CN1329586A - 对氯苯基丙醇衍生物的制备方法 - Google Patents

对氯苯基丙醇衍生物的制备方法 Download PDF

Info

Publication number
CN1329586A
CN1329586A CN99814048A CN99814048A CN1329586A CN 1329586 A CN1329586 A CN 1329586A CN 99814048 A CN99814048 A CN 99814048A CN 99814048 A CN99814048 A CN 99814048A CN 1329586 A CN1329586 A CN 1329586A
Authority
CN
China
Prior art keywords
preparation
compound
reaction
chlorophenyl
processes
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
CN99814048A
Other languages
English (en)
Inventor
松本浩郎
上川路美奈子
堀内贵
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nissan Chemical Corp
Original Assignee
Nissan Chemical Corp
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 Nissan Chemical Corp filed Critical Nissan Chemical Corp
Publication of CN1329586A publication Critical patent/CN1329586A/zh
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
    • C07C17/16—Preparation of halogenated hydrocarbons by replacement by halogens of hydroxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
    • C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
    • C07C29/14—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of a —CHO group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
    • C07C45/511—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups
    • C07C45/512—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups the singly bound functional group being a free hydroxyl group

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Catalysts (AREA)

Abstract

以在氯化四甲基铵存在下将对碘氯苯与烯丙醇进行Pd偶联后再进行还原为特征的醇化合物(1)的制备方法,及以将该法制得的醇化合物(1)进行溴化为特征的化合物(2)的制备方法。

Description

对氯苯基丙醇衍生物的制备方法
技术领域
本发明涉及可作为抗血小板剂的有用中间体的对氯苯基丙醇衍生物的制备方法。
背景技术
式(3)所示化合物是日本专利公开公报107055/95、欧洲专利公开公报No.482208和美国专利No.5314883公报记载的作为抗血小板剂有用的化合物。
Figure A9981404800031
上述专利公报中记载的化合物(3)的制备方法如流程1所示，将化合物(2)和化合物(4)缩合，再与3-吡啶甲基胺反应，然后制成盐酸盐。
                        流程1
Figure A9981404800032
为了获得此溴化合物(2)，原来是经对氯肉桂酸衍生物的方法制备的，但难以抑制双键氢化时的脱氯反应。
                         流程2
因此，我们关注了1984年J.C.S.报告的在氯化四丁基铵等含较大烷基的季铵盐存在下，在较低温度下将对碘氯苯与烯丙醇进行Pd偶联合成化合物(7)的反应(J.Chem.Soc.Commun.，1984，19，1287-1289)，因为如果还原该化合物，可容易地得到需要的醇化合物。然而，在该文献中记载的反应条件下，乙酸钯的用量较多，为1-2mol％，而且，季铵盐价格昂贵、分子量大，不适合于作为工业制备方法(该文献中也讨论了季铵盐的种类，结果选择了氯化四丁基铵)。而且，生成的百分之几支化异构体(化合物(8))及其还原体(9)的混入也是必须解决的问题。
发明的揭示
我们在进行锐意研究的过程中发现，将季铵盐改为氯化四甲基铵而文献记载的其他条件保持不变，反应速度极慢(反应温度：室温)，而反应温度升高到50℃以上则极有效地进行目的反应。其结果，乙酸钯的用量为0.1mol％即可。该反应中约生成6％上述支化异构体，直接进行溴化生成化合物(2)后，与化合物(4)缩合，支化的溴化合物经碱脱溴化氢，不与化合物(4)反应。因而，由Pd偶联生成的支化异构体无需特别进行分离操作。
另外，偶联生成的醛中间体也可进行分离，其结构已确认，但现已实验证明可不经分离而进行下面的反应。即，确认偶联进行后，仅在反应液中加入硼氢化钠即可产生醇化合物(1)。
即，本发明涉及哒嗪酮化合物(式(3))中间体的制备方法，其特征为在氯化四甲基铵存在下，将对碘氯苯与烯丙醇进行Pd偶联后，还原所得的醇化合物(1)，再进行溴化，得到化合物(2)。
Figure A9981404800051
实施发明的最佳状态
化合物(1)的制备方法(Pd偶联反应及还原)
反应中使用的溶剂可为二甲基甲酰胺、二甲基乙酰胺、N-甲基吡咯烷酮、二甲基咪唑啉酮等酰胺，它可单独使用或与甲苯、二甲苯等芳烃等混合使用。使用最廉价的小分子量(即用量少)氯化四甲基铵是本发明的特点，用量为0.5-3倍摩尔，较佳为0.9-1.5倍摩尔。催化剂乙酸钯可减少也是本发明的特点，其量为0.01-0.2mol％，较佳为0.05-0.15mol％。作为碱，要求使用碳酸氢钠或碳酸钠，用量为等摩尔-20倍摩尔，较佳为3-10倍摩尔。反应温度为50-150℃，较佳为50-100℃。
蒸去溶剂后，可用乙酸乙酯或甲苯提取醛化合物，可作为中间体分离出来，但较佳为不经分离直接用于下面的步骤。即用气相色谱法确认醛中间体的生成后，可将反应液冷却于-20～10℃，加入0.25-1倍摩尔(较佳为0.25-0.35倍摩尔)的硼氢化钠，进行反应时间为1小时的还原反应。
化合物(2)的制备方法(溴化反应)
用甲苯、二甲苯等芳烃溶剂，用三溴化磷可进行醇化合物(1)的溴化。三溴化磷的用量为0.3-2倍摩尔，较佳为0.5-1.2倍摩尔，反应温度为50-150℃。
本发明的对氯苯基丙醇衍生物的制备方法是不发生以往方法中产生的脱氯反应的有效方法。偶联时使用的也是钯的用量也在1/10以下。
下面列举实施例对本发明作详细描述，但是并不限于这些实施例。
实施例1 Pd偶联反应和醛的还原
将95.38g(400mmol)对氯碘苯、34.85g(600mmol)烯丙醇、0.089g(0.4mmol)乙酸钯、47.99g(438mmol)氯化四甲基铵和168.2g(2000mmol)碳酸氢钠加入200ml二甲基甲酰胺(DMF)中，该悬浮液的内温控制为50℃，进行加热。连续加热7小时，用气相色谱法确证醛的生成后，冷却至5℃。然后，加入4.54g(120mmol)硼氢化钠，搅拌30分钟后，加入100ml饱和氯化铵溶液、100ml水、200ml甲苯，搅拌1小时。经硅藻土过滤除去不溶物后，分液，水层用200ml甲苯再次提取。合并甲苯层，浓缩后，蒸馏(107℃/1mmHg)，得到63.4g(收率93％)3-对氯苯基-1-丙醇(化合物(1))，为无色油状物。用气相色谱法分析，该产物含6％支化异构体。
实施例2溴化
将66.0g(387mmol)3-对氯苯基-1-丙醇溶于350ml甲苯，滴加溶于50m1甲苯的105g(387mmol)三溴化磷。滴加结束后，反应液的内温上升至90℃，3小时后回到室温。加入1N氢氧化钠水溶液250ml，振摇后静置、分液，水层用150ml甲苯再次提取。合并甲苯层，用150ml饱和食盐水洗涤后，经硅藻土过滤，蒸去溶剂。残渣蒸馏得到目的化合物(2)3-对氯苯基-1-丙基溴75.2g(收率83％)，为无色油状物(85-89℃/0.3mmHg)。
参考例(Pa偶联反应)
将11.9g(0.05mol)对氯碘苯溶于25ml二甲基甲酰胺，加入4.36g(0.075mol)烯丙醇、6.54g(0.06mol)氯化四甲基铵、21.0g(0.25mol)碳酸氢钠、225mg(2mol％)乙酸钯，室温搅拌。6小时后，用气相色谱法分析，为对氯碘苯95.5％，3-对氯苯基-1-丙醇3.8％。将其放置10天，对氯碘苯为3.70％，3-对氯苯基-1-丙醇为88.4％。

Claims (2)

1.醇化合物(1)的制备方法，其特征在于：在氯化四甲基铵存在下将对碘氯苯与烯丙醇进行Pd偶联后，进行还原。
Figure A9981404800021
2.化合物(2)的制备方法，其特征在于：将权利要求1所述制备方法制得的醇化合物(1)进行溴化。
Figure A9981404800022
CN99814048A 1998-12-11 1999-11-29 对氯苯基丙醇衍生物的制备方法 Pending CN1329586A (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP352529/1998 1998-12-11
JP35252998 1998-12-11

Publications (1)

Publication Number Publication Date
CN1329586A true CN1329586A (zh) 2002-01-02

Family

ID=18424696

Family Applications (1)

Application Number Title Priority Date Filing Date
CN99814048A Pending CN1329586A (zh) 1998-12-11 1999-11-29 对氯苯基丙醇衍生物的制备方法

Country Status (16)

Country Link
US (1) US6407298B1 (zh)
EP (1) EP1138660A4 (zh)
JP (1) JP4474773B2 (zh)
KR (1) KR20010086010A (zh)
CN (1) CN1329586A (zh)
AU (1) AU755010B2 (zh)
CA (1) CA2347813A1 (zh)
CZ (1) CZ20011368A3 (zh)
IL (1) IL143665A0 (zh)
NO (1) NO20012811D0 (zh)
NZ (1) NZ511022A (zh)
SK (1) SK6952001A3 (zh)
TW (1) TW538027B (zh)
UA (1) UA52841C2 (zh)
WO (1) WO2000035843A1 (zh)
ZA (1) ZA200103328B (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102757318A (zh) * 2011-04-29 2012-10-31 上海医药工业研究院 一种阿利克伦中间体的制备方法
CN114716296A (zh) * 2022-03-25 2022-07-08 北京大学 一种烷基卤化物的高效卤化合成方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7935173B1 (en) 2010-07-23 2011-05-03 Metals Recovery Technology Inc. Process for recovery of precious metals

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE299187C (zh)
US2184526A (en) * 1937-05-27 1939-12-26 Du Pont Perfume compositions and process of making the same
DE1132914B (de) * 1957-05-09 1962-07-12 Siegfried Ag Verfahren zur Herstellung von Carbaminsaeureestern von Aralkyl-alkoholen
US3487116A (en) * 1966-06-16 1969-12-30 Engelhard Ind Inc Method for hydrogenation of cinnamyl alcohols
US3663626A (en) * 1969-05-01 1972-05-16 Universal Oil Prod Co Hydrogenation of arylaldehydes
SE7407449L (zh) 1973-07-20 1975-01-21 Ciba Geigy Ag
US4070374A (en) * 1975-06-16 1978-01-24 Givaudan Corporation Process for the preparation of aryl substituted aldehydes, ketones and alcohols
JPS5581831A (en) 1978-12-15 1980-06-20 Toray Ind Inc Preparation of propionaldehyde derivative
CA1211754A (en) * 1980-07-09 1986-09-23 David Webb Process for the production of phenyl substituted alcohols
JPS59163336A (ja) * 1983-03-09 1984-09-14 Nippon Petrochem Co Ltd アルデヒドの製造法
FR2623798B1 (fr) 1987-11-26 1990-05-04 Lucien Laboratoires Derives de trifluoromethyl-1 tetralines, leur preparation et leur application pour la synthese de composes presentant des proprietes therapeutiques
DD299186A5 (de) * 1990-10-01 1992-04-02 E.R. Squibb U. Sons,Inc.,Us Phenylen-7-oxabicycloheptyl-substituierte heterocycloamid-prostaglandinanaloga
UA59384C2 (uk) * 1996-12-20 2003-09-15 Пфайзер, Інк. Похідні сульфонамідів та амідів як агоністи простагландину, фармацевтична композиція та способи лікування на їх основі

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102757318A (zh) * 2011-04-29 2012-10-31 上海医药工业研究院 一种阿利克伦中间体的制备方法
CN114716296A (zh) * 2022-03-25 2022-07-08 北京大学 一种烷基卤化物的高效卤化合成方法
CN114716296B (zh) * 2022-03-25 2023-12-12 润药仁智(北京)科技有限公司 一种烷基卤化物的高效卤化合成方法

Also Published As

Publication number Publication date
AU755010B2 (en) 2002-11-28
UA52841C2 (uk) 2003-01-15
KR20010086010A (ko) 2001-09-07
NO20012811L (no) 2001-06-07
TW538027B (en) 2003-06-21
NZ511022A (en) 2002-06-28
EP1138660A4 (en) 2002-10-23
US6407298B1 (en) 2002-06-18
SK6952001A3 (en) 2001-12-03
WO2000035843A1 (fr) 2000-06-22
EP1138660A1 (en) 2001-10-04
IL143665A0 (en) 2002-04-21
ZA200103328B (en) 2001-10-25
AU1411400A (en) 2000-07-03
CZ20011368A3 (cs) 2001-08-15
JP4474773B2 (ja) 2010-06-09
NO20012811D0 (no) 2001-06-07
CA2347813A1 (en) 2000-06-22

Similar Documents

Publication Publication Date Title
Yamamura et al. The reaction of σ-vinylpalladium complexes with alkyllithiums. Stereospecific syntheses of olefins from vinyl halides and alkyllithiums
CA1078864A (fr) Procede de transformation d'un ester d'acide chiral d'alcool secondaire .alpha.-cyane optiquement actif en ester d'acide chiral d'alcool secondaire .alpha.-cyane racemique
CN1329586A (zh) 对氯苯基丙醇衍生物的制备方法
Osawa et al. Mode of enantioface-differentiation in the hydrogenation of 2-alkanone over an asymmetrically modified nickel catalyst
Perez et al. Molybdenum (0)-catalyzed reductive dehalogenation of. alpha.-halo ketones with phenylsilane
US6020517A (en) Process for production of benzonitrile and benzyl alcohol
US3699169A (en) Process for preparation of terpene flavorants
US4118412A (en) Preparation cyano substituted cyclopropane
US4415748A (en) Intermediates for insecticidal synthetic pyrethroids
US3865884A (en) Preparation of orcinol
US6049001A (en) Fluorine-containing carboxylic acid compounds, methods for their production, and chemical processes utilizing the same
US1862000A (en) Preparation of para-phenylphenol
US4547586A (en) Preparation of 2-isopropenyl-or 2-isopropylidenyl-3-hexenoates from chrysanthemic acid esters
Tobe et al. Synthesis of bicyclo [n. 2.1] bridgehead alkenes acetoxy substituted at the opposite bridgehead position
US4329498A (en) Preparation of 6-aminocaproic acid via muconic acid mononitrile
EP0009369B1 (en) Preparation of muconic acid mononitriles and copper(ii)-ammonia reagent therefor
US4277419A (en) Preparation of muconic acid mononitriles and copper(II)-ammonia reagent therefor
CN112961030B (zh) 一种催化合成4-(反-4-烷基环己基)环己酮的方法
US4968844A (en) Process for preparing retinal
DE60110364T2 (de) Verfahren zur Herstellung von 1-(Cyan(aryl)methyl)cyclohexanol
JPS62158238A (ja) ポリフルオロ脂肪族モノおよびポリカルボン酸の分離精製方法
CA1291169C (en) Preparation process of 4-(4-hydroxophenyl)- cyclohaxanol
FR2458529A1 (fr) Procede de preparation d'alcool 3,3-dimethyl-allylique
JPH0371420B2 (zh)
JP3094597B2 (ja) 光学活性なシクロペンテノン類の製造方法

Legal Events

Date Code Title Description
C06 Publication
C10 Entry into substantive examination
PB01 Publication
SE01 Entry into force of request for substantive examination
C02 Deemed withdrawal of patent application after publication (patent law 2001)
WD01 Invention patent application deemed withdrawn after publication