2- acetamides, formation hydrolysis

Isomer separation beyond physical fractional crystallization has been accompHshed by derivatization using methyl formate to make /V-formyl derivatives and acetic anhydride to prepare the corresponding acetamides (1). Alkaline hydrolysis regenerates the analytically pure amine configurational isomers. 

The inclusion of aromatic rings as part of the side chains results in quite potent agents, possibly because the rigid rings better define the position of the basic nitrogen. Reaction of para-hydroxyacetanilide (19-1) with formaldehyde and diethylamine affords the corresponding Mannich product (19-2) hydrolysis of the acetamide then leads to the aniline (19-3). Treatment of that compound with dichloro-quinoline (17-6) leads to the displacement of chlorine on the heterocyclic ring and the formation of amodiaquine (19-4) [21]. 

One of the earliest reported reactions of coordinated ligands involves the hydrolysis of acetonitrile coordinated to platinum(II) and the formation of acetamide.93 Such hydration is general... 

Chlorophenyl)glutarate monoethyl ester 87 was reduced to hydroxy acid and subsequently cyclized to afford lactone 88. This was further submitted to reduction with diisobutylaluminium hydride to provide lactol followed by Homer-Emmons reaction, which resulted in the formation of hydroxy ester product 89 in good yield. The alcohol was protected as silyl ether and the double bond in 89 was reduced with magnesium powder in methanol to provide methyl ester 90. The hydrolysis to the acid and condensation of the acid chloride with Evans s chiral auxiliary provided product 91, which was further converted to titanium enolate on reaction with TiCI. This was submitted to enolate-imine condensation in the presence of amine to afford 92. The silylation of the 92 with N, O-bis(trimethylsilyl) acetamide followed by treatment with tetrabutylammonium fluoride resulted in cyclization to form the azetidin-2-one ring and subsequently hydrolysis provided 93. This product was converted to bromide analog, which on treatment with LDA underwent intramolecular cyclization to afford the cholesterol absorption inhibitor spiro-(3-lactam (+)-SCH 54016 94. 

In practice, these reactions do not take place quite as simply as represented above. After the formation of the oxime the compound is acetylated and the conversion into the acid nitrile and into the aldehyde occurs with these acetyl derivatives. The resulting acetyl derivative of the aldo-hexose is first converted into an acetamide compound which on hydrolysis yields the hydroxyl compound, i.e., the aldo-hexose. 

Laboratory studies have provided evidence that photochemical and photocatalytic (Section 6.8) steps might play an important role in the formation of amino acids or various heterocyclic compounds from very simple molecules. For example, UVC irradiation of acetonitrile ammonia water mixture produces hexamethylenetetramine, a potential precursor of amino acids, via two-step photoinitiated fragmentation of acetamide (formed by acetonitrile hydrolysis) to give carbon oxide, which undergoes further photochemical and dark reactions (Scheme 6.184).1183... 

The most important reaction of amides is that which takes place when they are heated with water. Hydrolysis results, and the bond between carbon and nitrogen is broken. Acetamide, for example, is converted into ammonium acetate as the result of the formation of acetic acid and ammonia —... 

In 2007, Crawford et al. observed a spontaneous enzymatically mediated DKR of 8-amino-5,6,7,8-tetrahydroquinoline in the presence of Candida antarctica lipase B, in which a >60% yield of the expected enantiopure (R)-acetamide was isolated from the racemic amine. " The spontaneous formation of 5,6,7,8-tetrahydroquinolin-8-one as a side product, followed by a con-densation/hydrolysis sequence with the remaining (5)-8-amino-5,6,7,8-tetra-hydroquinoline via the corresponding enamine, provided the necessary racemisation pathway (Scheme 3.52). 

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