Schönenberger, Helmut and Holzheu-Eckardt, Juergen and Bamann, Eugen (1964) Antimycotics. III. Comparative studies of the preparation of isomeric hydroxybenzamides. Arzneimittel-Forschung = Drug research 14 (4), pp. 324-328.
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cf. CA 60, 16248e. HOC6H4CONHR (I), active antimycotics (CA 59, 2070e), were prepd. by SOCl2 treatment of HOC6H4CO2H (II), MeOC6H4CO2H (III), AcOC6H4CO2H (IV), or MeO2COC6H4CO2H (V) and aminolysis of the resulting HOC6H4COCl (VI), MeOC6H4COCl (VII), AcOC6H4COCl (VIII), or MeO2COC6H4COCl (IX), followed by hydrolytic removal of the protecting Ac and MeO2C groups in AcOC6H4CONHR (X) and MeO2COC6H4CONHR (XI). In the reaction of II with amines and PCl3, POCl3, or P2O5, RNHP:NR, (R2N)3P, and (RNH)3PO were probably the reactive intermediates. Thus, a mixt. of 27.6 g. 2-HOC6H4CO2H, 47.6 g. SOCl2, 100 mL. petr. ether, and 0.1 g. AlCl3 was kept 5 h. at 55 Deg to yield 64.9% 2-HOC6H4COCl, b0.5 58-63 Deg. Similarly were prepd. 32.3% 3-HOC6H4COCl, b2 130 Deg, 15.3% 4-HOC6H4COCl, b1.5-2.0 105 Deg, and 70.5% 4-MeOC6H4COCl, b1-2 108-10 Deg, m. 24 Deg. 2-AcOC6H4COCl (36.03 g.) and 47.6 g. SOCl2 was refluxed 4 h. to yield 78.4% 2-AcOC6H4COCl, b12 135 Deg, m. 43 Deg. Similarly prepd. were 73.4% 3-AcOC6H4COCl, b10 140-1 Deg, 90.9% the 4-isomer, b12 145-6 Deg, m. 29 Deg, 81.1% 2-MeO2COC6H4COCl, b0.1 197-210 Deg, 86.5% the 3-isomer, b16 150-5 Deg, m. 63 Deg, and 89.7% the 4-isomer, m. 82 Deg. With cooling and shaking 0.05 mol 2-HOC6H4COCl in 25 mL. CHCl3 was dropped into 25 mL. CHCl3 contg. 0.1 mol PhNH2, the mixt. kept at 25 Deg several hrs., shaken with satd. aq. NaHCO3 soln., and CHCl3, and excess PhNH2 removed by steam distn. to yield 37.6% 2-HOC6H4CONHPh, m. 137 Deg. Similarly prepd. were the following I (position of OH group, R, % yield, and m.p. given): 2, 4-ClC6H4, 88, 169 Deg; 2, 4-O2NC6H4, 53, 232-3 Deg; 2, 2,4-(O2N)2C6H3, 94.3, 186-7 Deg; 2, 2,5-Cl2C6H3, 80.8, 233 Deg; 3, Ph, 62.6, 155 Deg; 3, 4-ClC6H4, 76.7, 177-8 Deg; 4, Ph, 50.1, 201 Deg. Similarly prepd. were the following 4-AcOC6H4CONHR(R, % yield, and m.p. given): Ph, 83.1, 160-1 Deg; 2-ClC6H4, 84, 162-3 Deg; 3-ClC6H4, 91.5, 135-8 Deg; 4-ClC6H4, 82.9, 198-200 Deg; 4-BrC6H4, 96.3, 221 Deg; 2,4-Cl2C6H3, 75.1, 183.5-4.5 Deg. Also prepd. were 4-MeO2COC6H4NHR (XIa) (same data given): Ph, 98.1, 175 Deg; 2-ClC6H4, 82.2, 102-3 Deg; 4-ClC6H4, 74.1, 183-4 Deg; 4-BrC6H4, 80.5,181-2 Deg; 2,4-Cl2C6H3, 95.1,114-16 Deg; 2,5-Cl2C6H3, 88.5, 105 Deg. Aq. MeNH2 (0.1 mol) was dropped into a stirred suspension of 0.05 mol 4-MeOC6H4COCl in 10 mL. cold H2O, the mixt. kept 3 h. at 25 Deg, acidified with 10 mL. 12.5% HCl, and extd. with C6H6 to yield 86% 4-MeOC6H4CONHR (XII) (R = Me), m. 116 Deg. Similarly prepd. were XII (R, % yield, and m.p. given): H, 76.8, 166.5-7.5 Deg; Et, 61.4, 69-70 Deg; Pr, 75.6, 61 Deg; iso-Pr, 79.3, 120-1 Deg; Bu, 48.2, 54 Deg. Also prepd. were the following XIa (same data given): Me, 84.1, 78-9 Deg; Et, 97.7, 79 Deg; Bu, 77.4, 50-5 Deg (b. 225-30 Deg); iso-Pr, 66.2, 118-19 Deg; Pr, 83.7, --(b. 231-5 Deg). MeO2COC6H4CONEt2 (81.3%) b. 183-5 Deg. To 0.03 mol 4-AcOC6H4COCl in 10 mL. CHCl3 was added dropwise 0.06 mol BuNH2, the mixt. kept 15 min. at 25 Deg, and extd. with 15% HCl to yield 89% 4-AcOC6H4CONHR (XIII) (R = Bu), m. 125 Deg (aq. EtOH). Similarly prepd. were the following XIII (R, % yield, and m .p. given):H, 98, 179.5 Deg; Me, 81, 154 Deg; Et, 70, 124-5 Deg. A soln. of 0.01 mol 2-AcOC6H4CONHC6H4Cl-2 in 10 mL. 10% alc. KOH was heated 15 min. on a steam bath, dild. with 40 mL. H2O, acidified with 10 mL. concd. HCl, and kept 12 h. at 5 Deg to yield 61.3% x-HOC6H4CONHR (XIV) (x = 2, R = 2-ClC6H4), m. 166-7 Deg (aq. EtOH). Similarly prepd. were the following XIV (x, R, % yield, and m.p. given): 2, 3-ClC6H4, 80.6, 174.5 Deg; 3, 2-ClC6H4, 93.5, 163 Deg; 3, 3-ClC6H4, 96.7, 190-2 Deg; 3,2, 4-Cl2C6H3, 94.3, 148-9 Deg. Similarly but from the corresponding MeO2COC6H4CONHR derivs. were prepd. the following XIV (same data given): 2, 2-ClC6H4, 78.2, 167 Deg; 2, 3-ClC6H4, 86.2, 174 Deg; 3, 2-ClC6H4, 96.5, 164.5 Deg; 3, 4-ClC6H4, 93.1, 177-8 Deg; 3, 2,3-Cl2C6H3, 81.2, 177-9 Deg; 4, 2-ClC6H4, 80, 160-1 Deg; 4, 4-ClC6H4, 89,212 Deg; 4, 4-BrC6H4, 84.5, 226 Deg; 4, 2,4-Cl2C6H3, 91.8, 188-9 Deg; 4, 2,5-Cl2C6H3, 93.9, 197.5-8.5 Deg. Hydrolytic cleavage o 4-AcOC6H4CONHR is not possible by this method. PCl3 (0.02 mol) was dropped into a stirred soln. of 0.1 mol 2,3-Cl2C6H3NH2 in 150 mL. Bu2O and the mixt. kept with stirring 2 h. at 140-5 Deg, 0.04 mol 2-HOC6H4CO2H was added and heating (140-5 Deg) continued 4 h. to yield 81.9% XIV (x = 2, R = 2,3-Cl2C6H3), m. 221 Deg (aq. EtOH). Similarly prepd. were the following XIV (same data given): 3, 3-ClC6H4, 86.7, 189-91 Deg; 4, 3-ClC6H4, 77, 177-9 Deg; 4, 2,3-Cl2C6H3, 79.8, 176-8 Deg; 2, 4-BrC6H4, 43.2,171-2 Deg; 3, 4-BrC6H4, 57,180-2 Deg; 4,4-BrC6H4, 42.3, 224-5 Deg. A mixt. of 0.1 mol 2-HOC6H4CO2H, 0.3 mol PhNH2, and 0.1 mol P2O5 in 150 mL. xylene was refluxed with stirring 5 h., made alk. with aq. NaOH, and steam distd. The residue was heated with C, filtered hot, and acidified with cooling to yield 70% XIV (x = 4, R = Ph), m. 204 Deg (aq. EtOH). Similarly were prepd. the following XIV (x = 4) (R, % yield, and m.p. given): 3-ClC6H4, 52.4, 175-7 Deg; 4-ClC6H4, 54, 212-13 Deg; 2,5-Cl2C6H3, 36, 202-3 Deg; 2-MeC6H4, 56.4, 191-2 Deg; 4-MeC6H4, 58.6, 208 Deg.
|Additional information (public):||CAN 61:54660 35 Noncondensed Aromatic Compounds 22094-44-6; 79119-31-6 (Derived from data in the 7th Collective Formula Index (1962-1966); 87-17-2P (Salicylanilide); 100-07-2P (p-Anisoyl chloride); 619-57-8P (Benzamide, p-hydroxy-); 1152-51-8P (Salicylanilide, 4'-nitro-); 1441-87-8P (Salicyloyl chloride); 1697-18-3P (Salicylanilide, 2'-chloro-); 2280-99-1P (p-Anisamide, N-butyl-); 2627-77-2P (Salicylanilide, 4'-bromo-); 3400-22-4P (p-Anisamide, N-methyl-); 3424-93-9P (p-Anisamide); 3679-63-8P (Salicylanilide, 4'-chloro-); 3679-68-3P (Benzanilide, 4'-chloro-4-hydroxy-); 5538-51-2P (Salicyloyl chloride, acetate); 6137-53-7P (Salicylanilide, 2',5'-dichloro-); 7403-41-0P (p-Anisamide, N-ethyl-); 7464-43-9P (p-Anisamide, N-propyl-); 7464-44-0P (p-Anisamide, N-isopropyl-); 7465-86-3P (p-Anisamide, N,N-diethyl-); 7465-88-5P (p-Anisanilide); 7595-61-1P (p-Anisanilide, 4'-chloro-); 13410-91-8P (Salicylanilide, 2',3'-dichloro-); 14121-97-2P (Benzanilide, 4-hydroxy-); 16446-73-4P (Benzoyl chloride, m-hydroxy-, acetate); 19616-99-0P (Benzanilide, 4'-bromo-4-hydroxy-, acetate); 20978-57-8P (Salicylanilide, 2'-hydroxy-); 24448-71-3P (Salicylanilide, 3'-chloro-); 27522-79-8P (Benzamide, N-ethyl-p-hydroxy-); 27522-80-1P (p-Benzotoluidide, 4-hydroxy-); 27559-45-1P (Benzanilide, 3-hydroxy-); 27642-27-9P (Benzamide, p-hydroxy-N-methyl-); 27914-73-4P (Benzoyl chloride, p-hydroxy-, acetate); 28141-24-4P (Benzoyl chloride, p-hydroxy-); 33577-83-2P (Benzanilide, 4-hydroxy-, acetate); 36965-04-5P (Benzanilide, 4'-chloro-4-hydroxy-, acetate); 39114-64-2P (Benzamide, N-cyclohexyl-p-hydroxy-); 40812-76-8P (Benzoyl chloride, m-hydroxy-); 51074-95-4P (Benzamide, p-hydroxy-, acetate); 52189-56-7P (Benzanilide, 4'-bromo-4-hydroxy-); 60696-49-3P (Benzamide, N-butyl-p-hydroxy-); 62639-20-7P (Benzanilide, 2'-chloro-4-hydroxy-); 62639-21-8P (o-Benzotoluidide, 4-hydroxy-); 73544-81-7P (Benzanilide, 3'-chloro-3-hydroxy-); 73544-82-8P (Benzanilide, 4'-chloro-3-hydroxy-); 78152-12-2P (Benzoyl chloride, p-hydroxy-, methyl carbonate); 78154-58-2P (Salicylanilide, 3',5'-dichloro-); 79540-62-8P (Benzanilide, 2',3'-dichloro-4-hydroxy-); 79878-90-3P (Benzanilide, 2',3'-dichloro-4-hydroxy-, acetate); 83191-67-7P (Benzamide, p-hydroxy-N-isopropyl-); 90922-32-0P (Benzamide, p-hydroxy-N-methyl-, acetate); 90922-79-5P (Benzamide, p-hydroxy-N-methyl-, methyl carbonate); 91133-36-7P (Benzamide, N-ethyl-p-hydroxy-, acetate); 91134-10-0P (Benzamide, N-ethyl-p-hydroxy-, methyl carbonate); 91642-02-3P (Benzamide, p-hydroxy-N-isopropyl-, methyl carbonate); 92041-47-9P (Benzamide, N-butyl-p-hydroxy-, acetate); 92042-12-1P (Benzamide, N-butyl-p-hydroxy-, methyl carbonate); 92042-13-2P (Carbonic acid, methyl ester, ester with N,N-diethyl-p-hydroxybenzamide); 92044-46-7P (Benzanilide, 2'-chloro-3-hydroxy-); 92044-47-8P (Benzanilide, 3'-chloro-4-hydroxy-); 92401-00-8P (Benzoyl chloride, m-hydroxy-, methyl carbonate); 92428-62-1P (Benzanilide, 2',4'-dichloro-4-hydroxy-, acetate); 92428-65-4P (Benzanilide, 2',4'-dichloro-4-hydroxy-, methyl carbonate); 92428-66-5P (Benzanilide, 2',5'-dichloro-4-hydroxy-, methyl carbonate); 92433-11-9P (Benzanilide, 4'-bromo-4-hydroxy-, methyl carbonate); 92433-68-6P (Benzanilide, 2'-chloro-4-hydroxy-, acetate); 92433-69-7P (Benzanilide, 3'-chloro-4-hydroxy-, acetate); 92433-81-3P (Carbonic acid, methyl ester, ester with 2'-chloro-4-hydroxybenzanilide); 92433-81-3P (Benzanilide, 2'-chloro-4-hydroxy-, methyl carbonate); 92433-82-4P (Benzanilide, 4'-chloro-4-hydroxy-, methyl carbonate); 92433-82-4P (Carbonic acid, methyl ester, ester with 4'-chloro-4-hydroxybenzanilide); 92505-60-7P (Carbonic acid, methyl ester, ester with salicyloyl chloride); 92553-96-3P (Benzanilide, 4-hydroxy-, methyl carbonate); 92905-58-3P (Benzanilide, 4'-bromo-3-hydroxy-); 94311-59-8P (Benzamide, N-benzyl-p-hydroxy-N-isopropyl-, methyl carbonate); 97027-63-9P (Benzanilide, 2',3'-dichloro-3-hydroxy-); 97027-64-0P (Benzanilide, 2',4'-dichloro-3-hydroxy-); 97027-65-1P (Benzanilide, 2',4'-dichloro-4-hydroxy-); 97027-66-2P (Benzanilide, 2',5'-dichloro-3-hydroxy-); 462070-14-0P (Benzanilide, 2',5'-dichl ro-4-hydroxy-) Role: PREP (Preparation) (prepn. of)|
|Institutions:||Chemistry and Pharmacy > Institute of Pharmacy > Retired Professors > Prof. Schönenberger|
|Keywords:||Fungicides or Fungistats (hydroxyaryl amides as) Benzamide Benzamide Role: PREP (Preparation)|
|Subjects:||500 Science > 540 Chemistry & allied sciences|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||19 Nov 2010 10:16|
|Last Modified:||19 Nov 2010 10:16|
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