Сообщение
slavert » Вт июн 19, 2007 8:41 pm
йайтса даю на отсечение что есть
Рiperazine derivatives. (Science Union et Cie., Societe Francaise de Recherche Medicale). (1962), 19 pp. BE 616371 19621012 Patent language unavailable. Priority: FR 19610412.
Patent Family Information
Patent No. Kind Date Application No. Date
BE 616371 19621012 BE
DE 1193053 DE
DE 1198827 DE
FR 1311316 FR
FR 1312427 FR
FR M1734 FR
GB 963304 GB
US 3119826 19640128 US 1962-185855 19620409
Priority Application
FR 19610412
Abstract
The prepn. of I (n = 1 or 2, R' = H or Me, and R = substituted benzoyl, benzyl, benzhydryl, phenacyl, or hydroxyalkyl), which have antitussive, bronchodilatory, and vasodilatory properties, is described. Thus, 0.2 mole piperonyl chloride was added dropwise to 0.2 mole of a mixt. of equal parts piperazine-6H2O and piperazine-2HCl in 100 cc. MeOH to give (after 90 min. reflux) 15 g. 1-piperonylpiperazine (II), b2 147-9°; 2HCl salt m. 232-6° (alc.). By a different method, a mixt. of 121.7 g. K2CO3, 100 g. 1-formylpiperazine, 162.8 g. 3,4-ethylenedioxybenzyl chloride (prepd. by treatment of 3,4-ethylenedioxybenzyl alcohol with SOCl2) (b1.5 139-41°, n25D 1.5672), and 2 l. PhMe was refluxed 20 hrs., cooled and filtered, the PhMe soln. extd. with MeSO3H, and the solvent evapd. to give 138 g. 1-(3,4-ethylenedioxybenzyl)4-formylpiperazine, which was hydrolyzed by refluxing 15 hrs. with NaOH in aq. alc. to give 70 g. 3,4-ethylenedioxybenzylpiperazine, b0.8 165°. Similarly prepd. was a-methyl-3,4-methylenedioxybenzylpiperazine, b0.5 185° (from 1-chloro-1-piperonylethane, obtained from piperonylmethyl carbinol, b0.1 113°). 3,4,5-Trimethoxybenzoyl chloride (0.1 mole) was added to 0.1 mole II and 0.1 mole Et3N in 250 cc. benzene, the mixt. refluxed 3 hrs., 100 cc. H2O added, the org. layer sepd. and extd. with 10% aq. MeSO3H, and the aq. acid residue washed (Et2O), made alk., extd. with CHCl3, dried, and concd. to give I [n = 1, R' = H, R = 3,4,5-(MeO)3C6H2CO]; HCl salt (9.6 g.) m. 221°. Other I prepd. were (n, R', R, m.p., salt, and m.p. of salt given): 1, H, 3,4-(MeO)2C6H3CO, -, HCl, 210° (methanesulfonate m. 227°); 1, H, 2-HOC6H4CO, -, HCl, 221°; 1, H, 4,3,5-(MeO)2(EtO2C)C6H2CO (IIa), -, methanesulfonate, 218-19°; 1, H, 4-(EtO2C)C6H4CO (IIb), -, HCl, 240°; 1, H, 2,5-(HO)(EtO2C)C6H3CO, -, HCl, 220°; 1, H, 4-O2NC6H4CO (IIc), 172°, -, -; 2, H, 3,4-(CH2O2)C6H3CO, 130°, HCl,242°; 2, H, 3,4-(C2H4O2)C6H3CO, 160°, HCl, 237-40° (prepd. from 3,4-ethylenedioxybenzoyl chloride, m. 102°, which was prepd.
from 3,4-ethylenedioxybenzoic acid, m. 138°); 1, Me, 3,4-(CH2O2)C6H3CO, 206°, -, -; 1, H, 4,3,5-(HO)(MeO)2 C6H2CO, -, HCl,252-3° (base prepd. by hydrolysis of IIa with alc. NH3); 1, H, 4-HOC6H4CO, 188°, -, -, (from IIb); 1, H, 4-H2NC6H4CO, 115-49°, -, -, (prepd. by redn. of Ic with Fe-AcOH); 1, H, 3,4-(CH2O2)C6H3CH2, -, 2HCl, 260°; 1, H, benzhydryl, -, 2HCl, 288°; 1, H, 4-chlorobenzhydryl, -, 2HCl, 212°; 1, H, 3,4-methylenedioxybenzhydryl, -, 2HCl, 208°; 1, H, PhCOCH2, -, 2HCl, 225°; 1, H, 4-FC6H4COCH2, 100°, -, -; 1, H, 3,4-(CH2O2)C6H3COCH2, 115°, 2HCl, 235-9°; 1, H, HOCH2CH(OH)CH2, -, 2HCl, 204°; 1, H, HOCH2CH2OCH2CH2, -, 2HCl, 197°; 1, H, MeSCH2CH2, -, 2HCl, 222° (base b1.5 191-9°); 1, H, MeSO2CH2CH2, 127°, -, -.