Title of Invention	PROCESS FOR PREPARATION OF 3-METHYL-N-NITROIMINOPERHYDRO-1,3,5-OXADIAZINE
Abstract	The present invention relates to a process for preparation of 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine (MNIO) with improved and simplified process comprising the steps of: (a) converting Guanidine nitrate to Nitroguanidine by intramolecular rearrangement to obtain wet cake of Nitroguanidine; (b) alkylating wet cake of Nitroguanidine with an alkylating agent such as methyl amine to obtain wet cake of N-methyl nitroguanidine wherein wet cake of N-methyl nitroguanidine as obtained is dried under vacuum; (c) condensing N-methyl nitroguanidine with paraformaldehyde in the presence of formic acid without using an acid catalyst and solvent to obtain 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine; further wherein water of the reaction from step (c) is removed azeotropically and excess paraformaldehyde is removed by making formalin.

Title of Invention

PROCESS FOR PREPARATION OF 3-METHYL-N-NITROIMINOPERHYDRO-1,3,5-OXADIAZINE

Abstract

The present invention relates to a process for preparation of 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine (MNIO) with improved and simplified process comprising the steps of: (a) converting Guanidine nitrate to Nitroguanidine by intramolecular rearrangement to obtain wet cake of Nitroguanidine; (b) alkylating wet cake of Nitroguanidine with an alkylating agent such as methyl amine to obtain wet cake of N-methyl nitroguanidine wherein wet cake of N-methyl nitroguanidine as obtained is dried under vacuum; (c) condensing N-methyl nitroguanidine with paraformaldehyde in the presence of formic acid without using an acid catalyst and solvent to obtain 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine; further wherein water of the reaction from step (c) is removed azeotropically and excess paraformaldehyde is removed by making formalin.

Full Text	PROCESS FOR PREPARATION OF 3-METHYL-N-NITROIMINOPERHYDRO-1,3,5- OXADIAZINE FIELD OF INVENTION [0001] The present invention relates to a process for preparation of 3-methyl-N- nitroiminoperhydro-l,3,5-oxadiazine (MNIO) with improved and simplified process. MNIO prepared in accordance to the present invention can be used as an intermediate to manufacture a broad spectrum insecticide Thiamethoxam. BACKGROUND OF THE INVENTION AND THE PRIOR ART [0002] 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine (MNIO) is a known intermediate used in the manufacture of Thiamethoxam. Thiamethoxam is a broad spectrum insecticide for pest protection for numerous crops. It is a second generation neonicotinamide insecticide belonging to the thianicotinyl sub class of chemistry. [0003] Thiamethoxam is prepared by reacting two intermediates: 2-chloro-5- chloromethyl thiazole (CCMT) and 3-methyl-N-nitroimino perhydro-l,3,5-oxadiazine (MNIO). MNIO is structurally represented as: Formula removed:- [0004] The methods of preparation of MNIO have been disclosed in the literature. Thiamethoxam was discovered by the Ciba group of Japan. The Ciba group synthesizes 4-nitroimino-1,3,5-oxadinazinane which they used to synthesize thiamethoxam (MMG 445 Basic Biotechnology eJournal pp. 46-52, 2006). They started with readily available S-methyl-N-nitro-isothiourea and methylamine in 50 °C ethanol and this procedure produces the mono-substituted nitroguanidine in 94% yield. The monosubstituted nitroguanidine is heated in a 1:1 mixture of aqueous formaldehyde solution and formic acid to 90°C for several hours. This procedure produces the 4-nitroimino-1,3,5-oxadinazinane in 71% yield. Alkylation of 4-nitroimino-1,3,5-oxadinazinane with 2-chlrothiazol-5-ylmethyl chloride in N,N-dimethylform-amide in the presence of potassium carbonate led to synthesis of Thiamethoxam. [0005] The process for synthesizing MNIO starting from N-methylnitroguanidine has been described in US Patent US 5,852,012 and its divisional Patents US 7,655,650, US 5,852,012, US 6,022,871, US 6,376,487, US 6,627,753. The process for the preparation of MNIO from N-methyl nitro guanidine in the above patents is described reacting N-methyl nitroguanidine with paraformaldehyde in the presence of dioxane and toluene and using a base triethylamine. The process took place in the presence of acids like p-toluene sulfonic acid or methyl sulfonic acid as catalysts. The reaction is carried out for 18-20 hrs for the completion of the reaction. [0006] However the process as disclosed above has considerable disadvantages. It is a lengthy process requiring around 18-20 hours for the completion of the reaction. Dioxane and toluene are to be separated in this process and triethylamine cannot be recovered. Also the process involves crystallization by methanol. This not only leads to long cycle times in a production cycle but also add to the cost to the manufacturer making the entire process lesser efficient. Further as discussed above, the process uses solvents and acid catalysts to carry out the reaction which not only add to the cost but also makes the process more complex. Furthermore the existing process nowhere discloses the repeated recycling of starting material formic acid which is again problematical from ecological and toxicological viewpoint. [0007] There is therefore a need in the art to develop a process for preparation of MNIO with an improved and simplified synthesis which significantly reduces the time cycle in a production cycle as compared to existing methods. Moreover, such process must also significantly improve the purity of MNIO. It would also be desirable to reduce the ecological and toxicological problems arising from the existing methods. Lastly, such process must be cost-effective. OBJECTS OF THE INVENTION [0008] It is an object of the invention to provide an improved and simplified process for the synthesis of 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine (MNIO). [0009] It is an object of the invention to provide an improved and simplified process for the synthesis of MNIO from N-methyl nitroguanidine wherein the time cycle of the reaction has been significantly reduced to 6-7 hours only. [00010] It is an object of the invention to provide an improved and simplified process for the synthesis of MNIO from N-methyl nitroguanidine which involves removal of unreacted paraformaldehyde. [00011] It is an object of the invention to provide an improved and simplified process for the synthesis of MNIO from N-methyl nitroguanidine without using acid catalyst and solvent. [00012] It is an object of the invention to provide an improved and simplified process for the synthesis of MNIO from N-methyl nitroguanidine which involves the repeated recycling of the recoverd formic acid. [00013] It is an object of the invention to provide an improved and simplified process for the synthesis of MNIO which involves a significant improvement in the yield and the purity of the MNIO obtained. [00014] It is an object of the invention to provide an improved and simplified process for the synthesis of MNIO where the overall cost to the manufactures is significantly reduced. [00015] It is an object of the invention to provide an improved and simplified process for the synthesis of MNIO which significantly reduces the ecological and toxicological problems thereby overall making the process environment friendly. SUMMARY OF THE INVENTION [00016] The present invention relates to a preparation of 3-methyl-N- nitroiminoperhydro-l,3,5-oxadiazine (MNIO) with improved and simplified process comprising the steps of: (a) converting Guanidine nitrate to Nitroguanidine by intra-molecular rearrangement to obtain wet cake of Nitroguanidine; (b) alkylating wet cake of Nitroguanidine with an alkylating agent such as methyl amine to obtain wet cake of N-methyl nitroguanidine wherein wet cake of N-methyl nitroguanidine as obtained is dried under vacuum; (c) condensing N-methyl nitroguanidine with paraformaldehyde in the presence of formic acid without using an acid catalyst and solvent to obtain 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine; further wherein: water of the reaction from step (c) is removed azeotropically and excess paraformaldehyde is removed by making formalin. DETAILED DESCRIPTION OF THE INVENTION [00017] In one embodiment, the present invention relates to a preparation of 3- methyl-N-nitroiminoperhydro-l,3,5-oxadiazine (MNIO) with improved and simplified process. MNIO prepared in accordance to the present invention can be used as an intermediate to manufacture a broad spectrum insecticide Thiamethoxam by any synthetic process known in the literature. [00018] In an embodiment of the present invention, MNIO (I) is prepared by condensation of N-methyl nitroguanidine (III) with paraformaldehyde in the presence of formic acid under suitable conditions and without using any acid catalyst and solvent and is represented by the following equation: Formula removed:- [00019] In an embodiment, wet cake of Nitroguanidine is alkylated with an alkylating agent to obtain wet cake of N-methyl nitroguanidine wherein wet cake of N-methyl nitroguanidine as obtained is dried under vacuum. [00020] In a preferred embodiment, Nitroguanidine is alkylated in a presence of methyl amine as an alkylating agent in the presence of HC1. Formula removed:- [00021] In an embodiment, intramolecular rearrangement of Guanidine nitrate in the presence of sulfuric acid forms a wet cake of Nitroguanidine (II) Formula removed:- [00022] In a preferred embodiment, wet cake of nitroguanidine (II) obtained is taken for the preparation of N-methyl nitroguanidine (III) in the next step to avoid the risk of explosive nature of Nitroguanidine on heating. [00023] In another embodiment of the invention, the water of the reaction formed during the condensation of paraformaldehyde and MNIO is removed azeotropically [00024] In another embodiment of the invention, the unreacted (excess) paraformaldehyde is removed from reaction by forming formalin. [00025] In an embodiment, time taken for the completion of the reaction forming MNIO from N-methyl nitroguanidine is reduced to 6-7 hours which is significantly lesser as compared 18-20 hours taken by the known process. [00026] In a further embodiment, the recovered formic acid is repeatedly recycled. [00027] In a preferred embodiment, the recovered formic acid is recycled for 5-6 times upto strength of around 55%. [00028] In a further embodiment, the mother liquor comprising methyl amine, HC1 and Nitroguanidine, would be recycled which further increases the yield. [00029] In a preferred embodiment, wet cake of N-methyl nitroguanidine is dried under vacuum at 50-70°C. [00030] In a preferred embodiment, the purity of the MNIO obtained by the process of the present invention is greater than 96-97 %. [00031] MNIO contains asymmetric carbon atoms, as a result it can arise in an optically active form. MNIO as prepared in accordance to the present invention are intended to include all of its possible isomeric forms and mixtures thereof, for example racemate or E/Z-isomer mixture. [00032] MNIO as prepared in accordance to the present invention may be present as tautomers and therefore understood to encompass corresponding tautomers. [00033] MNIO as prepared in accordance to the present invention can form acid addition salts. These are formed, for example, with strong inorganic acids, such as mineral acids, e.g. perchloric acid, sulphuric acid, nitric acid, nitrous acid, a phosphoric acid or a hydrohalic acid, with strong organic carboxylic acids, such as acetic acid, such as optionally unsaturated dicarboxylic acids, e.g. oxalic acid, malonic acid , e.g. ascorbic acid, lactic acid, fumaric acid or phthalic acid, such as hydroxycarboxylic acids, e.g. ascorbic acid lactic acid, malic acid, tartaric acid or citric acid, or such as benzoic acid, or with organic sulphonic acids, such as optionally, e.g. methane- or p-toluenesulphonic acid. [00034] MNIO as prepared in accordance to the present invention is understood to encompass MNIO in free form and also the corresponding salts. The corresponding statement applies to tautomers of MNIO. Preference is generally given to a process for the preparation of the free form. EXAMPLES The present invention is further explained in the form of following examples. However it is to be understood that these examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention EXAMPLE 1 A. Preparation of Nitroguanidine (II) Charge 162.5 gm cone. Sulfuric acid (98%) in reactor fitted with mechanical agitator, thermopocket and condenser. Charge 117.0 gm Guanidine nitrate with in 1.5-2.0 hrs at 28-30°C under agitation. Agitation of reaction mass continues for further 12 hrs at 30±2°C. After completion of hold period, monitor the reaction mass on HPLC and agitation continue till the complete conversion of Guanidine nitrate to Nitroguanidine (II) (Guanidine nitrate 99% with 20% moisture. B. Preparation of N-methyl nitroguanidine (III) Charge 147.8 gm DM water, 103.7 gm 38% aqueous solution of Methyl amine in reactor fitted with mechanical stirrer, thermopocket and condenser. Slowly add 16.0 gm cone. HC1 below 30°C and agitate for 30 min at 30±2°C. Charge wet cake of 108.2 gm Nitroguanidine (II) in single lot at 30°C under agitation. Raise temperature to 35°C and agitation of reaction mass continue for further 2 hrs at 35±2°C. After completion of hold period, monitor the reaction mass on HPLC and agitation continue till complete conversion of Nitroguanidine (II) to N-methyl nitroguanidine (III) (Nitroguanidine 98% with 0.5% moisture. The mother liquor having Methyl amine, HC1 and Nitroguanidine (II), would be recycled. C. Preparation of 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine (I) from N-methyl nitroguanidine (III) Charge 75.0 gm N-methyl nitroguanidine (III), 57.2 gm Paraformaldehyde and 381.5 gm Formic acid (98-100%) at room temperature in reactor fitted with agitator, condenser and thermopocket on water bath. The reaction is carried out by refiuxing the mixture at 105°C -107°C for 5-6 hrs and separate out water with Formic acid azeotropically. Distill out formic acid by vacuum after completion of the reaction. After recovery of formic acid, add 38.0 ml DM water and agitate for 15.0 minute at room temperature and adjust pH to 7.0 by addition of 47% caustic lye. Excess Paraformaldehyde is removed by making formalin. Cool to 0-5°C and agitate for 2 hrs. Then filter it and wet cake washed with 70.0 gm chilled water under agitation. Filter and dry the cake at 80-90°C. Formic acid would be recycled. 81.5 gm 3-methyl-N-nitroiminoperhydro-l,3>5-oxadiazine (I) of > 96-97% purity is obtained. ADVANTAGES OF THE INVENTION [00035] The present invention provides an improved process for the synthesis of 3- methyl-N-nitroiminoperhydro-l,3,5-oxadiazine (MNIO) which is simplified and cost-effective. [00036] The present invention provides an improved process for the synthesis of MNIO from N-methyl nitroguanidine wherein the time cycle of the reaction has been significantly reduced to 6-7 hours only. [00037] The present invention provides an improved process for the synthesis of MNIO from N-methyl nitroguanidine which involves the removal of unreacted paraformaldehyde. [00038] The present invention provides an improved process for the synthesis of MNIO from N-methyl nitroguanidine without using an acid catalyst and a solvent. [00039] The present invention provides an improved process for the synthesis of MNIO from N-methyl nitroguanidine which involves the repeated recycling of the recoverd formic acid. [00040] The present invention provides an improved process for the synthesis of MNIO which involves a significant improvement in the yield and the purity of the MNIO obtained. [00041] The present invention provides an improved process for the synthesis of MNIO where the overall cost to the manufactures is significantly reduced. [00042] The present invention provides an improved process for the synthesis of MNIO which significantly reduces the ecological and toxicological problems thereby overall making the process environment friendly. -14- We claim 1. A process for preparation of 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine (MNIO) comprising steps of: (a) converting Guanidine nitrate to Nitroguanidine by intra-mo1ecular rearrangement to obtain wet cake of Nitroguanidine; (b) alkylating said wet cake of Nitroguanidine with an alkylating agent to obtain wet cake of N-methyl nitroguanidine wherein said wet cake of N-methyl nitroguanidine as obtained is dried under vacuum; (c) condensing said N-methyl nitroguanidine with paraformaldehyde in presence of formic acid without using an acid catalyst and a solvent to obtain said 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine. 2. The process as claimed in claim 1, wherein said step (b) comprises alkylating said Nitroguanidine with methyl amine in presence of HC1. 3. The process as claimed in claim 1, wherein unreacted paraformaldehyde from said step (c) is removed by making formalin. 4. The process as claimed in claim 1, wherein water of reaction from said step (c) is removed azeotropically. 5. The process as claimed in claim 1, wherein said wet cake of N-methyl nitroguanidine is dried under vacuum at 50-70°C. 6. The process as claimed in claim 1, wherein time for completion of reaction in preparation of said 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine from said N- methyl nitroguanidine is reduced to 6-7 hours. 7. The process as claimed in claim 1, wherein recovered said formic acid is recycled repeatedly. 8. The process as claimed in 7, wherein recovered said formic acid is recycled 5-6 times up to strength of 55 %. 9. The process as claimed in claim 1, wherein purity of said 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine obtained is greater than 96-97 %. 10. The process as claimed in claim 1, wherein said 3-methy1-N-nitroiminoperhydro-1,3,5-oxadiazine is used as an intermediate in synthesis of Thiamethoxam.

Full Text

PROCESS FOR PREPARATION OF 3-METHYL-N-NITROIMINOPERHYDRO-1,3,5-
OXADIAZINE
FIELD OF INVENTION
[0001] The present invention relates to a process for preparation of 3-methyl-N-
nitroiminoperhydro-l,3,5-oxadiazine (MNIO) with improved and simplified process.
MNIO prepared in accordance to the present invention can be used as an intermediate to
manufacture a broad spectrum insecticide Thiamethoxam.
BACKGROUND OF THE INVENTION AND THE PRIOR ART
[0002] 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine (MNIO) is a known
intermediate used in the manufacture of Thiamethoxam. Thiamethoxam is a broad
spectrum insecticide for pest protection for numerous crops. It is a second generation
neonicotinamide insecticide belonging to the thianicotinyl sub class of chemistry.
[0003] Thiamethoxam is prepared by reacting two intermediates: 2-chloro-5-
chloromethyl thiazole (CCMT) and 3-methyl-N-nitroimino perhydro-l,3,5-oxadiazine
(MNIO). MNIO is structurally represented as:
Formula removed:-
[0004] The methods of preparation of MNIO have been disclosed in the literature. Thiamethoxam was discovered by the Ciba group of Japan. The Ciba group synthesizes 4-nitroimino-1,3,5-oxadinazinane which they used to synthesize thiamethoxam (MMG 445 Basic Biotechnology eJournal pp. 46-52, 2006). They started with readily available S-methyl-N-nitro-isothiourea and methylamine in 50 °C ethanol and this procedure produces the mono-substituted nitroguanidine in 94% yield. The monosubstituted nitroguanidine is heated in a 1:1 mixture of aqueous formaldehyde solution and formic acid to 90°C for several hours. This procedure produces the 4-nitroimino-1,3,5-oxadinazinane in 71% yield. Alkylation of 4-nitroimino-1,3,5-oxadinazinane with 2-chlrothiazol-5-ylmethyl chloride in N,N-dimethylform-amide in the presence of potassium carbonate led to synthesis of Thiamethoxam.
[0005] The process for synthesizing MNIO starting from N-methylnitroguanidine
has been described in US Patent US 5,852,012 and its divisional Patents US 7,655,650, US 5,852,012, US 6,022,871, US 6,376,487, US 6,627,753. The process for the preparation of MNIO from N-methyl nitro guanidine in the above patents is described reacting N-methyl nitroguanidine with paraformaldehyde in the presence of dioxane and toluene and using a base triethylamine. The process took place in the presence of acids like p-toluene sulfonic acid or methyl sulfonic acid as catalysts. The reaction is carried out for 18-20 hrs for the completion of the reaction.
[0006] However the process as disclosed above has considerable disadvantages.
It is a lengthy process requiring around 18-20 hours for the completion of the reaction. Dioxane and toluene are to be separated in this process and triethylamine cannot be
recovered. Also the process involves crystallization by methanol. This not only leads to long cycle times in a production cycle but also add to the cost to the manufacturer making the entire process lesser efficient. Further as discussed above, the process uses solvents and acid catalysts to carry out the reaction which not only add to the cost but also makes the process more complex. Furthermore the existing process nowhere discloses the repeated recycling of starting material formic acid which is again problematical from ecological and toxicological viewpoint.
[0007] There is therefore a need in the art to develop a process for preparation
of MNIO with an improved and simplified synthesis which significantly reduces the time cycle in a production cycle as compared to existing methods. Moreover, such process must also significantly improve the purity of MNIO. It would also be desirable to reduce the ecological and toxicological problems arising from the existing methods. Lastly, such process must be cost-effective.
OBJECTS OF THE INVENTION
[0008] It is an object of the invention to provide an improved and simplified
process for the synthesis of 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine (MNIO).
[0009] It is an object of the invention to provide an improved and simplified
process for the synthesis of MNIO from N-methyl nitroguanidine wherein the time cycle
of the reaction has been significantly reduced to 6-7 hours only.
[00010] It is an object of the invention to provide an improved and simplified
process for the synthesis of MNIO from N-methyl nitroguanidine which involves
removal of unreacted paraformaldehyde.
[00011] It is an object of the invention to provide an improved and simplified
process for the synthesis of MNIO from N-methyl nitroguanidine without using acid
catalyst and solvent.
[00012] It is an object of the invention to provide an improved and simplified
process for the synthesis of MNIO from N-methyl nitroguanidine which involves the
repeated recycling of the recoverd formic acid.
[00013] It is an object of the invention to provide an improved and simplified
process for the synthesis of MNIO which involves a significant improvement in the yield
and the purity of the MNIO obtained.
[00014] It is an object of the invention to provide an improved and simplified
process for the synthesis of MNIO where the overall cost to the manufactures is
significantly reduced.
[00015] It is an object of the invention to provide an improved and simplified
process for the synthesis of MNIO which significantly reduces the ecological and
toxicological problems thereby overall making the process environment friendly.
SUMMARY OF THE INVENTION
[00016] The present invention relates to a preparation of 3-methyl-N-
nitroiminoperhydro-l,3,5-oxadiazine (MNIO) with improved and simplified process
comprising the steps of:
(a) converting Guanidine nitrate to Nitroguanidine by intra-molecular rearrangement to obtain wet cake of Nitroguanidine;
(b) alkylating wet cake of Nitroguanidine with an alkylating agent such as methyl amine to obtain wet cake of N-methyl nitroguanidine wherein wet cake of N-methyl nitroguanidine as obtained is dried under vacuum;
(c) condensing N-methyl nitroguanidine with paraformaldehyde in the presence of formic acid without using an acid catalyst and solvent to obtain 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine; further wherein:
water of the reaction from step (c) is removed azeotropically and excess paraformaldehyde is removed by making formalin.

DETAILED DESCRIPTION OF THE INVENTION
[00017] In one embodiment, the present invention relates to a preparation of 3-
methyl-N-nitroiminoperhydro-l,3,5-oxadiazine (MNIO) with improved and simplified
process. MNIO prepared in accordance to the present invention can be used as an
intermediate to manufacture a broad spectrum insecticide Thiamethoxam by any
synthetic process known in the literature.
[00018] In an embodiment of the present invention, MNIO (I) is prepared by
condensation of N-methyl nitroguanidine (III) with paraformaldehyde in the presence of
formic acid under suitable conditions and without using any acid catalyst and solvent and
is represented by the following equation:
Formula removed:-
[00019] In an embodiment, wet cake of Nitroguanidine is alkylated with an alkylating agent to obtain wet cake of N-methyl nitroguanidine wherein wet cake of N-methyl nitroguanidine as obtained is dried under vacuum.
[00020] In a preferred embodiment, Nitroguanidine is alkylated in a presence of methyl amine as an alkylating agent in the presence of HC1.
Formula removed:-
[00021] In an embodiment, intramolecular rearrangement of Guanidine nitrate in the presence of sulfuric acid forms a wet cake of Nitroguanidine (II)
Formula removed:-
[00022] In a preferred embodiment, wet cake of nitroguanidine (II) obtained is taken for the preparation of N-methyl nitroguanidine (III) in the next step to avoid the risk of explosive nature of Nitroguanidine on heating.
[00023] In another embodiment of the invention, the water of the reaction formed
during the condensation of paraformaldehyde and MNIO is removed azeotropically
[00024] In another embodiment of the invention, the unreacted (excess)
paraformaldehyde is removed from reaction by forming formalin.
[00025] In an embodiment, time taken for the completion of the reaction forming
MNIO from N-methyl nitroguanidine is reduced to 6-7 hours which is significantly lesser
as compared 18-20 hours taken by the known process.
[00026] In a further embodiment, the recovered formic acid is repeatedly recycled.
[00027] In a preferred embodiment, the recovered formic acid is recycled for 5-6
times upto strength of around 55%.
[00028] In a further embodiment, the mother liquor comprising methyl amine, HC1
and Nitroguanidine, would be recycled which further increases the yield.
[00029] In a preferred embodiment, wet cake of N-methyl nitroguanidine is dried
under vacuum at 50-70°C.
[00030] In a preferred embodiment, the purity of the MNIO obtained by the process
of the present invention is greater than 96-97 %.
[00031] MNIO contains asymmetric carbon atoms, as a result it can arise in an
optically active form. MNIO as prepared in accordance to the present invention are intended to include all of its possible isomeric forms and mixtures thereof, for example racemate or E/Z-isomer mixture.
[00032] MNIO as prepared in accordance to the present invention may be present as
tautomers and therefore understood to encompass corresponding tautomers.
[00033] MNIO as prepared in accordance to the present invention can form acid
addition salts. These are formed, for example, with strong inorganic acids, such as mineral acids, e.g. perchloric acid, sulphuric acid, nitric acid, nitrous acid, a phosphoric acid or a hydrohalic acid, with strong organic carboxylic acids, such as acetic acid, such as optionally unsaturated dicarboxylic acids, e.g. oxalic acid, malonic acid , e.g. ascorbic acid, lactic acid, fumaric acid or phthalic acid, such as hydroxycarboxylic acids, e.g. ascorbic acid lactic acid, malic acid, tartaric acid or citric acid, or such as benzoic acid, or with organic sulphonic acids, such as optionally, e.g. methane- or p-toluenesulphonic acid.
[00034] MNIO as prepared in accordance to the present invention is understood to
encompass MNIO in free form and also the corresponding salts. The corresponding statement applies to tautomers of MNIO. Preference is generally given to a process for the preparation of the free form.

EXAMPLES
The present invention is further explained in the form of following examples. However it is to be understood that these examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention
EXAMPLE 1
A. Preparation of Nitroguanidine (II)
Charge 162.5 gm cone. Sulfuric acid (98%) in reactor fitted with mechanical agitator, thermopocket and condenser. Charge 117.0 gm Guanidine nitrate with in 1.5-2.0 hrs at 28-30°C under agitation. Agitation of reaction mass continues for further 12 hrs at 30±2°C. After completion of hold period, monitor the reaction mass on HPLC and agitation continue till the complete conversion of Guanidine nitrate to Nitroguanidine (II) (Guanidine nitrate 99% with 20% moisture.
B. Preparation of N-methyl nitroguanidine (III)
Charge 147.8 gm DM water, 103.7 gm 38% aqueous solution of Methyl amine in reactor fitted with mechanical stirrer, thermopocket and condenser. Slowly add 16.0 gm cone.
HC1 below 30°C and agitate for 30 min at 30±2°C. Charge wet cake of 108.2 gm Nitroguanidine (II) in single lot at 30°C under agitation. Raise temperature to 35°C and agitation of reaction mass continue for further 2 hrs at 35±2°C. After completion of hold period, monitor the reaction mass on HPLC and agitation continue till complete conversion of Nitroguanidine (II) to N-methyl nitroguanidine (III) (Nitroguanidine 98% with 0.5% moisture. The mother liquor having Methyl amine, HC1 and Nitroguanidine (II), would be recycled.
C. Preparation of 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine (I) from N-methyl nitroguanidine (III)
Charge 75.0 gm N-methyl nitroguanidine (III), 57.2 gm Paraformaldehyde and 381.5 gm Formic acid (98-100%) at room temperature in reactor fitted with agitator, condenser and thermopocket on water bath. The reaction is carried out by refiuxing the mixture at 105°C -107°C for 5-6 hrs and separate out water with Formic acid azeotropically. Distill out formic acid by vacuum after completion of the reaction. After recovery of formic acid, add 38.0 ml DM water and agitate for 15.0 minute at room temperature and adjust pH to 7.0 by addition of 47% caustic lye. Excess Paraformaldehyde is removed by making formalin. Cool to 0-5°C and agitate for 2 hrs. Then filter it and wet cake washed with 70.0 gm chilled water under agitation. Filter and dry the cake at 80-90°C.

Formic acid would be recycled. 81.5 gm 3-methyl-N-nitroiminoperhydro-l,3>5-oxadiazine (I) of > 96-97% purity is obtained.
ADVANTAGES OF THE INVENTION
[00035] The present invention provides an improved process for the synthesis of 3-
methyl-N-nitroiminoperhydro-l,3,5-oxadiazine (MNIO) which is simplified and cost-effective.
[00036] The present invention provides an improved process for the synthesis of
MNIO from N-methyl nitroguanidine wherein the time cycle of the reaction has been significantly reduced to 6-7 hours only.
[00037] The present invention provides an improved process for the synthesis of
MNIO from N-methyl nitroguanidine which involves the removal of unreacted paraformaldehyde.
[00038] The present invention provides an improved process for the synthesis of
MNIO from N-methyl nitroguanidine without using an acid catalyst and a solvent.
[00039] The present invention provides an improved process for the synthesis of
MNIO from N-methyl nitroguanidine which involves the repeated recycling of the recoverd formic acid.
[00040] The present invention provides an improved process for the synthesis of
MNIO which involves a significant improvement in the yield and the purity of the MNIO obtained.

[00041] The present invention provides an improved process for the synthesis of
MNIO where the overall cost to the manufactures is significantly reduced.
[00042] The present invention provides an improved process for the synthesis of
MNIO which significantly reduces the ecological and toxicological problems thereby overall making the process environment friendly.
-14-

We claim
1. A process for preparation of 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine (MNIO) comprising steps of:
(a) converting Guanidine nitrate to Nitroguanidine by intra-mo1ecular rearrangement to obtain wet cake of Nitroguanidine;
(b) alkylating said wet cake of Nitroguanidine with an alkylating agent to obtain wet cake of N-methyl nitroguanidine wherein said wet cake of N-methyl nitroguanidine as obtained is dried under vacuum;
(c) condensing said N-methyl nitroguanidine with paraformaldehyde in presence of formic acid without using an acid catalyst and a solvent to obtain said 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine.

2. The process as claimed in claim 1, wherein said step (b) comprises alkylating said Nitroguanidine with methyl amine in presence of HC1.
3. The process as claimed in claim 1, wherein unreacted paraformaldehyde from said step (c) is removed by making formalin.
4. The process as claimed in claim 1, wherein water of reaction from said step (c) is removed azeotropically.
5. The process as claimed in claim 1, wherein said wet cake of N-methyl nitroguanidine is dried under vacuum at 50-70°C.
6. The process as claimed in claim 1, wherein time for completion of reaction in preparation of said 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine from said N-
methyl nitroguanidine is reduced to 6-7 hours.
7. The process as claimed in claim 1, wherein recovered said formic acid is recycled repeatedly.
8. The process as claimed in 7, wherein recovered said formic acid is recycled 5-6 times up to strength of 55 %.
9. The process as claimed in claim 1, wherein purity of said 3-methyl-N-nitroiminoperhydro-l,3,5-oxadiazine obtained is greater than 96-97 %.
10. The process as claimed in claim 1, wherein said 3-methy1-N-nitroiminoperhydro-1,3,5-oxadiazine is used as an intermediate in synthesis of Thiamethoxam.

Documents:

http://ipindiaonline.gov.in/patentsearch/GrantedSearch/viewdoc.aspx?id=h4OG1gT9GnMPuga9z0JeKg==&loc=+mN2fYxnTC4l0fUd8W4CAA==

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Patent Number

270837

Indian Patent Application Number

585/DEL/2011

PG Journal Number

05/2016

Publication Date

29-Jan-2016

Grant Date

22-Jan-2016

Date of Filing

04-Mar-2011

Name of Patentee

INSECTICIDES INDIA LIMITED

Applicant Address

E-401, 402, LUSA TOWER, AZADPUR COMMERCIAL COMPLEX, AZADPUR DELHI-110033

Inventors:

#	Inventor's Name	Inventor's Address
1	KUMAR, MUKESH	INSECTICIDES INDIA LIMITED E-401, 402, LUSA TOWER, AZADPUR COMMERCIAL COMPLEX, AZADPUR DELHI-110033
2	SINGHAL, B.S.	INSECTICIDES INDIA LIMITED E-401, 402, LUSA TOWER, AZADPUR COMMERCIAL COMPLEX, AZADPUR DELHI-110033
3	KALWADIA, BELA	INSECTICIDES INDIA LIMITED E-401, 402, LUSA TOWER, AZADPUR COMMERCIAL COMPLEX, AZADPUR DELHI-110033
4	GUPTA, M.M	INSECTICIDES INDIA LIMITED E-401, 402, LUSA TOWER, AZADPUR COMMERCIAL COMPLEX, AZADPUR DELHI-110033

PCT International Classification Number

C07

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA