2,3,4-Trimethoxybenzoic acid

Chemical Name 3,4,5-trimethoxybenzoic acid diester with tetrahydro-1H-1,4-diazepine-1,4(5H)-dipropanol dihydrochloride... 

Chamical Nama 3,4,5-Trimethoxybenzoic acid 1,2-athanediylbis-[(methylimino)-3,1-pro-panedlyl] ester... 

Trimethoxybenzoic acid Thionyl chloride Pyridine-2,6-dimethanol... 

CN 3,4,5-trimethoxybenzoic acid (tetrahydro-l/J-l,4-diazepine-l,4(5/J)-diyl)di-3,l-propanediyl ester dihydrochloride... 

Obtain 3,4,5-trimethoxybenzoic acid or synthesize as follows (Org. Synth. Coll. Vol 1,537(1946)) To a cold solution of 80 g NaOH in 500 ml water in 1 L flask, add 50 g gallic acid tightly... 

A. Do a Fisher esterification by refluxing 100 g 3,4,5-trimethoxybenzoic acid in ethanol with concentrated sulfuric acid for several hours. Cool, filter, to get the ester (I) (recrystallize-ethanol). 

A. (Alternative) 100 g 3,4,5-trimethoxybenzoic acid, 20 g NaOH, 55 g NaHC03 and 300 ml water and add with stirring 94 ml methyl or ethyl sulfate over twenty minutes and reflux one-half hour. Cool, filter, dissolve the precipitate in a small amount hot methanol or ethanol and cool to precipitate (I) (acidify the filtrate to recover unreacted trimethoxybenzoic acid). 

Reflux 100 g of 3,4,5-trimethoxybenzoic acid (this can be synthesized. Organic Synthesis Collection vol 1, 537 (1946), but it is almost cheaper to buy than to make and it is not that easy to make given the low purchase price) with concentrated sulfuric acid in ethanol for 2 to 3 hours. Cool, filter, recrystallize with ethanol to get the ester. Another method to get the ester is as follows Add, while stirring, over 20 min, 94 g of methyl or ethyl sulfate to 100 g of 3,4,5-trimethoxybenzioc acid, 20 g NaOH, 55 g NaHCOs, in 300 ml of water, and reflux Vi hour. Cool, filter, and dissolve this filtered substance in ethanol by heating and cool to precipitate. Filter this precipitate and acidify the filtrate to recover the unreacted 3,4,5-trimethoxybenzioc acid. 

Sodium in liquid ammonia and ethanol reduced benzoic acid to 1,4-dihy-drobenzoic acid. Reduction of p-toluic acid was more complicated and afforded a mixture of cis- and rranj-l,2,3,4-tetrahydro-p-toluic acid and cis-and tra j-l,4-dihydrotoluic acid. m-Methoxybenzoic acid yielded 1,2,3,4-tetrahydro-5-methoxybenzoic acid, and 3,4,5-trimethoxybenzoic acid gave l,4-dihydro-3,5-dimethoxybenzoic acid in 87% yield (after hydrogenolysis of the methoxy group para to carboxyl) [984. In the case of 4 -methoxy-biphenyl-4-carboxylic acid, sodium in isoamyl alcohol at 130° reduced completely only the ring with the carboxylic group, thus giving 92% yield of 4-(p-methoxyphenyl)cyclohexanecarboxylic acid [955]. 

Birch reduction of 3,4,5-trimethoxybenzoic acid gives in 94% yield a dihydrobenzoic acid which bears only two methoxy substituents. Suggest a plausible structure for this product based on the mechanism of the Birch reduction. 

There is no standard, universal, procedure for the Birch reduction. Experiment 7.19 illustrates some of the variants which have been reported in the literature. The original Birch procedure is to add small pieces of sodium metal to a solution of the aromatic compound in a mixture of liquid ammonia and the proton source (ethanol).18 After completion of the reaction, which is usually indicated by the disappearance of the blue colour, it is quenched by the addition of ammonium chloride and the ammonia allowed to evaporate before the cautious addition of water, and isolation of the product by ether extraction. In a modified procedure a co-solvent (ether, tetrahydrofuran, etc.) is initially added to the solution of aromatic compound/liquid ammonia prior to the addition of metal lithium metal is often used in place of sodium.19a,b In general these latter procedures are used for substrates which are more difficult to reduce. Redistilled liquid ammonia is found to be beneficial since the common contaminant iron, in collodial form or in the form of its salts, has a deleterious effect on the reaction.20 A representative selection of procedures is given in Expt 7.19 for the reduction of o-xylene, anisole, benzoic acid, and 3,4,5-trimethoxybenzoic acid. 

Chemical Name 3,4,5-Trimethoxybenzoic acid l-[(3-methylbutoxy)methyl]-2-(4-morpholinyl)ethyl ester hydrochloride... 

Methyl acrylate Lithium aluminum hydride N,N -Dimethylethylenediamine 3,4,5-Trimethoxybenzoic acid chloride... 

Reserpine (21) Mouse liver homogenate (3,4,5-Trimethoxybenzoic acid) (70) 43... 

In contrast to the oxidative reactions discussed above, the only reported biotransformations of reserpine (21) and rescinnamine (23) (42-44) appear to involve hydrolytic processes. Reserpine is readily metabolized by liver homogenates from the mouse (43), rat, guinea pig, dog, and cat (44) to yield methyl reserpate (22) and 3,4,5-trimethoxybenzoic acid in yields of up to 70% (43). The use of reserpine labeled with tritium in the 2 and 6 positions of the trimethoxybenzoate residue indicated that no significant metabolism of reserpine by another route occurred before hydrolysis, reserpine and 3,4,5-trimethoxybenzoic acid being the only detectable radioactive components of the incubation mixture at the conclusion of the reaction (44). An... 

The enzymic oxidative deamination of simple phenethylamines is exemplified by the reported bio transformations of mescaline (146) (114, 115) and ephedrine (148) (116). Mescaline is metabolized to 3,4,5-trimethoxy-phenylacetic acid by tissue homogenates of mouse brain, liver, kidney, and heart (114,115). 3,4,5-Trimethoxybenzoic acid is also formed as a minor metabolite. The formation of jV-acetylmescaline (147), a significant metabolite in vivo, was not observed in the in vitro studies. Both D-(—)-and L-(+)-ephedrine have been incubated with enzyme preparations from rabbit liver norephedrine (149), benzoic acid, and 1-phenyl-1,2-propanediol were characterized as metabolites (116). The D-(—)-isomer was the better substrate, being more rapidly converted. Similar results were previously reported with rabbit liver slices as the source of enzyme (153,154). The enzymic degradation of the side chain of /i-phenethylamines has been extensively investigated with nonalkaloid substrates such as amphetamine (151) and jV-methylamphetamine (150) (10,155-157), and the reader is referred to these studies for a more comprehensive coverage of this aspect of the subject. 

CN 3,4,5-trimethoxybenzoic acid (lctrahydro-1//-1,4-diazcpinc-l,4(5//)-diyl)di-3,1-propanediyl ester... 

CN 3,4,5-trimethoxybenzoic acid l,2-ethanediylbis[(mcthylimino)-3,l-propanediylj ester dihydrochloridc... 

MAVISERPIN MAYSERPIKE MEPHASERPIN METATENSIN METHYL RESERPATE 3,4,5-TRIMETHOXYBENZOIC ACID METHYL RESERPATE 3,4,5-TRIMETHOXYBENZOIC ACID ESTER MIO-PRESSIN MODENOL NAQUIVAL NCI-C50157... 

---