WO2020026260A1 - Novel 2-(3-halo-5-methyl-1 h-pyrazol-1-yl)-3-halopyridine compounds and intermediates thereof - Google Patents
Novel 2-(3-halo-5-methyl-1 h-pyrazol-1-yl)-3-halopyridine compounds and intermediates thereof Download PDFInfo
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- WO2020026260A1 WO2020026260A1 PCT/IN2019/000021 IN2019000021W WO2020026260A1 WO 2020026260 A1 WO2020026260 A1 WO 2020026260A1 IN 2019000021 W IN2019000021 W IN 2019000021W WO 2020026260 A1 WO2020026260 A1 WO 2020026260A1
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- 0 *c(cc1C(O)=O)n[n]1-c1c(*)cccn1 Chemical compound *c(cc1C(O)=O)n[n]1-c1c(*)cccn1 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/76—Nitrogen atoms to which a second hetero atom is attached
- C07D213/77—Hydrazine radicals
Definitions
- This invention relates to novel 2-(3-halo-5-methyl- JiT-pyrazol- l-yl)-3- halopyridine compounds and intermediates thereof, process for preparation and use. More specifically, present invention relates to title compounds, use and preparation starting from crotonoyl halide and 3-halo-2-hydrazinyl pyridine.
- Novel 2-(3-halo-5-methyl- i/i-pyrazol- l-yl)-3-halopyridines and intermediates thereof are not reported in the literature.
- Said halopyridine compounds are useful chemical-intermediates which are prepared from commercially available raw materials.
- Main object of invention is to provide novel 2-(3-halo-5-methyl- I/f- pyrazol-l-yl)-3-halopyridine compounds and intermediates thereof.
- Another object of invention is to provide method of preparation of 2- (3-halo-5-methyl- JH-pyra2ol- l-yl)-3-halopyridine compounds and intermediates thereof.
- Yet another object of invention is to disclose use of novel 2-(3-halo-5- methyl- IH-pyrazol-l-yl)-3-halopyridine compounds for preparation of chemical intermediates useful in synthesis of pesticides.
- Title compounds are prepared from crotonoyl halide and 3-halo-2- hydrazinyl pyridine.
- 3-Halo-2-hydrazinyl pyridine is reacted with crotonoyl halide in presence of an acid acceptor to produce lV -(3-halopyridin-2-yl)-2- alkenehydrazide as shown below:
- Preferred acid acceptors are alkali metal bicarbonates. Most preferred acid acceptor is sodium bicarbonate.
- Compound of Formula (III) reacts with phosphorus oxyhalide to form compound of Formula (IV) wherein R is a halogen which is same or different as R 1 .
- D2O Exchangeable protons 7.5246, 1H, singlet, -NH, 9.6506, 1H, singlet, -NH.
- UV spectra 205 nm, 254nm
- UV spectra 206 nm, 276nm
- UV spectra 211nm, 242nm, 271nm.
- Example-5 The product obtained in Example-5 was used as described in Example-6 below to prepare 3-bromo- l-(3-chloropyridin-2-yl)- li : /- pyrazole-5 -carboxylic acid which is an intermediate in the synthesis of pesticides.
- UV spectra 216nm, 266nm.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Present invention discloses novel 2-(3-halo-5-methyl-1H-pyrazol-1-yl)-3-halopyridine compounds and intermediates thereof. Method of preparation of said compounds is also provided. Disclosed compounds are useful as chemical intermediates.
Description
Novel 2-(3-halo-5-methyl-iH-pyrazol-l-yl)-3-halopyridine compounds and intermediates thereof
FIELD OF INVENTION
This invention relates to novel 2-(3-halo-5-methyl- JiT-pyrazol- l-yl)-3- halopyridine compounds and intermediates thereof, process for preparation and use. More specifically, present invention relates to title compounds, use and preparation starting from crotonoyl halide and 3-halo-2-hydrazinyl pyridine.
BACKGROUND AND PRIOR ART
Novel 2-(3-halo-5-methyl- i/i-pyrazol- l-yl)-3-halopyridines and intermediates thereof are not reported in the literature. Said halopyridine compounds are useful chemical-intermediates which are prepared from commercially available raw materials.
OBJECTS OF INVENTION
Main object of invention is to provide novel 2-(3-halo-5-methyl- I/f- pyrazol-l-yl)-3-halopyridine compounds and intermediates thereof.
Another object of invention is to provide method of preparation of 2- (3-halo-5-methyl- JH-pyra2ol- l-yl)-3-halopyridine compounds and intermediates thereof.
Yet another object of invention is to disclose use of novel 2-(3-halo-5- methyl- IH-pyrazol-l-yl)-3-halopyridine compounds for preparation of chemical intermediates useful in synthesis of pesticides.
DETAILED DESCRIPTION OF INVENTION
Title compounds are prepared from crotonoyl halide and 3-halo-2- hydrazinyl pyridine.
3-Halo-2-hydrazinyl pyridine is reacted with crotonoyl halide in presence of an acid acceptor to produce lV -(3-halopyridin-2-yl)-2- alkenehydrazide as shown below:
)
3-halo-2-hydrazinyl- crotonoyl N’-3-halopy ridi n-2-yl)-but-2-ene pyridine halide -hydrazide wherein R1 and R2 are same or different halogen atoms.
Preferred acid acceptors are alkali metal bicarbonates. Most preferred acid acceptor is sodium bicarbonate.
The compound of Formula (I) is reacted with hydrogen bromide to form 3-bromo-lV-(3-halopyridin 2-yl)-butanehydrazide i.e., compound of Formula (II).
3-bromo-N'-(3-halopyridin-2-yl)-butane- hydrazide
Upon heat treatment, compound of Formula (II) undergoes cyclization to form compound of Formula (III).
1 -(3-halopyridin-2-y l)-5-methyl- pyrazolidin-3-one wherein R1 is same as defined above.
Compound of Formula (III) reacts with phosphorus oxyhalide to form compound of Formula (IV) wherein R is a halogen which is same or different as R1.
2-{3-halo-5-methyl-4, 5-dihydro- 1 H- pyrazo -yl)-3-halopyridine
Compound of Formula (IV) is treated with an oxidizing agent to obtain compound of Formula (V) wherein R and R1 are same as defined above.
2-(3-halo-5-methyl-1 H-pyrazol-1-yl)
-3-halopyridine
Further oxidation of methyl group of the compound of Formula (V) can be carried out to obtain 3-halo- l -(3-chloropyridin-2-yl)- iH- pyrazole- 5 -carboxylic acid [Formula (VI)] which is a known compound used in synthesis of pesticides.
3-halo-1-(3-halopyridin-2-yl)- 1 H-pyrazole-5-carboxylic add
Example- 1
Synthesis of N'-(3-chloropyridin-2-yl)but-2-enehydrazide:
0.0465 mole 3-chloro-2-hydrazinyl pyridine and 0.093 mole sodium bicarbonate were taken in the reactor. 310 ml acetonitrile was added. The mixture was cooled to about 0°C. 0.0465 mole crotonoyl chloride was added with stirring over 45 min. The reaction mass was further stirred at room temperature for 3 hrs. Acetonitrile was then removed by distillation under reduced pressure. The residue was
quenched in water to obtain white solid which was filtered, washed with water and dried at about 80°C to obtain product with 92.6% yield and 95% purity.
The product was confirmed by GCMS, IR and proton NMR.
GCMS: m/e = 211.1, 196.1, 143. 1, 1 13, 69.1
IR spectra: 3156.92 cm 1 = -NH stretch, 2965.30 cm 1 = aliphatic -CH stretch, 1683.41 cm 1 = -C=0 stretch, 1643.78 cm 1 = C=N, 1594.52 cm 1 = C=C stretch, 1490.74cm 1 = -CH3 bending, 1037.53 cm 1 = C-N stretch, 798.15 cm-1 = C-Cl stretch.
UV spectra : 232 nm, 29lnm
Proton NMR (CDCb): 1.763- 1.7426, 3H, doublet split into doublet, -CH3, 5.870-5.9136, 1H, doublet split into doublet, -CH=, J=15.2, 6.680-6 7126, 1H, doublet split into doublet, Ar-H, 6.855-6.9456, 1H, doublet split into multiplet, -CO-CH=, J= 15.2, 7.482-7.5016, doublet split into doublet, Ar-H, 7.5246, 1H, singlet, -NH, 7.957-7.9736, 1H, doublet split into doublet, Ar-H, 9.6506, 1H, singlet, -NH.
D2O Exchangeable protons: 7.5246, 1H, singlet, -NH, 9.6506, 1H, singlet, -NH.
Example -2
Synthesis of 3-bromo-./V-(3-chloropyridin-2-yl) butanehydrazide
0.036 moles N-(3-chloropyridin-2-yl)but-2-enehydrazide (obtained as described in Example- 1) and 0.2 moles HBr in acetic acid were taken in the reactor and stirred at room temperature for 10 hrs. The
reaction mixture was quenched in 120 ml 20% Na2C03 solution to give precipitate which was filtered, washed with water and dried under vacuum to obtain 94.98% yield with 95.28% purity
The product was confirmed by GCMS, IR and proton NMR.
GCMS: m/e = 211.1, 196.1 , 169.0, 153.1, 113.1, 78.1 (shows cyclized product).
IR spectra: 3197.24 cm 1 = -NH stretch, 2984.39 cm 1 = aliphatic -CH stretch, 1685.92 cm·1 = -C=0 stretch, 1593.18 cm = C=N stretch, 1489.76cm 1 = -CH3 bending , 1034.85 cm 1 = C-N stretch, 796.23 cm 1 = C-Cl stretch.
UV spectra : 233 nm, 294nm
Proton NMR (DMSO-de): 1.517- 1.5015, 3H, doublet, -CH3, 2.633- 2.5335, 2H, multiplet, -CH2, 4.325-4.2145, 1H, quartet, -CH, 6.534- 6.5035, 1H, multiplet, -Ar-H, 7 466-7.4435, doublet split into doublet, Ar-H, 7.776-7.7605, doublet split into doublet, Ar-H, 8.2475, 1H, singlet, -NH, 9.6675, 1H, singlet, -NH.
Example- 3
Synthesis of l-(3-chloropyridin-2-yl)-5-methylpyrazolidin-3-one
0.0325 moles 3-bromo-JV'-(3-chloropyridin-2-yl) butanehydrazide (obtained as described in Example-2) was taken in 100 ml single neck round bottom flask and heated to about 115°C for 14 hrs. The reaction mass was neutralized with 20% Na2CC>3 to obtain solid product which was filtered, washed with water and dried at about 80°C to get white solid product with 84.13% yield and 97.46% purity.
The product was confirmed by GCMS, IR, and proton NMR.
GCMS: m/e = 211.1, 196.1, 169.0, 153.1, 1 13. 1, 78.1
IR spectra: 3203.56 cm 1 = -NH stretch, 3063.33 cm 1 = Aromatic -CH stretch, 2987.20 cm 1 = aliphatic -CH stretch, 1706.86 cm 1 = -C=0 stretch, 1593.18 cm 1 = -C=N stretch, 1489.76cm 1 = -CH3 bending, 1036.39 cm 1 = C-N stretch, 800.33 cm 1 = C-Cl stretch.
UV spectra: 205 nm, 254nm
Proton NMR (DMSO-de): 1.428- 1.4446, 3H, doublet, -CH3, 1.885- 1.9265, 1H, doublet, one proton of -CH2, 2.626-2.6865, 1H, doublet split into doublet, one proton of -CH2, Ar-H, 4.104-4.1395, 1H, triplet, -CH, 7 213-7.2445, doublet split into doublet, Ar-H, 7.975- 7.9945, 1H, doublet, Ar-H, 8.313-8.3245, 1H, doublet, Ar-H, 9.889, 1H, singlet, -NH.
D20 Exchangeable protons: 9.8895, 1H, singlet, -NH.
Example-4
Synthesis of 2-(3-bromo-5-methyl-4, 5-dihydro- lff-pyrazol- l-yl)-3- chloropyridine
0.0256 moles l-(3-Chloropyridin-2-yl)-5-methylpyrazolidin-3-one (obtained as described in Example-3) and 100 ml acetonitrile were taken in the reactor. 0.0308 moles POBr3 was added at once. The reaction mass was refluxed for 1 hr. TLC after 1 hr showed consumption of starting material and conversion to the product. GC also showed consumption of the starting material. Reaction mass was cooled to 50°C. Acetonitrile was removed by distillation under
reduced pressure to obtain residue which was quenched in 30 ml of 20% Na2C03 to pH 7-8 resulting into separation of oily product. It was extraction with EtOAc (2 X 50 ml), the organic layer was washed with 100 ml water, dried with Na2S04 and evaporated to get light orange colored oil, which solidified on standing. The yield was 99.2% and purity was 96.75%.
The product was confirmed by GCMS, IR, and proton NMR.
GCMS: m/e = 211.1, 196.1, 169.0, 153.1, 113.1, 78.1
IR spectra: 3062.06 cm 1 = Aromatic -CH stretch, 2966.79 cm- 1 = aliphatic -CH stretch, 1573.58 cm 1 = -C=N stretch, 1430.27cm·1 = - CH3 bending , 1055. 13 cm- 1 = C-N stretch, 795.65 cm 1 = C-Cl stretch.
UV spectra: 206 nm, 276nm
Proton NMR (DMSO-d6): 1.295-1.31 15, 3H, doublet, -CH3, 2.904- 2.9755, 1H, doublet of doublet, 1H, -CH2, 3.320-3.3795, 1H, doublet of doublet, 1H, -CH2, 4.740-4.8405, 1H, multiplet, -CH, 7.085- 7. 1175, 1H, doublet of doublet, Ar-H, 7.879-7.9025, 1H, doublet of doublet, Ar-H, 8.242-8.2585, 1H, doublet of doublet, Ar-H.
Example- 5
Preparation of 2 - (3- bromo- 5-methyl- 1 H-pyrazol- 1 -yl) -3 - chloropyridine
0.088 moles 2-(3-Bromo-5-methyl-4,5-dihydro- JH-pyrazol-l-yI)-3- chloropyridine (obtained as described in Example-4) and 60 ml water were taken in the reactor and the mixture was heated to 40°C. 0.0307 moles KMn04 was added. Effervescence were seen with
decolourization. The mixture was heated to 55°C for 2 hrs. Reaction mixture was filtered and washed with ethyl acetate. Filtrate was acidified with HC1 and then the organic layer was separated, washed with water and evaporated to get orange colored oily product with 32.2% yield and 84.62% purity. The product was purified by column chromatography to achieve 99.5% purity.
The product was confirmed by GCMS, IR, and proton NMR.
GCMS: m/e = 21 1. 1 , 196.1 , 169.0, 153.1 , 1 13.1, 78. 1
IR spectra: 3132.31cm 1 = Aromatic -CH stretch, 2850 cm·1 = aliphatic -CH stretch, 1571.02& 1535.65 cm 1 = -C=N stretch,
1347.19cm-1 = C-N Stretch (aryl), 1443.52cm 1 = -CH3 bending , 1029.67 cm 1 = C-N stretch , 797.40 cm 1 = C-Cl stretch.
UV spectra: 211nm, 242nm, 271nm.
Proton NMR (DMSO-de): 2.183-2.2336, 3H, doublet, -CH3, 6.173- 61756, 1H, doublet, -CH, 7.3-7.386, 1H, doublet of doublet, Ar- H, 7.853-7.8776, 1H, doublet of doublet, Ar-H, 8.435-8.4516, 1H, doublet of doublet, Ar-H.
The product obtained in Example-5 was used as described in Example-6 below to prepare 3-bromo- l-(3-chloropyridin-2-yl)- li:/- pyrazole-5 -carboxylic acid which is an intermediate in the synthesis of pesticides.
Example-6
Preparation of 3-bromo- l-(3-chloropyridin-2-yl)-lH-pyrazole-5- carboxylic acid
0.0022 moles 2-(3-bromo-5-methyl- l//-pyrazol-l -yl)-3-chloropyridine (obtained as described in Example-5) and 40 ml water were taken in the reactor. 0.011 moles KMhq4 was added and the mixture was refluxed for 7 hrs. 25 ml ethyl acetate was added to the reaction mixture. It was filtered and washed with 10 ml hot water. The filtrate was taken in separating funnel and organic layer was separated. The aqueous layer was acidified with acetic acid and then extracted with ethyl acetate (3 x 25 ml). The organic layer was evaporated to get off- white solid with 67% yield and 92% purity.
The product was confirmed by MS, IR and proton NMR.
MS: m/e = 303, 259, 178, 1 12, 85, 76.
IR spectra: 3154.10cm 1 = Aromatic CH stretch, 2850 cm 1 = aliphatic -CH stretch, 1704.1345cm-* = -C=0 stretch, 1585.45cm 1 = -C=N stretch, 1482.59cm 1 = -CH3 bending, 1357.12cm 1 = C-N
Stretch (aryl), 1057.26 cm 1 =C-N stretch, 766.58 cm 1 = C-Cl stretch.
UV spectra: 216nm, 266nm.
Proton NMR (DMSO-d6): 7.2586, 1H, singlet, -CH, 7.679-7.71 16, 1H, doublet of doublet, Ar-H, 8.255-8.2786, 1H, doublet of doublet, Ar- H, 8.563-8.5786, 1H, doublet of doublet, Ar-H, 13.9596, 1H, hump, - COOH.
Claims
1. A compound of Formula (I) wherein R1 is a halogen.
2. A method of producing compound of Formula (I) as claimed in claim 1, by reaction of 3-Halo-2-hydrazinylpyridine with crotonoyl halide in presence of an acid acceptor.
3. A compound of Formula (II) wherein R1 is a halogen.
4. A method of producing compound of Formula (II) as claimed in claim-3, by reaction of compound of Formula (I) as claimed in claim 1 with hydrogen bromide.
5. A compound of Formula (III) wherein R1 is a halogen.
6. A method of producing compound of Formula (III) as claimed in claim 5 by heat treatment of compound of Formula (II) as claimed in claim 3, wherein the compound of Formula (II) undergoes cyclization to form compound of Formula (III).
7. A compound of Formula (IV) wherein R and R1 are same or different halogens.
8. A method of producing compound of Formula (IV) as claimed in claim 7 comprising reaction of compound of Formula (III) as claimed in claim 5 with phosphorus oxyhalide.
9. A compound of Formula (V) wherein R and R1 are same or different halogens.
10. A method of producing compound of Formula (V) as
claimed in claim 9 comprising treatment of compound of Formula (IV) as claimed in claim 7 with an oxidizing agent.
1 1. A method of producing compound of Formula (VI) comprising treatment of compound of Formula (V) as claimed in claim 9 with an oxidizing agent.
12. A method as claimed in any of the claims 10 or 1 1,
wherein oxidizing agent is potassium permanganate.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020212991A1 (en) * | 2019-04-19 | 2020-10-22 | Adama Makhteshim Ltd. | Preparation of substituted pyrazoles and their use as anthranilamides precursors |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070203342A1 (en) * | 2001-08-13 | 2007-08-30 | Freudenberger John H | Subtituted dihydro 3-halo-1H-pyrazole-5-carboxylates their preparation and use |
| WO2008126933A2 (en) * | 2007-04-11 | 2008-10-23 | Sumitomo Chemical Company, Limited | Process for producing pesticidal benzamide compounds |
| US20100113794A1 (en) * | 2007-04-11 | 2010-05-06 | Yoshihiko Nokura | Method for producing amide compound |
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- 2019-07-18 WO PCT/IN2019/000021 patent/WO2020026260A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070203342A1 (en) * | 2001-08-13 | 2007-08-30 | Freudenberger John H | Subtituted dihydro 3-halo-1H-pyrazole-5-carboxylates their preparation and use |
| WO2008126933A2 (en) * | 2007-04-11 | 2008-10-23 | Sumitomo Chemical Company, Limited | Process for producing pesticidal benzamide compounds |
| US20100113794A1 (en) * | 2007-04-11 | 2010-05-06 | Yoshihiko Nokura | Method for producing amide compound |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020212991A1 (en) * | 2019-04-19 | 2020-10-22 | Adama Makhteshim Ltd. | Preparation of substituted pyrazoles and their use as anthranilamides precursors |
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