CN1285824A - 制备甲酰咪唑的方法 - Google Patents

制备甲酰咪唑的方法 Download PDF

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Publication number
CN1285824A
CN1285824A CN98813092A CN98813092A CN1285824A CN 1285824 A CN1285824 A CN 1285824A CN 98813092 A CN98813092 A CN 98813092A CN 98813092 A CN98813092 A CN 98813092A CN 1285824 A CN1285824 A CN 1285824A
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Prior art keywords
formula
formylimidazoles
platinum
water
alkaline
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CN98813092A
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Y·贝萨德
J·海韦林
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Lonza AG
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Lonza AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
    • B01J23/54—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals combined with metals, oxides or hydroxides provided for in groups B01J23/02 - B01J23/36
    • B01J23/56—Platinum group metals
    • B01J23/62—Platinum group metals with gallium, indium, thallium, germanium, tin or lead
    • B01J23/622—Platinum group metals with gallium, indium, thallium, germanium, tin or lead with germanium, tin or lead
    • B01J23/628—Platinum group metals with gallium, indium, thallium, germanium, tin or lead with germanium, tin or lead with lead
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
    • B01J23/54—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals combined with metals, oxides or hydroxides provided for in groups B01J23/02 - B01J23/36
    • B01J23/56—Platinum group metals
    • B01J23/64—Platinum group metals with arsenic, antimony, bismuth, vanadium, niobium, tantalum, polonium, chromium, molybdenum, tungsten, manganese, technetium or rhenium
    • B01J23/644—Arsenic, antimony or bismuth
    • B01J23/6447—Bismuth

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Steroid Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Treatment Of Liquids With Adsorbents In General (AREA)
  • Catalysts (AREA)

Abstract

本发明说明羟甲基咪唑催化转化成甲酰咪唑的新方法。所述反应在过氧化物存在下进行。甲酰咪唑是药物的重要中间产物。

Description

制备甲酰咪唑的方法
本发明是关于制备通式(Ⅰ)的甲酰咪唑的新方法式中R1表示烷基，由通式(Ⅱ)的羟甲基咪唑催化氧化而制备，式中R1如上面给出的含义。
甲酰咪唑是制备药物等，例如利尿剂或降压药重要的中间产物(WO-A-92/20651)。以前已经知道制备甲酰咪唑的几种方法。CH-A-685496中介绍一种方法，其中羟甲基咪唑催化氧化成甲酰咪唑，在活性炭载贵金属，例如铂铋、铂黑、铂或钯存在下，用氧吹入法进行。
因此，本发明的任务是提供制备甲酰咪唑的实用改进方法。
本发明中，该任务由权利要求1中限定的方法完成。
权利要求1中，通式(Ⅱ)的羟甲基咪唑，式中R1有上面给出的含义，在贵金属催化剂和过氧化物存在下催化氧化成通式(Ⅰ)的甲酰咪唑式中R1有上面给出的含义。
R1为氢或烷基，更具体地说，是含有1-6个C原子的直链或支链烷基。R1具体可以是甲基、乙基、丙基、异丙基、丁基、异丁基、叔丁基、戊基或其异构体，以及己基或其异构体。优选的R1含义是丁基。
羟甲基咪唑可以和例如WO-A-92/20651中或E.F.Godefroi等在Trav.Chim.Receuil Pays-Bas，91，1383(1972)中说明的起始化合物那样容易地制备。
铂、钯、铑或金可以用作贵金属催化剂。所述贵金属适合与作为第二组分的金属，例如铋、铅、铈或铟共同使用。优选的催化剂是铂/铋或铂/铅。
所述贵金属催化剂本身可以使用，或与载体结合，例如活性炭、二氧化硅、氧化铝、二氧化硅-铝、二氧化锆或二氧化钛。所述贵金属优选结合在活性炭上。
结合在活性炭上的贵金属催化剂市场上可以购得，例如从Degussa得到。
结合在载体上的贵金属合适百分比是载体物质的0.1-15％(重量)，优选0.5-7％(重量)。
所述贵金属催化剂优选使用量是羟甲基咪唑的0.05-1.0％(摩尔)，特别优选使用量是羟甲基咪唑的0.1-0.4％(摩尔)。
有机或无机过氧化物可用作过氧化物使用。例如，过氧化氢、过硼酸盐、过羧酸、叔丁基氢过氧化物、异丙苯氢过氧化物、过苯甲酸、间氯过苯甲酸、单过氧邻苯二甲酸或过乙酸较宜。以10％-30％水溶液形式使用的过氧化氢是特别合适的。
所述催化氧化适合在碱性介质中，在水，水混溶溶剂或其混合物存在下进行。
特别合适的水混溶溶剂是例如含有1-6个C原子的醇或羧酸、或酮，例如丙酮或甲乙酮。
优选使用水和水混溶溶剂的混合物。已经证明如果通过适当加入碱性氢氧化物、碱性碳酸盐或碱性乙酸盐将使用的水调至碱性是有利的。使用的碱性氢氧化物与通式Ⅱ羟甲基咪唑的摩尔比优选是1∶0.05-5，更优选1∶1-3。
所述催化氧化适合在温度20°-120℃，优选在50°-80℃下进行。
在标准过氧化物加入时间2-3小时后，在足够的二级反应时间后，通式Ⅰ的化合物可以用一般方法分离出。
所述产物通过适当结晶和过滤分离。使用的催化剂可以使用几次而活性不损失。
实施例
实施例1
4〔(2-丁基-5-甲酰基-1H-咪唑-1-基)甲基〕苯甲酸的制备
在室温下将9.5g(33mmol)4-〔(2-丁基-5-羟甲基-1H-咪唑-1-基)甲基〕苯甲酸，40ml水，10ml甲醇，4.2g(105mmol)NaOH和0.92g活性炭载5％铂和5％铋(含有60％水)放入100ml烧瓶中，加热至60℃。60℃下60分钟内向该悬浮液中加入6.6 g(39mmol)20％H2O2水溶液，混合物用HPLC转化。60分钟内再加入6.6g(39mmol)20％H2O2水溶液。然后20分钟内加入1.7g(10mmol)20％H2O2水溶液(转化率＞90％)。将混合物冷却至室温。在用17.6mlHCl(15％)酸化至pH6.0后，产物沉淀。将产物冷却至2℃，过滤，用2×20ml水洗涤，室温和15mbar下干燥。得到7.2g(70％)黄色的4-〔(2-丁基-5-甲酰基-1H-咪唑-1-基)甲基〕苯甲酸(HPLC含量95％)。
熔点：144-146℃
1H-NMR(DMSO-d6，400MHz)δ：12.9(1H，s)；
                            9.65(1H，s)；
                            7.94(1H，s)；
                            7.90 (2H，d)；
                            7.11 (2H，d)；
                            5.65 (2H，s)；
                            2.63 (2H，t)；
                            1.54 (2H，pent)；
                            1.36 (2H，hex)；
                            0.79 (3H，t) 。

Claims (7)

1．制备通式(Ⅰ)甲酰咪唑的方法，式中R1是C1-6烷基，包括在贵金属催化剂存在下，将通式(Ⅱ)羟甲基咪唑催化氧化，式中R1同上述定义，其中所述催化氧化用过氧化物进行。
2．根据权利要求1的方法，其中R1是丁基。
3．根据权利要求1或2的方法，其中所述贵金属催化剂是铂/铋催化剂或铂/铅催化剂。
4．根据权利要求1-3的方法，其中过氧化物是过氧化氢。
5．根据权利要求1-4的方法，其中所述催化氧化在碱性介质中在水，水混溶性溶剂或其混合物存在下进行。
6．根据权利要求5的方法，其中所述碱性介质通过将碱性氢氧化物、碱性碳酸盐或碱性乙酸盐加入反应混合物中得到。
7．根据权利要求1-6的方法，其中反应在温度20°-120℃下进行。
CN98813092A 1997-11-14 1998-11-10 制备甲酰咪唑的方法 Pending CN1285824A (zh)

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CH2638/1997 1997-11-14
CH263897 1997-11-14
CH273897 1997-11-27
CH2738/1997 1997-11-27

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JP (1) JP4418104B2 (zh)
KR (1) KR100550204B1 (zh)
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AR (1) AR016678A1 (zh)
AT (1) ATE376544T1 (zh)
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IL (1) IL136026A0 (zh)
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111978257A (zh) * 2020-08-26 2020-11-24 武汉药明康德新药开发有限公司 含有醛基和羧基的1-甲基芳烃-1h-咪唑系列化合物的合成方法

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WO1999065879A1 (en) * 1998-06-15 1999-12-23 Lonza Ag Procedure for producing formyl imidazoles

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US5336779A (en) * 1992-10-08 1994-08-09 Nippon Gohsei Kagaku Kogyo Kabushiki Kaisha Method of producing formylimidazoles
KR100587187B1 (ko) * 1997-10-29 2006-10-24 론자 아게 포르밀이미다졸의제조방법

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111978257A (zh) * 2020-08-26 2020-11-24 武汉药明康德新药开发有限公司 含有醛基和羧基的1-甲基芳烃-1h-咪唑系列化合物的合成方法

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AU743105B2 (en) 2002-01-17
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CA2309856C (en) 2009-05-19
HK1034064A1 (en) 2001-10-12
KR20010032089A (ko) 2001-04-16
EP1051401B1 (en) 2007-10-24
HUP0004950A3 (en) 2002-01-28
DE69838624T2 (de) 2008-07-24
EP1051401A1 (en) 2000-11-15
JP2001523668A (ja) 2001-11-27
WO1999025696A1 (en) 1999-05-27
DE69838624D1 (de) 2007-12-06
DK1051401T3 (da) 2007-12-27
TR200001349T2 (tr) 2001-01-22
NO20002476L (no) 2000-05-12
ES2296348T3 (es) 2008-04-16
CA2309856A1 (en) 1999-05-27
IN190803B (zh) 2003-08-23
HUP0004950A2 (hu) 2001-11-28
TW480251B (en) 2002-03-21
CY1108524T1 (el) 2014-04-09
AU1338499A (en) 1999-06-07
IL136026A0 (en) 2001-05-20
NO315466B1 (no) 2003-09-08
BR9814174A (pt) 2000-09-26
NO20002476D0 (no) 2000-05-12
PL340497A1 (en) 2001-02-12
JP4418104B2 (ja) 2010-02-17
PT1051401E (pt) 2007-12-24
AR016678A1 (es) 2001-07-25
ATE376544T1 (de) 2007-11-15
KR100550204B1 (ko) 2006-02-08

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