Patent GB-591683-A (GB)
Title: Improvements in and relating to the manufacture of heterocyclic compounds
IPC: C07D401/04
Filed: 1945-05-02
Abstract: Heterocyclic compounds represented by the ring-system <FORM:0591683/IV/1> or salts thereof, are obtained by heating a nitrile, R.CN (a) with a diprimary diamine R11(NH2)2 or (b) with a mono- or di-acid salt, R11(NH2)2.HX, respectively, R representing an alkyl, aralkyl, substituted or unsubstituted aryl, hetetocyclic or alicyclic group R11 consisting of 2, 3 or 4 methylene groups, and HX representing the acid used to form the salt.  When R11 represents two methylene groups, the product is a dihydroglyoxaline substituted in 2-position by a group R as above, and when it represents three methylene groups, a substituted tetrahydropyrimidine is obtained. When the product is a free base, it may be converted into salts by customary methods, and vice versa.  In examples, there is obtained by heating together the reactants: (1) a  : b -bis-(4 : 5 - dihydro - 2 - glyoxalinyl) - ethane from succinonitrile and ethylenediamine monotoluene-p-sulphonate, and treatment of the corresponding salt with 5N-sodium hydroxide; (2) a  : b -bis-(3 : 4 : 5 : 6-tetrahydro-2-pyrimidyl) - ethane di - toluene - p - sulphonate, from succinonitrile, trimethylenediamine ditoluene-p-sulphonate and trimethylenediamine; (3) a  : g -bis - (4 : 5 - dihydro - 2 - glyoxalinyl) - propane di-toluene-p-sulphonate, from glutaronitrile and ethylenediamine mono - toluene - p - sulphonate; (4) a  : d  - bis - (4 : 5 - dihydro - 2 - glyoxalinyl) - n - butane ditoluene-p-sulphonate, from adiponitrile and ethylenediamine mono-toluene-p-sulphonate; (5) a  : d -bis-(N : N1 - tetramethylene amidino)-n-butane ditoluene-p-sulphonate, from adiponitrile, putrescine ditoluene-p-sulphonate and putrescine; (6) a  : e -bis-(4 : 5-dihydro - 2 - glyoxalinyl) - n - pentane ditoluene - p - sulphonate, from pimelonitrile and ethylenediamine monotoluene-p-sulphonate; (7) a  : o -bis - (4 : 5 - dihydro - 2 - glyoxalinyl) - n - octane, from sebaconitrile and ethylenediamine monotoluene-p-sulphonate, and treatment as in (1); (8) a  : o  - bis - (4 : 5 - dihydro - 2 - glyoxalinyl)-n-undecane, from a  : o -dicyano-n-undecane and ethylenediamine monotoluene-p-sulphonate and treatment as in (1); (9) 2-benzyl-4 : 5-dihydroglyoxaline, from benzyl cyanide and ethylenediamine and isolating the product by fractional distillation; (10) 2-benzyl-4 : 5-dihydroglyoxaline, from benzyl cyanide and ethylenediamine monotoluene-p-sulphonate, basification with 5N-sodium hydroxide and fractional distillation of the chloroform extract (the picrate is described); (11) N : N1-tetramethylene phenylacetamidine picrate, from benzyl cyanide, putrescine ditoluene - p - sulphonate and putrescine, and isolating the product as in (10); (12) 2 - p - aminobenzyl - 4 : 5 - dihydroglyoxaline, from ethylenediamine dihydrochloride, p-aminobenzyl cyanide and ethylenediamine, basification as in (1) and extraction with chloroform to isolate the product; (13) 2-(p-sulphonamidobenzyl) - 4 : 5 - dihydroglyoxaline toluene - p - sulphonate, from p - sulphonamidobenzyl cyanide and ethylenediamine mono-toluene-p-sulphonate; (14) 2-(a -naphthylmethyl)-4 : 5-dihydroglyoxaline hydrochloride, from a -naphthylacetonitrile and ethylenediamine monotoluene-p-sulphonate, treatment as in (12) and adding 2N-hydrochloric acid; (15) 2-(a -naphthylmethyl)-3 : 4 : 5 : 6-tetrahydropyrimidine, from a  - naphthylacetonitrile, trimethylene - diamine ditoluene-p-sulphonate and trimethylene, and isolating the product as in (12); (16) 2 - phenyl - 4 : 5 - dihydroglyoxaline, from benzonitrile and ethylenediamine ditoluene-p-sulphonate, separating benzamidine toluene-p-sulphonate, and isolating the product from the aqueous mother liquor; (17) 2-phenyl-4 : 5-dihydroglyoxaline, from ethylenediamine dihydrochloride, ethylenediamine and benzonitrile; (18) 2-phenyl-3 : 4 : 5 : 6-tetrahydropyrimidine toluene-p-sulphonate, from benzonitrile, trimethylenediamine ditoluene - p - sulphonate and trimethylenediamine, treating as in (12) and isolating the product by adding isopropanolic toluene-p-sulphonic acid; (19) N : N1-tetramethylenebenzamidine toluene - p - sulphonate, from benzonitrile, putrescine ditoluene-p-sulphonate and putrescine; (20) 2 - (41 - chlorophenyl) - 4 : 5 - dihydroglyoxalinetoluene - p - sulphonate, from p - chlorobenzo - nitrile, and ethylenediamine monotoluene-p-sulphonate; (21) 2 - (41 - methoxyphenyl) - 4 : 5-dihydroglyoxaline toluene-p-sulphonate, from anisonitrile and ethylenediamine monotoluene-p - sulphonate; (22) 2 - (p - methylsulphonyl - phenyl) - 4 : 5 - dihydroglyoxaline, from p - methylsulphonylbenzonitrile and ethylene - diamine; (23) 2 - (p - methylsulphonylphenyl)-4 : 5 - dihydroglyoxaline; from p - methyl - sulphonyl benzonitrile and ethylenediamine mono-toluene-p-sulphonate and treatment as in (1); (24) 2 - (p - methylsulphonylphenyl)-4 : 5-dihydroglyoxaline hydrochloride, from p - methylsulphonylbenzonitrile, ethylenediamine dihydrochloride and ethylenediamine; (25) 2-(p - methylsulphonylphenyl) - 3 : 4 : 5 : 6 - tetrahydropyrimidine, from p - methylsulphonyl - benzonitrile and trimethylenediamine ditoluene-p-sulphonate and isolating the product as in (12); (26) p - methylsulphonyl - N : N1 - tetramethylenebenzamidine, from p - methylsul - phenylbenzonitrile, putrescine ditoluene - p - sulphonate and putrescine, and treatment as in (12); (27) 2 - (p - sulphonamidophenyl) - 4 : 5 - dihydroglyoxaline, from p - sulphonamido - benzonitrile and ethylenediamine mono-toluene-p-sulphonate and basifying the resulting salt by adding 2N-sodium carbonate; (28) pp1-bis-(4 : 5 - dihydro - 2 - glyoxalinyl) - diphenyl ditoluene - p - sulphonate, from pp1 - dicyano - diphenyl and ethylenediamine monotoluene-p-sulphonate; (29) pp1 - bis - (4 : 5 - dihydro - 2 - glyoxalinyl)-stilbene di - toluene - p - sulphonate, from pp1-dicyanostilbene and ethylenediamine monotoluene - p - sulphonate; (30) 2 - (a  - pyridyl) - 3 : 4 : 5 : 6 - tetrahydropyrimidine, from a -cyanopyridine and trimethylenediamine, and isolating the product by fractional distillation; (31) 2 - (a  - pyridyl) - 4 : 5 - dihydro - glyoxaline, from a -cyanopyridine and ethylenediamine monotoluene-p-sulphonate, and treatment as in (12); (32) 2-(b -pyridyl)-4 : 5-dihydro-glyoxaline toluene-p-sulphonate, from nicotinonitrile and ethylenediamine monotoluene-p-sulphonate; (33) 2 - n - butyl - 4 : 5 - dihydro - glyoxaline toluene - p - sulphonate, from n - butylcyanide and ethylenediamine p monotoluene-p - sulphonate; (34) N : N1 - tetramethylene - benzamidine-p-sulphonic acid, from ammonium p - cyanobenzene - sulphonate and putrescine; (35) 2 - cyclohexyl - 4 : 5 - dihydroglyoxaline, from cyclohexyl cyanide and ethylenediamine monotoluene - p - sulphonate; (36) 2 - (11 - cyclohexenyl) - 4 : 5 - dihydroglyoxaline, from 1-cyclohexenyl cyanide and ethylenediamine monotoluene-p-sulphonate.