CN1518539A - Process for preparing thiosemicarbazides - Google Patents
Process for preparing thiosemicarbazides Download PDFInfo
- Publication number
- CN1518539A CN1518539A CNA028078977A CN02807897A CN1518539A CN 1518539 A CN1518539 A CN 1518539A CN A028078977 A CNA028078977 A CN A028078977A CN 02807897 A CN02807897 A CN 02807897A CN 1518539 A CN1518539 A CN 1518539A
- Authority
- CN
- China
- Prior art keywords
- thiosemicarbazide
- ammonium
- mtsc
- preparation
- dipea
- 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
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
- C07D285/135—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C337/00—Derivatives of thiocarbonic acids containing functional groups covered by groups C07C333/00 or C07C335/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C337/06—Compounds containing any of the groups, e.g. thiosemicarbazides
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Abstract
A process is provided for producing a thiosemicarbazide which includes the steps of reacting an alkylamine with carbon disulphide in the presence of a base selected from N,N-diisopropylethylamine and N,N,-diisopropyl-methylamine to produce an intermediate and converting the intermediate into the thiosemicarbazide. The process has particular application to producing 4-methyl-3-thiosemicarbazide, an intermediate useful in producing the broad-spectrum herbicide tebuthiuron.
Description
Background of invention
The present invention relates to prepare the method for thiosemicarbazide.
4-methyl-3-thiosemicarbazide (MTSC) is the synthetic 5-tertiary butyl-2-methylamino--1,3,4-thiadiazoles (BTDA), a kind of intermediate of parent of broad-spectrum herbicide tebuthiuron.The chemical name of tebuthiuron is 1-(the 5-tertiary butyl-1,3,4-thiadiazoles-2-yl)-1,3 Dimethylurea.
The several of thiosemicarbazide that replace about the 4-position synthesize, and have in the literature and describe and roughly be summarized as follows:
The reaction of alkylisothiocyanate and hydrazine,
The reaction of hydrazine and active sulphur carbamic derivative of generation (chloride of acid, single thiuramsulfides etc.) and
N-monoalkyl and N, the hydrazinolysis of N-dialkyl dithiocarbamate.
At present, the preparation method of MTSC needs the hydrazinolysis of ammonium N methyl dithiocarba mate.Think that ammonium N methyl dithiocarba mate is subjected to hot in-place to generate Trapex in the presence of alkali.It and hydrazine hydrate reaction generate MTSC.The purity of the MTSC that this method provides is 93-94%.The purity of MTSC is the key factor of the BTDA of preparation high purity (98+%) and high yield.MTSC by this method preparation can not prepare high-quality BTDA.This method has also produced the waste liquid that contains the high density ammonium salt.The a large amount of waste liquids that generate in this method are an important problem (1 ton of MTSC of every preparation can produce about 4 tons waste liquid on the technical scale).
Summary of the invention
According to a first aspect of the invention, the method for preparing thiosemicarbazide comprises the following steps: to make alkylamine and dithiocarbonic anhydride being selected from N, N-diisopropylethylamine (DIPEA) and N, the existence of the alkali of N-diisopropyl methylamine (DIPMA) reaction down generates a kind of intermediate, and described intermediate is changed into described thiosemicarbazide.Being reflected under the excess base existence of preferred alkyl amine and dithiocarbonic anhydride carried out.
Described intermediate is dithiocarbamic acid N, N-di-isopropyl second ammonium or dithiocarbamic acid N, N-di-isopropyl first ammonium.Think that two kinds of intermediates all are novel and have formed another aspect of the present invention.N-alkyl dithiocarbamic acid N, the structure of N-di-isopropyl second ammonium is:
The present invention further provides a kind of method, this method is by making alkylamine and dithiocarbonic anhydride prepared in reaction dithiocarbamic acid N in the presence of DIPEA or DIPMA, N-di-isopropyl second ammonium or dithiocarbamic acid N, N-di-isopropyl first ammonium.
Specific embodiments
The general formula that is used for the described alkylamine of method of the present invention is alkyl-NH
2, just a kind of primary alkyl amine.Preferred alkyl is a methyl.
Thiosemicarbazide by method preparation of the present invention can be represented with following formula:
R
1NH-CS-NH-NH
2
R wherein
1It is alkyl.
The present invention is specifically applied to preparation MTSC and intermediate thereof, dithiocarbamic acid N, and N-di-isopropyl second ammonium, shown in following step 1 and 2:
Step 1
Step 2
In aforesaid method, preferably use excessive DIPEA.This carries out the reaction of step 1 to the right, and has improved the stability of intermediate (A).Typically, used DIPEA excessive 10% to 30%.
So can emitting big calorimetric, the reaction of step 1 generally need cooling to be lower than 30 ℃ with the temperature that keeps reaction medium.
In the preparation method of MTSC, use DIPEA as alkali, reduced the generation quantity of waste liquid substantially.In addition, described intermediate (A) shows to have satisfactory stability, and the result has reduced the formation of by product such as thiocarbohydrazide and dimethyl thiourea.In addition, the productive rate of the MTSC of acquisition is that 70-76% and purity are 97.5-98.5%.
Introduce embodiments of the invention now.
Embodiment 1 (DIPEA excessive 10%)
Methylamine (77.5g, 40% solution) and DIPEA (142.2g) are encased in 1 liter of reactor that reflux exchanger and agitator be housed.In 30 minutes, drip CS while stirring
2(76g).Drip CS
2The time, keep temperature of reaction to be lower than 30 ℃ by exterior cooling.This mixture restir 3 hours, batch distillate (60g) before adding then.Described reaction mixture dilute with water obtains concentration and is 24% DTC (dithiocar-bamate) solution.
Hydrazine hydrate (60.1g) is added in the described DIPEA-DTC mixture.This reaction mixture is heated to 89 ℃ and under refluxad kept 2 hours 20 minutes at 89-92 ℃.Distillate described DIPEA (temperature is elevated to when being higher than 95 ℃ and distills fully), make this reaction mixture be cooled to 15 ℃ while stirring, so the MTSC crystal is separated from supernatant liquid, the productive rate that obtains isolated MTSC is 73.8%.The purity of MTSC is 98.0%.
Embodiment 2 (DIPEA excessive 30%)
Methylamine (38.7g, 40% solution) and DIPEA (82.4g) are joined in 0.5 liter of reactor that reflux exchanger and agitator be housed.In 30 minutes, drip CS while stirring
2(38.1g).Drip CS
2The time, keep temperature of reaction to be lower than 30 ℃ by exterior cooling.This mixture restir 3 hours, batch distillate (30g) before adding then.This reaction mixture of dilute with water obtains DTC (dithiocar-bamate) solution of concentration 24%.
Hydrazine hydrate (30.1g) is added in the described DIPEA-DTC mixture.Described reaction mixture is heated to 92 ℃ and under refluxad kept 2 hours 20 minutes at 92 ℃.Distillate DIPEA (temperature is elevated to when being higher than 95 ℃ and distills fully), make this reaction mixture be cooled to 15 ℃ while stirring, so the MTSC crystal is separated from supernatant liquid, the productive rate that obtains isolated MTSC is 75.8%.
Claims (7)
1. method for preparing thiosemicarbazide, it comprises the following steps: to make alkylamine and dithiocarbonic anhydride being selected from N, N-diisopropylethylamine and N, the existence of the alkali of N-diisopropyl methylamine reaction down generates a kind of intermediate, then described intermediate is changed into described thiosemicarbazide.
2. method according to claim 1, the general formula of wherein said thiosemicarbazide is:
R
1NH-CS-NH-NH
2
R wherein
1It is alkyl.
3. method according to claim 1, wherein said thiosemicarbazide are 4-methyl-3-thiosemicarbazide.
4. according to each described method of aforementioned claim, being reflected under the excess base existence of wherein said alkyl ammonia and dithiocarbonic anhydride carried out.
5. one kind is selected from dithiocarbamic acid N, N-two different basic second ammonium and dithiocarbamic acid N, the compound of N-di-isopropyl first ammonium.
6. the purposes of compound according to claim 5 on the preparation thiosemicarbazide.
7. the purposes of compound according to claim 5 on preparation 1-(the 5-tertiary butyl-1,3,4-thiadiazoles-2-yl)-1,3 Dimethylurea.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ZA200102904 | 2001-04-09 | ||
| ZA2001/2904 | 2001-04-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1518539A true CN1518539A (en) | 2004-08-04 |
Family
ID=25589131
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA028078977A Pending CN1518539A (en) | 2001-04-09 | 2002-04-02 | Process for preparing thiosemicarbazides |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1377546A2 (en) |
| JP (1) | JP2004536795A (en) |
| KR (1) | KR20030086351A (en) |
| CN (1) | CN1518539A (en) |
| BR (1) | BR0208743A (en) |
| CA (1) | CA2446918A1 (en) |
| HU (1) | HUP0303844A2 (en) |
| IL (1) | IL158288A0 (en) |
| MX (1) | MXPA03009215A (en) |
| WO (1) | WO2002081438A2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103709081A (en) * | 2013-12-13 | 2014-04-09 | 黄河三角洲京博化工研究院有限公司 | Preparation method of thiosemicarbazide |
| CN104860857A (en) * | 2015-04-09 | 2015-08-26 | 山东华阳农药化工集团有限公司 | Methylthiosemicarbazide synthesis process |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102584661A (en) * | 2012-01-19 | 2012-07-18 | 中国科学院海洋研究所 | Preparation method of substituted phenylthiosemicarbazide compound |
| CN105772101B (en) * | 2016-04-06 | 2018-03-30 | 上海应用技术学院 | The Mn Anderson types heteropolyacid catalyst of 1 Phenethylthiourea modification, preparation method and applications |
| CN105797769B (en) * | 2016-04-06 | 2018-03-30 | 上海应用技术学院 | (R) the thiourea modified Mn Anderson types heteropolyacid catalyst of 1 (phenethyl of 2 hydroxyl 1), preparation method and applications |
| CN105797770B (en) * | 2016-04-06 | 2018-03-30 | 上海应用技术学院 | (S) the thiourea modified Cr Anderson types heteropolyacid catalyst of 1 (phenylpropyl of 3 hydroxyl 1), preparation method and applications |
| CN105854952B (en) * | 2016-04-06 | 2018-05-15 | 上海应用技术学院 | (S) Mn-Anderson types heteropolyacid catalyst thiourea modified -1- (2- hydroxyl -1- phenethyls), preparation method and applications |
| CN105772100B (en) * | 2016-04-06 | 2018-05-15 | 上海应用技术学院 | (R) Cr-Anderson types heteropolyacid catalyst thiourea modified -1- (1- (2- naphthyls) ethyl), preparation method and applications |
| CN105772086B (en) * | 2016-04-06 | 2018-03-30 | 上海应用技术学院 | (S) the thiourea modified Mn Anderson types heteropolyacid catalyst of 1 (isopropyl of 1 ethoxy 1), preparation method and applications |
| CN105772085B (en) * | 2016-04-06 | 2018-04-13 | 上海应用技术学院 | (S) the thiourea modified Cr Anderson types heteropolyacid catalyst of 1 (1 ethoxy, 1 isopropyl), preparation method and applications |
| CN105854940B (en) * | 2016-04-06 | 2018-05-15 | 上海应用技术学院 | (R) Cr-Anderson types heteropolyacid catalyst thiourea modified -1- (1- phenethyls), preparation method and applications |
| CN105833909B (en) * | 2016-04-06 | 2018-05-15 | 上海应用技术学院 | (S) Cr-Anderson types heteropolyacid catalyst thiourea modified -1- (2- hydroxyl -1- phenethyls), preparation method and applications |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA931961A (en) * | 1970-04-17 | 1973-08-14 | Gulf Research And Development Company | Combating unwanted vegetation with 1,3,4-thiadiazolylureas |
| JPH0211562A (en) * | 1988-04-27 | 1990-01-16 | Eli Lilly & Co | Production of 4-methyl-3-thiosemicarbazide |
-
2002
- 2002-04-02 HU HU0303844A patent/HUP0303844A2/en unknown
- 2002-04-02 BR BR0208743-0A patent/BR0208743A/en not_active Application Discontinuation
- 2002-04-02 EP EP02716977A patent/EP1377546A2/en not_active Withdrawn
- 2002-04-02 CA CA002446918A patent/CA2446918A1/en not_active Abandoned
- 2002-04-02 WO PCT/IB2002/001023 patent/WO2002081438A2/en not_active Application Discontinuation
- 2002-04-02 JP JP2002579426A patent/JP2004536795A/en active Pending
- 2002-04-02 IL IL15828802A patent/IL158288A0/en unknown
- 2002-04-02 KR KR10-2003-7013168A patent/KR20030086351A/en not_active Application Discontinuation
- 2002-04-02 MX MXPA03009215A patent/MXPA03009215A/en unknown
- 2002-04-02 CN CNA028078977A patent/CN1518539A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103709081A (en) * | 2013-12-13 | 2014-04-09 | 黄河三角洲京博化工研究院有限公司 | Preparation method of thiosemicarbazide |
| CN103709081B (en) * | 2013-12-13 | 2016-01-06 | 黄河三角洲京博化工研究院有限公司 | A kind of preparation method of thiosemicarbazide |
| CN104860857A (en) * | 2015-04-09 | 2015-08-26 | 山东华阳农药化工集团有限公司 | Methylthiosemicarbazide synthesis process |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1377546A2 (en) | 2004-01-07 |
| JP2004536795A (en) | 2004-12-09 |
| KR20030086351A (en) | 2003-11-07 |
| HUP0303844A2 (en) | 2004-03-29 |
| WO2002081438A3 (en) | 2002-11-28 |
| CA2446918A1 (en) | 2002-10-17 |
| BR0208743A (en) | 2004-06-22 |
| MXPA03009215A (en) | 2004-03-10 |
| WO2002081438A2 (en) | 2002-10-17 |
| IL158288A0 (en) | 2004-05-12 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| 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 |