Schaefer, Fred C.; Peters, Grace A. published the artcile< Base-catalyzed reaction of nitriles with alcohols. A convenient route to imidates and amidine salts>, Electric Literature of 6136-93-2, the main research area is .
The base-catalyzed reaction of nitriles with alcs. to form imidates was estimated as an attractive preparative method which was useful for a wide variety of electroneg. substituted aliphatic and aromatic nitriles. This reaction was used as the basis for a convenient procedure for the preparation of amidine salts. In general, 0.100 mole of the purified nitrile was mixed with MeOH, 0.010 mole NaOMe added, the solution diluted to 100 ml. at 25°, and liquors withdrawn at intervals, added to 0.100N HCl, and back titrated potentiometrically. In most cases, substantial conversion occurred within 0.5 hr. and the reaction was close to equilibrium in less than 24 hrs. The following results of comparative reactions were obtained under the standard conditions (nitrile, time in hrs., and % conversion to imidate given): NCCMe2CMe2CN, 22, 1; NC(CH2)4CN, 24, 1.5; MeCN, 2, 2; PhCH2CN, 24, 12; Et2NCH2CN, 48, 22; NC(CH2)2CN, 24, 69; BuOCH2OCHMeCN, 96, 86; [Et3NCH2CN]Cl, 48, 76; Me3COCH2CN, 30, 91; CH2:CClCN, 25, 90; MeCHClCN, 0.5, 91; CH2ClCN, 0.5, 93; (EtO)2CHCN, 1, 95; p-MeOC6H4CN, 96, 15; PhCN, 20, 20; p-ClC6H4CN, 48, 45; p-O2NC6H4CN, 8, 83; m-O2NC6H4CN, 4, 86; p-C6H4(CN)2, 7, 108; 3-(C5H4N)CN, 24, 71; (2-C5H4N)CN, 2, 97; Me2NCN, 24, 100 Et2NCN, 144, 100. Some nitriles gave no apparent imidate under the standard conditions. Titration of acid-hydrolyzed aliquots was carried out potentiometrically with 2 end points being observed (at pH 7 and 3.5). Addnl. experiments were carried out with p-O2NC6H4CN at different catalyst concentrations At 25° and 0.95M, the following equilibrium conversions were obtained: 0.050M NaOMe, 83%; 0.10M NaOMe, 81%; 0.20M NaOMe, 78%. (Effect of temperature). In 7 hrs. at 25°, 100 cc. MeOH containing 0.010 mole NaOMe dissolved 5.1 g. terephthalonitrile. Titration showed the presence of 0.042 mole of imidate. When the reaction mixture was heated 3 hrs. at 65°, the imidate content dropped to 0.025 mole; conversion 62.5%. In a similar experiment, it was shown that conversion to imidate in 0.04 M solution p-nitrobenzonitrile decreased from 80 to 50% on heating from 25° to 65°. The expected higher conversion at temperatures below 25° was noted with M p-chlorobenzonitrile in MeOH. When inert solvents were used the equilibrium conversions at 25° of p-nitrobenzonitrile were 13% in 90% C6H6 and 15% in 80% dioxane. With terephthalonitrile in 50% PhNO2, conversion was 19%; in 80% 2-methoxyethanol, 26%. With 2,2-diethoxyacetonitrile (I) as the standard reagent, a number of alcs. were studied with equilibria determined at 25°. The following results were obtained (R of ROH, and equilibrium conversion in % given): Me, 95; Me, 95; Me (3% H2O), 91; Et, 89; Pr, 82; Bu, 78; iso-Bu, 78; iso-Pr, 63. p-Nitrobenzonitrile (M) with anhydrous alc. containing 0.01M NaOMe gave 78% imidate at 25°. I (studied for reaction rate as a function of catalyst concentration) gave the following results (molar concentration of catalyst, k in min.-1, and k’ in l. mole-1 min.-1 given): 0.10, 0.098, 0.98; 0.071, 0.071, 0.99; 0.050, 0.048, 0.96. When KCN in MeOH was used as a catalyst, a clear solution was obtained after 120 hrs. with p-nitrobenzonitrile and in an addnl. 24 hrs. equilibrium was reached at 79% conversion. Cyanomethyltrimethylammonium chloride reacted normally with MeOH and KCN, although MeO- caused degradation. Isopropoxyacetonitrile (15 g.) and 0.5 g. NaOMe in 50 cc. MeOH was kept overnight at room temperature; titration indicated an 81% conversion and isolation gave 13.2 g. Me 2-isopropoxyacetimidate, b2 32-7°. 2-Cyanopyridine (26 g.) and 1.35 g. NaOMe in 225 cc. MeOH kept overnight at room temperature gave 31.4 g. Me pyridine-2-carboximidate, b23 118-22°. p-Nitrobenzonitrile (35 g.) and 100 cc. MeOH containing 1 g. NaOMe refluxed 4 hrs. gave 13.3 g. unchanged nitrile and 21.7 g. Me p-nitrobenzimidate, m. 75°, contaminated with some Me p-nitrobenzoate and p-nitrobenzamide. 2-Chloropropionitrile (65 g.) in 200 cc. alc. and 2.2 g. NaOMe kept 45 min. at 25° gave 53 g. Et 2-chloropropionimidate, b60 70-5°. Several amidine salts were prepared A MeOH solution of an imidate was treated with NH4Cl, the mixture stirred a few hrs. (reaction time 1-24 hrs.), solvent removed, and the product extracted with Et2O and recrystallized The following RC:NHNH2.HCl were thus prepared (R, molar concentration of original nitrile, molar concentration NaOMe catalyst, % yield, and m.p. given): CH2Cl, 2.5, 0.07, 96, 95-9°; MeCHCl, 3.1, 0.20, 73, 130-1°; Me3COCH2, 1.00, 0.10, 78, 157-9°; m-O2NC6H4, 1.00, 0.10, 80, 250-2°; p-O2NC6H4, 0.05, 0.050, 78, 285-7°; 3-C6H4N, 1.00, 0.10, 192-4°; 2-C5H4N, 1.00, 0.10, 95, 149-51°. In other work, excellent yields of amidine thiocyanates, acetates, and bromides were obtained by use of the appropriate ammonium salt. Terephthalonitrile (10 g.) and 100 cc. MeOH containing 0.50 g. NaOMe refluxed 2.5 hrs. and the hot solution added to 150 cc. ice H2O containing 12 cc. 12N HCl, kept overnight, and the product separated gave 61% Me p-cyanobenzoate, m. 59-61°. Di-Me terephthalate was expected to arise from the diimidate present, but could conceivably have been dissolved in the discarded aqueous MeOH.
Journal of Organic Chemistry published new progress about Alcohols Role: USES (Uses). 6136-93-2 belongs to class nitriles-buliding-blocks, and the molecular formula is C6H11NO2, Electric Literature of 6136-93-2.
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts