Halo-acids, reaction with amines

The interaction of alkyl halides, preferably iodides or bromides, with hexamine in chloroform or alcohol solution forms quaternary ammonium salts which on heating with hydrochloric acid are readily converted to primary amines. The procedure has been employed successfully in the reaction of primary, but not secondary or tertiary, aliphatic halides, certain benzyl halides, halo ketones, halo acids, and halo esters. The yields range from 40% to 85%. 

The limitations of this approach can be seen in the reaction of a saturated solution of ammonia in 90% ethanol with ethyl bromide in a 16 1 molar ratio, under which conditions the yield of primary amine was 34.2% (at a 1 1 ratio the yield was 11.3%). Alkyl amines can be one type of substrate that does give reasonable yields of primary amine (provided a large excess of NH3 is used) are a-halo acids, which are converted to amino acids. A-Chloromethyl lactams also react with amines to give good yields to the A-aminomethyl lactam. Primary amines can be prepared from alkyl halides by 10-43, followed by reduction of the azide (19-32), or by the Gabriel synthesis (10-41). 

Often, the carboxylic acid groups are converted to acyl chlorides with SOCI2109 110 prior to esterification with various alcohols and reaction with other nucleophiles.111 Both mono- and difunctional ester-substituted bipyridines have been generated in moderate yield by palladium(O)-catalyzed carboalkoxylation of halo- or triflate-substituted precursors in the presence of CO, an alcohol, and a tertiary amine.112... 

The same reagent (/ )-(+) -pantolactone 112 gives good results with a-halo acids that are good precursors for many other compounds such as a-amino acids by nucleophilic displacement. The a-halo acid chlorides 115 are prepared directly from the simple acids 114 and treated with the same tertiary amine EtNMe2 used above to give the unstable ketenes 116 and hence the esters 117 by reaction with (R)-(+) -pantolactone22112. 

BUTILTRICLOROSILANO (Spanish) (7521-80-4) Forms explosive mixture with air (flash point 126°F/52°C). Violent reaction with water, steam, alcohols, forming hydrogen chloride. Violent reaction with strong oxidizers, ammonia. Incompatible with alkalis, strong acids, aliphatic amines, alkanolamines, isocyanates, alkylene oxides, epichlorohydrin, halo-genated compounds, nitrogen oxides. Corrodes common metals in the presence of moisture and produces flammable hydrogen. 

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