Patent GB-1211134-A (GB)
Title: Improvements in or relating to naphthalene derivatives
IPC: C07C57/58
Filed: 1968-01-09
Abstract: 1,211,134. Naphthylacetic acids. SYNTEX CORP. 9 Jan., 1968 [13 Jan., 1967; 7 Dec., 1967], No. 1197/68. Heading C2C. [Also in Divisions A5 and C5] The invention comprises naphthylacetic acids of the formulµ wherein one of R<SP>1</SP> and R<SP>2</SP> is H and the other is F 2 CH-, F or Cl or R<SP>1</SP> and R<SP>2</SP> taken together are alkylidene halomethylene, or ethylene; R<SP>3</SP> is CF 3 , hydrolysable ester, F 2 CHO-, alkoxymethoxy, 4<SP>1</SP> - alkoxytetrahydropyran- 4<SP>1</SP> - yloxy, tetrahydrofuran - 2<SP>1 </SP>- yloxy, tetrahydropyran - 2<SP>1</SP>- yloxy, or thioether; R<SP>4</SP> is cycloalkyl, HOCH 2 -, alkoxymethyl, CF 3 , vinyl, ethynyl, hydrolysable ester, alkoxymethyloxy, alkylthiomethylthio, F 2 CHO-, alkoxymethylthio, alkylthiomethyloxy, F2- CHSHCO-, HOOC-, alkoxycarbonyl, CH 3 CO-, CN-, or aryl; each of R<SP>5</SP> (at positions 4, 7 or 8) and R<SP>6</SP> (at positions 1, 4, 7 or 8) is alkyl, CF 3 , F, Cl, OH, hydrolysable ester, oxyether, or thioether; provided that R<SP>5</SP> (when at position 7) is other than alkyl; R<SP>7</SP> is alkyl, cycloalkyl, HOCH 2 -, alkoxymethyl, CF 3 , vinyl, ethynyl, F, Cl, OH, hydrolysable ester, oxyether, thioether, HCO, -COOH, alkoxycarbonyl, CH 3 CO-, CN, or aryl; each of R<SP>8</SP> and R<SP>9</SP> (at positions 1, 4, 7 or 8) is alkyl, F, Cl, OH, hydrolysable ester, oxyether, or thioether; provided that when one of R<SP>8</SP> and R<SP>9</SP> is OH, oxyether or thioether, the other is the identical group or alkyl, F, Cl, or hydrolysable ester; one of R<SP>10</SP> and R<SP>11</SP> is H, the other being CH 3 , CH 3 CH 2 , F 2 CH-, F or Cl; or R<SP>10</SP> and R<SP>11</SP> taken together are alkylidene, halomethylene, or ethylene; provided that when one of R<SP>10</SP> or R<SP>11</SP> is CH 3  or CH 3 CH 2 -, R<SP>6</SP> (when at position 1 or 7) is other than alkyl; each of R<SP>12</SP> and R<SP>15</SP> (at positions 1 or 4) is OH, oxyether or thioether; each of R<SP>13</SP> (at positions 1 or 4) and R<SP>14</SP> is alkoxy or alkylthio; provided that when R<SP>12</SP> or R<SP>15</SP> is alkoxy or alkylthio, R<SP>13</SP> or R<SP>14</SP>, respectively, is a different alkoxy or alkylthio group; one of R<SP>16</SP> and R<SP>17</SP> is H, the other being H, CH 3 , CH 3 CH 2 , F 2 CH-, F or Cl or R<SP>16</SP> and R<SP>17</SP> taken together are alkylidene, halomethylene, or ethylene; R<SP>20</SP> (at position 1, 7 or 8) is alkyl, F, Cl, OH, hydrolysable ester, oxyether, or thioether; provided that when one of R<SP>8</SP> and R<SP>20</SP> is OH, oxyether or thioether, the other is the identical group or alkyl, F, Cl, or hydrolysable ester; R<SP>19</SP> (at position 1, 7 or 8) is alkyl, CF 3 , F, Cl, OH, hydrolysable ester, oxyether, or thioether; provided that when R<SP>18</SP> and R<SP>17</SP> are H or one of R<SP>16</SP> and R<SP>17</SP> is CH 3  or C 2 H 5 , R<SP>19</SP> (when at position 1) is other than OH and R<SP>21</SP> is H, alkyl, cycloalkyl, CF 3 , F, Cl, OH, hydrolysable ester, oxyether, thioether, or aryl; provided that at least one of R<SP>16</SP>, R<SP>17</SP> and R<SP>21</SP> is other than H; provided that when one of R<SP>18</SP> or R<SP>17</SP> is CH 3  or CH 3 CH 2 , R<SP>21</SP> is other than H, and the corresponding amides, esters, hydroxamic acids and pharmaceutically acceptable addition salts thereof. The above compounds and naphthylacetic acids, and amides, esters, hydroxamic acids and pharmaceutically acceptable addition salts of the formulµ wherein R<SP>18</SP> is H, alkyl, cycloalkyl, CF 3 , HOCH 2 -, alkoxymethyl, vinyl, ethynyl, F, Cl, OH, hydrolysable ester, oxyether, thioether, HCO-, HOOC-, alkoxycarbonyl, CH 3 CO, CN or aryl are prepared by standard methods. The following intermediates are prepared: 4 - (3<SP>1</SP>,4<SP>1</SP> - dimethoxyphenyl) - 4 - oxobutanoic acid, 4 - (3<SP>1</SP>,4<SP>1</SP> - dimethoxyphenyl) butanoic acid, 4 - (3<SP>1</SP>,4<SP>1</SP> - dimethoxyphenyl) butanoic acid chloride, 6,7 - dimethoxy - 1 - tetralone, 6,7 - dimethoxytetralin, 2,3 - dimethoxynaphthalene, 5 - fluoro - 7 - methyl - 1 - tetralone, 5 - methyl - 7 - fluoro - 1 - tetralone, 1- methyl - 3 - fluoronaphthalene, 1 - fluoro - 3 - methylnaphthalene, 2 - (1<SP>1</SP> - hydroxycyclobutyl)naphthalene, 2 - (α - bromoethyl)- naphthalene, 2 - (α,# - dibromoethyl)naphthalene, 2 - acetylnaphthalene, 2 - (α - acetoxyethyl)naphthalene, 2 - (α - hydroxyethyl)- naphthalene, 2 - carboxynaphthalene, 2- hydroxymethylnapht halene, 2 - formylnaphthalene, 2 - cyanonaphthalene, 2 - naphthaldehyde oxime, 2 - methoxy - 4 - (3<SP>1</SP>- carboxy- 1<SP>1</SP> - oxopropyl)toluene, 2 - methoxy - 5 - (3<SP>1</SP>- carboxy - 1<SP>1</SP> - oxopropyl)toluene, 6 - methyl- 7 - methoxy - 1 - tetralone, 7 - methyl - 6 - methoxy - 1 - tetralone, 6 - methyl - 7 - methoxy- 1 - hydroxy - 1,2,3,4 - tetrahydronaphthalene, 6 - methoxy - 7 - methyl - 1 - hydroxy - 1,2,3,4- tetrahydronaphthalene, 2 - methyl - 3 - methoxynaphthalene, 5 - ethoxy - 7 - chloro - 1 - tetralone, 5 - chloro - 7 - ethoxy - 1 - tetralone, 1 - ethoxy - 3<SP>1</SP> - chloronaphthalene, 1 - chloro- 3 - ethoxynaphthalene, 5 - ethoxy - 7 - chlorotetralin, 6 - chloro - 8 - ethoxy - 1 - tetralone, 7 - fluoro - 1 - tetralone, 2- fluoronaphthalene, 7 - methoxy - 1 - tetralone, 7 - isopropyl- 1 - tetralone, 7 - methylthio - 1 - tetralone, 6- chloro - 7 - methylthio - 1 - tetralone, 6 - fluoro- 7 - methyl - 1 - tetralone, 6 - methoxy - 7 - fluoro- 1 - tetralone, 6,8 - dimethyl - 1 - tetralone, 6- methylthio - 8 - cyclopropyl - 1 - tetralone, 6 - methyl - 8 - isopropyl - 1 - tetralone, 2- methylthio - 3 - chloronaphthalene, 2 - methyl- 3 - fluoronaphthalene, 2 - fluoro - 3 - methoxynaphthalene, 1 - methylthio - 3 - cyclopropylnaphthalene, 2 - p - fluorophenyl - 3,4 - dihydronaphthalene, 2 - p - fluorophenylnaphthalene, 2 - p - chlorophenylnaphthalene, 2- acetyl - 6 - methoxy - naphthalene, 6 - methoxy- 2 - naphthylthioacetmorpholide, 6 - methoxy- 2 - ethoxycarbonyl - 1 - tetralone, 6 - methoxy- 2 - ethoxycarbonyl - 2 - (ethoxycarbonylmethyl) - 1 - tetralone, 6 - methoxy - 2 - (carboxymethyl) - 1 - tetralone, 6 - methoxy- 1 - hydroxy - 1,2,3,4 - tetrahydro - 2 - naphthylacetic acid, 6 - methoxy - 1,2,3,4 - tetrahydro - 2 - naphthylacetic acid, methyl- 6 - methoxy - 1,2,3,4 - tetrahydro - 2 - naphthylacetate, methyl 6 - methoxy - 1 - hydroxy- 1,2,3,4 - tetrahydro - 2 - naphthylacetate, methyl 1,6 - dimethoxy - 1,2,3,4 - tetrahydro- 2 - naphthylacetate, 6 - methoxy - 2 - (methoxycarbonylmethylene) - 1 - tetralone, methyl 6 - methoxy - 1 - fluoro - 1,2,3,4 - tetrahydro- 2 - naphthylacetate, methyl 6 - methoxy- 1,2 - dihydro - 2 - naphthylacetate, dimethyl 3 - (p - chlorobenzoyl)glutarate, dimethyl 3- (p - chlorobenzyl)glutarate, 3 - (p - chlorobenzyl)glutaric acid, 7 - chloro - 3 - (carboxymethyl) - 1 - tetralone, 7 - chloro - 3 - (methoxycarbonylmethyl) - 1 - tetralone, 3 - methoxycarbonylmethyl) - 1 - tetralone, 7 - methyl- 3 - (methoxycarbonylmethyl) - 1 - tetralone, 7 - ethyl - 3 - (methoxycarbonylmethyl)- 1 - tetralone, 7 - isopropyl - 3 - (methoxycarbonylmethyl) - 1 - tetralone, 7 - methylthio- 3 - (methoxycarbonylmethyl) - 1 - tetralone, 7 - fluoro - 3 - (methoxycarbonylmethyl)- 1 - tetralone, 7 - methoxy - 3 - (methoxycarbonylmethyl) - 1 - tetralone, 7 - ethoxy - 3 - (methoxycarbonylmethyl) - 1 - tetralone, 7- ethylthio - 3 - (methoxycarbonylmethyl)- 1 - tetralone, methyl 6 - fluoro - 4 - hydroxy- 1,2,3,4 - tetrahydro - 2 - naphthylacetate, methyl 6 - methyl - 4 - hydroxy - 1,2,3,4 - tetrahydro - 2 - naphthylacetate, methyl p - (3<SP>1</SP>- carboxy - 1<SP>1</SP> - oxopropyl)phenylacetate, methyl p - (3<SP>1</SP>  -  carboxypropyl)phenylacetate, methylp - (3<SP>1</SP> - chlorocarbonylpropyl)phenylacetate, 7 - (methoxycarbonylmethyl) - 1 - tetralone, ethyl 6 - methoxy - 2 - naphthyl - α,α - hydroxymethyleneacetate, ethyl 6 - methoxy - 2 - naphthyl - α - formyl - α - chloroacetate, ethyl 6 - methoxy - 2 - naphthyl - α - carboxy- α - chloroacetate, methyl 6 - methyl - 2 - naphthyl - α - hydroxyacetate, methyl 6 - methyl- 2 - naphthyl - α - oxoacetate, difluoromethylene triphenyl phosphorane, chlorofluoromethylene triphenyl phosphorane, methyl 6-fluoro-2-naphthyl - α - hydroxymethylacetate, diethyl 6- methoxy - 2 - naphthylmalonate, diethyl 6- methoxy - 2 - naphthyl - α - difluoromethylmalonate, 6 - methoxy - 2 - naphthyl - α - difluoromalonic acid, diethyl 6 - methoxy- 2 - naphthyl - α - methylmalonate, methyl 6 - trichloromethyl - 2 - naphthyl - α - methyl acetate, methyl 6 - (α - bromoethyl) - 2 - naphthyl - α - methylacetate, methyl 6 - (α - acetoxyethyl) - 2 - naphthyl - α - methylacetate, methyl 6 - (α - hydroxyethyl) - 2 - naphthyl- α - methylacetate, the oxime of 6 - formyl- 2 - naphthyl - α - methylacetic, 1 - ethoxycarbonylethylidene triphenyl phosphorane, 2,2 - (1<SP>1</SP> - carbethoxyeth - 1<SP>1</SP>,1<SP>1</SP> - ylidene)- 6 - methoxytetralin, and methyl 6 - mercapto- 2-naphthyl-α-methylacetate.