Acetamide derivatives

Catalytic hydrogenation of the nitrile function of cyanohydrins can give amines. As in the case of ordinary nitriles, catalytic reduction of cyanohydrins can yield a mixture of primary, secondary, and tertiary amines. Addition of acid or acetic anhydride to the reaction medium minimizes formation of secondary or tertiary amines through formation of the amine salt or acetamide derivative of the primary amine. 

The hydrochloride salt of 4-amino-1-benzylimidazole (83 R = H) was acetylated readily by acetic anhydride to give the acetamide derivative (83 R = COCHj) (55%) (74JMC1168). Treatment with acetic-formic anhydride gave the corresponding formamide (83 R = CHO). 

Nucleophilic attack of substituted alkylamines including benzylamines to 6,7-dihydro-imidazo[l,2- ]imidazole-2,5-diones 34, cleaved the imidazolidinone ring to generate the acetamide derivatives 81 (Equation 34) <1998APH389, 2001JST73>. Reaction of the tricyclic thiazolium salt 45 with methoxylamine gave the oxime 82 (Equation 35) <1999JME2828>. 

The figure represents the chemical structure for paracetamol, which includes the N-(4-hydroxyphenyl) acetamide, derived from the interaction of p-aminophenol and an aqueous solution of acetic anhydride. The structure has two activating groups that make the benzene ring highly reactive toward electrophilic aromatic substitution. 

Nitrolysis reactions employing l,3,5-trisubstituted-l,3,5-triazacyclohexanes have been explored as alternative routes to RDX. Some of the results are illustrated in Table 5.4 and show the difference in the efficiency of the three nitrolysis agents used, namely, absolute nitric acid, phosphorus pentoxide-nitric acid and trifluoroacetic anhydride-nitric acid. The acetamide derivative (81) (TRAT) undergoes incomplete nitrolysis on treatment with absolute nitric acid and trifluoroacetic anhydride-nitric acid to give a crude product containing some l-acetyl-3,5-dinitro-1,3,5-triazacyclohexane (TAX) (82) (Table 5.4, Entry 1) the latter can be preferentially formed in 93 % by suitably modifying the reaction conditions. Interestingly, the nitrolysis of... 

Nitration of pyrido[l,2-f>]cinnolin-6-ium hydroxide inner salt 17 (R = H) and its 2-acetamide derivative afforded its 2-nitro and 2-acetamido-3-nitro derivatives, respectively. The reaction of 17 (R = H) with iodine monochloride afforded the 2-iodo derivative. The 2-cyano derivative was obtained from the 2-bromo derivative of 17 (R = H) with Cu(I)CN. Treatment of 17 (R = H) with P4S10 afforded the 11-mercapto derivative 41 (74JHC125). 

The air oxidation of phenylacetylene and secondary amines in the presence of cupric acetate in benzene solution yields ynamines [22], This reaction requires only catalytic amounts of cupric salts and gives high conversions in less than 30 min when the Cu+2/phenylacetylene ratio is only 0.02. Only 1,4-diphenylbutadiyne is produced if the stoichiometric amount of cupric ion is used in the absence of oxygen. The yield of ynamine can be increased from 45 to 90 % if the stoichiometric amounts of a reducing agent such as hydrazine are continuously added during the course of the reaction. The use of primary amines under similar conditions yields the acetamide derivative. 

Hydrolysis of the homologous esters has been reported but the direct amidation of these esters failed.131 133,261 The 3-acetamide derivative was prepared from the corresponding hydrazide with the aid of Raney nickel.131,133... 

Insertions into the metal - oxygen bond in mercuric acetate with aromatic isocyanides has given the compound 119 (R = Ph, xylyl), which readily hydrolyzed to give organic acetamide derivatives (480). 

The relative reactivity of a-haloacetates toward protein functionalities is sulfhydryl > imidazolyl > thioether > amine. Among halo derivatives the relative reactivity is I > Br > Cl > F, with fluorine being almost unreactive. The a-haloacetamides have the same trend of relative reactivities, but will obviously not create a carboxylate functional group. The acetamide derivatives typically are used only as blocking reagents. 

Ritter reaction of the triene 287 in triflic acid, performed to accomplish the synthesis of a marine sesquiterpene, gave the product acetamide derivative via a predominant trans antiparallel addition of H+ and acetonitrile to the endocyclic double bond920 [Eq. (5.343)]. 

Acetamide derivatives of dibenzoxazepine 113 were prepared and amidated with different alkyl and aralkyl side chains in order to function as a potential surrogate for the diacylhydrazine group of SC-51089, a potent PGE2 antagonist (Figure 15) <1996JME609>. 

In an earlier investigation by the author (1), 4-piperidinyl[amino-(2-hydroxypropyl)oxy-phenyl] acetamide derivatives were prepared, which were effective as MIP-la receptor antagonists. The derivative A-[2-(3- [l-(3,4-dichlorobenzylpiperidinyl]aminohydroxy-propoxy)-phenyl] acetamide, (I), was especially preferred. 

Table 2 Mechanical and physical properties of the unmodified and modified DGEBA/DDM epoxy polymers. Data taken from [85,86], AM Acetamide derivative (see Table 1)...

Fig. 21 In situ visualization pictures showing damage a in a fretting contact between an unmodified DGEBA/DDM epoxy network and a glass sphere, and b in a similar contact with a DGEBA/DDM network modified with the acetamide derivative shown in Table 1. The magnitude of the maximum tensile stress at the edge of the contact was found to be similar in both cases. Contact fatigue cracks were only observed in the neat DGEBA/DDM system...

Methods for preparing 1,2,3,4-tetrahydronaphthyl acetamide derivatives are described (2). 

N-Debenzylation.1 The P-D-glucopyranoside 1, when dissolved in DMSO containing KOC(CH3)3, is rapidly converted into the N-acetamide derivative 2 when air is passed into the stirred solution. This conversion of an N-benzylacetamido group into an acet-amido group is a general reaction. It can also be used to prepare acetylated amines. Thus... 

Izawa et have reported the photochemical alcoholysis of the acetamide derivatives (122) to afford the esters (123). Related to this is the photochemical alcoholysis of ft),a>,ft)-tribromoacetophenone yielding benzoyl formate. Irradiation of the cycloalkanones (124) in methanol at 300 nm affords high yields of the corresponding dimethylacetals. The authors discount an acid-catalysed process even though the presence of sodium acetate suppresses the acetal formation. 

A number of 2-substituted 3,4-dihydroquiiiazolines, prepared in situ by Raney nickel desulfurization of the corresponding quinazoline-4(3//)-thiones 3, undergo alumina-catalyzed hydration across the C—N double bond followed by ring opening, leading to substituted acetamide derivatives 4 in approximately 7% yield. ... 

Distillation of Amm nitroacetamide with coned KOH gives a tribasic acid, C HjNjOj and the Amm salt of this acid gives with Ag nitrate a yel solid which is expl. Another nitro acetamide deriv, C4HjN,Oj, gives with Ag nitrate a wh ctyst compd, AgC H NjO, which expl violently on heating... 

Earlier mention has been made of the use of Lewis acid and Friedel-Crafts reagents as initiators of carbenium ion formation. Another versatile device is to employ a metal to assist in generation of the carbenium ion. In its simplest form, addition of silver(I) ion to an alkyl halide is an excellent technique for encouraging reaction by means of the 5n 1 pathway. This process was first applied to the Ritter reaction by Cast and Stevens, but yields obtained were modest. A recent elegant application of this technique is the two-step conversion of dodecahedrane into its acetamide derivative (Scheme 45). ... 

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