Acetamide preparation

The simplest method for acetamide preparation involves reaction of the amine with acetic anhydride or acetyl chloride with or without added base. Some other methods are listed below. 

Perfluoro[AT-fluoro-Af-(4-pyridyl)acetamide], prepared via direct fluorination of the sodium salt of perfluoro[/V-(4-pyridyl)acetamide], readily fluorinates diethyl sodio(phenyl)malonate, 1-morpholinocyclohexene, phenol and anisole under mild conditions.129... 

Y-Unsaturated amides can be prepared from allylamino [1], allylphosphate [2], or allylalcohol [3] with a one-carbon atom increase. Some of these are not stereodefined, and others require the use of valuable noble metal catalysts and carbon monoxide. However, it is possible to synthesize in a stereodefined manner ( )-p,-y-unsaturated amides from -9-alkenyl-9-BBN with N,N-dialkyl(di-methylsulfuranylidene)acetamide [4] with a two-carbon increase. N,N,-Di-alkyl-a-sulfonium substituted amides are easily prepared by the reaction of dimethylsulfide and N,N-dialkyl-a-bromoacetamide [5]. The terminal -9-al-kenyl-9-BBN generated [6] in situ reacts (Scheme 11.1) with N,N-dialkyl(dimet hylsulfuranylidene)acetamide, prepared from JV,JV-dialkyl-a-sulfonium-substi-tuted amide and sodium hydroxide at 0 °C in THE The reaction mixture after oxidation with HjOj/OAc affords ( )-p,y-unsaturated amides in 60-70% yields (Table 11.1) [4], The mechanism of the reaction is depicted in Scheme 11.2. 

An excess of acetic acid is usually added before heating in order to repress the hydrolysis (and also the thermal dissociation) of the ammonium acetate, thus preventing the escape of ammonia. The excess of acetic acid, together with the water, is removed by slow fractional distillation. The method is rarely used except for the preparation of acetamide. 

Dimethylthiazole (III) may be prepared from thloacetamide (I) and monochloroacetone (II). The thloacetamide is conveniently formed in the reaction mixture from acetamide and phosphorus pentasulphide. 

Nitrosomethylurea is conveniently prepared by treating acetamide (2 0 mols) with bromine (1 1 mols), followed by 10-25 per cent aqueous caustic alkali (2 0 mols) when acetylmethylurea is produced ... 

One of the virtues of the Fischer indole synthesis is that it can frequently be used to prepare indoles having functionalized substituents. This versatility extends beyond the range of very stable substituents such as alkoxy and halogens and includes esters, amides and hydroxy substituents. Table 7.3 gives some examples. These include cases of introduction of 3-acetic acid, 3-acetamide, 3-(2-aminoethyl)- and 3-(2-hydroxyethyl)- side-chains, all of which are of special importance in the preparation of biologically active indole derivatives. Entry 11 is an efficient synthesis of the non-steroidal anti-inflammatory drug indomethacin. A noteworthy feature of the reaction is the... 

Ohta (344) prepared 2,4-dimethylthiazole (10), Rj=R2 = Me, Rj H, in fairly low yield by condensing a-mercaptoacetone with acetamide in the presence of anhydrous zinc chloride. 

Adamantylamine is prepared from the corresponding alcohol or bromide by bridgehead cation generation in the presence of acetonitrile (49). Selective hydrolysis of the resultant acetamide to the rigid cycloahphatic amine by acid or base is difficult. 

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. 

Furium. N[4-(5-Nitro-2-furanyl)-2-thia2olyl]acetamide, has demonstrated activity against baciUi and pathogenic enterobacteria (24). The product, prepared from thiourea and 2-bromo-l-(5-nitro-2-furanyl)ethanone followed by acetylation of the intermediate aminothia2ole with acetic anhydride in pyridine (25), is marketed in several countries for both human and veterinary use. 

Sulfation by sulfamic acid has been used ia the preparation of detergents from dodecyl, oleyl, and other higher alcohols. It is also used ia sulfating phenols and phenol—ethylene oxide condensation products. Secondary alcohols react ia the presence of an amide catalyst, eg, acetamide or urea (24). Pyridine has also been used. Tertiary alcohols do not react. Reactions with phenols yield phenyl ammonium sulfates. These reactions iaclude those of naphthols, cresol, anisole, anethole, pyrocatechol, and hydroquinone. Ammonium aryl sulfates are formed as iatermediates and sulfonates are formed by subsequent rearrangement (25,26). 

Amino-5-nitrosopyrimidines also condense with benzoylacetonitrile, phenacyl-pyridinium bromide and acetonylpyridinium chloride in the presence of sodium cyanide to produce. 7-amino-6-pteridinyl ketones (63JOC1197). Pteridine syntheses from pyridinium salts are not limited to the preparation of pteridyl ketones since pyridinium acetamide... 

A newer method for the preparation of nitronic esters, namely utilizing the (9-trimethyl-silyl ester, has been reported and these are prepared by the reaction of alkylnitro compounds and (V,(V-bis(trimethylsilyl)acetamide. These nitronic esters also undergo cycloaddition with alkenes to produce isoxazolidines (equation 54) (74MIP41601, 74DOK109, 78ACS(B)ll8). 

The thiophene analog of methadone (253) and isomethadone have been prepared and shown to be active analgesies. Heterocyclic acetamides of the type (254) have been prepared for evaluation of their analgesic and antipyretic activity. - ... 

The A-substituted derivatives of 4-oxo-4//-pyrido[l,2-n]pyrimidine-3-carboxamides and -3-acetamides and l,6-dimethyl-4-oxo-1,6,7,8-tetrahy-dro-4//-pyrido[l,2-n]pyrimidine-3-carboxamide were prepared by treatment of the appropriate 3-carboxylic acids and acetic acid, first with an alkyl chloroformate in the presence ofNEt3 in CHCI3 below — 10°C, then with an amine (98ACH515). A-Phenethyl and A-[2-(3,4-dimethoxyphenyl)ethyl] derivatives of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetamide were obtained in the reaction of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-3-acetic acid and phenethylamines in boiling xylene under a H2O separator. Hydrazides of 4-oxo-4//- and 4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic acid were prepared from the appropriate ester with H2NNH2 H2O in EtOH. Heating 4-oxo-4//- and 6-methyl-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic hydrazides in EtOH in the presence of excess Raney Ni afforded fhe appropriafe 4-oxo-6,7,8,9-fefrahydro-4//-pyrido[l,2-n]pyrimidine-3-acefa-mide. In the case of the 4-oxo-4// derivative, in addition to N-N bond... 

Finally, attachment of a rather complex side chain to the para position of the benzene ring on the sulfonamide leads to the very potent, long-acting oral antidiabetic agent, glyburide (215). Preparation of this compound starts with the chlorosul-fonation of the acetamide of 3-phenethylamine (209). The resulting sulfonyl chloride (210) is then converted to the sulfonamide (211) and deacylated (212). Reaction with the salicylic acid derivative, 213, in the presence of carbodiimide affords the amide, 214. Condensation of that with cyclohexylisocyanate affords glyburide (215). ... 

Preparation of 1 -(/3-D-arabinofuranosyl)-2-thiocytosine A solution of 2.0 g of 1 -(2, 3, 5 -0-triacetyl-/3-D-arabinofuranosyl)-2,4-dithiouracil in 100 ml of methanol is saturated with anhydrous ammonia at 0°C. The mixture, in a glass liner, is heated in a pressure bomb at 100°C for three hours. The reaction mixture is concentrated to a gum in vacuo, and most of the byproduct acetamide is removed by sublimation at 60°C/0.1 mm. The residue is chromatographed on 100 g of silica gel. Elution of the column with methylene chloride-methanol mixtures with methanol concentrationsof 2-25% gives fractions containing acetamide and a series of brown gums. The desired product is eluted with 30% methanol-methylene chloride to give a total yield of 0.386 g (30%), MP 175°-180°C (dec.). Recrystallization from methanol-iso-propanol furnishes an analytical sample, MP 180°-182°C (dec.). 

Preparation of 7-(D-0t-phenyigiycyiamido)-3-chioro-3-cephem-4-carboxyiic acid To a suspension of 280 mg (1.2 mmol) of 7-amino-3-chloro-3-cephem-4-carboxylic acid in 14 ml of acetonitrile was added with stirring at room temperature 0.5 ml of N, 0-bis-(trimethylsilyl)acetamide to form the soluble disilylmethyl derivative thereof. The solution was cooled to 0°C and was slowly added to a solution of the mixed anhydride formed by reacting 408 mg (1.5 mmol) of methyl-3-a-carboxybenzylaminocrotonate sodium salt with 161 mg (1.7 mmol) of methyl chloroformate in the presence to 2 drops of N, N-dimethylbenzyl amine in 7 ml of acetonitrile. 

Conversion of Acid Anhydrides into Amides Acetic anhydride is also commonly used to prepare iV-substituted acetamides from amines. For example, acetaminophen, a drug used in over-the-counter analgesics such as Tylenol, is prepared by reaction of p-hydroxyaniline with acetic anhydride. Note that the more nucleophilic -NH2 group reacts rather than the less nucleophilic -OH group. 

Nitriles are organic derivatives of hydrocyanic acid in which the substituting group is attached to carbon. Their formula is R.C N. Because most nitriles can be derived from corresponding acid amides, R.CO.NH2, by removal of w, they are called nitriles. For instance, the compd CH3.CN is called acetonitrile because it is derived from acetamide. It can also be called methyl cyanide. The compd C2HS.CN is called either propionitrile or ethyl cyanide, etc The first nitrile to be prepared was propionitrile which J. Pelouze obtained in 1834 by distg Ba ethyl sulfate with K cyanide... 

A. N-(Hydroxymethyl)acetamide. A solution of 10 g. (0.07 mole) of anhydrous potassium carbonate in 137 g. of a 36-38% solution of formaldehyde (1.7 moles) in water (Note 1) is prepared in a 2-1., round-bottomed flask, and lOOg. (1.7 moles) of... 

The enolized form of 2-acetyl-2-cyclohexen-l-one has been synthesized in low yield by dehydrochlorination of 2-acetyl-2-chlorocyclohexanone in collidine at 180° and by elimination of acetamide from 3-acetamido-2-acetylcyclohexanone at 120-140°. The preparation of other a,/3-unsaturated /3-dicarbonyl compounds has been attempted with varying degrees of success. The... 

To prepare the corresponding cytosine containing nucleoamino acid 9, N -Boc cytosine was first silylated using N,0-bis(trimethylsilyl)acetamide (BSA) under carefully controlled conditions to produce mono-silylated-N -Boc cytosine 7. The mono-silylated product 7 undergoes l2-mediated nucleosidation with the O-MTM... 

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