Benzamide methyl

Chloro-2-(ethoxycarbonyl)-3-(4-fluorophenyl) N-[5-Chloro-2-(4-fluorobenzoyl]benzamide, methyl bromoacetate (1) NaH (2) NaOMe 30 [2]... 

II 1 A -Melhylformamide A, A -Dimethylformamide Benzamide Methyl dimelhylcarbamate Urea Thiourea... 

Roberts and Whiting developed a method for effecting the anhydrous hydrolysis of esters and nitriles in DMSO. A solution of sodium methylsulfinylmethide is prepared from sodium hydride and DMSO and titrated with a solution of an appropriate amount of water in DMSO, using triphenylmethane as indicator. This produces a fine suspension of sodium hydroxide which hydrolyzes ethyl benzoate very rapidly at room temperature. As compared with reactions in hydroxylic solvents, rates are enhanced by a factor of 10 -10 . Benzonitrile is hydrolyzed to benzamide. Methyl and ethyl mesitoates are hydrolyzed readily at 25°. 

A mixture of 2-chloro-A-(2-hydroxyl-l-methyl-2-phenylethyl)benzamide (44) (9.5g, 24.9 mmol) and P2O5 in o-chlorobenzene (1,50 mL) was refluxed overnight. Upon completion, the reaction was cooled to room temperature and then chilled to 0 °C. To the crude reaction mixture, 300 mL of water was cautiously added. The resulting dark solution was washed with toluene (2 x 50 mL). The aqueous layer was cooled to 0 °C and 50% NaOH added to final pH of 11. The resulting mixture was extracted with toluene (4 x 50 mL). The toluene fractions were combined, dried, filtered and concentrated in vacuo. The residue was crystallized from benzene to afford l-(2-chlorophenyl)-3-methylisoquinoline (45) as a white solid (6.68g, 80%). M.P. = 107-108 °C H NMR (CDCI3) S 8.45 (s, IH), 8.11 (d, IH), 7.85 (dt, IH), 7.41-7.68 (bm, 6H), 2.51 (s, 3H). 

The benzoic acid moiety common to many of the benzamides is prepared in straightforward manner from the methyl ether of p-aminosalicylic acid 141. Acylation on nitrogen (142) followed by chlorination gives intermediate 143 benzoic acid 144 is then obtained by removal of the acetyl group. Condensation of this acid with an aminopiperidine could be achieved by means of the mixed anhydride (prepared by reaction with ethyl chlonoformate), which affords clebopride (145). Reaction with 3-aminoquinuclidine (146) of the intermediate prepared from acid 144 with carbonyldiimidazole affords zacopride (147) [36]. 

Chemical Name 3-(aminosulfonyl) 4-chloro-N-(2,3-dihydro-2-methyl-1 H-indol-Tyl)-benzamide... 

Chemical Name N-[7 [[3-0-(aminocarbonyl)-5,5 di-C-methyl-4-0-methyl-a-L-lyxo-pyranosylj oxyj -4-hydroxy-8-methyl-2-oxo-2H-1 -benzopyran-3-yl] -4-hydroxy-3-(3-methyl-2-butenyl)benzamide... 

Chemical Name N-(1-Methylethyl)-4-[ (2-methylhydrazino)methyl] benzamide HCI Common Name Ibenmethyzin Structural Formula coNHCHfCHjij... 

The all-d.v benzamide 12, readily obtainable from 8 at low temperature with methyllithium,16 is cleanly transformed to the mono-trans isomer 13 above O C. Both anions 12, 13 can be trapped at low temperature with methyl chloroformate to yield the corresponding methyl azepinc-A -carboxylates 14 and 15, respectively, with retention of the configuration.17... 

Das Naphthyl-benzamid I liefert bei der Reduktion an Hg, in DMF/[(C3H7)4N]C104 mit mittlerer Ausbeute (44% d. Th.) das 6,7-Methylendioxy- -(4,5-dimethoxy-2-methyl-aminocarbonyl-phenyl)-naphthalin3 ... 

Hydroxylamine werden i.a. an der N-O-Bindunggespalten so entsteht aus N-Methoxy-N-methyl-benzamid N-Methyl-henzamid (33% d. Th. bei geringem Gesamtumsatz)5. 

CN [7 -(7 , / )]-2-hydroxy-5-[l-hydroxy-2-[(l-methyl-3-phenylpropyl)amino]ethyl]benzamide monohydrochloride... 

CN yV-[3 Chloro-2-[[methyl[2-(4-morpholinyl)-2-oxoethyl]aminoJmethyl]phenyl]benzamide... 

CN 4-Amino-5-chloro-2-ethoxy-A-[[4-[(4-fluorophenyl)methyl]-2-morpholinyl]methyl]benzamide citrate... 

CN cw-5-chloro-2-methoxy-4-(methylamino)-A-[2-methyl-l-(phenylmethyl)-3-pyrrolidinyl]benzamide... 

CiuHiiClNO,) see Ketorolac /V-benzoyl tV-(3-chloro-2-methylphenyl)benzamide (C21H1JCINO2 42313-35-9) see Fominoben Ai-(2-benzoyl-4-chlorophenyl)-2-chloro-tV-methyl acetamide... 

The carbonyl group of methyl benzoate condenses with Na-HMDS 486 to give methoxytrimethylsilane 13a and 51% yield of N,0-bis(trimethylsilyl)benzamide 296 [99], which is also accessible by silylation of benzamide with TCS 14/triethyla-mine. Benzamide or N-silylated benzamide, however, are converted by Na-HMDS 486 in benzene and subsequent quenching with MesSiCl 14 into 34% N,0-bis(trimethylsilyl)benzamide 296, 24% crystalline N-silylated benzamidine 524, and HMDSO 7 [99] (Scheme 5.32). 

Similarly, reactions which are substantially enhanced by the use of PTC can be carried out even with reduced use of PTC with substantial enhanced rates of reaction as has been demonstrated by Sivakumar and Pandit (2000) in the case of conversion of benzamide to benzonitrile. In the case of A-alkylation of diphenylamine with benzyl bromide, in the presence of KOH as the anion source and PEG methyl ether as the PTC, some improvement in the rate has been observed. (Cains et al., 1998). Metal catalysed hydrogenations, such as those based on Ni, Pd/C, and Ru/C also benefit from ultra-sound. 

Derivatives of (S) N-[(l-ethyl-2-pyrrohdinyl)methyl]-6-methoxy benzamide 3 are dopamine D2 receptor antagonists. Samanta et al. obtained the following MLR QSAR for 49 derivatives with the general structure 3 [30] ... 

Diethyl ether, methyl n-propyl ether, diethylamine, N-methyl-1 -propanamine, acetone, allyl alcohol, dimethylformamide, propanamide, 2-methylpropan-amide, 2,2-dimethylpropanamide, benzamide, dichloromethane, toluene, ethyl N-acetyl-glycinate, -alaninate, -methioninate, and -aspartate, ethyl acetate, tetrahydrofuran... 

Tandem mass spectrometry has been used to demonstrate that M+ as well as MH+ of substituted A-(ort/zo-cyclopropylphenyl)benzamides isomerizes before the fragmentation, with formation of 3-aryl-1-ethyl-lH-benzoxazines and 5-ethyl-2-oxodi-benzoazepines (Scheme 5.14). The methyl group in /V-[ortho-( 1 -methylcvclopropyl )-phenyl]benzamides quenches the latter process, leaving the formation of benzoxazines as the only cyclization reaction. A subsequent chemical experiment in solution confirmed the mass spectral predictions [24]. A similar study confirmed the analogy of cyclization of substituted A-(ort/zo-cyclopropylphenyl)-A -aryl ureas and N- ortho-cyclopropylphenyl)-A -aiyl thioureas in the ion source of mass a spectrometer and in solution [25]. 

Mannschreck et al. (44) examined the effect of substituents on the barriers to rotation in 2,4,6-trisubstituted benzamides. In /V-benzyl-A(-methyl-2,4,6-tri-bromobenzamide, the rotational barrier (AG ) is 23.8 kcal/mol at 35.8 to 40.6°C for the Z -> E process in quinoline (44). This should be compared with AG of 23.4 kcal/mol for the same process with the trimethyl compound (5). It is seen that steric effects are of primary importance, inasmuch as the van der Waals radii of the methyl and bromo groups are almost the same. 

The simplest structures in this series are A-methyl- and A-ethylbenz-amide (4.73 and 4.74, respectively). When administered intraperitoneally in rats, these amides yielded methylamine and ethylamine, respectively, plus benzoic acid, which was detected in the urine as hippuric acid [47]. An alternative metabolic pathway is possible, involving A-dealkylation to the primary amide followed by hydrolysis its contribution, if any, must be minor, since benzamide levels in urine were negligible. 

Of interest is also that the rate of liberation of penicillin G from the prodrug was much faster than the breakdown of the former by opening of its /3-lactam ring. Furthermore, no breakdown of the pro-moiety A-(hydroxy-methyl)-A-[(ethoxycarbonyl)methyl]benzamide (8.58) to liberate formaldehyde was detected over the timescale of ester hydrolysis. 

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