WO2000027818A1 - Preparation of chloromethylpyridine hydrochlorides - Google Patents
Preparation of chloromethylpyridine hydrochlorides Download PDFInfo
- Publication number
- WO2000027818A1 WO2000027818A1 PCT/CA1999/001005 CA9901005W WO0027818A1 WO 2000027818 A1 WO2000027818 A1 WO 2000027818A1 CA 9901005 W CA9901005 W CA 9901005W WO 0027818 A1 WO0027818 A1 WO 0027818A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- chloromethylpyridine
- thionyl chloride
- hydrochloride
- solution
- pyridyl carbinol
- Prior art date
Links
Classifications
-
- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/26—Radicals substituted by halogen atoms or nitro radicals
Definitions
- This invention relates to chemical synthetic processes for preparing pyridine compounds, useful as synthetic intermediates in manufacture of pharmaceuticals. More specifically, it relates to processes for preparing chloromethylpyridine hydrochlorides, such as 3-chloromethylpyridine hydrochloride, otherwise known as 3-picolyl chloride hydrochloride.
- the present invention provides a process for preparing chloromethylpyridine hydrochlorides which comprises reacting the corresponding pyridyl carbinol with a slight excess of thionyl chloride, in a reaction medium comprising an inert organic solvent.
- a reaction medium comprising an inert organic solvent.
- Thionyl chloride is a hazardous substance, the reduction in use of which is beneficial for environmental and cost reasons.
- the chloromethylpyridine hydrochloride is initially formed in the process of the invention as an oily semi-solid, which is readily converted to a crystalline solid in a high degree of purity, e.g. by application of a vacuum or nitrogen purge aid to complete the precipitation of the product, followed by filtration to obtain the substantially pure crystalline solid product.
- a suitable, preferred organic solvent for use in the process of the invention is toluene, although other similar solvents (benzene, xylenes, cyclohexane etc.) can also be used.
- Toluene is especially preferred on account of its low cost and low toxicity. Moreover, its use as the sole solvent in the process allows its substantial recovery for further use.
- the reaction scheme can be represented as follows:
- a scrubber containing an aqueous solution of alkali, such as sodium hydroxide, attached to the reaction vessel.
- alkali such as sodium hydroxide
- Gaseous by-products of the reaction notably sulfur dioxide flow into the scrubber as they are evolved, or purged from the reaction mixture, and are neutralized with the formation of salts such as sodium bisulfite.
- the order of addition of the reagents when forming the reaction mixture preferably involves the addition of the pyridyl carbinol solution to the thionyl chloride solution, rather than the reverse.
- This allows for better temperature control of this exothermic reaction (the rate of addition is preferably controlled so that the reaction mixture does not exceed 35°C), as well as permitting the operator to arrange for substantially instant mixing of the reagents, e.g. by use of a dip tube to introduce the pyridyl carbinol solution below the surface of the thionyl chloride solution, to enable the process to produce highly pure chloromethyl pyridine hydrochloride.
- the product of the process of the invention forms initially as an oily semi-solid.
- the preferred recovery processes for the product are the application of vacuum, or a nitrogen purge, to the reaction suspension medium, more effectively to remove most the residual sulfur dioxide and cause the complete precipitation and crystallization of the product. Then the solid product can be readily filtered off and washed, to yield a highly pure white or off-white crystalline solid, normally in greater than 90% yield.
- a dry 500 ml 3 necked round bottom flask fitted with a mechanical stirrer, thermometer and an addition funnel with nitrogen inlet was linked to a caustic scrubber.
- the solution in the flask was stirred and the temperature adjusted to about 25°C. Slow addition of the 3-pyridyl carbinol solution from the addition funnel was started, maintaining the reaction temperature in the range 23-35°C. A water bath was used to help maintain the reaction temperature. The reaction mixture was agitated as the addition was made under the surface of the solution, thus achieving an instant mix of the added portion. After the addition had been completed, the reaction mixture was stirred at room temperature for 1 hour. Vacuum was applied to the reaction mixture, and agitation was continued for a period of 2 hours, during which complete precipitation of the product occurred.
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP99952196A EP1124803B1 (en) | 1998-11-06 | 1999-10-29 | Preparation of 3-chloromethylpyridine hydrochloride |
DE69918157T DE69918157D1 (en) | 1998-11-06 | 1999-10-29 | PREPARATION OF 3-CHLOROMETHYLPYRIDINE HYDROCHLORIDE |
AU64566/99A AU6456699A (en) | 1998-11-06 | 1999-10-29 | Preparation of chloromethylpyridine hydrochlorides |
AT99952196T ATE269308T1 (en) | 1998-11-06 | 1999-10-29 | PRODUCTION OF 3-CHLOROMETHYLPYRIDINE HYDROCHLORIDE |
MXPA01004527A MXPA01004527A (en) | 1998-11-06 | 1999-10-29 | Preparation of chloromethylpyridine hydrochlorides. |
CA002347374A CA2347374C (en) | 1998-11-06 | 1999-10-29 | Preparation of chloromethylpyridine hydrochlorides |
HK02101282.3A HK1039934A1 (en) | 1998-11-06 | 2002-02-21 | Preparation of chloromethylpyridine hydrochlorides |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/187,402 | 1998-11-06 | ||
US09/187,402 US5942625A (en) | 1998-11-06 | 1998-11-06 | Preparation of chloromethylpyridine hydrochlorides |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000027818A1 true WO2000027818A1 (en) | 2000-05-18 |
Family
ID=22688835
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CA1999/001005 WO2000027818A1 (en) | 1998-11-06 | 1999-10-29 | Preparation of chloromethylpyridine hydrochlorides |
Country Status (9)
Country | Link |
---|---|
US (1) | US5942625A (en) |
EP (1) | EP1124803B1 (en) |
AT (1) | ATE269308T1 (en) |
AU (1) | AU6456699A (en) |
CA (1) | CA2347374C (en) |
DE (1) | DE69918157D1 (en) |
HK (1) | HK1039934A1 (en) |
MX (1) | MXPA01004527A (en) |
WO (1) | WO2000027818A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105085377A (en) * | 2015-09-07 | 2015-11-25 | 陈吉美 | Synthetic method of 3-(chloromethyl)pyridine hydrochloride |
CN105085378A (en) * | 2015-09-07 | 2015-11-25 | 陈吉美 | Synthetic method of 4-(chloromethyl)pyridine hydrochloride |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5521316A (en) * | 1994-05-20 | 1996-05-28 | Cytec Technology Corp. | Chloroalkyl pyridinum hydrochloride compounds and processes for their preparation |
-
1998
- 1998-11-06 US US09/187,402 patent/US5942625A/en not_active Expired - Fee Related
-
1999
- 1999-10-29 EP EP99952196A patent/EP1124803B1/en not_active Expired - Lifetime
- 1999-10-29 DE DE69918157T patent/DE69918157D1/en not_active Expired - Lifetime
- 1999-10-29 WO PCT/CA1999/001005 patent/WO2000027818A1/en active IP Right Grant
- 1999-10-29 MX MXPA01004527A patent/MXPA01004527A/en not_active IP Right Cessation
- 1999-10-29 CA CA002347374A patent/CA2347374C/en not_active Expired - Fee Related
- 1999-10-29 AT AT99952196T patent/ATE269308T1/en not_active IP Right Cessation
- 1999-10-29 AU AU64566/99A patent/AU6456699A/en not_active Abandoned
-
2002
- 2002-02-21 HK HK02101282.3A patent/HK1039934A1/en unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5521316A (en) * | 1994-05-20 | 1996-05-28 | Cytec Technology Corp. | Chloroalkyl pyridinum hydrochloride compounds and processes for their preparation |
US5686619A (en) * | 1994-05-20 | 1997-11-11 | Cytec Technology Corp. | Chloroalkyl pyridinium hydrochloride compounds and processes for their preparation |
Non-Patent Citations (4)
Title |
---|
DATABASE XFIRE Beilstein; XP002127562 * |
DATABASE XFIRE Beilstein; XP002127563 * |
DATABASE XFIRE Beilstein; XP002127564 * |
DATABASE XFIRE Beilstein; XP002127565 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105085377A (en) * | 2015-09-07 | 2015-11-25 | 陈吉美 | Synthetic method of 3-(chloromethyl)pyridine hydrochloride |
CN105085378A (en) * | 2015-09-07 | 2015-11-25 | 陈吉美 | Synthetic method of 4-(chloromethyl)pyridine hydrochloride |
Also Published As
Publication number | Publication date |
---|---|
EP1124803A1 (en) | 2001-08-22 |
CA2347374C (en) | 2004-11-23 |
US5942625A (en) | 1999-08-24 |
CA2347374A1 (en) | 2000-05-18 |
AU6456699A (en) | 2000-05-29 |
HK1039934A1 (en) | 2002-05-17 |
DE69918157D1 (en) | 2004-07-22 |
EP1124803B1 (en) | 2004-06-16 |
MXPA01004527A (en) | 2002-09-18 |
ATE269308T1 (en) | 2004-07-15 |
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