, equal amounts of (4) and (5) (X1, X2 = CN) are produced in the presence of benzyltriethylammonium chloride, whereas compound (4) predominates in the absence of the catalyst. In contrast, a,p-unsatu-rated ketones or esters and a-chloroacetic esters [e.g. 48] produce the cyclopropanes (6) (Scheme 6.27) stereoselectively under phase-transfer catalysed conditions and in the absence of the catalyst. Phenyl vinyl sulphone reacts with a-chloroacetonitriles to give the non-cyclized Michael adducts (80%) to the almost complete exclusion of the cyclopropanes. 

Catalysis of the C-alkylation of 5-methyoxy-l,3-dimethyloxindole with chloroacetonitrile by A-(3,4-dichlorobenzyl)cinchoninium or quininium chloride leads in good yield to the (5)-3-alkylatcd derivative (78% ee), which provides an efficient stereospecific route to the anticholinesterase agent, (-)-physostigmine [9]. Other analogous alkylation reactions have been reported [10]. 

To an ice-cooled solution of the nitrile, in absolute alcohol (see Table II above) is added dry hydrogen chloride until 1.1 moles has been taken up. The resulting solution is allowed to stand at 0°C for the times shown in Table II, column 2. After this time, ether is added in the amounts shown in column 3 for the purpose of preventing the formation of a hard cake of the salt. In the case of very reactive nitriles such as acetonitrile and chloroacetonitrile it is advisable to have the ether present before the hydrogen chloride is added in order to prevent solidification of the reaction mixture. After allowing the reaction mixture to stand for 15-20 hr in a refrigerator, it is cooled to —30°C to hasten crystallization. The product salt is filtered, washed with cold (—40°C) ether, and dried... 

Reaction of an Ar,AT-unsubstituted selenourea with chloroacetonitrile in aqueous ethanol affords 2-amino-4,5-dihydro-l,3-selenazol-4-iminium chlorides 35 via selenocarboimidate hydrochlorides. Reaction in anhydrous solvent gave only the selenocarboimidate hydrochlorides, whilst reaction in aqueous ethanol proceeded through to the cyclization step to give 35 (Scheme 13) <2005CL1260>. 

Gtycidic nitriles.20 Glycidic nitriles can be obtained in good yield by the reaction of ketones with chloroacetonitrile in aqueous sodium hydroxide with benzyltriethylammonium chloride as catalyst. 

There has been continued interest in the synthesis of oxazoles from a-diazo carbonyl compounds and nitriles catalyzed by Lewis acids. The BFa-catalyzed reaction of a-diazoacetophenones or methyl p-nitrophenyldiazoacetate with chloroacetonitrile affords 5-aryl-2-chloromethyloxazoles or 2-chloromethyl-5-methoxy-4-(p-nitrophenyl)oxazole, respectively (Equation (19)) <89BCJ618>. The former products react with primary, secondary, and tertiary amines by nucleophilic displacement of the chloride group. Methyl or ethyl isocyanate may be used as the nitrile component to prepare... 

A series of 2-amino-1,3-selenazole-5-carbonitriles 290 are readily prepared from selenazadienes 287 upon treatment with chloroacetonitrile in the presence of triethylamine <05JHC831>. Similarly, reaction of selenoazadiene 291 with chloroacetyl chloride generates acyl chloride 292, which is trapped with various amines to yield the corresponding amides 293... 

Obtained by reaction of chloroacetonitrile on 2-chloro-phenol with aluminium chloride and boron trichloride mixture in ethylene dichloride at r.t. (21%) [4549,4550],... 

Preparation by reaction of chloroacetonitrile on resorcinol with zinc chloride (Hoesch reaction) (90%) [4590], (82%) [4591] or with triflic acid (trifluoromethanesulfonic acid) (23%) [4592]. 

Preparation by reaction of chloroacetonitrile on 1,2,4-benzenetriol (hydroxyhydroquinone) with zinc chloride in ethyl ether (Hoesch reaction) [4431,4608,4609],... 

Preparation by reaction of chloroacetonitrile on m-cresol with boron trichloride and aluminium chloride in refluxing ethylene dichloride (quantitative yield) [4549]. 

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