Benzamide: dehydration

Dehydration of pyridine-3-carboxylic acid amide (Nicotinamide) Dehydration of nicotinamide was carried out at different temperatures using conditions similar to those employed for benzamide. The results are shown in Fig.4. The reaction followed zero order kinetics and rate of reaction is very comparable to that of dehydration of benzamide. The kinetic constants are given in Table 2. In contrast with benzamide dehydration of nicotinamide in the absence of catalyst was negligible. 

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. 

Because of resonance stabilization of the anion, a tet-nazolyl moiety is often employed successfully as a bioisosteric replacement for a carboxy group. An example in this subclass is provided by azosemide (27). Benzonitrile analogue is prepared by phosphorus oxychloride dehydration of the corresponding benzamide. Next, a nucleophilic aromatic displacement reaction of the fluorine atom leads to The synthesis concludes with the 1,3-dipolar addition of azide to the nitrile liinction to produce the diuretic azosemi de (27). ... 

Dehydration of the aminopyrimidin-6-yl-benzamide 288 with polyphosphoric acid gives rise to the purin-4-one angular tricyclic system 289 in moderate yield (Equation 78) <1995JHC1725>. 

A convenient route to 2-alkylthio-4-alkyl-4-hydroxy-5,6-dihydro-4/7-l,3-thiazine derivatives 176 is the reaction of A-alkyldithiocarbamates with a,/3-unsaturated ketones in the presence of boron trifluoride etherate at 0°C (Scheme 15) <2002HAC377>. The predominant diastereomer displayed a m-relationship between the hydroxyl group and the C-4 substituent. Subsequent dehydration led to two isomeric products 177 and 178 with an equilibrium mixture resulting in a ratio of 94 6 in the case of 2-benzylthio-4-hydroxy-4-methyl-5,6-dihydro-4/7-l,3-thiazine. 2-Phenyl-4-alkyl-4-hydroxy-5,6-dihydro-4/7-l,3-thiazine derivatives are similarly prepared by reacting thio-benzamide with o ,/3-unsaturated ketones at room temperature <2002EJP307>. 

Amides react in certain cases to form ammonium salts of sulfonated amides (22). For example, treatment with benzamide yields ammonium A-benzoylsulfamate [83930-12-5], C5H5C0NHS03 NH4, and treatment with ammonium sulfamate yields diammonium imidodisulfonate [13597-84-1], HN(S020NH4)2. Ammonium sulfamate or sulfamic acid and ammonium carbonate dehydrate liquid or solid amides to nitriles (27). 

Dehydration of benzamide, nicotinamide, stearamide and oleamide is studied using sulphated zirconia as catalyst. Complete conversion to corresponding nitriles could be achieved when the reactions were carried out in water immiscible solvents. The order of reactivity of the different amides seems to be governed by the ease of the dissociation of the C=0 bond of the amide. 

In the preliminary experiments dehydration of benzamide was first investigated without using any solvent. The reaction was carried out using 40% w/w sulphated zirconia in molten benzamide at... 

Fig.2. Dehydration of benzamide using sulphated zirconia in (a) dipheny lether (b) 2-nitrotoiuene (c) tetralin.

Fig. 1. Dehydration of benzamide in diphenyiether (a)with sulphated zirconia (b) with untreated zirconia (c) without catalyst.

The higher rate of dehydration of benzamide and nicotinamide appears to be due to electron withdrawing effect of the aromatic ring which facilitates dissociation of the C=0 bond. 

A method for making benzonitrile by dehydrogenation of the Diels-Alder adduct of butadiene and acrylonitrile also has been described (79). Benzonitrile also can be made on a small scale by the dehydration of benzamide in an inert solvent with phosphorus oxychloride or benzenesulfonyl chloride and an organic amine (80,81). 

When the reaction is carried out in boiling DMSO, no significant gain in the yield of benzamide (30%) is observed. Since under these conditions the primary dehydration of aldoximes is evident, the formation of benzamide is most likely to result from hydration of the intermediate benzonitrile rather than by the Beckmann rearrangement scheme. 

In strongly acid solution 213 is dehydrated to the easily reducible 3-oxoisoindole (214) which is reduced to phthalimidine (215) a further reduction to isoindoline (216) may take place under conditions similar to those used for the reduction of benzamides.223-225... 

That the amide might be dehydrated by the sulfuric acid reaction mixture seems to be ruled out by the fact that benzamide shows a molar freezing point depression of two in sulfuric acid solution. Dehydration would cause a molar freezing point depression of four. Accordingly, it seems more likely58 that dehydration of the intermediate XC occurs before rearrangement since a series of steps similar to those outlined in equations 25 to 29 would lead to the nitrile directly ... 

The small amount of benzamide was considered to arise from isomerization of oxime before rearrangement, rather than from migration of a syn methyl group. Aldoximes (R2 = H) dehydrate to the nitrile under conditions causing ketoximes to rearrange to the corresponding lactams [29]. 

Triphenylphosphine and its derivatives provide another method of dehydration under relatively mild conditions. Benzamide reacts with triphenylphosphine and carbon tetrachloride in tetrahydrofuran (THF) to form probably the chloro-imine (7) which on warming at 45—55° with more of the phosphine, loses hydrogen chloride [29] an attempt to use pyridine as solvent and to facilitate the removal of the hydrogen chloride, gave a very low yield of nitrile. Under optimum conditions the yield was 83%. 

A variation in the dehydration of amides by phosphorus pentachloride [39] is described in a patent [40]. This reagent together with an alkali metal salt and an amine (such as diethylamine) dehydrates cyanoacetamide (in 95% yield) on heating under reduced pressure until a temperature of 200° is reached. This procedure however gives only a 39.9% yield of benzonitrile from benzamide. 

The dehydrating action of cyanuric chloride on benzamide was known [60] in 1886 but its efficacy in converting aldoximes to nitriles under mild conditions was only recently demonstrated [61]. The chloride and an oxime in pyridine at room temperature gave benzonitrile (82%), 4-nitrobenzonitrile (92%) or 2-cy-anopyridine (63%). An 0-triazine intermediate may be involved ... 

Aliphatic amine derivatives such as amides, carbamates and sulfonamides also participate in Pd - catalyzed intramolecular C-N bond formation. The relative reactivity of these amino nucleophiles toward cyclization has been evaluated in the PdCL-catalyzed cyclization of iV-protected 4-pentenylamines and 5-hexenylamines, and it was found to be urea > carbamate > tosylamide > benzamide. The PdCl2(CH3CN)2-catalyzed dehydrative cyclization of alkenyl urethanes bearing an allylic hydroxyl group has been elegantly applied to the synthesis of chiral piperidine alkaloids. The cyclization reaction occurs with complete stereocontrol in good yields in the presence of 15-20 mol % of catalyst without any reoxidant (eq 16). 

Nitriles are important organic intermediates for a variety of ene products. Rao tt al. reported the dehydration of amides to nitriles by passing the vapor of amides through ZSM-5 zeolites at 673 Benzamide, phenacetamide, nicotinamide and isovaleramide gave the corresponding nitriles in 90%, 85%, 89% and 85% yields, respectively. 

Since the primary dehydration of aldoximes in these conditions has been proved, the conclusion is made [7] that benzamide is generated not via the Beckmann rearrangement, but owing to hydration of the benzonitrile formed (Scheme 1.181). 

Nitriles and Isocyanides via Amide Dehydration. Thionyl chloride dehydrates primary amides to form nitriles (eq 8) for example, 2-ethylhexanonitrile is produced in about 90% yield by heating with SOCI2 in benzene. Substituted benzonitriles are readily produced from benzamides. These reactions may also be catalyzed by DMF. A -Alkylformamides may be dehydrated to isocyanides. ... 

Widely used as polar, aprotic solvent which activates the synth. and use of organometallic compds. (e.g. Li, Mg derivs.). Widespread use in organic synthesis converts benzamides into dimethylaminoquinolines, dehydrating agent for alcohols and amides. Used in combination with SOCI2 for synth. of alkyl chlorides. Used for extraction separation of metals (CHCI3, as SCN-complexes) photometric detn. of Os, Ru, Fe(//7), Ti. 

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