Title of Invention

PROCESS FOR PREPARING TRIAZOLE COMPOUNDS

Abstract A process for the preparation of a compound of Formula (I), wherein R1 is independently H or X, where X is a halogen; R2 is independently selected from a group consisting of H, alkyl, halogen, alkoxy, aryloxy and substituted with at least one halogen; R3 is independently H or alkyl, is provided.
Full Text FORM-2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
PROVISIONAL
Specification
(See section 10 and rule 13) TRIAZOLE FUNGICIDES
INDOFIL CHEMICALS CO.
(a division of MODIPON LTD.)
an Indian Company
of Nirlon House, Dr. Annie Besant Road, Mumbai 400 025,
Maharashtra, India,









THE FOLLOWING SPECIFICATION DESCRIBES THE INVENTION.

Field of invention
This is a invention relates to the new simple economical synthesis process of 1,2,4 triazole fungicides.
Background of invention
Worldwide most of the crop and ornamental plants are subject to attack by several fungi. Thus fungi and other disease incitants cause extensive losses in crops annually. While there are commercially available materials effective in preventing many plant disease still further improvement is needed for simple and cost effective process for their large scale manufacturing. This invention relates to a simple and economical process for synthesis of useful 1H, 1,2,4 triazole fungicides. The compounds of this invention is systemic foliar fungicide with a broad range of activity. On cereal, it controls diseases caused by Erysiphe graminis, Leptosphaeia nodorum, Pucccinia spp., Pyrenophora teres, Rhynchosporium secalis. In banana control of Mycosphaella musicola and Mycosphaerella fijionsis var. difformis. Other uses are in turf against Sclerotinia homeocarpa, Rhizoctonia solani, Puccinia spp. In rice against Rhizoctonia solani, helminthosporium oryzae, dirty panicle complex etc.in coffee against Hemileia vastatrix ; in peanuts against Cercospora spp ; in stone fruit against Monilinia spp., in maize Helminthosporium spp and Puccinia spp.
Details of prior art
Patent US 4079062 , US 4,160,838 , US 524,587; EP 300413 , DE 2547954, US 4940799 all these patent mainly described the usual process for
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manufacturing the 1,2,4 triazole based fungicides. The usual process consist of first a ketal formation by reaction of omega halo acetophenones with a range of diol and then condensation of the halo ketal with the 1H, 1,2,4 triazole in the presence of a strong base like sodium methoxide/ potassium hydroxide, potassium carbonates etc in a polar approtic solvent like dimethyl formamide or dimethyl sulfoxide or 2 methyl pyrilidone etc. Patent ZA 9604976A described first ketal formation and then bromination of the ketal to get the bromo ketal derivative i.e 2 Bromo methyl -2- ( 2,4 dichloro phenyl) -4-propyl dioxolane. Next step is usual condensation with 1H, 1,2,4 triazole to form the fungicide.
GB 1522657 Also describes the usual procedure for synthesis of 1,2,4 triazole fungicides.
Summary of invention
This invention discloses a simple and economical process for synthesis of 1,2,4 triazole fungicides.
This invention relates to a simple economical procedure for synthesis of 1H 1,2,4 triazole fungicides. The difficulties involved in selectively alkylating a specific ring nitrogen of a polynitrogen heteroatomic compound represent a major problem in the area of heterocyclic chemistry ( see for example R.A Olofson and R.V. Kendal, J. Org Chem, 35, 2246, 1970) The N alkylation of 1,2,4 triazoles to afford the unsymmetrical 1H- 1,2,4 -alkyl triazoles is no exception (see C. Temple and J.A Montgomary, Triazoles, vol 37 of the chemistry of Heterocyclic Compounds.) While such alkylation reactions can
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be conveniently carried out by treatment of a metal salt of the 1,2,4 triazole with an alkylating agent , mixtures of the unsymmetrical 1H, 1,2,4 alkyl triazole and symmetrical 4H, 1,2,4 triazole results.(see J. Org. Chem 35,2246, 1970)
In general the unsymmetrical 1H, 1,2,4 triazole is the major product with the amounts of the symmetrical 4H, 1,2,4-triazole by product varying with the reaction conditions (solvent, temperature) , nature of the metal ion, and the nature of the alkylating agent. Some separation procedure is then required to obtain the pure isomer.
In the case of the biologically active 1,2,4 triazole derivatives with for example, antifungal, antimycotic or microbicidal properties, activity usually resides in the unsymmetrical 1H, 1,2,4 triazole isomer. The formation of the by-product symmetrical isomer represents a cost penalty because it then reduces the yield of the desired compound and requires an additional step of separation and disposal of the unwanted isomer, which again increases the cost of the final product.
This problem has previously been addressed either by devising a procedure for the selective preparation of the desired 1H, 1,2,4 triazole compound other than through alkylation's of a triazole or by a process for the conversion of the symmetrical by product to its unsymmetrical counterpart [EP 0296745]. Both the above process is not a practical solution for large-scale manufacturing. The present invention represents a totally new and simple approach to addressing the problem.
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Our present process involves condensation of 1H, 1,2,4 triazole with the alkylating agent first, which is selective and gives only desired 1H, 1,2,4 triazole compound as a major product. The next step involves the ketalisation of this triazole salt with a desired 1,2 diol to form the final product. So the formation of undesired isomer in the final product is easily avoided with no additional cost.
Therefore the invention relates to the manufacture of a compound having general formula

R2 = C,.3 Alkyl
PROPICONAZOLE DIFENCONAZOLE
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Examples of compounds made in accordance with this invention having ACTUAL STRUCTURS are


EXAMPLE 1. SYNTHESIS OF ETHANONE-l-[2,4-DI CHLORO PHENYL]-2-[1H-1,2,4- TRIAZOL-1-YL]
A) Reactants ~

1) α-bromo, 2,4- dichloro acetophenone (268) = 26.8 gm( 0.1 moles)
2) Triazole (69) = 13.8 gm (0.2 moles)
3) Potassium Hydroxide (56) = 11.2 gm (0.2 moles)
4) Toluene = 200 ml
5) Di-methyl formamide = 200 ml
6) KI(199) = 0.1 gm
Molar Ratio:
Bromo
Acetophenone Triazole KOH
1.0 : 2.0 : 2.0
B) Reactor --
1) Four necked R.B. Flask = 1.0 lit.
2) Double Suface Condenser.
3) Dean & stark apparatus
4) Sealed Stirrer with Teflon Blade.
5) Thermometer Pocket.
6) Addition Funnel.
7) Water bath.
C) Order Of Charging -
1) Triazole
2) KOH
3) Toluene.
4) DMF
5) α-bromo-2, 4-di chloro Acetophenone
6) KI
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D) Reaction Conditions -
l)Temperature - 60°-100°C . 2) Pressure - Atmospheric.
E) Agitation -
RPM = 400.
F ) Reaction Duration -
Time -7-12hrs
G) Procedure -
!) Use clean and dry reactor having Teflon blade stirrer, condenser with calcium chloride guard tube.
2) Charge KOH, Toluene, and Triazole in the reactor
3) Start stirring and heating for the set temperature 100°c for removal of water from Dean &Stark apparatus.
4) Charge DMF, oc-bromo, 2,4- dichloro acetophenone, KI and remove toluene
5) Cook the reaction mass at 60°-100°C for 7-12 hrs
6) After reaction completion, reaction mass taken for dmf recovery.
7) Extracted mass with toluene and crude obtained after recovery.
H) Vacuum Parameters-Vacuum^ 0-12 mm/Hg
I) Final Specification of the product —
l)Ethanone-l-[2,4-di chloro phenyl]-2-[lH-l,2,4-triazol-l-yl] = 97.0 % min.w/w 2) Moisture Content = 0.2 % max. w/w
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EXAMPLE 2. SYNTHESIS OF l-[(2-(2,4-DICHLORO PHENYL) 4-PROPYL-l, 3-DIOXOLAN-2-YL]METHYL-lH-l,2,4-TRIAZOLE
A.) Reactants:
1) Ethanone-l-[2,4-di chloro phenyl]-2-[lH-l,2,4-triazol-l-yl] (256) = 25.6 gm (0.1 moles)
(Step I)
2) 1,2-pentanediol (104) = 20.8 gm (0.2 moles)
3) PTSA(190) =3.8 gm(0.02 moles)
4) Toluene =200 ml
Molar Ratio:
Step I 1,2-pentanediol PTSA
1.0 : 2.0 : 0.2
B) Reactor —
1) Four necked R.B. Flask = 1.0 lit.
2) Double Surface Condenser.
3) Dean & stark apparatus
4) Sealed Stirrer with Teflon Blade.
5) Thermometer Pocket.
6) Addition Funnel.
7) Water bath.
C) Order Of Charging -
1) Ethanone-l-[2,4-di chloro phenyl]-2-[lH-l,2,4-triazol-l-yl]
2) 1,2-Pentane diol

3) PTSA
4) Toluene
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D ) Reaction Conditions -
1) Temperature - 80°-90°C .
2) Pressure - Atmospheric.
E) Agitation -
RPM = 400.
F ) Reaction Duration -
Time : 5-7 hrs
G) Procedure —
1) Use clean and dry reactor having teflon blade stirrer, condenser with calcium
chloride guard tube.
2) Charge Ethanone-l-[2,4-di chloro phenyl]-2-[lH-l, 2,4-triazol-l-yl], 1,2-
pentane diol, PTSA and toluene in the reactor .
3) Start stirring and heating for the set temperature 80-90°c for period of 5-6 hrs
4) After reaction completion, add water to the above reaction mass and separate the layers
5) Recover toluene under vacuum.
6) Final product obtained.
7) Extracted mass with toluene and crude obtained after recovery.
H ) Vacuum Parameters--
Vacuum=10-12 mm/Hg
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I) Final Specification of the product -
1) Propiconazole (Technical) = 89.0 % min .w/w
2) Moisture Content = 0.2 % max. w/w
While considerable emphasis has been placed herein on the steps and reactant chemical compounds of the preferred embodiments, it will be appreciated that many permutations and combinations of the process steps and the composition can be made and that many changes can be made in the preferred scheme without departing from the principles of the invention. These and other changes in the preferred process steps as well as other steps of the process of the invention will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the invention and not as a limitation.
Dated this 4h day of May 2006.
Mohan Dewan
Of R. K. Dewan &Co Applicants Patent Attorneys
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Documents:

697-mum-2006-abstract(15-10-2009).pdf

697-mum-2006-abstract(3-5-2007).pdf

697-MUM-2006-ABSTRACT(GRANTED)-(12-10-2011).pdf

697-MUM-2006-ASSIGNMENT(16-4-2008.pdf

697-mum-2006-cancelled pages(15-10-2009).pdf

697-mum-2006-claims(15-10-2009).pdf

697-mum-2006-claims(3-5-2007).pdf

697-MUM-2006-CLAIMS(AMENDED)-(15-10-2009).pdf

697-MUM-2006-CLAIMS(GRANTED)-(12-10-2011).pdf

697-mum-2006-correspondance-po.pdf

697-MUM-2006-CORRESPONDENCE(11-2-2011).pdf

697-MUM-2006-CORRESPONDENCE(13-12-2010).pdf

697-MUM-2006-CORRESPONDENCE(14-2-2012).pdf

697-mum-2006-correspondence(2-5-2008).pdf

697-MUM-2006-CORRESPONDENCE(25-10-2011).pdf

697-MUM-2006-CORRESPONDENCE(IPO)-(20-1-2012).pdf

697-mum-2006-correspondence(ipo)-(30-6-2009).pdf

697-mum-2006-description (provisional).pdf

697-mum-2006-description(complete)-(15-10-2009).pdf

697-mum-2006-description(complete)-(3-5-2007).pdf

697-MUM-2006-DESCRIPTION(GRANTED)-(12-10-2011).pdf

697-mum-2006-form 13(13-12-2010).pdf

697-mum-2006-form 13(16-4-2008).pdf

697-mum-2006-form 18(2-5-2008).pdf

697-mum-2006-form 2(15-10-2009).pdf

697-mum-2006-form 2(3-5-2007).pdf

697-MUM-2006-FORM 2(GRANTED)-(12-10-2011).pdf

697-mum-2006-form 2(title page)-(15-10-2009).pdf

697-mum-2006-form 2(title page)-(3-5-2007).pdf

697-MUM-2006-FORM 2(TITLE PAGE)-(GRANTED)-(12-10-2011).pdf

697-MUM-2006-FORM 2(TITLE PAGE)-(PROVISIONAL)-(4-5-2006).pdf

697-MUM-2006-FORM 26(13-12-2010).pdf

697-mum-2006-form 5(3-5-2007).pdf

697-mum-2006-form-1.pdf

697-mum-2006-form-2.doc

697-mum-2006-form-2.pdf

697-mum-2006-form-3.pdf

697-MUM-2006-OTHER DOCUMENT(13-12-2010).pdf

697-mum-2006-power of attorney(4-5-2006).pdf

697-MUM-2006-REPLY TO EXAMINATION REPORT(15-10-2009).pdf

697-MUM-2006-SPECIFICATION(AMENDED)-(15-10-2009).pdf

abstract1.jpg


Patent Number 249242
Indian Patent Application Number 697/MUM/2006
PG Journal Number 42/2011
Publication Date 21-Oct-2011
Grant Date 12-Oct-2011
Date of Filing 04-May-2006
Name of Patentee INDOFIL INDUSTRIES LIMITED
Applicant Address KALPATARU SQUARE, 4TH FLOOR, OFF ANDHERI KURLA ROAD, ANDHERI(EAST), MUMBAI-400 059 INDIA
Inventors:
# Inventor's Name Inventor's Address
1 PATEL DARPAN 804/A, LAXMAN SMRUTI, SHRIKHANDEWADI, MANPADA ROAD, DOMBIVLI (EAST) - 421 201,
2 KAULGAUD PRASANNA B/I, HEENA URMIRAJ APT, MAHAVIR NAGAR. BAZARPETH, KULGAON, BADLAPUR (W)-421 503, MAHARASTRA, INDIA
PCT International Classification Number C07D521/00
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA