Acetamide synthesis

Synthesis of Acetamide from Acetic Acid and Urea... 

Synthesis of Acetamide from Ethyi Acetate and Ammonia... 

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... 

Acetamide [60-35-5] C2H NO, mol wt 59.07, is a white, odorless, hygroscopic soHd derived from acetic acid and ammonia. The stable crystalline habit is trigonal the metastable is orthorhombic. The melt is a solvent for organic substances it is used ia electrochemistry and organic synthesis. Pure acetamide has a bitter taste. Unknown impurities, possibly derived from acetonitrile, cause its mousy odor (1). It is found ia coal mine waste dumps (2). 

Heico Chemicals is the only producer of acetamide in the United States. Small amounts are imported from Europe and Asia. It is shipped in 32-L (35-gal) dmms weighing about 80 kg. Acetamide appears to have a wide spectmm of appHcations. It suppresses acid buildup in printing inks, lacquers, explosives, and perfumes. It is a mild moisturi2er and is used as a softener for leather, textiles, paper, and certain plastics. It finds some appHcations in the synthesis of pharmaceuticals, pesticides, and antioxidants for plastics. 

Nucleophilic Substitution Route. Commercial synthesis of poly(arylethersulfone)s is accompHshed almost exclusively via the nucleophilic substitution polycondensation route. This synthesis route, discovered at Union Carbide in the early 1960s (3,4), involves reaction of the bisphenol of choice with 4,4 -dichlorodiphenylsulfone in a dipolar aprotic solvent in the presence of an alkaUbase. Examples of dipolar aprotic solvents include A/-methyl-2-pyrrohdinone (NMP), dimethyl acetamide (DMAc), sulfolane, and dimethyl sulfoxide (DMSO). Examples of suitable bases are sodium hydroxide, potassium hydroxide, and potassium carbonate. In the case of polysulfone (PSE) synthesis, the reaction is a two-step process in which the dialkah metal salt of bisphenol A (1) is first formed in situ from bisphenol A [80-05-7] by reaction with the base (eg, two molar equivalents of NaOH),... 

The most convenient synthesis of 6-hydroxy-2-pyridones is by the condensation of a P-ketoester, eg, ethyl acetoacetate, with an active methylene compound, eg, malonic ester, cyanoacetic ester, and an amine. The amine can be omitted if an acetamide is used and in some cases this modification results in a higher yield. 

BREDERECK Imidazole synthesis Synthesis o( imidazoles Irom (ormamide (acetamide) and a-diketones, a-ketols, a-aminoketones, a-oziminoketones... 

An alternative to Gabriel synthesis is based on the alkylation of tnfluoro-acetamide [770, 777[ or Al-benzyl triflamide [772] in place of the classical phtalimide (equations 96 and 97). 

The first improvement of the Bucherer-Bergs reaction was the Bucherer-Lieb variation using the diluted alcoholic solution as described at the end of section 7.2.2. The Bucherer-Lieb variation is possibly the most popular process for synthesizing hydantoins. Another notable variation is the Henze modification using fusing acetamide as the solvent in place of water, benzene or 50% alcohol. Recently, ultrasound-promoted hydantoin synthesis has been reported to accelerate the reaction. 

This replacement reaction has been reported to take place on treatment of 5-R-l,3-dimethyluracil derivatives (R = H, Me, CN, F, Br, Cl,) with of-substituted (R ) acetamides (R =C0NH2, CN, COMe, Ph) in basic medium. The reaction provides an easy entry to the synthesis of 3-R-5-R -2,6-dihydroxypyridines (Scheme 22). 

This is by far the most versatile route to the synthesis of ester-substituted aziridines, especially as the benzhydryl group can easily be cleaved by hydrogenolysis. Wulff has applied this methodology to a short asymmetric synthesis of the antibiotic (-)-chloramphenicol in four steps from p-nitrobenzaldehyde (Scheme 1.34) [61]. In this case it was found that treatment of the aziridine 111 with excess dichloroacetic acid gave the hydroxy acetamide directly, so no separate deprotection step was required. 

Fig. 24 Solid-phase synthesis of 5-carboxamido-iV-acetyltriptamine. Reagents and conditions a piperidine 20%, DMA, rt, 60 min b 4-amino-3-iodo-benzoic acid, TBTU, HOBT, NEt3, DMAP, dioxane, MW 45 W, 3 min, 100%, open vessel c N-(4-Trimethylsilanyl-but-3-ynyl)-acetamide, Pd(OAc)2, PPhs, LiCl, NaOAc, DMA, MW 60 W, 2x13 min, 100%, open vessel d NIS, CH2CI2, MW 60 W, 14 min, 100%, open vessel e cleavage, TFA, 20%, CH2CI2, rt...

Phenacyl benzoate condenses with acetamide in boiling xylene under boron trifluoride etherate catalysis to give a high yield of 2,4-diphenyloxazole in a general synthesis of diaryloxazoles (Scheme 7) <96T10131>. 

The mono-silylated or free acetamides, which are liberated during silylation with 22 a, can, furthermore, interfere with any subsequent reaction, e.g. with electrophiles. Thus in the one-pot/one-step silylation, Friedel-Crafts catalyzed, nucleoside synthesis starting from protected sugar derivatives and pyrimidine or purine bases, the mono- or bis-silylated amides such as 22 a can compete with less reactive silylated heterocycHc bases for the intermediate electrophilic sugar cation to form protected 1-acetylamino sugars in up to 49% yield [42, 47]. On silylation with trimethylsilylated urea 23 a the Hberated free urea is nearly insoluble in most solvents, for example CH2CI2, and thus rapidly precipitated [43]. 

Deoxy-3-[ F]fluoro-D-glucose ( F-3DFG) was prepared - 454,467,473-476 essentially according to the procedure for the cold synthesis (see Section 11,2), namely, treatment of248 with Cs F (in DMF or HMPA), tetraalkylammonium [ F]fluoride (DMF, HMPA, or MeCN) or K F (in acetamide). 6-Deoxy-6-[ F]fluoro-a-D-galactopyranose was likewise pre-pared aceording to the cold synthesis. ... 

Organic synthesis 28 [OS 28] Transgalactosylation of p-nitrophenyl-2-acetamide-2-deoxy-y D-glucopyranoside... 

Acyl hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. Reaction of acyl hydrazides 149 with imidoylbenzotriazoles 148 in the presence of catalytic amounts of acetic acid under microwave irradiation afforded 3,4,5-trisubstituted triazoles 150 <06JOC9051>. Treatment of A-substituted acetamides with oxalyl chloride generated imidoyl chlorides, which reacted readily with aryl hydrazides to give 3-aryl-5-methyl-4-substituted[ 1,2,4]triazoles <06SC2217>. 5-Methyl triazoles could be further functionalized through a-lithiation and subsequent reaction with electrophiles. ( )-A -(Ethoxymethylene)hydrazinecarboxylic acid methyl ester 152 was applied to the one-pot synthesis of 4-substituted-2,4-dihydro-3//-1,2,4-triazolin-3-ones 153 from readily available primary alkyl and aryl amines 151 <06TL6743>. An efficient synthesis of substituted 1,2,4-triazoles involved condensation of benzoylhydrazides with thioamides under microwave irradiation <06JCR293>. 

A slightly modified procedure facilitated the synthesis of the acetamide (118 R = Me, R2 = 3-methanesulfonyl-imidazolidin-2-on-l-yl, R3 = Me). Thus, a solution of the requisite 5-nitroimidazole (97 R = Me, R2 = 3-methanesulfonyl-imidazolidin-2-on-l-yl) in a mixture of dimethylform-... 

Behforouz s synthesis employed more highly substituted quinoline aldehyde 30, which, when condensed with ester 21, produced /3-carboline 31 without need of a separate oxidation step. Selective hydrolysis of the acetamide group then provided lavendamycin methyl ester in high yield. A few years later, Behforouz and coworkers reported an improved synthesis of 30, thus boosting the overall yield of their lavendamycin synthesis [33]. 

The cyclization of IV-allyl-o-haloanilines was adapted to the solid phase for both indoles [332, 333] and oxindoles [334]. For example, as illustrated below, a library of l-acyl-3-aIkyl-6-hydroxyindoles is readily assembled from acid chlorides, allylic bromides, and 4-bromo-3-nitroanisole [332], Zhang and Maryanoff used the Rink amide resin to prepare Af-benzylindole-3-acetamides and related indoles via Heck cyclization [333], and Balasubramanian employed this technology to the synthesis of oxindoles via the palladium cyclization of o-iodo-N-acryloylanilines [334], This latter cyclization route to oxindoles is presented later in this section. 

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