CN103420749B - Green synthesis method of thiourea derivative - Google Patents
Green synthesis method of thiourea derivative Download PDFInfo
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- CN103420749B CN103420749B CN201310385883.8A CN201310385883A CN103420749B CN 103420749 B CN103420749 B CN 103420749B CN 201310385883 A CN201310385883 A CN 201310385883A CN 103420749 B CN103420749 B CN 103420749B
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- sulfuryl chloride
- thiourea derivative
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- primary amine
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- ZASDGLJUXIVFDL-UHFFFAOYSA-N S=C(N1)Nc2cccc3cccc1c23 Chemical compound S=C(N1)Nc2cccc3cccc1c23 ZASDGLJUXIVFDL-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention provides a green synthesis method of a thiourea derivative. The green synthesis method of the thiourea derivative overcomes the defects that raw materials are high in toxicity and unsafe in production when amine is used as the raw materials to synthesise a thiourea derivative in the prior art. According to the green synthesis method of the thiourea derivative, water is used as solvent, and phenoxy sulfuryl chloride or substituted phenoxy sulfuryl chloride and primary amine are used as raw materials to synthesise the thiourea derivative in one step. The method comprises the specific steps that (1) the phenoxy sulfuryl chloride or the substituted phenoxy sulfuryl chloride and the primary amine are used as the raw materials, and meanwhile water is added into the raw materials, wherein reaction temperature is 65-100 DEG C, and reaction time is 1-30 hours; (2) after the reaction is finished, cooling, standing and suction filtration are conducted on the raw materials, 10% hydrochloric acid and clear water are used in sequence for washing a filter cake, and then the pure thiourea derivative is obtained. Due to the facts that the phenoxy sulfuryl chloride or the substituted phenoxy sulfuryl chloride and the primary amine are used as the raw materials to synthesise the thiourea derivative in the water in one step, compared with a preparation method in the prior art, the green synthesis method of the thiourea derivative has the advantages that raw materials are easy to obtain and low in toxicity, reaction conditions are gentle, separation and purification are convenient, and the environment is protected; the green synthesis method of the thiourea derivative has high application value.
Description
Technical field
The present invention relates to organic chemical industry field, particularly a kind of with the method for water as solvent one-step synthesis thiourea derivative.
Background technology
Containing thioureido (-NH-CS-NH-) active structure in thiourea, thus this compounds many have stronger biological activity.Nowadays, research about thiourea has extensively set foot in chemistry of pesticide, pharmaceutical chemistry, supramolecular chemistry, chiral synthesize, clinical medicine, environmental monitoring and the every field such as biological metabolism and Chemical Manufacture, therefore, the Study of synthesis method of thiocarbamide is a vitochemical important topic always.
Be that the method for Material synthesis thiocarbamide mainly contains following three kinds of approach with amine:
Thio phosgene synthesis method: rapidly addition reaction occurs with amine again after the active intermediate lsothiocyanates of thio phosgene and aminated compounds condensation preparation key, generate corresponding thiourea (D.C.Schroeder, Chem.Rev.1955,55,181 – 228.).But this reaction needed uses thio phosgene, and thio phosgene is the volatile liquid of severe toxicity, and it is produced, transport and use all dangerous, also larger to the harm of environment.
Dithiocarbonic anhydride method: in prior art, phenylthiourea (CN 103130694A is prepared in many employing aniline and dithiocarbonic anhydride addition under the effect of mineral alkali; N.Azizi, A.Khajeh-Amiri, H.Ghafuri, M.Bolourtchian, Mol Divers 2011,15,157 – 161.).But the method still needs the dithiocarbonic anhydride using toxicity larger, and mineral alkali corrosive equipment and contaminate environment.
Lsothiocyanates synthesis method: with lsothiocyanates and amine for Material synthesis thiourea.But the prerequisite of the method to prepare corresponding lsothiocyanates, and many lsothiocyanates are difficult to synthesis, and poor stability or produce dangerous.
Therefore, one of the thiocarbamide new synthetic method vital task being still chemist of easy, the atom economy type of development and operation and greenization.
Summary of the invention
Material toxicity that the present invention overcomes in prior art when taking amine as Material synthesis thiourea derivative is large, produce unsafe deficiency, provides a kind of green synthesis method of thiourea derivative.Be using water as solvent, phenoxy group sulfuryl chloride or substituent phenoxy sulfuryl chloride and primary amine are raw material one-step synthesis thiourea derivative.Reaction equation is as follows:
Concrete steps are as follows: (1), with phenoxy group sulfuryl chloride or substituent phenoxy sulfuryl chloride and primary amine for raw material, add water, temperature of reaction is 65 ~ 100 DEG C simultaneously, and the reaction times is 1 ~ 30h;
(2), after reaction terminates, cooling leaves standstill, and suction filtration, uses 10% hydrochloric acid, clear water washing leaching cake successively, get and can obtain pure thiourea derivative.
As preferably, the structural formula of the substituent phenoxy sulfuryl chloride described in step (1) is
wherein substituent R
1for the one in the alkoxyl group of the alkyl of 1-6 carbon atom, a 1-6 carbon atom, halogen atom, amino, substituted-amino or nitro; Wherein substituent R
1at the ortho position of phenoxy group sulfuryl chloride, a position or contraposition.
Further, the primary amine described in step (1) is fats primary amine or aromatics primary amine.
As preferably, described fats primary amine is the alkylamine containing heteroatoms or heterocycle, and described aromatics primary amine is the one in benzylamine, alpha substituted benzylamine, condensed ring amine or heterocyclic aromatic amine.
As preferably, described heterocyclic aromatic amine is aminopyrazole derivatives, amino furan derivative, aminothiophene derivative, aminopyridine derivative, amino-pyrazol-derivatives or aminoimidazole derivative.
Further, the phenoxy group sulfuryl chloride described in step (1) or substituent phenoxy sulfuryl chloride and primary amine mol ratio are 1:2-5.
As preferably, the consumption of water described in step (1) is phenoxy group sulfuryl chloride or substituent phenoxy sulfuryl chloride with the molecular volume of water than being 1:15mmol/mL.
As preferably, the temperature of reaction described in step (1) is 100 DEG C; Reaction times is 8 hours; Described phenoxy group sulfuryl chloride or the mol ratio of substituent phenoxy sulfuryl chloride and primary amine are 1:3.5.
Beneficial effect of the present invention is as follows: adopt phenoxy group sulfuryl chloride or substituent phenoxy sulfuryl chloride and primary amine compound to be raw material, one-step synthesis thiocarbamide in water, compared with preparation method of the prior art, have that reaction raw materials is easy to get, low toxicity, reaction conditions are gentle, separating-purifying is convenient and many advantages such as environmental protection, have very high using value.
Embodiment
Describe the present invention below in conjunction with embodiment, but the present invention is not limited to these embodiments.
Embodiment 1
In the single port flask of 50mL, add aniline (3.5mmol), phenoxy group thioacid chloride (1mmol) and 15mL water successively, 100 DEG C of heated and stirred reaction 8h, there is a large amount of white solid in flask walls.Stopped reaction, cooling leaves standstill, and suction filtration, uses 10% hydrochloric acid, clear water washing leaching cake successively, obtain pure diphenyl thiourea, productive rate 98%.
1H?NMR(300MHZ,DMSO):δ=9.81(s,2H,NH),7.48(d,J=7.5Hz,4H,ArH),7.33(t,J=7.5Hz,4H,ArH),7.13(t,J=7.5Hz,4H,ArH).
13C?NMR(75MHZ,DMSO):δ=179.7,140.1,128.8,124.5,123.5.MS(ESI):m/z=227[(M-H)
-,100].
Comparative example 2
With reference to the method for embodiment 1,60 DEG C of reactions, the productive rate of diphenyl thiourea is only 5%, and now primary product is O-phenoxy group thioamides intermediate
Embodiment 3
With reference to the method for embodiment 1, with to fluorophenoxy sulfuryl chloride for raw material participates in reaction, the productive rate of target product is 92%.
Embodiment 4
With reference to the method for embodiment 1, the mol ratio of phenoxy group sulfuryl chloride and aniline is 1:2, and the productive rate of target product is 62%.
Embodiment 5
With reference to the method for embodiment 1, the mol ratio of phenoxy group sulfuryl chloride and aniline is 1:5, and the productive rate of target product is 98%.
Embodiment 6
With reference to the method for embodiment 1, take P-nethoxyaniline as raw material, react 8 hours, the productive rate of target product is 99%.
1H?NMR(300MHZ,DMSO):δ=9.43(s,2H,NH),7.30(d,J=9.0Hz,4H,ArH),6.89(d,J=9.0Hz,4H,ArH),3.74(s,6H,CH
3).
Embodiment 7
With reference to the method for embodiment 1, take p-Nitroaniline as raw material, temperature is 65 DEG C, reacts 30 hours, and the productive rate of target product is 80%.
1H?NMR(300MHZ,DMSO):δ=10.78(s,2H,NH),8.24(d,J=9.3Hz,4H,ArH),7.85(d,J=9.3Hz,4H,ArH).
Embodiment 8
With reference to the method for embodiment 1, take p-Chlorobenzoic acid amide as raw material, react 9 hours, the productive rate of target product is 99%.
1H?NMR(300MHZ,DMSO):δ=9.94(s,2H,NH),7.49(d,J=8.7Hz,4H,ArH),7.39(d,J=8.7Hz,4H,ArH).
Embodiment 9
With reference to the method for embodiment 1, take naphthalidine as raw material, react 9 hours, the productive rate of target product is 91%.
1H?NMR(300MHZ,DMSO):δ=10.08(s,2H,NH),8.06(d,J=8.1Hz,2H,ArH),7.96(d,J=7.5Hz,2H,ArH),7.85(d,J=8.1Hz,2H,ArH),7.60-7.49(m,8H,ArH).
Embodiment 10
With reference to the method for embodiment 1, take benzylamine as raw material, react 6 hours, the productive rate of target product is 94%.
1H?NMR(300MHZ,DMSO):δ=8.11(br?s,2H,NH),7.34-7.21(m,10H,ArH),4.68(s,2H,CH
2).
Embodiment 11
With reference to the method for embodiment 1, take furylamine as raw material, temperature of reaction is 85 DEG C, reacts 9 hours, and the productive rate of target product is 81%.
1H?NMR(300MHZ,DMSO):δ=7.84(br?s,2H,NH),7.59(dd,J
1=1.8Hz,J
2=0.9Hz,2H,ArH),6.40(dd,J
1=3.2Hz,J
2=1.9Hz,2H,ArH),6.27(d,J=2.7Hz,2H,ArH),4.64(d,J=4.8Hz,4H,CH
2).
Embodiment 12
With reference to the method for embodiment 1, take thiophene methyl amine as raw material, react 7 hours, the productive rate of target product is 89%.
1H?NMR(300MHZ,DMSO):δ=8.09(br?s,2H,NH),7.38(dd,J
1=5.1Hz,J
2=1.2Hz,2H,ArH),7.00(d,J=2.4Hz,2H,ArH),6.95(dd,J
1=5.1Hz,J
2=3.3Hz,2H,ArH),4.83(d,J=4.5Hz,4H,CH
2).
Embodiment 13
With reference to the method for embodiment 1, take hexahydroaniline as raw material, react 3 hours, the productive rate of target product is 92%.
1H?NMR(300MHZ,DMSO):δ=7.07(d,J=7.8Hz,2H,NH),3.96-3.94(m,2H,CH),1.85-1.06(m,20H,CH
2).
Embodiment 14
With reference to the method for embodiment 1, take O-Phenylene Diamine as raw material, react 1 hour,
productive rate be 81%.
1H?NMR(300MHZ,DMSO):δ=12.52(s,2H,NH),7.16-7.09(m,4H,ArH).
Embodiment 15
With reference to the method for embodiment 1, with 1,8-dinaphthylamine for raw material, temperature of reaction is 80 DEG C, reacts 12 hours,
productive rate be 82%.
1H?NMR(300MHZ,DMSO):δ=11.40(s,2H,NH),7.26-7.15(m,4H,4H),6.63(dd,J
1=7.2Hz,J
2=0.9Hz,2H,ArH)。
Claims (6)
1. a green synthesis method for thiourea derivative, is characterized in that: step is as follows:
(1) with phenoxy group sulfuryl chloride or substituent phenoxy sulfuryl chloride and primary amine for raw material, add water, temperature of reaction is 65 ~ 100 DEG C simultaneously, and the reaction times is 1 ~ 30h;
(2), after reaction terminates, cooling leaves standstill, and suction filtration, uses 10% hydrochloric acid, clear water washing leaching cake successively, can obtain pure thiourea derivative;
The structural formula of the substituent phenoxy sulfuryl chloride described in step (1) is
wherein substituent R
1for the one in the alkoxyl group of the alkyl of 1-6 carbon atom, a 1-6 carbon atom, halogen atom, amino, substituted-amino or nitro; Wherein substituent R
1at the ortho position of phenoxy group sulfuryl chloride, a position or contraposition;
Primary amine described in step (1) is fats primary amine or aromatics primary amine.
2. the green synthesis method of thiourea derivative according to claim 1, is characterized in that: described fats primary amine is for containing heteroatomic alkylamine; Described aromatics primary amine is the one in benzylamine, alpha substituted benzylamine, condensed ring amine or heterocyclic aromatic amine.
3. the green synthesis method of thiourea derivative according to claim 2, is characterized in that: described heterocyclic aromatic amine is aminopyrazole derivatives, amino furan derivative, aminothiophene derivative, aminopyridine derivative, amino-pyrazol-derivatives or aminoimidazole derivative.
4. the green synthesis method of thiourea derivative according to claim 1, is characterized in that: the phenoxy group sulfuryl chloride described in step (1) or substituent phenoxy sulfuryl chloride and primary amine mol ratio are 1:2-5.
5. the green synthesis method of thiourea derivative according to claim 1, is characterized in that: the consumption of water described in step (1) is phenoxy group sulfuryl chloride or substituent phenoxy sulfuryl chloride is 1:15mmol/mL with the molecular volume ratio of water.
6. the green synthesis method of thiourea derivative according to claim 1, is characterized in that: the temperature of reaction described in step (1) is 100 DEG C; Reaction times is 8 hours; Described phenoxy group sulfuryl chloride or the mol ratio of substituent phenoxy sulfuryl chloride and primary amine are 1:3.5.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0126934A2 (en) * | 1983-04-21 | 1984-12-05 | BASF Aktiengesellschaft | Process for the preparation of 1,1-disubstituted thioureas |
| CN102503872A (en) * | 2011-12-15 | 2012-06-20 | 常州大学 | Method for preparing isothiocyanate |
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2013
- 2013-08-30 CN CN201310385883.8A patent/CN103420749B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0126934A2 (en) * | 1983-04-21 | 1984-12-05 | BASF Aktiengesellschaft | Process for the preparation of 1,1-disubstituted thioureas |
| CN102503872A (en) * | 2011-12-15 | 2012-06-20 | 常州大学 | Method for preparing isothiocyanate |
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Effective date of registration: 20201126 Address after: Wuzhuang village, Liuyuan Town, Yicheng District, Zaozhuang City, Shandong Province Patentee after: Zaozhuang Xinxing Steel Structure Co.,Ltd. Address before: Gehu Lake Road Wujin District 213164 Jiangsu city of Changzhou province No. 1 Patentee before: CHANGZHOU University |
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