Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Reexamination Certificate
2002-12-11
2004-07-27
Trinh, Ba K. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
C568S029000
Reexamination Certificate
active
06768022
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a method for efficiently producing thiosalicylic acid which is a useful intermediate in the manufacture of medicines, pesticides, dyes, etc. More particularly, the present invention relates to a process for manufacturing thiosalicylic acid from anthranilic acid in a two step reactive process.
DESCRIPTION OF THE RELATED ART
The process for manufacturing thiosalicylic acid from anthranilic acid as the raw material has been historically known. This process generally necessitates the following three-step reactive process. That is to say, firstly anthranilic acid is converted to diazonium salt by reaction with sodium nitrite in hydrochloric acid; secondly, the resulting salt is converted to dithiosalicylic acid by reaction with an equimolar mixture of sodium sulfide and sulfur; and thirdly and lastly the resulting dithiosalicylic acid is converted to thiosalicylic acid by reduction by zinc in acetic acid solvent (Org. Synth. Coll., vol. 2, p 580(1943)). This three-step reactive process is illustrated in the following diagrams.
As for the third step in the above diagram which constitutes the process to reduce dithiosalicylic acid, there have been proposed some number of various processes, such as the method based on reduction by a metal selected from among zinc, aluminum, and tin in aqueous solution of an alkali metal hydroxide (Japan Laid-open Patent Application No. Hei-11 (1999)-140045), the method based on reduction by a metal like zinc, iron, etc., which generates hydrogen by reaction with acid, and a hydrogen halide in a lower aliphatic alcohol solvent (Japan Laid-open Patent Application No. Sho-57 (1982)-11961), and the method based on reduction by hydrogen in the presence of a Raney nickel catalyst in aqueous solution of an alkali (Japanese Patent No. Sho-64 (1989)-11017).
Notwithstanding their time-honored positions, those manufacturing methods can be hardly said satisfactory from the contemporary industrial standpoint, for they disclose certain problematic aspects. Above all, in those processes for synthesizing thiosalicylic acid from anthranilic acid some sort of reductive step has to be followed through after the isolation of dithiosalicylic acid. Obviously, the isolation of dithiosalicylic acid constitutes an indispensable element of the whole process. Such need to run a multi-step operation no doubt makes those processes less economical, and, moreover, the reductive step adds to disadvantages due to inevitable requirements for disposal of waste liquids, waste water, etc. In particular, so long as zinc or another metal is employed for the reduction, the waste disposal problem involving metal containing sulfur compounds remains to be resolved.
SUMMARY OF THE INVENTION
Under the circumstance, the present inventor has made keen research efforts to develop such a simpler process for producing thiosalicylic acid that would do away with the isolation of dithiosalicylic acid, thus dispensing with the reductive reaction step. In the arena of the manufacture of thiosalicylic acid based on the conversion of anthranilic acid into diazonium salt by diazotization, such reaction needs to be followed by its reaction with sodium sulfide along with sulfur. The present inventor, as the result of such efforts, discovered that thiosalicylic acid, the target product, can be directly produced in a high yield by means of adjusting the ratio between sodium sulfide and sulfur, while these chemicals have been historically utilized in production of dithiosalicylic acid (the intermediate), and what thus has been finally arrived at is the present invention.
It is, therefore, the object of the present invention to provide an economical process for manufacturing thiosalicylic acid which is able to dispense with the individual process of isolating and reducing dithiosalicylic acid.
According to the invention there is provided a manufacturing process for producing thiosalicylic acid which comprises reacting diazonium salt formed by diazotizing anthranilic acid with sodium sulfide or a mixture of sodium sulfide and sulfur under such condition that the sodium to sulfur (Na/S) atomic ratio as calculated on the basis of the employed sodium sulfide and sulfur is fixed to within the range of 1.33 to 2.0.
DETAILED DESCRIPTION
The time-honored reaction of diazotizing anthranilic acid is carried out typically by reacting it with a mineral acid and sodium nitrite in aqueous solution. Although choice of the mode of reaction is optional, it is the typical practice to add sodium nitrite or an aqueous solution of sodium nitrite to aqueous solution of a mineral acid into which anthranilic acid has been dissolved beforehand.
There can be cited hydrochloric acid and sulfuric acid as a few examples of the mineral acid to be employed for the diazotization reaction. The amount of mineral acid to be employed per mole of anthranilic acid is to be preferably in the range of 1.3 to 10.0 moles, and more preferably 1.5 to 5.0 moles. In cases where the amount of mineral acid is too short, the yield of diazonium salt drops off, and where it is on the contrary excessively large, the efficiency declines, even though the reaction per se is not adversely affected. Therefore, neither case is desirable.
As for the type of water to be selected for use in the reaction as disclosed in the present invention, industrial water, ion-exchanged water, pure water, and distilled water are all suitably useable. The amount of water to be employed in the diazotizing reaction is to be preferably 1.5 to 10.0 times, and particularly preferably 2.0 to 5.0 times as much as anthranilic acid by weight. In cases where the amount of water is too short, the concentration of the crystal of the mineral acid salt formed from anthranilic acid in the reactant liquid gets too high to employ agitation. In cases where the amount of water is excessively large, the yield drops off, even though the reaction is not disrupted at all. Hence, neither case is desirable.
For diazotization of anthranilic acid, sodium nitrite is employed as the diazotizing agent. Sodium nitrite which is available normally in the solid state may be added to the reaction system as it is, while the typical practice is to employ it in the state of being dissolved in water. The amount of sodium nitrite per mole of the raw material anthranilic acid is to be preferably in the range of 0.8 to 1.5 moles, and more preferably in the range of 0.9 to 1.4 moles. In cases where the amount of sodium nitrite is too short, the conversion rate of the raw material declines to an undesirable degree. On the contrary, impurities in the reaction product increase with use of an excessive amount of sodium nitrite. Therefore, neither case is desirable. As for the fashion of adding sodium nitrite, there is imposed no particular limitation. That is to say, it may be added by dropping or pouring into the reactant liquid.
The temperature at which addition and reaction of sodium nitrite are to be made may be set within the range of 10° C. below zero to 30° C., and preferably zero to 20° C. With reaction temperatures kept to below the lower ends of said ranges, the reaction rate gets slower. On the contrary, when the reaction temperature exceeds the upper end of said ranges, decomposition of diazonium salt progresses with the result that the yield drops off and more impurities come to be included. Therefore, deviation from said ranges is by no means desirable.
There is no particular limitation to the time frame in which addition of sodium nitrite is to be completed, but the time frame may be regulated in the light of the state of bubbling of generated nitrogen gas and cooling capacity. It is typically 0.1 to 24 hr. The reaction may be terminated as soon as the addition of sodium nitrite is finished, although the reaction is to be terminated typically after having stirred the reactants for 0.1 to 3 hr.
As for the reaction caused to take place according to the present invention between the diazonium salt thus formed from anthranilic acid and sodium sulfide or a mixture of
Air Water Chemical Inc.
Oh Taylor V.
Trinh Ba K.
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