DESC:FIELD OF INVENTION
The invention relates to a commercially viable process for manufacturing 4-cyanothiazole (I) from 4-methylthiazole (II) using a novel ammoxidation catalyst composed of oxides of Antimony, Calcium, Chromium, Iron, Potassium, Titanium, Vanadium and Zirconium is disclosed with high selectivity and chemical purity.

BACKGROUND OF INVENTION
4-cyanothiazole (I) is an important chemical intermediate, used in the preparation of many different compounds. One of the most important products prepared from 4-cyanothiazole is thiabendazole (2-(4'-thiazolyl)benzimidazole). Thiabendazole is an important antihelmintic and fungicidal agent known to those skilled in the arts of veterinary medicine, animal husbandry, and agricultural fungicides. The compound is also an important industrial fungicide with uses in the paint industry and in circulating water systems such as in cooling towers and in the paper industry.

4-cyanothiazole (I) is prepared in various ways and several catalysts are employed in various conditions. The ammoxidation is an industrial process to produce nitriles using ammonia and oxygen. It is also known as the Sohio process, acknowledging that ammoxidation was first discovered by Standard Oil of Ohio in 1957.

The patent GB 988,956 discloses a method for producing 4-cyanothiazole which comprises forming a vapour mixture comprising 4-(C1-C5 alkyl)thiazole, ammonia and oxygen in the molar ratio of from 0.5 to 10 moles of ammonia per mole of 4-alkyl thiazole and from 5 to 100 moles of oxygen per mole of 4-alkyl thiazole, and contacting the mixture with an oxide of a heavy metal having an atomic weight of between 50 and 100 and belonging to Group IB, IIB, IIIB, IVB, VB, VIB, VIIB or VIII of the periodic system of classification at a temperature in the range of from 300°C to 500°C.

The patent GB 1,117,630 and GB 1,117,526 discloses a catalyst used for the ammoxidation and its composition comprising by weight from 2 to 13% of cobalt oxide, 1 to 5% of molybdenum oxide, and from 3 to 7% of vanadium oxide, supported on an alumina support material, which makes up the remainder of the catalyst, the composition having a surface area of from 1 to 10 m2/g.

The US patent US 3,544,616 discloses the oxidation catalysts comprising oxides of uranium and arsenic optionally incorporating promoters, which are useful for the catalytic oxidation of olefins to aldehydes and conjugated dienes, and for the catalytic ammoxidation of olefins to nitriles, but not for the preparations of 4-cyanothiazole (I).

The US patent US 4,010,173 discloses the preparation of 4-cyanothiazoles by reacting in the presence of acidic catalyst ß,ß-dichloro-a-amino-acrylonitrile with a thioformamide.

According to the disclosures of US 4,055,511 and US 4,055,514 the 4-cyanothiazole (I) is prepared by the catalytic vapor phase ammoxidation of 3-4-methylthiazoline or 4-methylthiazole, using as catalyst a novel composition comprising a slurried chromium cobalt molybdate. In US 4,055,511 the molar ratio of chromium chloride: cobalt molybdate is disclosed in the range from 0.8:1.0 to 1.1:1.0 and in US 4,055,514 the ammoxidation catalyst composition of molybdenum: cobalt molar ratio is 1.15:1.0 and the potassium: cobalt molar ratio is from 0.005:1.0 to 0.025:1.0 is disclosed.

According to the disclosure of US 4,363,751 the ammoxidation process utilizes a catalyst composed of oxides of manganese, chromium and molybdenum only.

The US patent US 6,072,070 discloses the synthesis of mixed vanadium, antimony and titanium oxides comprising a crystalline phase of rutile TiO2 type, and catalysts for the ammoxidation of alkanes, but not for the preparations of 4-cyanothiazole.
It is well known that some catalysts are more efficient than others and that the search for economically competitive catalysts continues unremittingly. The oxidation catalyst of the present invention is a superior distinct catalyst and none of the aforesaid prior art or related art discloses the preparations of 4-cyanothiazole (I) using a novel ammoxidation catalyst composed of oxides of Antimony, Calcium, Chromium, Iron, Potassium, Titanium, Vanadium and Zirconium in a simple, economical and commercially viable process.

OBJECT OF THE INVENTION
The main object of the present invention is to provide a process for the preparation of a compound of formula (I), which is simple, economical, user- friendly and commercially viable. The process may be further used for the preparation of Thiabendazole.

Another objective of the present invention is to provide a process for the preparation of a compound of formula (I), which would be easier to implement on commercial scale, and requires less amount of reagent(s), and solvent(s). The reagent and solvent can be reused making the more present invention eco-friendly as well.

Yet another objective of the present invention is to provide a process for the preparation of a compound of formula (I) with a higher conversion and easier to isolate with high chemical purity.

Still another objective of the present invention is to provide a process for the preparation of a compound of formula (I), wherein the catalyst can be effectively used for longer duration with superior selectivity, which makes the process industrially more suitable.

SUMMARY OF THE INVENTION
The invention relates to a commercially viable process for manufacturing 4-cyanothiazole (I) from 4-methylthiazole (II) using a novel ammoxidation catalyst composed of oxides of Antimony, Calcium, Chromium, Iron, Potassium, Titanium, Vanadium and Zirconium is disclosed with high selectivity and chemical purity.

The above process is illustrated in the following general synthetic scheme:

The process can be commercially exploited for manufacturing of thiabendazole, which is an important antihelminthic and fungicidal agent.

BRIEF DESCRIPTION OF FIGURES
Figure 1 depicts the percentage of average conversion of 4-methylthiazole to 4-cyanothiazole by reference catalyst, catalyst used in the invention, and 40% diluted catalyst.

Figure 2 depicts percentage of average selectivity of reference catalyst, catalyst used in the invention, and 40% diluted catalyst.

DETAILED DESCRIPTION OF THE INVENTION
The present invention discloses an improved process for the preparation of a compound of formula (I), comprising the steps of:

a. vaporizing 4-methylthiazole of formula (II) in presence of air and ammonia at high temperature to get vapor mixture;

b. contacting the preheated vapor mixture of step (a) with catalyst containing oxides or a mixture thereof at high temperature with appropriate specific velocity to get gaseous adduct; and
c. purging gaseous adduct of step (b) in water and isolating with organic solvent to get 4-cyanothiazole of formula (I).

The present invention provides an improved process for the preparations of 4-cyanothiazole (I) from 4-methylthiazole (II) using a novel ammoxidation catalyst composed of oxides of Antimony, Calcium, Chromium, Iron, Potassium, Titanium, Vanadium and Zirconium as tabulated in Table 1.

Table 1: Composition of catalyst
Sr. No. Element / (Group - Periodic table) Name of oxides Values (%) Wt
1 Antimony / (VA) Antimony(III) oxide content 40.0-50.0
2 Calcium / (IIA) Calcium oxide Content =0.20
3 Chromium / (VIB) Chromium(III)oxide content =0.10
4 Iron / (VIII) Iron(III)oxide content =1.00
5 Potassium / (IA) Potassium oxide content 0.20-0.40
6 Titanium / (IVB) Titanium dioxide content 20.0-27.0
7 Vanadium / (VB) Vanadium(V)oxide content 5.5-8.5
8 Zirconium / (IVB) Zirconium(IV)oxide content =0.10

The catalyst is composed of the group of oxides of Antimony, Calcium, Chromium, Iron, Potassium, Titanium, Vanadium and Zirconium as tabulated in Table 1.

The vaporization disclosed in the step (a) and step (b) is carried out at temperature of 375°C to 420°C, more preferably at 380°C to 410°C and most preferably at 385°C to 400°C. The said velocity disclosed in step (b) is linear velocity preferably in the range of 8 cm/s to 13 cm/s.
The contact time disclosed in step (b) is preferably in the range of 0.1 s to 1.0 s, more preferably 0.2 s to 0.7 s. The experimental facts establish that the less contact time results in the better selectivity of the catalyst.

Table 2: Catalyst screening summary
Sr. No. Reaction Conditions Average Conversion Average Selectivity
1 Reference catalyst 18.62% 97.23%
2 Catalyst used in the invention 39.13% 96.72%
3 40 % dilution of catalyst used in the invention 15.63% 97.99%

The catalyst composition (Table 1) provides the best selectivity and best conversion of 4-methylthiazole of formula (II) in to 4-cyanothiazole of formula (I). The results are tabulated in Table 2. In the present invention, the reference catalyst used is oxides of molybdenum and cobalt, wherein molybdenum and cobalt ratio was 1.09 to 1.19 and successfully established the best selectivity of the catalyst.

The organic solvent in step (c) is selected from the group comprising of benzene, dichloromethane, ethyl acetate, toluene or in combination thereof; most preferably dichloromethane.

The crude compound of formula (I) disclosed in the present invention can be used as such or can be further purified by distillation or by other alternative different techniques well understood by those skilled in the art.

Substantial Advantages of the present invention
• The present invention discloses a process which provides superior selectivity of catalyst alongwith higher chemical purity of the 4-cyanothiazole.
• The present invention discloses a process, which has effectively less number of operations. The operations can also be automated resulting in shortening of reaction time and less labor intensive.
• The present invention is an improved process using lower amounts of ammonia in ammoxidation step, thereby promoting green chemistry and ensuring a cleaner surrounding by putting lesser load on the environment.
• The process of the present invention is economically and commercially viable process and significantly reduces the production cost of Thiabendazole.

The example supporting the invention is described as below. The following example is given by the way of illustration of the present invention and therefore should not be construed to limit the scope of the present invention.

Example 1: Preparation of 4-cyanothiazole of formula (I)
A vapor mixture feed of 4-methylthiazole of formula (II), air and ammonia is made to contact a catalyst containing the mixed oxides of Antimony, Calcium, Chromium, Iron, Potassium, Titanium, Vanadium and Zirconium (Table 1) on an Alundum support at a temperature of about 375°C to 420°C and a linear velocity between 8 cm/s to 13 cm/s (equivalent to contact time between 0.2 s to 0.7 s). The composition of the vapour mixture feed is presented in Table 3.

Table 3: Molar Ratio of reactants
Reactants Flow rate basis (STP) Molar ratio
4-methylthiazole 0.10 cc/min 1.0
Ammonia 22 cc/min 1.5 moles per mole 4-methylthiazole
Oxygen (from air) 183 L/h 120 – 125 moles per mole 4-methylthiazole

The gaseous adduct from reactor is purged in cold water (150 to 180 ml) followed by scrubbing in cold water (400 to 800 mL). After every 4 h water was replaced with fresh water and extracted with dichloromethane (150 ml X 3). The organic layer was analyzed by Gas Chromatography (GC) for purity, which represents 38% conversion and 96% selectivity. Based on GC assay 60 to 70% mass balance is achieved. The remainder of the reaction gases i.e. the gaseous adduct (ammonia and air) from the scrubber is quenched through a dilute hydrochloric acid scrubber. The crude product 4-cyanothiazole is isolated after concentration of dichloromethane layer and further purification was done by distillation to obtain 4-cyanothiazole of formula (I) having GC purity upto 99.62%. The 4-methylthiazole can be reused again after purification. ,CLAIMS:1. An improved process for the preparation of a compound of formula (I), comprising the steps of:

a. vaporizing 4-methylthiazole of formula (II) in presence of air and ammonia at high temperature to get a vapor mixture;

b. contacting the preheated vapor mixture of step (a) with catalyst composed of oxides of Antimony, Calcium, Chromium, Iron, Potassium, Titanium, Vanadium and Zirconium at high temperature with appropriate specific velocity to get gaseous adduct; and
c. purging gaseous adduct of step (b) in water and isolating with organic solvent to get 4-cyanothiazole of formula (I).
2. The process as claimed in claim 1 wherein, the catalyst is composed of oxides of Antimony, Calcium, Chromium, Iron, Potassium, Titanium, Vanadium and Zirconium.
3. The process as claimed in claim 1(a) & (b) wherein, the vaporization is carried out at temperature of 375°C to 420°C, more preferably at 380°C to 410°C and most preferably at 385°C to 400°C.
4. The process as claimed in claim 1(b) wherein, the said velocity is linear velocity preferably in the range of 8 cm/s to 13 cm/s.
5. The process as claimed in claim 1(b) wherein, the contact time is preferably in the range of 0.1 s to 1.0 s, preferably 0.2 s to 0.7 s.
6. The process as claimed in claim 1(c) wherein, the said organic solvent is selected from the group comprising of benzene, dichloromethane, ethyl acetate, toluene or in combination thereof, preferably dichloromethane.
7. Use of 4-cyanothiazole of formula (I) prepared according to claim 1, for preparation of Thiabendazole.
8. A process substantially hereinbefore described with reference to the cited embodiments and examples.