Carboxylic acids acetamidation

Amides. For primary amides the suffix -amide is added to the systematic name of the parent acid. For example, CH3—CO—NHj is acetamide. Oxamide is retained for HjN—CO—CO—NHj. The name -carboxylic acid is replaced by -carboxamide. 

A/,0-Bis(trimethylsilyl)trifluoroacetamide. This reagent is suitable for the silylation of carboxylic acids, alcohols, phenols, amides, and ureas. It has the advantage over bis(trimethylsilyl)acetamide in that the byproducts are more volatile. 

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... 

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. 

To 13 of ethyl acetate were added 85.1 g (2.59 mols) of 7-emino-3-(1 -methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid and 1,361 g (10.37 mols) of monotrimethylsilyl acetamide, and the mixture was stirred at 50°C until a clear solution was obtained. The solution was cooled to 20°C and 514 g (2.59 mols) of 0-formyl mandeloyl chloride was added at a rate such that the temperature of the reaction solution was maintained between about 20°C to 25°C with ice-cooling. 

A suspension of 37.3 g (0.1 mol) of 7/3-amino-3-methoxy-3-cephem-4-carboxylic acid hydrochloride dioxanate in 500 ml methylene chloride is stirred for 15 minutes at room temperature under an argon atmosphere and treated with 57.2 ml (0.23 mol) of bis-(trimethylsilyl)-acetamide. After 45 minutes the faintly yellow slightly turbid solution is cooled to 0°C and treated within 10 minutes with 31.2 g (0.15 mol) of D-Ct-amino-Ct-d, 4-cyclohexadienyl (acetyl chloride hydrochloride. Thirty minutes thereafter 15 ml (about 0.21 mol) of propylene oxide is added and the mixture is further stirred for 1 hour at 0°C. A cooled mixture of 20 ml of absolute methanol in 200 ml of methylene chloride is added within 30 minutes, after another 30 minutes the precipitate is filtered off under exclusion of moisture, washed with methylene chloride and dried under reduced pressure at room temperature. The obtained hygroscopic crystals of the hydrochloride of 7j3-[D-a-(1,4-cyclohexadienyl)acetylamino] -... 

Non-Kolbe electrolysis of carboxylic acids in acetonitrile/water leads to acetamides as main products [294] (Table 10). The mechanism has been investigated by using " C-labeled carboxylic acids. The results are rationalized by assuming a reaction layer rich of carboxylate resulting in the formation of a diacylamide that is hydrolyzed... 

CjjH(,F2N20S 97963-62-7) see Pantoprazole sodium 4-(difluoromethoxy)-2-nitrobenzenamine (C7H(,F2N203, 97963-76-3) see Pantoprazole sodium A -[4-(difluoromethoxy)phenyl]acetamide (0)HyF2N02 22236-11-9) see Pantoprazole sodium 2-(difluoromethoxy)-l,l,l-trifiuoroethane (C3H3F5O 1885-48-9) see Isoflurane (5)-9,10-difluoro-3-methyI-7-oxo-2,3-dihydro-7/f-pyrb do[l,23-d ]-Iy4 benzoxazine-6-carboxylic acid (C,3Hyp2N04 100986-89-H) see Levofloxacin... 

The range of products formed on gamma radiolysis of N-acetylglycine was similar to that formed on radiolysis of the aliphatic carboxylic acids, but there are some noticeable differences in the yields of products. Carbon dioxide is by far the major volatile product of radiolysis and the corresponding product of the decarboxylation reaction, N-methyl acetamide, is also present in large yield, but the yield of this product was not quantitatively determined. By contrast, carbon monoxide is found in very small yield. The yield of acetamide, the product of N-Ca bond scission, is found in much greater yield. 

Alkylidene 5-acylmalonates were reacted with O-substituted hydroxyl-amine to give aminomethylenemalonates (451) [82JAP(K)62274], However, when 7/3-amino-ceph-3-em-4-carboxylic acids (452) were first reacted with A,0-bis(trimethyIsilyl)acetamide in THF and then with isopropylidene 5-acylmalonate (449, R1 = R2 = Me), instead of the corresponding aminomethylenemalonate, 7/3-acylamido-ceph-3-em-4-carboxylic acids (453) were obtained (83EUP54970). 

The instability of primary nitramines in acidic solution means that the nitration of the parent amine with nitric acid or its mixtures is not a feasible route to these compounds. The hydrolysis of secondary nitramides is probably the single most important route to primary nitramines. Accordingly, primary nitramines are often prepared by an indirect four step route (1) acylation of a primary amine to an amide, (2) A-nitration to a secondary nitramide, (3) hydrolysis or ammonolysis with aqueous base and (4) subsequent acidification to release the free nitramine (Equation 5.17). Substrates used in these reactions include sulfonamides, carbamates (urethanes), ureas and carboxylic acid amides like acetamides and formamides etc. The nitration of amides and related compounds has been discussed in Section 5.5. 

There has been considerable interest in hydroxy-3,3 -bipyridines and 3,3 -bipyridinones. Following from some very early work on the oxidation of citrazinic acid (2,6-dihydroxypyridine-4-carboxylic acid), which was considered to give some polyhydroxy-3,3 -bipyridines, it has been shown that the 3,3 -bipyridinone 59, a product of the hydrolysis of a natural blue pigment from Corynehacterium insidiosum, is obtained by oxidation of 2-hydroxy-5-aminopyridine (60) or 2,6-dihydroxypyridine-4-carboxylic acid 61) 80,83 similar oxidation of 2,6-dihydroxy-3-aminopyridine-4-carboxylic acid affords the natural product indigoidine (20). Numerous related oxidative condensations have been reported subsequently. Cyano-acetamide condensations analogous to those discussed in the synthesis of 2,3 -bipyridines afford, for example, the cyano-substituted 3,3 -bipyridinone 62 588 v, lereas condensation of 3-pyridylacetonitrile with ethyl phenyl-propiolate and ethanol affords compound 63. To complete the section on... 

Carboxylic Acids, R—C02H 0 // ch3—c OH ethanoic acid (acetic acid) Esters, R—C02R 0 // ch3—c 0—ch3 methyl ethanoate (methyl acetate) Amides, R—CONH2 P CH3—c nh2 ethanamide (acetamide) ... 

This section deals with the coordination chemistry of amides of carboxylic acids, predominantly formamide, acetamide and their -substituted derivatives. Lactams are also mentioned briefly. 

It is possible to oxidize alcohols in the presence of free carboxylic acids.206 Nevertheless, sometimes better results are obtained if the acid is protected, for example by methylation.207 Sometimes, free carboxylic acids have a low solubility in cold CH2C12. In such cases, an in situ protection with the silylating agent, bis(trimethylsilyl)acetamide (BSA) normally allows the solubilization of the acid as trimethylsilyl ester, and an easy Swern oxidation. The resulting silylated acid is easily deprotected during the work-up.208... 

Substituted and /V,7V-disubstituted 4-oxo-4//-pyrido[l,2-a]pyrimi-dine-3-carboxamides and -3-acetamides 428 (n = 0,1) were prepared from the corresponding carboxylic acid 427 when the carboxylic acids were reacted first with methyl chloroformate in the presence of triethylamine in chloroform at -20°C, after which the mixed anhydrides were treated with an amine at - 10°C overnight (89EUP326981). 

---