Reactions of organomagnesium compounds with aliphatic azomethines and with hexamethylenetetramine. I.
Vera Evdokimoff
Chem. Abs. 42, 2586 (1948) [Gazz. chim. ital. 77, 318–26(1947)]
Whereas the reaction RMgX + R'CH=NR" --> R'CHRN(MgX)R" -H2O-> RR'NHR" has been studied by Busch (Ber. 37, 2691(1904); 38, 1761(1905) ; C.A. 2, 2231) with arylaliphatic and aromatic azomethines, there is no literature on the same reaction with aliphatic azomethines, perhaps because the latter tend to polymerize to products without azomethinic function. This difficulty can be overcome by making equimol. wts. of the primary amine and aldehyde react in Et2O, fixing with anhyd. Na2SO4 the water formed in the condensation, and pouring the soln. immediately into excess organomagnesium reagent.
PhCH2Cl (24.4 g) in anhyd. Et2O, added slowly to 4.8 g. Mg (the reaction can best be started by inoculating with a little Mg previously heated with iodine), and heated on a steam bath, yields a soln. of PhCH2MgCl (I). MeNH2.HCl (15 g) and 30 cc. 40% aq. NaOH, distd. into ice-cold anhyd. Et2O contg. Na2SO4, give a soln. of MeNH2 (II), the concn. of which is detd. by titration. An ice-cold mixt. of 3.1 g. II in anhyd. Et2O, 4.4 g. freshly prepd. AcH, and excess anhyd. Na2SO4, agitated, allowed to stand cold several min., the Et2O soln. added slowly to the ice-cold soln. of I, refluxed 2 hrs., the Et2O distd., the residue heated 2 hrs. on a steam bath, Et2O added, ice and dil. H2SO4 added, the Et2O layer sepd., and the aq. layer (III) extd. with Et2O, gives a combined Et2O soln. (IV). The residual acidic aq. soln. (V) contains bases which give a ppt. with picric acid (VI).
A riptographic study of this reaction (cf. Toffoli, C.A. 33, 697; T. and Flamini, C.A. 40, 33604) indicated that VI ppts. a single compd. rather than a mixt., that under the exptl. conditions the soly. of the picrate is approx. 7 millimolar or 2.6%, that its soly. as an undissocd. compd. is very low, that the quantity of base formed is 0.04 M (160 µmols. per 250 cc.), and that the reaction gives a theoretical yield of approx. 40%.
The main products of the reaction were sepd. by 2 methods. V, made alk. with NaOH, extd. with Et2O, the ext. dried by Na2SO4, filtered, evapd. to dryness, the oil residue salified by HCl, kept several days in a desiccator contg. H2SO4 and NaOH, and purified by acetone, yields PhCH2CHMe-NHMe.HCl (VII), mp 140°C. A mixt. (VIII) of VII and d-rotatory VII (4:1) mp 140-5°C; a mixt. of VII and VIII (1:1) mp 143-8°C.
VI (0.2 that required for complete pptn.), added to V, filtered, excess VI added to the filtrate, and the ppt. dissolved in hot water, cooled very slowly, concd. below 45°C in vacuo, and the part of the ppt. which mp 115-20°C purified by water, yields the picrate, PhCH2CHMeNHMe.C6H2(NO2)2OH, mp 126°C. IV, concd. and fractionally distd., yields liquids below 200°, and bibenzil (IX), mp 52°C, bp 284°C.
By the same general procedure, I (0.2 mol.), HCHO, and II yield an acidic aq. liquor (X) and an Et2O soln. (XI). X, made alk. by NaOH, steam-distd., the distillate extd. with Et2O, the ext. dried by Na2SO4, evapd., 0.5 mL concd. HCl added, dried 2 days over H2SO4 and NaOH, dissolved in anhyd. EtOH, excess anhyd. Et2O added, and this last treatment repeated until cryst., yield PhCH2CH2NHMe.HCl, mp ~156°C (cf. 156-7°C of Decker and Becker, C.A. 7, 84, 1513). XI, evapd., and the residue fractionally distd., yields PhMe, PhCH2Cl, alc. substances (probably approx. 60% alcs. as judged by benzoylation), and IX.
From a mixt. of an Et2O soln. of 0.1 mol. I and 0.025 mol. anhyd. hexamethylenetetramine (XII) the Et2O was distd., 40 cc. xylene added, the mixt. heated 6 hrs. at 140°C then to 180°C (allowing the xylene to evap.), decompd. by ice, extd. with Et2O, NH4OH and NH4Cl added to the aq. liquor, extd. with Et2O, and the combined Et2O exts. evapd., yielding chiefly a basic resinous mixt. which could not be purified and was discarded. The aq. soln., neutralized by HCl, and 0.7 g. VI added, gives a resinous ppt., whereas the addn. of 2 g. of VI ppts. the picrate of II.
The reaction between I and XII, started as above but, after the xylene is distd., Et2O added, decompd. by ice and dil. HCl to obtain an acidic soln., the Et2O sepd., the aq. portion extd. with Et2O, the ext. evapd., and the residue fractionally distd., yields PhMe, PhCH2Cl, IX, and alcs., and a relatively large amt. of PhCH:CH2. The aq. soln., made alk., steam-distd., the distillate extd. with Et2O, the ext. dried by Na2SO4, evapd., the residue salified by concd. HCl, kept several days over H2SO4 and NaOH, dissolved in anhyd. EtOH, anhyd. Et2O added, allowed to stand several weeks, and the ppt. washed with anhyd. Et2O, yields PhCH2CH2NHMe.HCl.2H2O, mp 139-40°C.