WO1992013840A1 - PROCEDE DE PRODUCTION D'AMINOMETHYLPYRIDINES α-CHLOREES - Google Patents

PROCEDE DE PRODUCTION D'AMINOMETHYLPYRIDINES α-CHLOREES Download PDF

Info

Publication number
WO1992013840A1
WO1992013840A1 PCT/JP1992/000094 JP9200094W WO9213840A1 WO 1992013840 A1 WO1992013840 A1 WO 1992013840A1 JP 9200094 W JP9200094 W JP 9200094W WO 9213840 A1 WO9213840 A1 WO 9213840A1
Authority
WO
WIPO (PCT)
Prior art keywords
chlorine atom
reaction
catalytic reduction
present
reduction reaction
Prior art date
Application number
PCT/JP1992/000094
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
Toshinari Nabata
Original Assignee
Koei Chemical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Koei Chemical Co., Ltd. filed Critical Koei Chemical Co., Ltd.
Priority to DE4290290A priority Critical patent/DE4290290C2/de
Priority to US07/927,425 priority patent/US5300650A/en
Publication of WO1992013840A1 publication Critical patent/WO1992013840A1/ja

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
    • C07D213/60—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
    • C07D213/61—Halogen atoms or nitro radicals

Definitions

  • the present invention relates to a method for producing aminomethylpyridines having a chlorine atom at the tertiary position.
  • Aminomethylpyridines having a chlorine atom at the ⁇ -position are useful compounds as raw materials for synthesis of pharmaceuticals, agricultural chemicals and the like.
  • a method for producing an aminomethylpyridin having a chlorine atom at the tertiary position includes, for example, 6-chloro-3-cyanopyridin prepared by adding ammonia, water,
  • 6-chloro-3-cyanopyridin prepared by adding ammonia, water
  • there is known a method of producing a 6-cyclo-3-aminoaminopyridin by a catalytic reduction reaction using Raney nickel in the presence of an organic solvent West German Patent Publication). No. 37 2 6 9 3 3).
  • the yield of the target product is about 50%, and it cannot be said that the yield is necessarily high. It is hard to be satisfied.
  • An object of the present invention is to produce aminomethylpyridines having a chlorine atom at the ⁇ -position in a better yield than the conventional method.
  • the idea is to provide a way. Means for solving the problem
  • the present inventor focused on aminomethyl pyridine (see Comparative Example described later) that is produced in large amounts by the conventional method.
  • the chlorine atom bonded to the position of the pyridin nucleus has high activity, and therefore, the by-product aminomethylpyridine is produced as a result of the dechlorination of the high-order chlorine atom under the conditions of catalytic reduction reaction. It was speculated that this would be done.
  • the present inventor has conducted intensive research on a method for suppressing such a dechlorination reaction, and surprisingly, hydrogenating cyanopyridines having a chlorine atom at the ⁇ -position of the starting material in a nonaqueous reaction system.
  • the catalytic reduction reaction is carried out in the presence of a catalyst, the dechlorination of the chlorine atom at the position is suppressed, and other side reactions are also suppressed.
  • the present inventors have found that the yield of pyridines is improved, and have completed the present invention.
  • the present inventor has found that when a tertiary amine is present in the reaction system and a catalytic reduction reaction of cyano pyridines having a chlorine atom at the position is performed, the ⁇ -position is obtained.
  • the dechlorination reaction of chlorine atoms and other side reactions are more favorably suppressed, and the yield of aminomethyl pyridines having a chlorine atom at the ⁇ -position, which is the target product, is further improved.
  • the inventors have found that the present invention has been completed and completed the present invention.
  • the present invention has a chlorine atom at the ⁇ -position
  • the catalytic reduction reaction of the cyanopyridines in the presence of a hydrogenation catalyst to produce the desired aminomethylpyridine having a chlorine atom at the l-position A method for producing aminomethylpyridines having a chlorine atom at the position, and a chlorine atom at the position, characterized in that the cyanopyridine is subjected to a catalytic reduction reaction in a water reaction system.
  • the present invention relates to a method for producing aminomethylpyridines having a chlorine atom at the ⁇ -position, characterized by causing a catalytic reduction reaction of the cyanopyridines by causing the cyanopyridines to be present in a reaction system.
  • Examples of the cyanopyridines having a chlorine atom at the tertiary position which are used as starting materials in the production method of the present invention include: 21-clauric 13-cyanopyridine, 6-chloro Mouth 3 — Cyanobilizine, 2 — Black Mouth 4 — Cyanopyridine, 2 — Chlorine 6 — Cyanopyridine
  • General formula (I) such as Lorcia Noviline
  • R represents an alkyl group.
  • ⁇ represents 0, 1, or 2.
  • the non-aqueous reaction system in the present invention includes a reaction system in which water does not exist at all and a reaction system in which water exists within a range that does not inhibit the object of the present invention.
  • the solvent used in the production method of the present invention is a non-aqueous solvent and includes alcohols such as methanol and ethanol; carbonizations such as benzene, toluene and cyclohexane. Hydrogen; cyclic ethers such as tetrahydrofuran and dioxane; and the like.
  • alcohol solvents are preferred in view of the yield of the desired product.
  • the solvent is preferably used in an amount ranging from 1 to 5 times (weight) the amount of the starting cyanopyridines having a chlorine atom at the a-position.
  • the tertiary amines used in the production method of the present invention include tritylamine, triethylenamine, tributylamine, diisopropylethylamine, tetramethylethylamine.
  • Aliphatic tertiary amines such as rangeamine, tetramethylhexanemethylenamine and aromatic tertiary amines such as N, N'-dimethylbenzylamine
  • a heterocyclic compound such as N-methylpyrrolidin may be mentioned.
  • aliphatic tertiary amines are preferred in view of the yield of the desired product.
  • the tertiary amine is preferably used in an amount ranging from 1 to 20% by weight of the cyanopyridine having a chlorine atom at the starting position.
  • performing a catalytic reduction reaction in the presence of an ammonia in the reaction system means that the target product produced in the reaction system is an aminomethyl pyridine having a chlorine atom at the octyl position. It is effective in suppressing the undesired dimerization reaction of amines.
  • Ammonia is preferably used in an amount ranging from 20 to 200% by weight based on the starting material, cyanopyridines having a chlorine atom at the tertiary position. It is effective to use the same amount as in consideration of the reaction efficiency.
  • Examples of the hydrogenation catalyst used in the production method of the present invention include catalysts generally used for catalytic reduction reactions. Specific examples thereof include Raney nickel, Raney cobalt, etc. , And ⁇ ,. Noble metal catalysts such as radium-carbon, ruthenium-carbon, rhodium-carbon, platinum-carbon and the like are listed. Raney nickel is particularly preferred in view of yield.
  • the use of a large amount of the catalyst promotes the catalytic reduction reaction, but also promotes the dechlorination reaction. Therefore, the preferred amount of the catalyst to be used is a cyano catalyst having a chlorine atom at the starting material. The amount is in the range of 1 to 30% by weight based on the weight of the pyridine.
  • reaction temperature employed in the production method of the present invention is relatively low to control the dechlorination reaction.
  • the preferred reaction temperature is 0 to 60, more preferably 20 to 50 ° C in view of the reaction rate.
  • starting materials such as cyanopyridines having a chlorine atom at the ⁇ -position, a hydrogenation catalyst, a non-aqueous solvent and, if desired, a tertiary amine and ammonia are used.
  • a method is adopted in which the reaction is performed by charging the high-pressure reactor and raising the temperature to introduce hydrogen that is consumed as needed.
  • a cyanopyridine having a chlorine atom at the ⁇ -position which is a starting substance dissolved in a non-aqueous solvent
  • a reaction system in a preferred embodiment of the present invention.
  • starting materials were charged with cyano pyridines having a chlorine atom at the position of the starting material, a non-aqueous solvent, a tertiary amine, and a hydrogenation catalyst in an autoclave, and then charged with ammonia.
  • the temperature is gradually increased while introducing hydrogen, and the reaction is continued while supplying hydrogen at normal pressure or more preferably at 3 to 10 atm while maintaining the above-mentioned reaction temperature.
  • the starting material, cyanopyridine having a chlorine atom at the ⁇ -position is completely consumed and the reaction is completed. But like this Even under the reaction pressure, the catalytic reduction reaction of the present invention can achieve the object of the present invention.
  • Example 1 Separation and purification of the desired product, aminomethylpyridine having a chlorine atom at the ⁇ -position, produced by the production method of the present invention are carried out by filtering the catalyst from the reaction solution, distilling off the solvent, and then distilling the solvent. It can be done more easily.
  • Example 1 will be described more specifically with reference to the following examples, but the present invention is not limited to these examples.
  • Example 4 The reaction and after-treatment were carried out in the same manner as in Example 1 except that 5 g of triethylamine was coexisted, and 80.6 g (yield of 6-chloro-3-aminoaminopyridine) was obtained. 78.3%) and 3.2 g of 3-15 picolinylamine (4.1% yield).
  • Example 4
  • Example 2 Same as in Example 1 except that triisopropylamine was replaced by diisopropylpropylamine as a tertiary amine.
  • the starting material is used in a non-aqueous reaction system.
  • Canopyridines having a chlorine atom at a certain ⁇ -position are subjected to a catalytic reduction reaction, and are useful target substances as starting materials for pharmaceuticals, agricultural chemicals, etc., and intermediates. It is possible to produce aminotyl pyridines with a higher yield than the conventional method.
  • a tertiary amine is present in the reaction system, and the starting material, a cyanopyridine having a chlorine atom at the ⁇ -position, is subjected to a catalytic reduction reaction to have a chlorine atom at the target position. It is possible to produce aminotyl pyridines with higher yield than the conventional method.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
PCT/JP1992/000094 1991-02-04 1992-01-31 PROCEDE DE PRODUCTION D'AMINOMETHYLPYRIDINES α-CHLOREES WO1992013840A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
DE4290290A DE4290290C2 (de) 1991-02-04 1992-01-31 Verfahren zur Herstellung von 2-Chlor-5-aminomethylpyridin
US07/927,425 US5300650A (en) 1991-02-04 1992-01-31 Process for producing aminomethylpyridine having a chlorine atom at α-

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP3035598A JP3031727B2 (ja) 1991-02-04 1991-02-04 α位に塩素原子を有するアミノメチルピリジン類の製造方法
JP3/35598 1991-02-04

Publications (1)

Publication Number Publication Date
WO1992013840A1 true WO1992013840A1 (fr) 1992-08-20

Family

ID=12446253

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1992/000094 WO1992013840A1 (fr) 1991-02-04 1992-01-31 PROCEDE DE PRODUCTION D'AMINOMETHYLPYRIDINES α-CHLOREES

Country Status (4)

Country Link
US (1) US5300650A (en, 2012)
JP (1) JP3031727B2 (en, 2012)
DE (2) DE4290290T1 (en, 2012)
WO (1) WO1992013840A1 (en, 2012)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5453506A (en) * 1992-07-06 1995-09-26 Bayer Aktiengesellschaft Process for the preparation of 2-chloro-5-aminomethyl-pyridine
US5744608A (en) * 1995-09-08 1998-04-28 Nippon Soda Co., Ltd. Method for manufacturing 3-(aminomethyl)-6-chloropyridines

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3098099B2 (ja) 1992-04-17 2000-10-10 広栄化学工業株式会社 ハロゲン化ピリジンカルバルデヒド誘導体及びその製造方法
DE4423353A1 (de) 1994-07-04 1996-01-11 Bayer Ag Verfahren zur Herstellung N-acylierter 2-Chlor-5-aminomethylpyridine
US6239280B1 (en) 1999-06-30 2001-05-29 Merck & Co., Inc. Process for synthesizing biaryl inhibitors of farnesyl-protein transferase
BR0113259B1 (pt) * 2000-08-25 2014-09-02 Bayer Cropscience Sa Processo para a preparação de um composto 2-aminometilpiridina de fórmula (I)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4924969A (en, 2012) * 1972-06-30 1974-03-05

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4123537A (en) 1977-05-26 1978-10-31 Merck & Co., Inc. 2-Halo-4-aminomethyl-6-alkyl-3-pyridinols useful as diuretics in treating hypertension and edema
DE3726993A1 (de) 1987-08-13 1989-02-23 Bayer Ag Verfahren zur herstellung von 2-chlor-5-aminomethylpyridin
DE3911224A1 (de) * 1989-04-07 1990-10-11 Bayer Ag Verfahren zur herstellung von 2-chlor-5-aminomethylpyridin
DE4028047A1 (de) * 1990-09-05 1992-03-12 Bayer Ag Verfahren zur herstellung von n-(2-chlor-pyridin-5-yl-methyl)-ethylendiamin
DE4222152A1 (de) * 1992-07-06 1994-01-13 Bayer Ag Verfahren zur Herstellung von 2-Chlor-5-aminomethyl-pyridin

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4924969A (en, 2012) * 1972-06-30 1974-03-05

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5453506A (en) * 1992-07-06 1995-09-26 Bayer Aktiengesellschaft Process for the preparation of 2-chloro-5-aminomethyl-pyridine
US5744608A (en) * 1995-09-08 1998-04-28 Nippon Soda Co., Ltd. Method for manufacturing 3-(aminomethyl)-6-chloropyridines

Also Published As

Publication number Publication date
JP3031727B2 (ja) 2000-04-10
US5300650A (en) 1994-04-05
DE4290290T1 (en, 2012) 1993-01-28
DE4290290C2 (de) 1998-04-30
JPH04247069A (ja) 1992-09-03

Similar Documents

Publication Publication Date Title
WO1992013840A1 (fr) PROCEDE DE PRODUCTION D'AMINOMETHYLPYRIDINES α-CHLOREES
JP3208298B2 (ja) ３−（テトラヒドロフリル）メチルアミンの製造法
JP3205648B2 (ja) ２−クロロ−５−アミノメチルピリジンの製造法
JPS60156638A (ja) バルプロ酸の製造方法
JP3123815B2 (ja) ２−クロロ−５−クロロメチルピリジン及び／又は２−クロロ−５−ジクロロメチルピリジンの製造方法
JP4409057B2 (ja) ベンゼンジメタノール化合物の製造方法
JPH07138209A (ja) 含ハロゲンアミノメチル化合物の製造法
JP3149989B2 (ja) ２−クロロ−５−置換アミノメチルピリジン類の製法
JP2851274B2 (ja) Ｎ，ｎ−ジイソプロピルエチルアミンの製造法
JP4378488B2 (ja) ２−アミノメチルピリミジン及びその塩の製造法
KR20030013478A (ko) 벤젠디메탄올 화합물의 제조방법
JP3098100B2 (ja) ２−クロロ−５−アミノメチルピリジン類の製造方法
JP3959178B2 (ja) ヒドラジン誘導体の製造方法、その中間体および中間体の製造方法
JPS61251663A (ja) アミノメチルピリジンの製造法
JP2815636B2 (ja) ２‐アミノメチルピラジン類および／または２‐アミノメチルピペラジン類の製造法
JPH10101646A (ja) アミノメチルピリジン化合物の製造法
JP2944793B2 (ja) アミンの製造方法
JPH0616636A (ja) ６−クロロ−３−ピリジルメチルアミン類の製造方法
US9029547B1 (en) Synthesis of 4-aryl 4-acyl piperidine, its salts and analogs using indium metal
JPS6396166A (ja) 芳香族ヒドラゾ化合物の製造法
JPS61251659A (ja) ２−又は３−アミノメチルピペリジンの製造法
JP2004026754A (ja) アミノメチルピリジン化合物の製造方法
JPH05286935A (ja) ２−クロロ−５−置換アミノメチルピリジン類の製造方法
JP2003238499A (ja) ベンジルアミン類の製造方法
JPH08109170A (ja) ヘキサヒドロピリダジンの製造方法

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): DE US

RET De translation (de og part 6b)

Ref document number: 4290290

Country of ref document: DE

Date of ref document: 19930128

WWE Wipo information: entry into national phase

Ref document number: 4290290

Country of ref document: DE