FR2760013A1 - PROCESS FOR THE INDUSTRIAL MANUFACTURE OF NAPHTO- [2,3-D] -THIAZOLE-4,9-DIONE COMPOUNDS - Google Patents

Abstract

The invention concerns a method which consists in reacting 2-amino-3-halo-1,4-naphthoquinone with sulphides in a basic aqueous medium, adding aldehydes and reacting in the presence of acetic acid. It is characterised by steps which consist in: (a) dissolving in an aprotic solvent the crude product resulting from the reaction of sulphides in basic water, of 2-amino-3-halo-1,4-naphthoquinone, aldehydes and acetic acid; (b) treating the product resulting from step (a) with diatom silica; (c) evaporating at least partly the aprotic solvent; and (d) precipitating the resulting product in a solvent with high boiling point while cooling.

Description

 The present invention relates to a process for the industrial manufacture of naphtho- [2,3-d] thiazole-4,9-dione compounds.

 The naphtho- [2,3-d] -thiazole-4,9-dione compounds are used as bactericides, fungicides, woodwork protection or dyes.

The only manufacturing methods known to date consist of reacting
- 2-amino-3-chloro-1,4-naphthoquinone with sodium sulfide in an aqueous medium and then adding aldehydes and leaving to act in the presence of acetic acid (catalyst). (UK patents 262, 141 US 1, 726, 265 JP 61, 257, 903 and JP 61, 251, 675 where dimethylformamide (DMF) is added as a co-solvent) (J. Het. Chem 1988, 25, 901906)
- 2,3-dichloro-1,4-naphthoquinone with thioamide derivatives: in the presence of 1,4-diazabicyclo [2,22] octane (DABCO) and dimethylsulfoxide (DMSO) (J. Het. Chem 1988, 25 , 901-906) or sodium bicarbonate in ethanol at reflux (Coll. Czech. Chem. Commun. 1985, 50, 71; J. Het. Chem. 1993, 30, 1679) or triethylamine in DMF (J. Het. Chem. 1992, 29, 439)
- 2-amino-3-mercapto-1,4-naphthoquinone with aldehydes in the presence of a catalytic amount of acetic acid (Cur. Science 1967, 36, 176)
- 2-chloro-3-acetamido-1,4-naphthoquinone with ammonium thiocyanate provides 2-amino-naphtho- [2,3-d] thiazole-4,9-dione which after a Sandmeyer reaction delivers 2-chloro-naphtho- [2, 3-d -thiazole-4, 9-dione. This compound is susceptible to a nucleophilic attack on chlorine to provide the desired products. (Nippon Kagaku Kaishi 1982, 1, 105-110).

However, the methods described above have numerous drawbacks which make them impractical on an industrial scale.
- purity and yield of mediocre products
- requirement of a high reaction temperature
- the use of co-solvent or organic solvent
- extended reaction times
- use of oxygen or peroxides.

 Indeed, the product obtained is often a reducing compound of naphtho- [2,3-d] -thiazole-4,9-dione which oxidizes on contact with air if the concentration of the product obtained is sufficiently low if not pure oxygen or peroxides should be used, which in terms of safety is always a problem.

 The object of the present invention is to remedy the drawbacks mentioned above by proposing a process for the industrial manufacture of naphtho- [2,3d] -thiazole-4,9-dione compounds in which, without being bound by any theory, supposes that the final oxidation is controlled using an appropriate agent which makes it possible to replace the action of peroxides, oxygen or air while providing a purification effect, which leads to yields unexpected.

 Following in-depth studies with a view to developing a process which escapes the abovementioned drawbacks, the applicant has found that the reaction carried out in an aqueous medium can be carried out below the boiling point of water and over a period of twice fifteen minutes. After isolating the reaction crude, the applicant has found that the use of diatomaceous silica as an effective reprocessing agent avoids the use of dangerous oxidizing agents such as oxygen or the peroxides of the prior art. The naphtho- [2,3-d] thiazole-4,9-dione compounds are thus obtained directly with a purity greater than 99% and a good yield.

The present invention therefore provides a process for the industrial manufacture of naphtho- [2,3-d] thiazole-4,9-dione compounds in which 2 amino-3-halo-1,4-naphthoquinone is reacted with sulphides in basic aqueous medium, aldehydes are added and the reaction is allowed to take place in the presence of acetic acid which is characterized by the steps consisting in
(a) dissolving the crude product obtained in a basic solvent, the reaction of sulphides in basic water, 2-amino-3-halo-1,4-naphthoquinone, aldehydes and acetic acid, in an aprotic solvent;
(b) treating the product obtained in step (a) with diatomaceous silica,
(c) at least partially evaporating the aprotic solvent, and
(d) precipitating the resulting product in a high boiling solvent while cooling.

The invention also relates to the following characteristics
the method further comprises an additional step consisting in
(e) washing the resulting product with a suitable solvent and with water
- the aprotic solvent is chosen from chlorinated solvents
- the chlorinated solvent is chosen from dichloromethane, dichloroethane and trichloromethane
- the diatomaceous silica has the following composition SiO2, A1203, Fe203, Na2O, CaO
- the weight ratio in percent of the various constituents of diatomaceous silica is within the following ranges
SiO2: 80 to 90 W
Au203: 2 to 3 W
Fie 203: 3 to 4 W
Na2O: 2 to 4 Co
CaO 1 to 3 W
- the precipitation solvent with high boiling point is a polar solvent
- the precipitation solvent is dimethylformamide
- diatomaceous silica is used at a rate of 0.2 to 0.5 equivalent by weight relative to the equivalent of crude product passing through it
- The reaction before obtaining the crude treated with diatomaceous silica is carried out during a period of approximately 15 minutes hot and approximately 15 minutes cold to avoid the degradation of fragile aldehydes.

 The present invention therefore provides a process for the industrial manufacture of naphtho- [2,3-d] thiazole-4,9-dione compounds characterized in that 2-amino-3-halo-1,4-naphthoquinone compounds are reacted with sulphides and an alkaline hydroxide, in particular sodium hydroxide in order to adjust the pH under an inert atmosphere in the presence of osmosis water, then the reaction mixture obtained containing 2-amino-3-mercapto-1,4naphthoquinone compounds is reacted with aldehydes in the presence of acetic acid. After filtration and drying, the reaction crude is solubilized in an aprotic solvent, refiltered on diatomaceous silica, the aprotic solvent is evaporated, the product is crystallized from dimethylformamide and the naphtho- [2,3-d] -thiazole4 compounds, 9-dione are obtained with a purity greater than 99% after washing with reverse osmosis water.

 The 2-amino-3-halo-1,4-naphthoquinone compounds constituting the starting material according to the invention are varieties in which the benzene nucleus can be indifferently substituted or not.

 The sulfides used in the invention are varieties capable of substituting the halogen radical of 2-amino-3-halo-1,4-naphthoquinone compounds such as sodium sulfide. Regarding the determination of sulfides, 1.5 molar equivalent is used. The sulfides can also be used in the form of hydrates such as sodium sulfide nonahydrate.

 The dosage of alkali hydroxide, in particular sodium hydroxide, is generally between 0.001 and 0.01 molar equivalent relative to the starting product, but usually 0.003 molar equivalent is used.

 The amount of the reaction solvent, the osmosis water is calculated to obtain a concentration of between 0.15 and 0.25 mol / l and preferably in the range of 0.16 and 0.19.

 As regards the aldehydes used in the invention, the only condition is that their substitution radicals other than the aldehyde radicals are inert with respect to the reaction process of the present process. Mention may be made, for example, of furaldehyde, benzaldehyde, pyridinecarboxaldehyde, thiophenecarboxaldehyde. The dosage of aldehydes is generally between 1 and 1.5 molar equivalent relative to the starting product.

 Acetic acid is added in such a way that the pH is adjusted to 6.5.

 In the process, the reaction of the compounds of sodium sulfide nonahydrate and of 2-amino-3-halo-1,4naphthoquinone is generally carried out between 800C and 1000C and preferably between 900C and 950C, and either under normal or increased pressure . Likewise, the condensation reaction of the 2-amino-3mercapto-1,4-naphthoquinone compounds and of the aldehydes is generally carried out at the same temperatures and pressure as the preceding stage.

 The dosage of diatomaceous silica for filtration relative to the dry gross weight of the reaction product is generally between 0.2 and 0.5 equivalent by weight for the equivalent of dry crude product and preferably in the range 0.2 and 0.3.

 The filtration solvent retained after numerous tests is dichloromethane.

 The recrystallization solvent retained after numerous tests is dimethylformamide.

 A general mode of implementation of the method according to the invention is described below.

 Dissolve sulfides such as sodium sulfide and alkali hydroxide like sodium hydroxide in the appropriate amount of RO water, replace the ambient air with an inert gas such as nitrogen, add the compounds of 2- amino-3-halo-1,4-naphthoquinone all at once and the whole is brought to the appropriate temperature for 15 minutes. The appropriate amount of aldehyde is added to the reaction mixture obtained at once and allowed to cool to 250C and the whole is left at this temperature for 15 minutes. Add the appropriate amount of catalytic acid such as acetic acid. The reaction medium is cooled to a temperature between OOC and 50C, then the precipitate obtained is filtered and dried. The product obtained is dissolved in hot dichloromethane and the solution is passed over diatomaceous silica. To the recovered solution, a suitable quantity of dimethylformamide is added hot, the dichloromethane is evaporated and the crystalline naphtho- [2,3-d] -thiazole-4,9-dione compounds are obtained. The traces of residual solvent are filtered and removed and washed with reverse osmosis water. There are thus obtained naphtho- [2,3-d] -thiazole-4,9-dione compounds with a purity greater than 99%.

 The method according to the invention makes it possible to conduct the reaction process in an aqueous medium and to obtain the final compound after passing through diatomaceous silica avoiding the use of peroxides or pure oxygen, and makes it possible to produce compounds naphtho- [2,3-d] thiazole-4,9-dione with excellent pu re performance and large-scale yield by avoiding a specific purification step, which gives it great industrial interest.

The invention will be better understood on reading the exemplary embodiments mentioned below
Example 1
In a pilot reactor equipped with mechanical agitation of the impeller type, temperature control at the bottom of the tank and in the breakwater, equipped with a device for feeding solids and liquids and inerting with l 'nitrogen is poured 240 l of reverse osmosis water, 14.3 kg of sodium sulfide nonahydrate and 4.8 g of sodium hydroxide. After cold dissolution, the reaction medium is brought to 920C with stirring and under a nitrogen atmosphere, 8.31 kg of 2-amino-3-chloro-1,4-naphthoquinone are added all at once. The reaction medium is maintained at 920C for 15 minutes. The reaction medium becomes blue and 4.4 l of 2-furaldehyde are added all at once. After cooling to 250C, 3.7 l of acetic acid are added (pH 6.5) while maintaining the temperature at 250C for 15 minutes then the reaction medium is cooled to 50C. The reaction medium is drained by centrifugation to give 40.6 kg of wet crude product which, after drying at 800C under vacuum for 24 h, provides 15 kg of dry product. After dissolving the dry product in 660 l of dichloromethane brought to reflux, the reaction medium is filtered in a büchner type filter covered with a filter cloth containing 4 kg of diatomaceous silica. The filtrate is reintroduced into the reactor and the dichloromethane is evaporated to 75%. 105 l of dimethylformamide are added and the remainder of dichloromethane is evaporated. After cooling to OOC, the solution is filtered and the precipitate is washed with 7 l of dimethylformamide and 50 l of reverse osmosis water.

After drying at 500C for 24 h, 9.6 kg of 4,9-dihydro 4,9-dioxo-2- (2-furyl) -naphtho- [2,3-d] -thiazole are obtained with a purity of 99 , 9% and 64% yield.

Example 2
In a pilot reactor equipped with mechanical agitation of the impeller type, temperature control at the bottom of the tank and in the breakwater, equipped with a device for feeding solids and liquids and inerting with l 'nitrogen is poured 240 l of reverse osmosis water, 14.3 kg of sodium sulfide nonahydrate and 4.8 g of sodium hydroxide. After cold dissolution, the reaction medium is brought to 920C with stirring and under a nitrogen atmosphere, 8.31 kg of 2-amino-3-chloro-1,4-naphthoquinone are added all at once. The reaction medium is maintained at 920C for 15 minutes. The reaction medium becomes blue and 5.4 l of benzaldehyde are added all at once. After cooling to 25 ° C., 3.7 l of acetic acid are added (pH 6.5) while maintaining the temperature at 250 ° C. for 15 minutes then the reaction medium is cooled to 50 ° C. The reaction medium is drained by centrifugation to give 40.6 kg of wet crude product which, after drying at 800C under vacuum for 24 h, provides 15 kg of dry product. After dissolving the dry product in 660 l of dichloromethane brought to reflux, the reaction medium is filtered in a büchner type filter covered with a filter cloth containing 4 kg of diatomaceous silica. The filtrate is reintroduced into the reactor and the dichloromethane is evaporated to 75%. 105 l of dimethylformamide are added and the remainder of dichloromethane is evaporated. After cooling to OOC, the solution is filtered and the precipitate is washed with 7 l of dimethylformamide and 50 l of reverse osmosis water.

After drying at 500C for 24 h, 9.6 kg of 4,9-dihydro 4,9-dioxo-2-phenyl-naphtho- [2,3-d] -thiazole are obtained with a purity of 99.3% and 57% yield.

Example 3
In a pilot reactor equipped with mechanical agitation of the impeller type, temperature control at the bottom of the tank and in the breakwater, equipped with a device for feeding solids and liquids and inerting with l 'nitrogen is poured 240 l of reverse osmosis water, 14.3 kg of sodium sulfide nonahydrate and 4.8 g of sodium hydroxide. After cold dissolution, the reaction medium is brought to 920C with stirring and under a nitrogen atmosphere, 8.31 kg of 2-amino-3-chloro-1,4-naphthoquinone are added all at once. The reaction medium is maintained at 920C for 15 minutes. The reaction medium becomes blue and 5.055 l of 2-pyridinecarboxyaldehyde are added at one time. After cooling to 250C, 3.7 l of acetic acid are added (pH 6.5) while maintaining the temperature at 250C for 15 minutes then the reaction medium is cooled to 50C. The reaction medium is drained by centrifugation to give 40.6 kg of wet crude product which, after drying at 800C under vacuum for 24 h, provides 15 kg of dry product.

After dissolving the dry product in 600 l of dicnloromethane brought to reflux, the reaction medium is filtered in a büchner type filter covered with a filter cloth containing 4 kg of diatomaceous silica. The filtrate is reintroduced into the reactor and the dichloromethane is evaporated to 75%. 105 l of dimethylformamide are added and the remainder of dichloromethane is evaporated. After cooling to OOC, the solution is filtered and the precipitate is washed with 7 l of dimethylformamide and 50 l of reverse osmosis water. After drying at 500C for 24 h, 9.6 kg of 4, 9-dihydro-4, 9-dioxo-2- (2-pyridyl) -naphtho- 2, 3-d] - thiazole are obtained with a purity of 99 , 9% and 52% yield.

Example 4
In a pilot reactor equipped with mechanical agitation of the impeller type, temperature control at the bottom of the tank and in the breakwater, fitted with a device for feeding solids and liquids and inerting at nitrogen, 240 l of reverse osmosis water, 14.3 kg of sodium sulfide nonahydrate and 4.8 g of sodium hydroxide are poured. After cold dissolution, the reaction medium is brought to 920C with stirring and under a nitrogen atmosphere, 8.31 kg of 2-amino-3-chloro-1,4-naphthoquinone are added all at once. The reaction medium is maintained at 920C for 15 minutes. The reaction medium turns blue and 4.97 1 of 2-thiophenecarboxyaldehyde are added all at once. After cooling to 250C, 3.7 l of acetic acid are added (pH 6.5) while maintaining the temperature at 250C for 15 minutes then the reaction medium is cooled to 50C. The reaction medium is drained by centrifugation to give 40.6 kg of wet crude product which, after drying at 800C under vacuum for 24 h, provides 15 kg of dry product.

After dissolving the dry product in 660 l of dichloromethane brought to reflux, the reaction medium is filtered in a büchner type filter covered with a filter cloth containing 4 kg of diatomaceous silica. The filtrate is reintroduced into the reactor and the dichloromethane is evaporated to 75%. 105 l of dimethylformamide are added and the remainder of dichloromethane is evaporated. After cooling to OOC, the solution is filtered and the precipitate is washed with 7 l of dimethylformamide and 50 l of osmosis water. After drying at 500C for 24 h, 9.6 kg of 4,9-dihydro-4,9-dioxo-2- (2-thienyl) -naphtho- [2,3-d] - thiazole are obtained with a purity of 99.9% and 52% yield.

Claims (10)

 1. Process for the industrial manufacture of naphtho- [2,3-d] -thiazole-4,9-dione compounds in which 2-amino-3-halo-1,4-naphthoquinone is reacted with sulfides in basic aqueous medium, aldehydes are added and allowed to react in the presence of acetic acid, characterized by the steps consisting in  (a) dissolving the crude product obtained in a basic solvent, the reaction of sulphides in basic water, 2-amino-3-halo-1,4-naphthoquinone, aldehydes and acetic acid, in an aprotic solvent;  (b) treating the crude product obtained in step (a) with diatomaceous silica,  (c) at least partially evaporating the aprotic solvent, and  (d) precipitating the resulting product in a high boiling solvent while cooling.  2. Method according to claim 1, characterized in that it further comprises an additional step consisting in  (e) washing the resulting product with a suitable solvent and with water.  3. Method according to one of claims 1 or 2, characterized in that the aprotic solvent is chosen from chlorinated solvents.  4. Method according to claim 3, characterized in that the chlorinated solvent is chosen from dichloromethane, dichloroethane and trichloromethane.  5. Method according to any one of claims 1 to 4, characterized in that the diatomaceous silica has the following composition: SiO2, Au203, Fe2O3, Na2O, CaO.  6. Method according to claim 4, characterized in that the weight ratio in percent of the various constituents of diatomaceous silica lies in the ranges below  SiO2: 80 to 90  Au203: 2 to 3 W  Fe2O3: 3 to 4 W  Na2O: 2 to 4 W  CaO: 1 to 3%  7. Method according to any one of claims 1 to 6, characterized in that the precipitation solvent with high boiling point is a polar solvent.  8. Method according to claim 7 characterized in that the precipitation solvent is dimethylformamide.  9. Method according to any one of claims 1 to 8 characterized in that the diatomaceous silica is used in an amount of 0.2 to 0.5 equivalent by weight relative to the equivalent of crude product passing through it.  10. Method according to any one of claims 1 to 9, characterized in that the reaction before obtaining the crude treated with diatomaceous silica is carried out for a period of approximately 15 minutes hot and approximately 15 minutes cold to avoid the degradation of fragile aldehydes.