Title of Invention

PROCESS OF MANUFACTURING CYMOXANIL

Abstract A process for the synthesis of Cymoxanil comprising the steps of i) nitrosation, without the formation of excess nitrogen dioxide, of 1-Cyano acetyl -3-ethyl urea in a solvent in the presence of PTSA or Benzene sulfonic acids or Naphthalene sulfonic acids to form 2-Cyano-2-hydroxyimino-N- ethyl carbomyl acetamide; and ii) methylation of 2-Cyano-2-hydroxyimino- N-ethyl carbomyl acetamide to form cymoxanil.
Full Text FORM - 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
PROVISIONAL
Specification
(See section 10 and rule 13) PROCESS OF MANUFACTURING CYMOXANIL
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 invention particularly relates to a process of manufacturing Cymoxanil.
CYMOXANIL
IUPAC: 1 - (2 -Cyano-2- methoxyiminoacetyl) -3- ethylurea.
CAS: 57996-95-7
FORMULA: C7 H10 N4 03
MOLECULAR WEIGHT: 198.18
USE: This is a foliar fungicide with protective and curative action. Cymoxanil has a contact and local systemic activity, and also inhibits sporulation. It is being used for control of Peronosporales, especially Peronospora, Phytophithora and Plasmopara. This is normally used in combination with protecting fungicides on a range of crops including vines, hops, potatoes, and tomatoes.
BACKGROUND OF THE INVENTION
Worldwide most of the crop and ornamental plants are subject to attack by fungi. Fungi and other disease incitants cause extensive losses in crops annually. While there are commercially available materials effective in preventing many plant diseases, still further improvement is needed for a more environment friendly and cost effective process for large scale manufacturing.
This invention relates to a more environment friendly and simple process for synthesis of Cymoxanil. This compound is effective for the control of the fungus plant diseases like potato and tomato late bright as well as the downy mildews.
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Patent DE 227390 provides a process of manufacturing and describes the nitrosation of 1-Cyano acetyl 3-ethyl urea by HNO2 and subsequently the sodium/ potassium salt of the resulting oxime is isolated by using the corresponding carbonate or hydroxide salt.
US patent 3957847; US 3954992, US 4051255, US 4,886,833 also disclose similar procedures. In these procedures nitrosation is done by using sodium nitrite in the presence of acetic acid or hydrochloric acid.
Cymoxanil may also be prepared from the corresponding hydroxamyl chloride and an alkali or alkaline earth cyanide [US 3957, 847]. Conversion of this compound to the corresponding methoxyimino derivative is achieved by using different methylating agents. However prior to methylating the free oxime is first converted to the salt form by using the base for example sodium, potassium or ammonium hydroxide, or carbonates. This is followed by methylation with Methyl iodide/ Methyl bromide/ dimethyl sulfate. In some cases diazomethane is used for the same. In some other cases this reaction is done in non aqueous medium like DMF, Acetone and the like and at the presence of Sodium/ potassium carbonate powder.
All the reported process describe a two-step process where the first step involves nitrosation using NaN02 and an inorganic/ organic acid.
In the presence of acid, NaN02 generates HN02 which in turn acts as the nitrosation agent; but in this process nitrogen oxides are generated in large volumes which is very difficult to scrub and those are potential threats for human health. This is a
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environmental problem for manufacturing of this compound in a large scale. In the subsequent step this free oxime is converted to its sodium or potassium salt by using a large quantity of corresponding carbonate/ hydroxide /bicarbonates and the like which is then methylated to give the product. . This excess salts essentially goes downstream and increases the effluent load which is equally a serious environmental problem.
SUMMARY OF THE INVENTION
This invention discloses a simple and environmentally friendly process for synthesis of Cymoxanil.
This invention relates to a simple single pot environmentally friendly procedure for synthesis of Cymoxanil.
The improved process in accordance with this invention is a single pot reaction where no inorganic acid is used. Consequently there is less or no hazardous nitrogen oxides generated. There is no need to isolate the product formed in the nitrosation (1st step) step and directly the second step is done in the same pot which eliminates the generation of huge quantity of effluent in this step completely. Again in the second step no alkali metal salts for example Sodium/Potassium carbonate/ hydroxide or any other organic base like triethyl amine, pyridine and the like is being used. The improved process generates lesser quantities of toxic effluent and gives Cymoxanil with improved color.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with one embodiment of the invention, the reactants used are 1-Cyano acetyl 3-ethyl urea, PTSA ( 190 )
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(p-Toluenesulfonic acid monohydrate) (or alternately : H2S04/ or Acetic acid), Sodium Nitrite ( 69) ( or alternately : Potassium nitrite OR Ammonium nitrite), Methanol analytical reagent grade (or alternately: Water OR Dichloromethane OR Isopropyl alcohol) and Dimethyl Sulphate ( 126 ) ( or alternately : Methyl iodide OR Methyl bromide OR Diazomethane).
In accordance with another embodiment of the invention, molar quantity of 1-Cyano acetyl 3-ethyl urea is typically 1 molar.
In accordance with another embodiment of the invention, molar quantity of PTSA is typically in the range of 0.1 to 1.0 and preferably is 0.2 molar.
In accordance with another embodiment of the invention, molar quantity of NaN02 is typically in the range of 1.0 to 2.0 and preferably is 1.36 molar.
In accordance with another embodiment of the invention, molar quantity of DMS is typically in the range of 1.0 to 2.0 and preferably is 1.33 molar.
In accordance with another embodiment of the invention, the reaction in the laboratory is are carried out in 1.0 lit four necked R.B. Flask with double Surface Condenser, sealed Stirrer with Teflon Blade, thermometer Pocket, addition Funnel and water bath.
In accordance with another embodiment of the invention, the order of charging the reactants is 1-Cyano acetyl 3-ethyl urea, PTSA, Sodium Nitrite, Methanol analytical reagent grade, Dimethyl Sulphate and Water.
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In accordance with another embodiment of the invention, reactions are carried out at temperature typically in the range of 10 degree C and 100 degree C or preferably at 60 degree C for step I and at temperature typically in the range of 10 degree C - 100 degree C, preferably at 30 degree C for step II and at atmospheric pressure.
In accordance with another embodiment of the invention, reactions are agitated typically in the range of 100 RPM to 600 RPM, preferably at 400 RPM.
In accordance with another embodiment of the invention, reactions are carried out typically in the range of 30 minutes to 4 hrs, preferably for 1.5 hrs in step I and typically in the Range of 30 minutes to 4 hrs, preferably for 1.5 hrs in step II.
The process for preparation of Cymoxanil as per the invention
involves the following steps:
Step I. Charging:
1-Cyano acetyl 3-ethyl urea, PTSA, Sodium Nitrite and Methanol
are charged in a reactor.
Step II. Heating the reactants
The reactants are stirred and heated for a set temperature,
typically around 60 degree C. for 1.5 hrs.
Step III. Cooling the reactants
The resultant mixture is cooled to around 28 degree C under
stirring.
Step IV. Adding DMS
DMS is added to the above mixture in 1/2 hour controlling
temperature between 28 -32 degree C.
Step V. Cooking the reaction
The reaction mass is cooked at 30 degree C for 1 hr.
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Step VI. Adding Water
After completion of reaction, water (300 ml) is added to the
above reaction mass under stirring and maintained for 15 min.
Step VII. Filtration
The resultant mass is filtered, typically using ordinary filter paper
under vacuum to produce cake.
Step VIII. Washing
The cake is washed with water (2 x 100 ml) till the pH neutral.
Step IX. Drying
The cake is squeezed with maximum vacuum and the material is dried in oven typically in the range of 40 degree C to 100 degree C and preferably at 70 degree C for typically 1-6 hrs, preferably for 2-3 hr.
In accordance with one embodiment of the invention, final Specification of the product is as follows
1) Cymoxanil -Technical = 96.0 % min. w/w
2) Moisture Content = 0.2 % max. w/w
3) Acidity as H2S04 = 0.2 % max. w/w
4) Acetone insolubles. = 0.1 % 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
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is to be interpreted merely as illustrative of the invention and not as a limitation.

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ABSTRACT
A process for the synthesis of Cymoxanil comprising the steps of
i) nitrosation, without the formation of excess nitrogen dioxide, of 1-Cyano
acetyl -3-ethyl urea in a solvent in the presence of PTSA or Benzene sulfonic
acids or Naphthalene sulfonic acids to form 2-Cyano-2-hydroxyimino-N-
ethyl carbomyl acetamide; and
ii)methylation of 2-Cyano-2-hydroxyimino- N-ethyl carbomyl acetamide to
form cymoxanil.












08/FEB/2007





Documents:

227-MUM-2006-ABSTRACT(11-5-2009).pdf

227-mum-2006-abstract(complete)-(8-2-2007).pdf

227-mum-2006-abstract(granted)-(12-10-2009).pdf

227-mum-2006-abstract.doc

227-mum-2006-abstract.pdf

227-mum-2006-assignment(17-2-2006).pdf

227-MUM-2006-CANCELLED PAGES(11-5-2009).pdf

227-MUM-2006-CLAIMS(11-5-2009).pdf

227-mum-2006-claims(complete)-(8-2-2007).pdf

227-mum-2006-claims(granted)-(12-10-2009).pdf

227-MUM-2006-CORRESPONDENCE(11-5-2009).pdf

227-mum-2006-correspondence(5-12-2007).pdf

227-mum-2006-correspondence(ipo)-(23-10-2009).pdf

227-mum-2006-correspondence-received.pdf

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

227-MUM-2006-DESCRIPTION(COMPLETE)-(11-5-2009).pdf

227-mum-2006-description(complete)-(8-2-2007).pdf

227-mum-2006-description(granted)-(12-10-2009).pdf

227-MUM-2006-FORM 1(17-2-2006).pdf

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

227-mum-2006-form 18(5-12-2007).pdf

227-mum-2006-form 2(11-5-2009).pdf

227-mum-2006-form 2(complete)-(8-2-2007).pdf

227-mum-2006-form 2(granted)-(12-10-2009).pdf

227-MUM-2006-FORM 2(TITLE PAGE)-(11-5-2009).pdf

227-mum-2006-form 2(title page)-(complete)-(8-2-2007).pdf

227-mum-2006-form 2(title page)-(granted)-(12-10-2009).pdf

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

227-mum-2006-form 6(13-12-2010).pdf

227-mum-2006-form-1.pdf

227-mum-2006-form-2.doc

227-mum-2006-form-2.pdf

227-mum-2006-form-26.pdf

227-mum-2006-form-3.pdf

227-mum-2006-form-5.pdf

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


Patent Number 236231
Indian Patent Application Number 227/MUM/2006
PG Journal Number 42/2009
Publication Date 16-Oct-2009
Grant Date 12-Oct-2009
Date of Filing 17-Feb-2006
Name of Patentee INDOFIL CHEMICALS CO.(A DIVISION OF MODIPON LTD)
Applicant Address NIRLON HOUSE DR.ANNIE BESANT ROAD MUMBAI 400 025,
Inventors:
# Inventor's Name Inventor's Address
1 KHADILKAR SHEKHAR VISHWANATH 003/D-1 SHIRISH LOKUDYAN SOC KALYAN SHIL ROAD KALYAN (W) 431 301
2 BANERJEE TARUN KUMAR BRAHMANAD (ANNEX)PHASE 8 G-9/103 AZADNAGAR THANE (W) 400 607
3 KHAIRNAR VILAS LAXMAN B/302 SHIVNERI SOCIETY MAJIWADE THANE 400 601
4 LOKHANDE MANISH SUDAM A.T.I. STAFF QTRS TYPE III/8 V.N.PURAV MARG CHUNNABHATTI SION MUMBAI 400 601
PCT International Classification Number A01N57/00
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA