Benzamides

Following administration to poultry, dinitolmide is mainly metabolized to 

3-amino-5-nitro-( -toluamide and 5-amino-3-nitro-o-toluamide metabolites that are bound to tissues. Residue depletion studies of dinitolmide in chicken, also showed the formation in chicken liver of an acid-labile conjugate of the 5-amino- 

3-nitro-o-toluamide metabolite, presumably the 7V5-glucoside conjugate (2). However, no evidence was presented for the formation of the corresponding 3-amino-5-nitro-o-toluamide conjugate in chicken tissues. 

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Homogeneous catalysts may also be effective in the hydrogenation of sulfur-containing compounds. (Z)-2-Benzamide(acetamido)-3-(2-thienyl)-2-propenoic acid was reduced in 100% yield and 78% enantiomeric excesses over Rh(I)-DlOP catalysts (25),... 

Fig. 3.1. Separation of the unbonded silica test mixture using in-house packed (A) Hypersil silica, (B) Hypersil BDS silica, (C) Hypersil HyPURITY and (D) Kromasil silica capillaries (100 pm i.d., 33.5 cm total length and 25 cm effective). Conditions 8 2 v/v ACN-50 mM MES, pH 6.1, 20 kV, 20°C, 5 kV for 3 sec. injections, 254 nm. Peak identities 1 = biphenyl, 2 = benzamide, 3 = benzyl alcohol and 4 = thiourea. Adaptation of [20]. Reproduced with die permission of Chromatographia.

Figure 4-22. Selectivity differences at pH 2,7, and 12 on Waters XBridge CIS column. Analytes 1, doxylamine (base) 2, benzamide (neutral) 3, hydroxyisophthalic acid (acid) 4, doxepine (base) 5,flavone (neutral) 6,5 fenoprofen (acid). (Reprinted from reference 57, with permission.)...

The Erlenmeyer azalactone synthesis generally affords predominantly, and often exclusively, (Z) isomers (32). However, a simple method for the synthesis of ( ) isomers (33), obtained previously by separation of isomeric mixtures or isomerization procedures, has been reported. Aromatic aldehydes condense with hippuric acid when heated in polyphosphoric acid (PPA) to afford (33) in 80-90% yields (equation 17 Table 4). Alternatively, the (Z) isomers may be heated in PPA to afford the corresponding ( ) isomers in excellent yield. The authors note that hippuric acid is not converted to (26) in PPA, the generally accepted intermediate in the Erlenmeyer synthesis. Furthermore, both isomers of 2-(benzamid-oyl)cinnamic acid, (34) and (35), obtained by the alkaline hydrolysis of (32 R = H, Ar = Ph) and (33 R = H, Ar = Ph), respectively are converted to (33 R = H, Ar = Ph) in PPA (Scheme 9). The authors therefore suggest a mechanism involving condensation, first of the aldehyde and hippuric acid followed by... 

Ammophthalazin-2-ium mesitylenesulfonate (41) gave phthalazin-2-ium-2-benzamidate (42) (neat BzCl, 90°C, 3 h residue from evaporation, NaOH, H2O 86%) analogs likewise ... 

Table 2. Benzamide can inhibit and induce Friend cell differentiation...

Prepared by the dehydration of benzamide. Hydrolysed by dilute acids and alkalis to benzoic acid. Good solvent. benzopheDone,C]3HioO,PhC(0)Ph. Colourless rhombic prisms, m.p. 49 C, b.p. 306°C. Characteristic smell. It is prepared by the action of benzoyl chloride upon benzene in the presence of aluminium chloride (Friedel-Crafts reaction) or by the oxidation of di-phenylmethane. It is much used in perfumery. Forms a kelyl with sodium. 

Prepared by stirring phthalimide with cold concentrated ammonia solution. Hydrolysed to phlhalic acid with dilute acids. Dehydration with ethanoic anhydride gives first n-cyano-benzamide and then phthalonitrile. 

Naphthalene, oxalic acid (hydrated), cinnamic acid, acetamide, benzamide, m-dinitrobenzene,/>-nitrophenol, toluene p-sulphon-... 

Carry out this preparation in precisely the same way as the above preparation of oxamide, using 2 ml. (2-4 g.) of benzoyl chloride instead of the ethyl oxalate, and observing the same precautions. Considerably more heat is generated in this reaction therefore hold the cork very securely in position during the shaking. After vigorous shaking for 15 minutes, no trace of oily benzoyl chloride remains. Filter off the fine flakes of benzamide, wash with cold water, and then recrystallise from hot water yield, 1-5 g. Colourless crystals, m.p. 130°. 

Hydrolysis of Benzamide. When acid amides are hydrolysed, the corresponding acid and ammonia are formed. Consequently the hydrolysis, which is extremely slow with water alone, is hastened con-... 

Place I g. of benzamide and 15 ml. of 10% aqueous sodium hydroxide solution in a 100 ml. conical flask fitted with a reflux water-condenser, and boil the mixture gently for 30 minutes, during which period ammonia is freely evolved. Now cool the solution in ice-water, and add concentrated hydrochloric acid until the mixture is strongly acid. Benzoic acid immediately separates. Allow the mixture to stand in the ice-water for a few minutes, and then filter off the benzoic add at the pump, wash with cold water, and drain. Recrystallise from hot water. The benzoic acid is obtained as colourless crystals, m.p. 121°, almost insoluble in cold water yield, o 8 g. (almost theoretical). Confirm the identity of the benzoic acid by the tests given on p. 347. 

Mercury Benzamide. (CeH5CONH)2Hg. (Semi-micro Scale.)... 

Add I g. of finely powdered mercuric oxide and o-8 g. of benzamide to 10 ml. of ethanol, and boil the mixture under a reflux water condenser for 30 minutes. Now filter the hot solution through a fluted filter-... 

Hofmann s amine synthesis can be applied to both aliphatic and aromatic carboxylic acid amides, benzamide, C HsCONH, thus giving aniline, C4H5NH,. 

Benzamide from Benzonitrile. (A) Although benzonitrile when boiled with 70% sulphuric acid undergoes ready hydrolysis to benzoic acid (see above), treatment with hot 90% sulphuric acid gives the intermediate benzamide. This difference arises partly from the difference in temperature employed, but also... 

Method(B). Add3g. (3ml.)ofbenzonitrileto50ml.of lo-volumes hydrogen peroxide in a beaker, stir mechanically and add i ml. of 10% aqueous sodium hydroxide solution. Warm the stirred mixture at 40° until the oily suspension of the nitrile has been completely replaced by the crystalline benzamide (45-60 minutes). Cool the solution until crystallisation of the benzamide is complete, and then filter at the pump and recrystallise as above. One recrystallisation gives the pure benza-mide, m.p. 129-130° yield of purified material, 2-2-5 S ... 

B) Formamide, acetamide, oxamide, urea, benzamide, salicylamide thiourea. 

It frequently happens that more than one volatile product is evolved, a fact which may be of considerable value. For example, benzamide, CeHjCONHt, will give off first ammonia, and then benzonitrile and benzene on stronger heating salicylamide, HOC H CONHj, will give off ammonia and then phenol. Sulphanilamide, NH,C,H,SO,NH (p. 181), gives off ammonia and aniline. 

Amine B.P. M.P., 20 20 Benzene- sulphonamlde />-Toluene- sulphoiuunide Phenyl- thiourea a-Naphthyl- thlourea Pierate iV-Substituted Phthallmlde Benzamide... 

Place 50 ml. of concentrated ammonia solution (sp. gr. 0 88) in a 200 ml. conical flask (1) and cool in ice. Add 12 1 g. (10 0 ml.) of redistilled benzoyl chloride (Section IV.185) drop by drop from a separatory funnel whilst shaking the flask frequently. Filter off the precipitated benzamide, wash with a little cold water, and recrystallise from hot water (about 50 ml.) dry upon filter paper in the air (2). The yield of pure benzamide, m.p. 129°, is 9 g. 

An alternative procedure, which does not require ice cooling, is to add all the 10 ml. of benzoyl chloride rapidly to a mixture of 50 ml. of concentrated ammonia solution and 60 ml. of water contained in a 200 ml. conical flask, stopper securely and shake vigorously for about 15 minutes. Heat is evolved So that the stopper should be held down tightly. After 30 minutes the benzamide is filtered off and worked up as above. 

The benzamide should not be dried in the Steam oven, since it will undergo partial decomposition at 100° into benzonitrile and thus give an impure product of low m.p. 

The hydrolysis by alkali is illustrated by the following experimental details for benzamido. Place 3 g. of benzamide and 50 ml. of 10 per cent, sodium hydroxide solution in a 150 ml. conical or round-bottomed flask equipped with a reflux condenser. Boil the mixture gently for 30 minutes ammonia is freely evolved. Detach the condenser and continue the boiling in the open flask for 3-4 minutes to expel the residual ammonia. Cool the solution in ice, and add concentrated hydrochloric acid until the mixture is strongly acidic benzoic acid separates immediately. Leave the mixture in ice until cold, filter at the pump, wash with a little cold water and drain well. RecrystaUise the benzoic acid from hot water. Determine the m.p., and confirm its identity by a mixed m.p. test. 

Place 45 g. of benzamide (Section IV, 188) and 80 g. of phosphorus pentoxide in a 250 ml. Claisen flask (for exact experimeutal details on the handling and weighing out of phosphoric oxide, see under Acetamide, Section 111,111). Mix well. Arrange for distillation (Fig.//, 29, 1 or Fig. II, 20, 1) under reduced pressure use a water pump with an air leak in the system so that a pressure of about 100 mm. is attained. Heat the flask with a free flame until no more liquid distils the nitrile will pass over at 126-130°/100 mm. Wash the distillate with a little sodium carbonate solution, then with water, and dry over anhydrous calcium chloride or magnesium sulphate. Distil under normal pressure (Fig. II, 13, 2 or II, 13, 6) from a 50 ml. flask the benzonitrile passes over as a colourless liquid at 188-189° (compare Section IV,66). The yield is 28 g. 

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