Sodium anisate

The K-R reaction has also been useful for structural confirmation of natural products such as tambulin (71), a flavonoid isolated from the seeds of Xanthoxylum acanthopodium In the critical reaction (O-ethoxyphloroacetophenone (72) was allowed to react with anisic anhydride (38b) in the presence of sodium anisate (73) at 170 C to deliver flavone 74 in 65% yield. Flavone 74 was then converted after multiple steps to diethyl ether 75 which corresponded to the diethyl ether of tambulin (71). 

Sodium thenoate is bromodecarboxylated in low yield, slower than sodium anisate, but more rapidly than sodium benzoate. However, the Hunsdiecker reaction with silver salts has been used preparatively for the synthesis of 2,3-dibromo-4-nitrothiophene from 3-bromo-4-nitro-2-thiophenecarboxylic acid. ... 

An additional useful test is to distil the acid or its sodium salt with soda lime. Heat 0.5 g. of the acid or its sodium salt with 0 2 g. of soda lime in an ignition tube to make certain that there is no explosion. Then grind together 0-5 g. of the acid with 3 g. of soda hme, place the mixture in a Pyrex test-tube and cover it with an equal bulk of soda hme. Fit a wide dehvery tube dipping into an empty test-tube. Clamp the tube near the mouth. Heat the soda lime first and then the mixture gradually to a dull-red heat. Examine the product this may consist of aromatic hydrocarbons or derivatives, e.g., phenol from sahcyUc acid, anisole from anisic acid, toluene from toluic acid, etc. 

There is a solid aubepine met with in commerce, which appears usually to be the sodium bisulphite compound of anisic aldehyde. 

Kinetics studies of acid-catalysed chlorination by hypochlorous acid in aqueous acetic acid have been carried out, and the mechanism of the reactions depends upon the strength of the acetic acid an<( the reactivity of the aromatic. Different groups of workers have also obtained different kinetic results. Stanley and Shorter207 studied the chlorination of anisic acid by hypochlorous acid in 70 % aqueous acetic acid at 20 °C, and found the reaction rate to be apparently independent of the hydrogen ion concentration because added perchloric acid and sodium perchlorate of similar molar concentration (below 0.05 M, however) both produced similar and small rate increases. The kinetics were complicated, initial rates being proportional to aromatic concentration up to 0.01 M, but less so thereafter, and described by... 

Cooling is continued. A solution of 8.31 g. (0.05 mole) of methyl anisate (methyl 4-methoxybenzoate) (Notes 7 and 8) in 100 ml. of anhydrous tetrahydrofuran is added to the stirred mixture during a 6-10-minute period, and the resulting mixture is then stirred for an additional 30 minutes (Note 9). At the end of this period, 300 ml. of aqueous 3N hydrochloric acid is added. The nitrogen-inlet tube is removed and replaced by a reflux condenser, and the dropping funnel is replaced by a ground-glass stopper. The ice bath is removed, and the mixture is heated under reflux for 1 hour. The flask is then cooled, and its contents are poured into a 2-1. Erlenmeyer flask, and solid sodium bicarbonate is added to the mixture until neutralization is complete (Note 10). 

The creamy suspension is allowed to cool to room temperature, and the electrodes of a pH meter are inserted (Note 4). A solution of 20.5 g. (0.15 mole) of zinc chloride (Note 5) in 75 ml. of water is added dropwise with vigorous stirring over a period of 45 minutes, while the pH is maintained at 7 by the simultaneous dropwise addition of a 4A aqueous solution of sodium hydroxide (Note 6). The mixture is stirred for 1 hour and is then filtered with suction the solid product is dried under reduced pressure over phosphorus pentoxide. The dry material is slurried with 200 ml. of petroleum ether (b.p. 30-60°), and the solvent is decanted. This process is repeated five times, and the combined extract is evaporated at reduced pressure. The yield of almost pure -chlorophenyl isothiocyanate, obtained as a readily crystallizing oil with a pleasant anise-like odor, is 33-35 g. (65-68%), m.p. 44-45°. The product can be recrystallized from the minimum amount of ethanol at 50°. 

Another example is the synthesis of anisaidehyde from anethole obtained from star anise oil from the fruit and leaves of lllicium verum. Anethole can be oxidised, for instance, by chromic acid (a mixture of sodium dichromate and sulfuric acid) to anisaidehyde (Scheme 13.7). Star anise oil is produced in China in annual quantities of 500-800 t [3]. 

Prepare a solution of 6 g of potassium permanganate in a mixture of 20 ml of 5 per cent sodium hydroxide solution and 150 ml of water, add 2.0 g of p-cresyl methyl ether and heat under reflux for 2-3 hours. If any permanganate remains at the end of this period, destroy it by the addition of a few drops of ethanol. Remove the precipitated manganese dioxide by filtration at the pump, evaporate the filtrate to a volume of 25-30 ml and acidify it (to Congo red) with dilute sulphuric acid. Anisic acid, m.p. 183-184°C, crystallises out on cooling. 

The most critical raw material for the production of Dilitiazem is p-anisic aldehyde. Approximately, 2.3-2.4 kg of /3-anisic aldehyde is required per kg of dilitiazem. Other important raw materials are D(+) alpha phenyl ethylamine (0.35kg/kg), 2-aminothiophenol (1.9kg/kg), methyl chloroacetate (1.9kg/kg), sodium methoxide (1.6kg/kg), chloroform (5.5kg/kg), methanol (9 kg kg), isopropyl alcohol (5kg/kg), etc. 

In the same process during the up-stream conversion of say, p-cresol to PCME during etherification process, sodium sulfate is invariably produced as a liquid by-product and that needs careful processing of liquid PCME and separation of the inorganic layer from the organic mass. A proper system for recovery of sodium sulfate from the mass is no doubt one of the preconditions for a GMP and production of p-anisic aldehyde with a proper eco-system. 

Sodium sulfate is also obtained as a major by-product along with manganese sulfate during production of 79-anisic aldehyde from 79-cresol. It may be mentioned that during reaction of 79-cresol with dimethyl sulfate for production of the intermediate 79-cresyl-methyl ether sodium sulfate is the main by-product. These reactions are briefly shown below ... 

As in the case of many fine chemicals, waste minimization in the liquid streams is a must in the field of cresols and allied products. Many plants producing cresols from coal carhonization process have been closed down because of inherent problems of production of waste materials and byproducts. Same is the story with producers of p-anisic aldehyde using Mn02 as the catalyst. Some manufacturers found it economically not viable to recover both sodium sulfate and manganese sulfate from the waste streams involving etherification of para-cresol and oxidation of p-cresyl methyl ether. These plants were eventually closed down which has been discussed adequately in earlier chapters. 

Some Type A crystals have space groups that are indicated unambiguously by the absent reflexions. Sodium hydrogen di-acetate, for instance, crystallizes in Ia3, and potassium hydrogen di-anisate in... 

For the preparation of p-hydroxybenzoic acid, /7-anisic acid (0.79 g dried over P2Os) is dissolved in warm benzene (35 ml), treated with a solution of AlBr3 (4.9 g) in benzene (30ml), and boiled for 4.5 h under reflux. After cooling, the solution is decomposed with concentrated hydrochloric acid and extracted with ether, the hydroxy acid is removed from the ether by sodium hydroxide solution, liberated from the alkaline solution by acid, taken up again in ether, and recovered on evaporation (0.37 g). 

Thomeis, J. [Analysis of theophylline and its sodium (or potassium) anisates by ultrafast high-performance liquid chromatography in different pharmaceutical preparations]. J.Chromatogr., 1989, 479, 430-436... 

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