CN1163888A - 制备n-甲基-n'-硝基胍的方法 - Google Patents
制备n-甲基-n'-硝基胍的方法 Download PDFInfo
- Publication number
- CN1163888A CN1163888A CN97104941A CN97104941A CN1163888A CN 1163888 A CN1163888 A CN 1163888A CN 97104941 A CN97104941 A CN 97104941A CN 97104941 A CN97104941 A CN 97104941A CN 1163888 A CN1163888 A CN 1163888A
- Authority
- CN
- China
- Prior art keywords
- nitroguanidine
- methyl
- formula
- preparing
- present
- 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.)
- Granted
Links
- XCXKNNGWSDYMMS-UHFFFAOYSA-N 2-methyl-1-nitroguanidine Chemical compound CNC(N)=N[N+]([O-])=O XCXKNNGWSDYMMS-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims abstract description 13
- IDCPFAYURAQKDZ-UHFFFAOYSA-N 1-nitroguanidine Chemical compound NC(=N)N[N+]([O-])=O IDCPFAYURAQKDZ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229940043265 methyl isobutyl ketone Drugs 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/30—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to nitro or nitroso groups
- C07C279/32—N-nitroguanidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/30—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to nitro or nitroso groups
- C07C279/32—N-nitroguanidines
- C07C279/36—Substituted N-nitroguanidines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及通过在0-40℃使硝基胍与甲胺水溶液反应制备N-甲基-N’-硝基胍的新方法。
Description
本发明涉及新的制备N-甲基-N’-硝基胍的方法。
人们知道，N-甲基-N’-硝基胍按照下述反应式通过先按常规方法对式(A)的5-甲基异硫脲硫酸盐硝基化、随后在第二步反应中用甲胺取代巯基得到：(cf.JACS76，1877(1954))
然而，该方法的缺点是，它是一个两步反应。虽然在两步中产率都比较好，但是甲硫醇的除去、尤其是在工业规模制备时引起了技术问题。
人们还知道，N-甲基-N’-硝基胍可以按照下述反应式在60℃使硝基胍的碱溶液(氢氧化钾)与甲胺盐酸盐反应制备：(cf.JACS69，3028(1947))。
然而，该方法的缺点是，要得到纯的产物，需要进行一到两次重结晶除去无机杂质，这样使得产率显著降低了。
现已发现，当式(II)的硝基胍与甲胺水溶液在0℃和40℃之间的温度反应时，得到了式(I)的N-甲基-N’-硝基胍：
令人惊奇的是，式(I)的N-甲基-N’-硝基胍可以通过本发明的方法以简单的方式以非常好的产率和高纯度得到，尽管先有技术中没有任何建议说所述的反应在本发明所述的温和的条件下会如此的成功。此外，本发明反应的高选择性是令人惊讶的；没有观察到二烷基化。
因此，本发明的优点是具有较好的工业实用性同时给出高的产率。具体的好处是：不需要辅助剂、反应温度低、终产物的分离简单而不需要独立的纯化步骤以及避免了甲硫醇。
本发明方法的反应可以用下述反应式概括：
起始原料，式(II)的硝基胍和甲胺，是有机化学中通常已知的化合物。
本发明的方法在水作为稀释剂存在下进行。然而，也可以在有机/水体系中进行，在这种情况下，可以使用所有的常规的可与水混溶的有机溶剂。实例有酮类如丙酮、甲乙酮或甲基异丁基酮；腈类如乙腈或丙腈；以及也可以是醇类如甲醇或乙醇。
当进行本发明的方法时，反应温度可以在较宽的范围内变化。通常，反应在10℃至30℃的温度、优选在室温下进行。
当进行本发明的方法时，就每摩尔式(II)的硝基胍而言一般使用1-3摩尔、优选1-2摩尔的甲胺。
在本发明方法的一个具体的实施方案中，所述的起始原料都是作为水溶液直接使用。
后处理按通常的方式进行。
按照本发明的方法制备的式(I)的N-甲基-N’-硝基胍可以用作制备生物活性化合物例如杀虫剂的中间体(参见例如EP-A 0 376 279和EP-A 0 428 941)。制备实施例实施例1
在18-20℃，于10分钟内，将150g(大约1.5mol)、大约30％的甲胺水溶液滴加到138.8g(1mol)硝基胍(含大约25％的水)在750ml水中的悬浮液中。随后将反应混合物在20-25℃搅拌24小时。然后将温度降低到大约5℃，吸滤除去沉淀，用母液洗涤，吸干，用石油醚再洗一次，于45℃在真空炉中干燥。
得到了100.8g(理论量的85.4％)、熔点为159℃的N-甲基-N’-硝基胍，纯度100％(用HPLC测定)。
Claims (1)
1.制备式(I)的N-甲基-N’-硝基胍的方法，其特征在于，在0℃和40℃的温度之间使式(II)的硝基胍与甲胺水溶液反应，
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19611654.6 | 1996-03-25 | ||
| DE19611654A DE19611654A1 (de) | 1996-03-25 | 1996-03-25 | Verfahren zur Herstellung von N-Methyl-N'-nitroguanidin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1163888A true CN1163888A (zh) | 1997-11-05 |
| CN1065526C CN1065526C (zh) | 2001-05-09 |
Family
ID=7789289
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN97104941A Expired - Lifetime CN1065526C (zh) | 1996-03-25 | 1997-03-25 | 制备n-甲基-n'-硝基胍的方法 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US5783734A (zh) |
| EP (1) | EP0798293B1 (zh) |
| JP (1) | JP3927274B2 (zh) |
| KR (1) | KR100434991B1 (zh) |
| CN (1) | CN1065526C (zh) |
| DE (2) | DE19611654A1 (zh) |
| ES (1) | ES2150714T3 (zh) |
| HK (1) | HK1002070A1 (zh) |
| TW (1) | TW362094B (zh) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101565392A (zh) * | 2008-04-21 | 2009-10-28 | 南通天泽化工有限公司 | 一种甲基硝基胍及其制备方法 |
| CN103641746A (zh) * | 2013-11-22 | 2014-03-19 | 张亚峰 | 一种n-甲基-n’硝基胍的合成工艺 |
| CN106986790A (zh) * | 2017-05-25 | 2017-07-28 | 宁夏贝利特生物科技有限公司 | 用生产硝基胍后的稀硫酸生产n‑甲基‑n′‑硝基胍的方法 |
| CN107382789A (zh) * | 2017-06-29 | 2017-11-24 | 南通天泽化工有限公司 | 一种甲基硝基胍的制备方法 |
| CN107698466A (zh) * | 2017-11-09 | 2018-02-16 | 宁夏贝利特生物科技有限公司 | 一种n‑甲基‑n′‑硝基胍的制备方法 |
| CN109053498A (zh) * | 2018-09-27 | 2018-12-21 | 南通天泽化工有限公司 | 一种1-甲基-1,2-二硝基胍的制备方法 |
| CN110128300A (zh) * | 2019-05-10 | 2019-08-16 | 宁夏贝利特生物科技有限公司 | 一种制备1-甲基-3-硝基胍的方法 |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19712411A1 (de) | 1997-03-25 | 1998-10-01 | Bayer Ag | Verfahren zur Herstellung von 1,3-disubstituierten 2-Nitroguanidinen |
| ATE247638T1 (de) * | 1998-11-25 | 2003-09-15 | Dynamit Nobel Ag | Verfahren zur herstellung von n-alkyl-n'- nitroguanidin |
| DE19939609A1 (de) * | 1999-08-20 | 2001-02-22 | Nigu Chemie Gmbh | Verfahren zur Herstellung von 1-Methyl-3-nitroguanidin |
| DE10000891A1 (de) * | 2000-01-12 | 2001-07-19 | Bayer Ag | Verfahren zur Herstellung von N-Methyl-N'-nitroguanidin |
| DE10003834A1 (de) * | 2000-01-28 | 2001-08-02 | Nigu Chemie Gmbh | Verfahren zur Herstellung von 1-Methyl-3-nitroguanidin |
| CN103172545A (zh) * | 2013-04-02 | 2013-06-26 | 常州大学 | 一种微通道反应器制备硝基胍的方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2559085A (en) * | 1948-10-22 | 1951-07-03 | Honorary Advisory Council Sci | Preparation of n-substituted-n'-nitroguanidines |
-
1996
- 1996-03-25 DE DE19611654A patent/DE19611654A1/de not_active Withdrawn
-
1997
- 1997-03-12 ES ES97104120T patent/ES2150714T3/es not_active Expired - Lifetime
- 1997-03-12 DE DE59702117T patent/DE59702117D1/de not_active Expired - Lifetime
- 1997-03-12 EP EP97104120A patent/EP0798293B1/de not_active Expired - Lifetime
- 1997-03-14 TW TW086103151A patent/TW362094B/zh not_active IP Right Cessation
- 1997-03-18 US US08/820,274 patent/US5783734A/en not_active Expired - Lifetime
- 1997-03-19 JP JP08469997A patent/JP3927274B2/ja not_active Expired - Lifetime
- 1997-03-21 KR KR1019970009842A patent/KR100434991B1/ko not_active IP Right Cessation
- 1997-03-25 CN CN97104941A patent/CN1065526C/zh not_active Expired - Lifetime
-
1998
- 1998-02-17 HK HK98101213A patent/HK1002070A1/xx not_active IP Right Cessation
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101565392A (zh) * | 2008-04-21 | 2009-10-28 | 南通天泽化工有限公司 | 一种甲基硝基胍及其制备方法 |
| CN103641746A (zh) * | 2013-11-22 | 2014-03-19 | 张亚峰 | 一种n-甲基-n’硝基胍的合成工艺 |
| CN103641746B (zh) * | 2013-11-22 | 2016-03-30 | 青岛文创科技有限公司 | 一种n-甲基-n’硝基胍的合成工艺 |
| CN106986790A (zh) * | 2017-05-25 | 2017-07-28 | 宁夏贝利特生物科技有限公司 | 用生产硝基胍后的稀硫酸生产n‑甲基‑n′‑硝基胍的方法 |
| CN107382789A (zh) * | 2017-06-29 | 2017-11-24 | 南通天泽化工有限公司 | 一种甲基硝基胍的制备方法 |
| CN107698466A (zh) * | 2017-11-09 | 2018-02-16 | 宁夏贝利特生物科技有限公司 | 一种n‑甲基‑n′‑硝基胍的制备方法 |
| CN109053498A (zh) * | 2018-09-27 | 2018-12-21 | 南通天泽化工有限公司 | 一种1-甲基-1,2-二硝基胍的制备方法 |
| CN110128300A (zh) * | 2019-05-10 | 2019-08-16 | 宁夏贝利特生物科技有限公司 | 一种制备1-甲基-3-硝基胍的方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| US5783734A (en) | 1998-07-21 |
| JPH09255651A (ja) | 1997-09-30 |
| ES2150714T3 (es) | 2000-12-01 |
| HK1002070A1 (en) | 1998-07-31 |
| JP3927274B2 (ja) | 2007-06-06 |
| EP0798293B1 (de) | 2000-08-09 |
| DE19611654A1 (de) | 1997-10-02 |
| DE59702117D1 (de) | 2000-09-14 |
| TW362094B (en) | 1999-06-21 |
| KR970065513A (ko) | 1997-10-13 |
| CN1065526C (zh) | 2001-05-09 |
| EP0798293A1 (de) | 1997-10-01 |
| KR100434991B1 (ko) | 2004-09-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1065526C (zh) | 制备n-甲基-n'-硝基胍的方法 | |
| JP4700880B2 (ja) | Ｎ−メチル−ｎ’−ニトログアニジンの製造方法 | |
| CN1098250C (zh) | 制备取代的缬氨酰胺衍生物的方法 | |
| JPH085811B2 (ja) | アミド化合物の改良された製造方法 | |
| US4189591A (en) | Method of preparing 4-methyl-5-hydroxymethyl-imidazole | |
| US4659837A (en) | Method for the preparation of 1,3-disubstituted 4,5-cis-dicarboxy-2-imidazolidones | |
| EP0260588B1 (en) | Process for the preparation of alpha-N-[(hypoxanthin-9-yl)-pentyloxycarbonyl]-arginine | |
| CN1006888B (zh) | 制备2，4-二氯-5-氟-苯甲酸的方法 | |
| KR910001998B1 (ko) | 2-(2-나프틸옥시)프로피온산 유도체의 제조방법 | |
| KR900006556B1 (ko) | 2-구아니디노티아졸 유도체의 제조방법 | |
| US4670561A (en) | Process for obtaining hydrochloric salts of 2, 5, 6-triamino-4 (1h)-pyrimidinone | |
| NZ201412A (en) | Preparation of 4-aminobutyramide | |
| EP0437567B1 (en) | Phenyl-glycine derivatives | |
| KR820000119B1 (ko) | 아미노산 유도체의 제조방법 | |
| JPS62288102A (ja) | ジシアナミド金属塩の製造方法 | |
| EP1841725B1 (en) | A process for the purification of gabapentin | |
| KR810001135B1 (ko) | 탈암피실린 염산염의 제조방법 | |
| JP2821700B2 (ja) | ４―アミノ―ｃｉｓ―２―ブテン―１―オールの製造方法 | |
| JP3569428B2 (ja) | ホモアリルアミン類の製造方法 | |
| US5693772A (en) | Desalaninebenanomicin A derivatives and processes for the preparation thereof | |
| KR100198829B1 (ko) | 4-아미노페닐-2-아세톡시에틸설폰의 제조방법 | |
| CN115232113A (zh) | 5r-(((四氢-2h-吡喃-2-基)氧基)氨基)哌啶-2s-羧酸酯盐的制备方法 | |
| KR950002836B1 (ko) | 3-아미노-4-메톡시아세트아닐리드의 제조방법 | |
| JPS6317869A (ja) | ２−低級アルキル−４−アミノ−５−ホルミルピリミジンの製造法 | |
| JPH05388B2 (zh) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| FG4A | Grant of patent | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: BAYER INTELLECTUAL PROPERTY GMBH Free format text: FORMER OWNER: BAYER AKTIENGESELLSCHAFT Effective date: 20150609 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20150609 Address after: German Monheim Patentee after: Bayer Pharma Aktiengesellschaft Address before: Germany Leverkusen Patentee before: Bayer Aktiengesellschaft |
|
| CX01 | Expiry of patent term | ||
| CX01 | Expiry of patent term |
Granted publication date: 20010509 |