Benzoic acid, 4-hydroxy-, phenylmethyl ester
If the heat of the reactioncauses the benzene to boil, decrease the rate of addition of the aceticanhydride and, if necessary, bring a cooling bath up around the flask.
Benzoic acid, 4-hydroxy-, butyl ester
As well as the effect on the rate of reaction, with methylbenzene you also have to think about where the sulphonic acid group ends up on the ring relative to the methyl group.
The amine and carboxylic acid functional groups found in s allow them to have amphiprotic properties. Carboxylic acid groups (-COOH) can be deprotonated to become negative carboxylates (-COO-) and α-amino groups (NH2¯) can be protonated to become positive a-ammonium groups (+NH3¯). Out of the essential and non-essential s, some are acidic: aspartic acid, glutamic acid, anthranilic acid; basic: arginine, histidine, lysine; amidic s: asparagine, glutamine; sulphur containing s: cysteine, methionine etc. Out of these various uses as different precursors they are not being used in any synthesis except peptide synthesis. Hence this article is an effort to try catalytic capacity of s in the synthesis of 1,5-benzodiazepines. In continuation with our research for the development of simple and novel methods for the synthesis of different 1,5-benzodiazepine derivatives, we have done comparative study on various acidic s catalyzed synthesis of 1,5-benzodiazepines by condensation of -phenylenediamine with acetophenone (model reaction) under solvent free conditions (). We are gratified to report a simple, efficient and practical method for 1,5-benzodiazepine synthesis using 10 mol% -amino benzoic acid (PABA).
Benzoic acid, 2-hydroxy-, methyl ester
Warm benzene under reflux at 40°C with fuming sulphuric acid for 20 to 30 minutes. Fuming sulphuric acid, H2S2O7, can usefully be thought of as a solution of sulphur trioxide in concentrated sulphuric acid.
Benzoic acid, 4-hydroxy-, ethyl ester
Recently have studied the catalytic activity of various organo acids and found nitrobenzoic acid as the efficient acid among them. But they use 100 mol% of nitrobenzoic acid for excellent yield. On the same pattern our study is an effort to try catalytic capacity of various s in the synthesis of 1,5-benzodiazepines. Among the various s screened, -amino benzoic acid (PABA) was found to be the best catalyst at 10 mol% in terms of yields (entry 3, ). To the best of our knowledge, there are no earlier reports on the preparation of 1,5-benzodiazepines using -amino benzoic acid.
Benzoic acid, 3,4,5-trihydroxy-, propyl ester
Initially we studied the influence of -amino benzoic acid for the synthesis of 1,5-benzodiazepine using phenylenediamine and acetophenone as a model and varying the amount of -amino benzoic acid by simple optimization study (). The investigation was initiated with phenylenediamine, acetophenone (1:2.5) and -amino benzoic acid 15 mol% under solvent free conditions on continuous stirring for 24 hrs and 1,5-benzodiazepine was isolated in 92% yields (entry 2, ). Further, the catalyst quantity was optimized to 10 mol% of -amino benzoic acid and excellent results were achieved. Using less amount of catalyst, i.e., 5 mol% resulted in the decrease of product yield. Increasing the amount of catalyst (i.e., 20 mol%) did not show any significant effect on the reaction rate as well as yields. However, this reaction yielded a trace amount of product (difficult to isolate) in the absence of catalyst after stirring for more than 36 hrs showing the influence of -amino benzoic acid as reaction catalyst. Similarly, other 1,5-benzodiazepine derivatives have been synthesized from -phenylenediamines and ketones in 85-92% yields (). Diamines with electron releasing group (entry 6-9) also reacted smoothly with ketones to afford products in good yields. Both of the linear and cyclic ketones react with the diamines without any significant difference, to give the corresponding 1,5-benzodiazepine derivatives in quantitative yields. Easy work-up of the reaction was also the advantageous aspect of this method. It includes the pouring the reaction mixture in water which on filtration gave the corresponding 1,5-benzodiazepines. This method was superior in regards with yield and reaction time than the previously reported methods.
Benzoic acid, 4-hydroxy-, 1-methylethyl ester
In conclusion, we have reported an efficient, inexpensive, non-hazardous ecofriendly new catalyst -amino benzoic acid for the one pot synthesis of 1,5-benzodiazepines under solvent free condition at room conditions. The solvent-free green procedure as well as high yield and selectivity, makes this protocol an attractive and user friendly alternative for the synthesis of 1,5-benzodiazepines.