CN1046708C - 2,3,5,6－四氯吡啶的制备 - Google Patents

2,3,5,6－四氯吡啶的制备 Download PDF

Info

Publication number
CN1046708C
CN1046708C CN94193818A CN94193818A CN1046708C CN 1046708 C CN1046708 C CN 1046708C CN 94193818 A CN94193818 A CN 94193818A CN 94193818 A CN94193818 A CN 94193818A CN 1046708 C CN1046708 C CN 1046708C
Authority
CN
China
Prior art keywords
chloro
butyric acid
solvent
temperature
cyano butyric
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.)
Expired - Fee Related
Application number
CN94193818A
Other languages
English (en)
Other versions
CN1133037A (zh
Inventor
Y·施沃
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.)
LIMADELT CO
Original Assignee
LIMADELT CO
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 LIMADELT CO filed Critical LIMADELT CO
Publication of CN1133037A publication Critical patent/CN1133037A/zh
Application granted granted Critical
Publication of CN1046708C publication Critical patent/CN1046708C/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

一种新的、简单而高产率的制备2，3，5，6-四氯吡啶的方法，包括在催化量的氯化氢存在下和任选在质子惰性溶剂存在下，必要时在升高的压力下，使2，2，4-三氯-4-氰基丁酸酯与过量的磷酰氯在100-160℃，优选120-140℃的温度下反应约5-10小时。

Description

2,3,5,6-四氯吡啶的制备
本发明涉及制备2,3,5,6-四氢吡啶(也称为Symtet)的改良的新方法。
2,3,5,6-四氯吡啶在各种除草剂、杀真菌剂和杀虫剂(例如重要的杀虫剂0,0-二乙基-3,5,6-三氯-2-吡啶基硫代磷酸酯)的制备中用作中间体。
对于2,3,5,6-四氯吡啶的制备，已知有各种方法。例如它可通过β-甲基吡啶(US专利4,483,993)或吡啶(US专利4,515,953)的液相氯化或通过2-氯吡啶或2,6-二氯吡啶(US专利3,251,848)的气相氯化来制备。
以色列专利61581描述了一种方法，其中通过用各种金属作催化剂在约170℃使三氯乙酰氯和丙烯腈在溶剂中反应，得到2,3,5,6-四氯吡啶和3,5,6-三氯吡啶-2-醇的混合物(没报告收率)。
欧洲专利申请0 030 215描述了3,3,5-三氯戊二酸酰亚胺的制备，随后用脱水剂如POCl3将其转化成2,3,5,6-四氯吡啶。
不可预料地，我们已发现了2,2,4-三氯-4-氰基丁酸酯(例如乙酯)如下列反应式所示，经历一步被转化成2,3,5,6-四氯吡啶：
Figure C9419381800031
其中R是烷基、芳烷基或芳基。
本文所用的“芳基”意指可任意用低级烷基和或卤素取代的C6-C10芳烃基。本文所用的“芳烷基”意指用上述定义的芳基取代的C1-C6烷基。
本发明新的和明显简单的转化导致2,3,5,6-四氯吡啶的60-90％的收率，取决于R的化学性质。该反应用易得的常用物质POCl3，在催化量的氯化氢存在下，在100-160℃，优选120-140℃的温度下进行。在优选的温度范围，反应时间为5-10小时。POCl3与2,2,4-三氯-4-氰基-丁酸酯的摩尔比为10∶1至1∶1，优选的范围为2∶1至3∶1。如果使用高比率时，建议在反应结束时蒸馏出过量的POCl3，再循环使用。反应完成后，蒸去过量的POCl3，向残余物中加入水，用有机溶剂提取，得2,3,5,6-四氯吡啶粗产物。通过常规方法如升华、结晶或水蒸汽蒸馏，得到纯产物。得到的纯产物m.p.为89-90℃；1H-NMR(CDCl3):δ7.88ppm(单峰)。经分析在所有方面均与标准样品2,3,5,6-四氯吡啶一致。
推荐以合并的反应物和溶剂总重量的0.5-5％的量使用干燥的HCl气体，优选的使用量为1.5-3％。就反应进行时产物HCl这个意义上讲，此反应是自动催化的。
反应也可以在非质子传递的和非反应性的溶剂(如芳烃和脂肪烃及卤代烃)存在下进行，而不严重影响反应效率。
按照本领域已知的方法可容易地制备上述式Ⅰ的原料，即2,2,4-三氯-4-氰基丁酸乙酯和2,2,4-三氯-4-氰基丁酸的其它酯。所述已知方法描述于化学文献中，例如：J.Org.Chem,Vol.29,PP2104-5(1964)；Tetrahedron,Vol.29,PP.827-832(1973)；J.Org.Chem.,Vol.41,PP396-398(1976)；和US 5,017,705。
本发明描述的方法的简单性使其完全可用于大规模生产。用低级烷基酯获得的高产率使本发明方法从经济的观点看具有吸吲力。尽管必须使用过量的POCl3，但其80％可被回收并循环使用。本发明方法也是经济合理的，因为在本高产率反应中的主要副产物是磷酸和其酯(后者可水解成前者)。
下面通过非限定性的实施例更详细描述本发明。实施例1
将2,2,4-三氯-4-氰基丁酸乙酯(12.0g)和磷酸氯(40ml)和干燥的HCl气体放入密封的玻璃反应器中，反应器浸入140℃的热调节的油浴中。在该温度10小时后，反应器冷却至室温，并在106℃蒸出挥发物得POCl3 32ml。向蒸馏残余物中加入碎冰，该浆液搅拌15分钟，然后用二氯甲烷提取。蒸去二氯甲烷，残余物在30-35℃/0.2mmHg升华，得白色结晶性固体，2,3,5,6-四氯吡啶，重9.6g(90.6％产率)，m.p.88-90℃。实施例2
如上所述重复实施例1，但在140℃的加热时间减少至5小时，升华后得到的2,3,4,6-四氯吡啶是7.2g(68％产率)。实施例3
将2,2,4-三氯-4-氰基丁酸苯酯(12.0g)、磷酰氯(40ml)和干燥氯化氢气体(1.4g)于140℃加热10小时。得到的反应混合物按实施例1所述进行后处理。回收33ml POCl3。升华的产物2,3,5,6-四氯吡啶重5.34g(60％产率)。实施例4
如上所述重复实施例3，但反应温度降至110℃且反应时间减少至5小时。蒸发二氯甲烷溶液，称重并用内标法经GLC分析。结果表明2,3,5,6-四氯吡啶的产率为62％。实施例5
将2,2,4-三氯-4-氰基丁酸丁酯(12g)、磷酰氯(40ml)和干燥氯化氢气体(1.6g)在140℃加热10小时，得到的反应混合物按实施例1所述进行后处理，回收到32ml POCl3。后处理得到的二氯甲烷溶液用GLC内标法分析。分析表明2,3,5,6-四氯吡啶的产率为62％。实施例6
将2,2,4-三氯-4-氰基丁酸对甲苯基酯(12g)、磷酰氯(40ml)和干燥的氯化氢气(1.6g)于140℃加热10小时。冷却至室温后加入冰。将水浆液进行水蒸汽蒸馏，从水蒸馏液中滤出白色固体，在60℃真空干燥至恒重。干燥的固体，2,3,5,6-四氯吡啶的m.p.为87-88℃，重6.03g(71％产率)。实施例7
将2,2,4-三氯-4-氰基丁酸甲酯(12g)、磷酰氯(16.5ml)和二甲苯(16ml)放入玻璃管反应器中，并用干燥HCl气加压至4个大气压，然后在140℃加热10小时，压力逐渐增加至20个大气压。得到的冷却的反应混合物注入冷水中，进行水蒸汽蒸馏。分离出蒸馏液的有机相，测定2,3,5,6-四氯吡啶(HPLC),9.4g(83％产率)。实施例8
重复实施例7，但用同体积的环己烷代替二甲苯。得到的冷却的反应混合物注入冷水中，分离有机相。水相用2×15ml热环己烷提取。合并的有机相用碳酸钠溶液和水洗，并测定2,3,4,6-四氯吡啶(HPLC),9.06g(80％产率)。实施例9
重复实施例8，但用同体积的1,2-二氯乙烷代替环己烷，按实施例8处理反应混合物后，得2,3,5,6-四氯吡啶8.8g(78％产率)。实施例10
按实施例7所述，处理2,2,4-三氯-4-氰基丁酸甲酯(12g)和磷酰氯(20g)的混合物。冷却至70℃后，将该稠的黑色反应混合物倒入冷水中，得到的浆液水蒸汽蒸馏，得白色结晶性固体，2,3,5,6-四氯吡啶干燥后重8.9g(79％产率)。

Claims (8)

1．一种制备2,3,5,6-四氯吡啶的方法，它包括在催化量的氯化氢存在下和任选在质子惰性溶剂存在下，任选在升高的压力下，使通式Ⅰ的2,2,4-三氯-4-氰基丁酸酯与过量的磷酰氯在100-160℃的温度下反应5-10小时，
Figure C9419381800021
其中R是烷基、芳基或芳烷基。
2．权利要求1的方法，其中R是C1-C6烷基。
3．权利要求1的方法，其中所述酯是2,2,4-三氯-4-氰基丁酸乙酯。
4．权利要求1-3中任一权利要求的方法，其中POCl3与2,2,4-三氯-4-氰基丁酸酯的摩尔比为10∶1至1∶1。
5．权利要求4的方法，其中所述的摩尔比为2∶1至3∶1。
6．权利要求1-3中任一权利要求的方法，在质子惰性的溶剂中实施。
7．权利要求6的方法，其中所述溶剂选自芳烃、脂肪烃和卤代烃。
8．权利要求1的方法，其中所述反应在120-140℃的温度下进行。
CN94193818A 1993-09-03 1994-09-02 2,3,5,6－四氯吡啶的制备 Expired - Fee Related CN1046708C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IL10690193A IL106901A (en) 1993-09-03 1993-09-03 Production of 2,3,5,6-tetrachloropyridine
IL106901 1993-09-03

Publications (2)

Publication Number Publication Date
CN1133037A CN1133037A (zh) 1996-10-09
CN1046708C true CN1046708C (zh) 1999-11-24

Family

ID=11065237

Family Applications (1)

Application Number Title Priority Date Filing Date
CN94193818A Expired - Fee Related CN1046708C (zh) 1993-09-03 1994-09-02 2,3,5,6－四氯吡啶的制备

Country Status (16)

Country Link
EP (1) EP0716651B1 (zh)
JP (1) JP3463937B2 (zh)
KR (1) KR100201803B1 (zh)
CN (1) CN1046708C (zh)
AU (1) AU675005B2 (zh)
BR (1) BR9407392A (zh)
CA (1) CA2170778C (zh)
ES (1) ES2111333T3 (zh)
GR (1) GR3026170T3 (zh)
HU (1) HU214023B (zh)
IL (1) IL106901A (zh)
NZ (1) NZ273780A (zh)
RO (1) RO115257B1 (zh)
TW (1) TW265334B (zh)
WO (1) WO1995006639A1 (zh)
ZA (1) ZA946440B (zh)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5688953A (en) * 1996-07-31 1997-11-18 Dowelanco Process for the preparation of 3,3,5-trichloroglutarimide

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4327216A (en) * 1979-11-30 1982-04-27 Ciba-Geigy Corporation Process for producing 2,3,5,6-tetrachloropyridine and 3,5,6-trichloropyridin-2-ol
US4360676A (en) * 1979-11-30 1982-11-23 Ciba-Geigy Corporation 3,3,5-Trichloroglutaric acid imide

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3251848A (en) * 1963-11-12 1966-05-17 Dow Chemical Co Vapor phase production of 2-chloropyridine and 2, 6-dichloropyridine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4327216A (en) * 1979-11-30 1982-04-27 Ciba-Geigy Corporation Process for producing 2,3,5,6-tetrachloropyridine and 3,5,6-trichloropyridin-2-ol
US4360676A (en) * 1979-11-30 1982-11-23 Ciba-Geigy Corporation 3,3,5-Trichloroglutaric acid imide

Also Published As

Publication number Publication date
KR100201803B1 (ko) 1999-06-15
HU214023B (en) 1997-12-29
GR3026170T3 (en) 1998-05-29
TW265334B (zh) 1995-12-11
AU675005B2 (en) 1997-01-16
CN1133037A (zh) 1996-10-09
JP3463937B2 (ja) 2003-11-05
EP0716651B1 (en) 1997-12-03
HUT74294A (en) 1996-11-28
IL106901A0 (en) 1993-12-28
ZA946440B (en) 1995-03-31
CA2170778C (en) 1999-04-27
IL106901A (en) 1996-11-14
RO115257B1 (ro) 1999-12-30
AU7720694A (en) 1995-03-22
EP0716651A4 (en) 1996-08-07
WO1995006639A1 (en) 1995-03-09
BR9407392A (pt) 1996-11-05
CA2170778A1 (en) 1995-03-09
HU9600488D0 (en) 1996-04-29
JPH09506590A (ja) 1997-06-30
EP0716651A1 (en) 1996-06-19
NZ273780A (en) 1996-12-20
ES2111333T3 (es) 1998-03-01

Similar Documents

Publication Publication Date Title
JPH1192423A (ja) トリフルオロ酢酸及びクロロジフルオロ酢酸のメチルエステル又はエチルエステルの製造方法
CN106045834A (zh) 一种龙涎酮的制备方法
EP2513030B2 (en) Beta-gamma unsaturated esters and process of production of beta-gamma unsaturated esters.
CN1046708C (zh) 2,3,5,6－四氯吡啶的制备
CN116410192B (zh) 具有多个手性中心的2,3-多取代吲哚嗪、其衍生物及其制备方法和应用
FI72508B (fi) Foerfarande foer framstaellning av n-propylacetonitrilderivat.
CN108558944B (zh) 一种4-磷酰基-1,4,5-三取代的1,2,3-三氮唑的制备方法
US4458086A (en) Process for the preparation of 2-(thienyl-2)-and 2-(thienyl-3)-ethylamines
US4018771A (en) Process for the production of 2-alkyl or 2-cycloalkyl-4-methyl-6-hydroxypyrimidines
Lim et al. Rhodium-catalyzed coupling reaction of 2-vinylpyridines with allyl ethers
DE19858594A1 (de) Verfahren zur Herstellung von Cyanbenzolboronsäuren
CN111995636B (zh) 一种邻羟基-氮硅烷化合物及其合成方法
JP3855570B2 (ja) ４−アセチルテトラヒドロピランの製法
US4692523A (en) Process for the preparation of 1-substituted aza-cycloalkan-2-ones
CN110627718B (zh) 一种(E)-β-单氟烷基-β,γ-不饱和酰胺的合成方法
CN111777582B (zh) 一种2-氟烷基-3-炔基取代萘并呋喃化合物及其制备方法
US5412146A (en) Process for the preparation of 2-cyanoacetoxypropionic esters
CA1246608A (en) Dichlorotrifluoropropion-aldehyde and a process for its preparation
US5710299A (en) Production of bridged metallocene complexes and intermediates therefor
PL144018B1 (en) Method of obtaining alpha-cyanenamines
US5618942A (en) Production of 2,3,5,6-tetrachloropyridine
CN104628644A (zh) 一种3-氮杂二环[4,1,0]庚醛及制备方法
JPH06157459A (ja) ピリジルケトアルコールの製造法
CN116003445A (zh) 一类烷基锌试剂及其制备方法与应用
Palominos et al. Generation and C-ethoxythiocarbonylation of enolates using ultrasound

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C53 Correction of patent of invention or patent application
CB02 Change of applicant information

Applicant after: Limadelt Co.

Applicant before: Luxembourg Indutries (Pamol) Ltd.

COR Change of bibliographic data

Free format text: CORRECT: APPLICANT; FROM: LUXEMBOURG INDUTRIES (PAMOL) LTD. TO: LIMA DELTE CO.,LTD.

C14 Grant of patent or utility model
GR01 Patent grant
C19 Lapse of patent right due to non-payment of the annual fee
CF01 Termination of patent right due to non-payment of annual fee