Trichloroacetamide, hydrolysis

Alkylation of trifluoro- and trichloroacetamides with a-bromoacetic esters has been utilized for the synthesis of a wide range of a-aminoacetic acids [11-13] (Table 5.13). Hydrolysis of the intermediate a-trihaloacetamidoacetic esters with methanolic potassium hydroxide converts the methyl and ethyl esters directly into the amino carboxylic acids. /-Butyl a-aminoacetates are more stable, but they are hydrolysed under phase-transfer catalytic conditions (see Chapter 9.2). Reaction of the trihaloacetamides with 1,4-dibromobutane and 1,5-dibromopentane and subsequent hydrolysis provides a simple route to pyrrolidine-2-carboxylic acid (75%) and piperidine-2-carboxylic acid (58%) [11, 12],... 

Amides can also be removed by partial reduction. If the reduction proceeds only to the carbinolamine stage, hydrolysis can liberate the deprotected amine. Trichloroacetamides are readily cleaved by sodium borohydride in alcohols by this mechanism.84 Benzamides, and probably other simple amides, can be removed by careful partial reduction with diisobutylaluminum hydride.85... 

The reactions of TMSA (14) with aldehydes165 23° gives a-trimethylsiloxy-alkyl azides (246, 413-417) they are highly stable against hydrolysis and higher temperatures (Scheme 62). Thermolysis of the azides 246, 413-417 gives directly N-TMS-butyr- (246), valero- (413), capro- (414)-, isobutyr- (415)-, pival- (416) and trichloroacetamide (417), respectively. 

Finally, in order to directly incorporate the nitrogen and sulphur functionalities in a single step with total stereoselectivity, the chiral allylic trichloroacetimidate 16 was treated with methyl sulfenyl triflate to give the corresponding A -sulfenyl imidate 17 in good yield. Further reaction of 17 with methyl sulfenyl triflate gave the 4,5-dihydro-l,3-oxazole 18, together with a minor amount of the trichloroacetamide 19, formed by hydrolysis of 18246. 

Heating the 2,4,6-trisubstituted-l,2,3,5-oxathiadiazine 2-oxide 111 (X = Cl, NR2 = piperidino or pyrrolidine) at 60 °C in benzene, toluene, or chloroform with an equimolar amount of water resulted in conversion to the salts 26 (Scheme 10). This process apparently involves initial hydrolysis of the trichloroacetamide fragment followed by an unusual substitution of the piperidino or pyrrolidino moiety by the CCI3 group with concomitant loss of CO2. Treatment of salts 26 with sulfuric acid affords the 1,2,4,6-thiatriazine 1,1-dioxide 112 which revert to salts 26 with piperidine or pyrrolidine <2002RJ01702>. 

Under some circumstances, it is possible to effect removal of amide groups by selective hydride reduction. Trichloroacetamides are readily cleaved by sodium borohydride in alcohols. Another reductive method that can be applied to ben-zamides, and probably to other simple amides, involves treatment with diisobutylaluminum hydride. At low temperatures, this reduction stops at the carbinolamine stage. Hydrolysis then yields the amine. 

Acetamides have been prepared in moderate to good yield from alcohols by reaction with acetonitrile and sulphuryl chloride. It has been found that the hydrolysis of nitriles to amides can be effected in excellent yield using potassium hydroxide in t-butanol if the amide produced is relatively insoluble in water. Experimental details for the large scale anodic oxidation of iV-formyl derivatives of amines to a-methoxyalkylamides have been recorded, and an interesting synthesis of trichloroacetamides from allylic alcohols via a thermal [Att + 2a] rearrangement has been described (Scheme 50). ... 

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