CN115368282A - Method for synthesizing 1, 3-disubstituted thiourea in aqueous phase - Google Patents
Method for synthesizing 1, 3-disubstituted thiourea in aqueous phase Download PDFInfo
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- CN115368282A CN115368282A CN202210950633.3A CN202210950633A CN115368282A CN 115368282 A CN115368282 A CN 115368282A CN 202210950633 A CN202210950633 A CN 202210950633A CN 115368282 A CN115368282 A CN 115368282A
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- -1 1, 3-disubstituted thiourea Chemical class 0.000 title claims abstract description 44
- 238000000034 method Methods 0.000 title claims abstract description 29
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 17
- 239000008346 aqueous phase Substances 0.000 title description 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 52
- 239000002904 solvent Substances 0.000 claims abstract description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 25
- 150000002540 isothiocyanates Chemical class 0.000 claims abstract description 18
- 239000000758 substrate Substances 0.000 claims abstract description 14
- 150000001412 amines Chemical class 0.000 claims abstract description 9
- 238000006482 condensation reaction Methods 0.000 claims abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 51
- QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 claims description 24
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 claims description 22
- HBNYJWAFDZLWRS-UHFFFAOYSA-N ethyl isothiocyanate Chemical compound CCN=C=S HBNYJWAFDZLWRS-UHFFFAOYSA-N 0.000 claims description 19
- 238000001035 drying Methods 0.000 claims description 18
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 17
- 238000004440 column chromatography Methods 0.000 claims description 17
- 238000000605 extraction Methods 0.000 claims description 15
- 238000000926 separation method Methods 0.000 claims description 13
- 229940117953 phenylisothiocyanate Drugs 0.000 claims description 12
- 238000012544 monitoring process Methods 0.000 claims description 9
- ABQKHKWXTUVKGF-UHFFFAOYSA-N 1-isothiocyanato-4-methylbenzene Chemical compound CC1=CC=C(N=C=S)C=C1 ABQKHKWXTUVKGF-UHFFFAOYSA-N 0.000 claims description 7
- BDPQUWSFKCFOST-UHFFFAOYSA-N 1-isothiocyanato-3-methylbenzene Chemical compound CC1=CC=CC(N=C=S)=C1 BDPQUWSFKCFOST-UHFFFAOYSA-N 0.000 claims description 6
- FCSHMCFRCYZTRQ-UHFFFAOYSA-N N,N'-diphenylthiourea Chemical compound C=1C=CC=CC=1NC(=S)NC1=CC=CC=C1 FCSHMCFRCYZTRQ-UHFFFAOYSA-N 0.000 claims description 6
- 230000006837 decompression Effects 0.000 claims description 6
- MZZVFXMTZTVUFO-UHFFFAOYSA-N 1-chloro-4-isothiocyanatobenzene Chemical compound ClC1=CC=C(N=C=S)C=C1 MZZVFXMTZTVUFO-UHFFFAOYSA-N 0.000 claims description 4
- VRPQCVLBOZOYCG-UHFFFAOYSA-N 1-isothiocyanato-4-methoxybenzene Chemical compound COC1=CC=C(N=C=S)C=C1 VRPQCVLBOZOYCG-UHFFFAOYSA-N 0.000 claims description 4
- 238000009987 spinning Methods 0.000 claims description 4
- YDUGLSQPIVEIMP-UHFFFAOYSA-N 1-ethyl-3-(3-methylphenyl)thiourea Chemical compound CCNC(=S)NC1=CC=CC(C)=C1 YDUGLSQPIVEIMP-UHFFFAOYSA-N 0.000 claims description 3
- 238000010189 synthetic method Methods 0.000 claims description 3
- ULNVBRUIKLYGDF-UHFFFAOYSA-N 1,3-bis(4-methylphenyl)thiourea Chemical compound C1=CC(C)=CC=C1NC(=S)NC1=CC=C(C)C=C1 ULNVBRUIKLYGDF-UHFFFAOYSA-N 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 11
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- 238000003541 multi-stage reaction Methods 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 238000002955 isolation Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 150000003585 thioureas Chemical class 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 3
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 2
- SRYLJBWDZZMDSK-UHFFFAOYSA-N (4-methoxyphenyl)thiourea Chemical compound COC1=CC=C(NC(N)=S)C=C1 SRYLJBWDZZMDSK-UHFFFAOYSA-N 0.000 description 1
- VXLFMCZPFIKKDZ-UHFFFAOYSA-N (4-methylphenyl)thiourea Chemical compound CC1=CC=C(NC(N)=S)C=C1 VXLFMCZPFIKKDZ-UHFFFAOYSA-N 0.000 description 1
- HNDPPFMCVAHWCO-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-ethylthiourea Chemical compound CCNC(=S)NC1=CC=C(Cl)C=C1 HNDPPFMCVAHWCO-UHFFFAOYSA-N 0.000 description 1
- FNGYBATZKHIECN-UHFFFAOYSA-N 1-ethyl-3-(4-methylphenyl)thiourea Chemical compound CCNC(=S)NC1=CC=C(C)C=C1 FNGYBATZKHIECN-UHFFFAOYSA-N 0.000 description 1
- OROCFDLTBPBLFS-UHFFFAOYSA-N 1-ethyl-3-phenylthiourea Chemical compound CCNC(=S)NC1=CC=CC=C1 OROCFDLTBPBLFS-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- FLVIGYVXZHLUHP-UHFFFAOYSA-N N,N'-diethylthiourea Chemical compound CCNC(=S)NCC FLVIGYVXZHLUHP-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- UXHQMSUJQLPRAW-UHFFFAOYSA-N benzene;isothiocyanic acid Chemical compound N=C=S.C1=CC=CC=C1 UXHQMSUJQLPRAW-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000002912 waste gas Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/16—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/06—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms
- C07C335/08—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms of a saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/16—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C335/18—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention provides a method for synthesizing 1, 3-disubstituted thiourea, which comprises the steps of taking isothiocyanate as a reaction substrate, dissolving the isothiocyanate by a solvent under an alkaline condition to generate an amine intermediate, carrying out condensation reaction on the amine intermediate and the isothiocyanate under the alkaline condition for 8-10 hours to prepare the 1, 3-disubstituted thiourea; according to the method, the isothiocyanate is used as a reaction substrate, the water is used as a solvent, highly toxic raw materials and multi-step reactions are avoided, and the reaction substrate is wide in applicability, simple and convenient to operate, low in cost, high in yield and environment-friendly.
Description
Technical Field
The invention relates to the technical field of organic chemistry, in particular to a method for synthesizing 1, 3-disubstituted thiourea in a water phase.
Background
Numerous chemical reactions are involved with thiourea compounds. Is an important organic intermediate. In medicine, some thiourea derivatives have been confirmed to have good antitumor activity (Medicinal Chemistry Research 2007,16 (6), 300-318). In the agricultural field, many thiourea derivatives are used for herbicides, pesticides (Chinese j. Org. Chem.2014,34 (12), 2517-2522). In the field of organic synthesis, thiourea compounds are not only synthesis intermediates for many important compounds, but also can be used as organic catalysts (Chinese j. Org. Chem.2007,27 (12), 1491-1501).
A common synthetic method of thiourea compounds is to prepare the thiourea compounds from thiophosgene and aniline (Chinese j. Org. Chem.2010,30 (02), 173-180), but the thiophosgene used in the method is a highly toxic raw material, potential safety hazards exist in the using process, and a large amount of waste gas is discharged in the reaction process to cause environmental pollution. In addition, the compound can be synthesized by taking isothiocyanate and amine as raw materials (J.Am.chem.Soc.2007, 129 (35), 10632-10633), but the method generally needs toxic organic solvents. Therefore, the development of a 1, 3-disubstituted thiourea synthesis method which is efficient, simple, convenient, environment-friendly and wide in substrate adaptability has higher theoretical and practical application values.
Disclosure of Invention
The invention aims to provide a method for synthesizing 1, 3-disubstituted thiourea in a water phase, which takes isothiocyanate as a raw material, takes Dimethylaminopyridine (DMAP) as alkali and is a novel method for preparing the 1, 3-disubstituted thiourea at the temperature of 100 ℃, and in the method, the isothiocyanate is taken as the raw material to simply and efficiently synthesize the 1, 3-disubstituted thiourea, and the reaction raw material is simple and easy to obtain, the operation is convenient, and the yield is higher.
The purpose of the invention is realized by the following technical scheme: a synthetic method of 1, 3-disubstituted thiourea uses isothiocyanate as a reaction substrate, and is dissolved by a solvent under an alkaline condition to generate an amine intermediate, and the amine intermediate and the isothiocyanate undergo a condensation reaction under the alkaline condition to prepare the 1, 3-disubstituted thiourea;
the method comprises the following steps:
in the air atmosphere, 0.2-0.4mmol of phenyl isothiocyanate and 0.2-0.4mmol of dimethylaminopyridine are magnetically stirred in water for 8-10h at the temperature of 90-100 ℃, TLC is used for monitoring the reaction process till complete reaction, ethyl acetate is added for extraction, anhydrous sodium sulfate is used for drying, the solvent is dried by decompression and spin drying, and then pure diphenylthiourea is obtained by column chromatography separation.
Further, the isothiocyanate is any one of phenyl isothiocyanate, ethyl isothiocyanate, 4-methoxyphenyl isothiocyanate, p-tolyl isothiocyanate, m-tolyl isothiocyanate and 4-chloro phenyl isothiocyanate.
Further, the solvent is water.
Further, the base is dimethylaminopyridine.
Further, the temperature of the condensation reaction is 90-100 ℃.
A method for synthesizing 1, 3-disubstituted thiourea comprises the following steps:
in the air atmosphere, 0.4mmol of phenyl isothiocyanate and 0.4mmol of dimethylaminopyridine are magnetically stirred in water at 100 ℃ for 10 hours, TLC is used for monitoring the reaction process till complete reaction, ethyl acetate is added for extraction, anhydrous sodium sulfate is used for drying, the solvent is dried by decompression and spinning, and then column chromatography is carried out to obtain pure diphenylthiourea 3a, wherein the separation yield is as follows: and 90 percent.
A method for synthesizing 1, 3-disubstituted thiourea comprises the following steps:
in the air atmosphere, 0.4mmol of p-methyl phenyl isothiocyanate and 0.4mmol of dimethylaminopyridine are magnetically stirred in water at 100 ℃ for 10 hours, TLC is used for monitoring the reaction process till complete reaction, ethyl acetate is added for extraction, anhydrous sodium sulfate is added for drying, the solvent is dried in a spinning mode under reduced pressure, and then column chromatography is carried out to obtain pure 1, 3-bis (4-methylphenyl) thiourea 3c, wherein the separation yield is as follows: 89 percent.
A method for synthesizing 1, 3-disubstituted thiourea comprises the following steps:
in the air atmosphere, 0.2mmol of ethyl isothiocyanate, 0.2mmol of m-toluyl isothiocyanate and 0.4mmol of dimethylaminopyridine are magnetically stirred in water at 100 ℃ for 10 hours, TLC is used for monitoring the reaction process till complete reaction, ethyl acetate is added for extraction, anhydrous sodium sulfate is used for drying, the solvent is dried in a spinning mode under reduced pressure, and 3g of pure 1-ethyl-3- (3-methylphenyl) -2-thiourea is obtained through column chromatography separation, and the separation yield is as follows: 72 percent.
Compared with the prior art, the invention has the beneficial effects that:
the invention adopts benzene isothiocyanate as a raw material to synthesize 1, 3-disubstituted thiourea in water. The reaction takes water as a solvent, and the raw materials are simple and easy to obtain, so the reaction cost is low;
the method has the advantages of one-step synthesis reaction, simple operation, high reaction efficiency, wide applicability of reaction substrates, high yield, greenness, environmental protection and considerable application prospect.
Drawings
FIG. 1: hydrogen spectrum of compound 3a.
FIG. 2 is a schematic diagram: carbon spectrum of compound 3a.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments, and all other embodiments obtained by a person of ordinary skill in the art without creative efforts based on the embodiments of the present invention belong to the protection scope of the present invention.
The invention is further explained by combining with a figure 1-2, a method for synthesizing 1, 3-disubstituted thiourea, which takes isothiocyanate as a reaction substrate, is dissolved by a solvent under an alkaline condition to generate an amine intermediate, and the amine intermediate and the isothiocyanate undergo a condensation reaction under the alkaline condition to prepare the 1, 3-disubstituted thiourea;
the method comprises the following steps:
in the air atmosphere, 0.2-0.4mmol of phenyl isothiocyanate and 0.2-0.4mmol of dimethylaminopyridine are magnetically stirred in water for 8-10h at the temperature of 90-100 ℃, TLC is used for monitoring the reaction process till complete reaction, ethyl acetate is added for extraction, anhydrous sodium sulfate is used for drying, the solvent is dried by decompression and spin drying, and then pure diphenylthiourea is obtained by column chromatography separation.
The invention further adopts the preferable technical scheme that: the isothiocyanate is any one of phenyl isothiocyanate, ethyl isothiocyanate, 4-methoxyphenyl isothiocyanate, p-tolyl isothiocyanate, m-tolyl isothiocyanate and 4-chloro phenyl isothiocyanate.
The invention further adopts the preferable technical scheme that: the solvent is water.
The invention further adopts the preferable technical scheme that: the base is dimethylaminopyridine.
The invention further adopts the preferable technical scheme that: the temperature of the condensation reaction is 90-100 ℃.
Detailed description of the preferred embodiment 1
0.4mmol of phenyl isothiocyanate and 0.4mmol of dimethylaminopyridine are magnetically stirred in water for 10 hours at the temperature of 100 ℃ in an air atmosphere, and the reaction process is monitored by TLC until the reaction is completed. After treatment, ethyl acetate is added to extract, and the mixture is dried by anhydrous sodium sulfate. Decompressing, spin-drying the solvent and separating by column chromatography to obtain the pure diphenyl thiourea 3a. Isolation yield: 90 percent.
1 H NMR(400MHz,DMSO)δ9.70(s,2H),7.40(d,J＝7.6Hz,4H),7.24(t,J＝7.5Hz,4H),7.03(t,J＝6.8Hz,2H). 13 C NMR(101MHz,DMSO)δ180.10,139.92,128.92,124.91,124.14.
Specific example 2
0.4mmol of 4-methoxyphenyl isothiocyanate and 0.4mmol of dimethylaminopyridine are magnetically stirred in water at 100 ℃ for 10h in an air atmosphere, and the reaction process is monitored by TLC until complete reaction. After the post-treatment, a proper amount of ethyl acetate is added for extraction, and the mixture is dried by anhydrous sodium sulfate. Decompressing, spin-drying the solvent and separating by column chromatography to obtain pure 1, 3-bi (4-methoxyphenyl) thiourea 3b. Isolation yield: 88 percent.
1 H NMR(400MHz,DMSO)δ9.47(s,2H),7.32(d,J＝8.9Hz,4H),6.90(d,J＝8.9Hz,4H),3.74(s,6H). 13 C NMR(101MHz,DMSO)δ180.64,156.96,132.70,126.57,114.09,55.68.
Example 2 deals primarily with the applicability of electron donating group (methoxy) containing substrates. The results of the examples show that electron donating substrates are equally suitable for this reaction to give 1, 3-disubstituted thiourea 3b.
Specific example 3
0.4mmol of p-methyl phenyl isothiocyanate and 0.4mmol of dimethylaminopyridine are magnetically stirred in water for 10 hours at 100 ℃ in an air atmosphere, and the reaction process is monitored by TLC until the reaction is completed. After the post-treatment, a proper amount of ethyl acetate is added for extraction, and the mixture is dried by anhydrous sodium sulfate. Decompressing, spin-drying the solvent and separating by column chromatography to obtain pure 1, 3-bi (4-methylphenyl) thiourea 3c. Isolation yield: 89 percent.
1 H NMR(400MHz,DMSO)δ9.59(s,1H),7.37–7.29(m,4H),7.13(d,J＝8.0Hz,4H),2.28(s,6H). 13 C NMR(101MHz,DMSO)δ179.97,137.24,134.08,129.34,124.31,20.98.
Example 3 mainly investigates the applicability of electron donating group (methyl) containing substrates. The results of the examples show that methyl-substituted phenylisothiocyanate gives the corresponding 1, 3-disubstituted thiourea 3c.
Specific example 4
0.4mmol of isothiocyanic acid ethyl ester and 0.4mmol of dimethylamino pyridine are magnetically stirred in water at 100 ℃ for 10h in an air atmosphere, and the reaction process is monitored by TLC until the reaction is completed. After the post-treatment, a proper amount of ethyl acetate is added for extraction, and the mixture is dried by anhydrous sodium sulfate. Decompressing, spin-drying the solvent and separating by column chromatography to obtain pure diethyl thiourea 3d. Isolation yield: 94 percent.
1 H NMR(400MHz,CDCl 3 )δ5.93(s,2H),3.44(s,4H),1.21(t,J＝7.2Hz,6H). 13 C NMR(101MHz,CDCl 3 )δ181.11,39.14,14.28.
Example 4 mainly considers the suitability of alkyl substrates. The results of the examples show that alkyl isothiocyanates can give the corresponding 1, 3-disubstituted thiourea 3d.
Specific example 5
0.2mmol of ethyl isothiocyanate, 0.2mmol of phenyl isothiocyanate and 0.4mmol of dimethylaminopyridine are magnetically stirred in water at 100 ℃ for 10 hours in an air atmosphere, and the reaction process is monitored by TLC until the reaction is completed. After treatment, ethyl acetate is added to extract, and the mixture is dried by anhydrous sodium sulfate. Decompressing, spin-drying the solvent and separating by column chromatography to obtain pure 1-ethyl-3-phenyl-2-thiourea 3e. Isolation yield: 72 percent.
1 H NMR(400MHz,CDCl 3 )δ8.26(s,1H),7.41(t,J＝7.7Hz,2H),7.31–7.26(m,1H),7.21(d,J＝7.7Hz,2H),6.03(s,1H),3.73–3.58(m,2H),1.17(t,J＝7.3Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ180.21,136.18,130.22,127.23,125.25,40.34,14.33.
Example 5 mainly investigated the feasibility of synthesizing asymmetric thioureas. The results of the examples show that the reaction of alkyl isothiocyanate with phenyl isothiocyanate gives the corresponding asymmetric 1, 3-disubstituted thiourea 3e.
Specific example 6
0.2mmol of ethyl isothiocyanate, 0.2mmol of p-tolyl isothiocyanate and 0.4mmol of dimethylaminopyridine are magnetically stirred in water at 100 ℃ for 10 hours in an air atmosphere, and the reaction process is monitored by TLC until the reaction is completed. After the post-treatment, a proper amount of ethyl acetate is added for extraction, and the mixture is dried by anhydrous sodium sulfate. Decompressing, spin-drying the solvent and separating by column chromatography to obtain pure 1-ethyl-3- (4-methylphenyl) -2-thiourea 3f. Isolation yield: 74 percent.
1 H NMR(400MHz,CDCl 3 )δ8.07(s,1H),7.22(d,J＝8.1Hz,2H),7.11(d,J＝8.2Hz,2H),6.00(s,1H),3.70–3.60(m,2H),2.36(s,3H),1.17(t,J＝7.3Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ180.47,137.40,133.46,130.72,125.50,40.27,21.07,14.34.
Example 6 mainly examines substrate compatibility of aryl (methyl) isothiocyanate containing electron donating group and alkyl isothiocyanate. The results of the examples show that the reaction of alkyl isothiocyanate with methyl-substituted phenyl isothiocyanate gives the corresponding asymmetric 1, 3-disubstituted thiourea 3f.
Specific example 7
0.2mmol of ethyl isothiocyanate, 0.2mmol of m-toluyl isothiocyanate and 0.4mmol of dimethylaminopyridine are magnetically stirred in water at 100 ℃ for 10 hours in an air atmosphere, and the reaction process is monitored by TLC until the reaction is completed. After the post-treatment, a proper amount of ethyl acetate is added for extraction, and the mixture is dried by anhydrous sodium sulfate. Decompressing and spin-drying the solvent, and separating by column chromatography to obtain 3g of pure 1-ethyl-3- (3-methylphenyl) -2-thiourea. Isolation yield: 72 percent.
1 H NMR(400MHz,CDCl 3 )δ8.17(s,1H),7.32–7.26(m,1H),7.08(d,J＝7.5Hz,1H),7.00(d,J＝6.3Hz,2H),6.06(s,1H),3.69–3.58(m,2H),2.34(s,3H),1.16(t,J＝7.2Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ180.29,140.40,136.16,129.93,128.03,125.86,122.24,40.31,21.42,14.37.
Specific example 8
0.2mmol of ethyl isothiocyanate, 0.2mmol of 4-chloro phenyl isothiocyanate and 0.4mmol of dimethylaminopyridine are magnetically stirred in water at 100 ℃ for 10 hours in an air atmosphere, and the reaction process is monitored by TLC until the reaction is completed. After the post-treatment, a proper amount of ethyl acetate is added for extraction, and the mixture is dried by anhydrous sodium sulfate. The solvent is dried by decompression and spin, and pure 1-ethyl-3- (4-chlorphenyl) -2-thiourea is obtained by column chromatography separation for 3h. Isolation yield: and 63 percent.
1 H NMR(400MHz,DMSO)δ9.63(s,1H),7.90(s,1H),7.46(d,J＝8.8Hz,2H),7.35(d,J＝8.8Hz,2H),3.47(s,2H),1.11(t,J＝7.2Hz,3H). 13 C NMR(101MHz,DMSO)δ180.54,138.89,129.10,128.83,124.87,120.18,39.12,14.58.
Example 8 deals primarily with the substrate compatibility of aryl isothiocyanates containing halogen atoms with alkyl isothiocyanates. The results of the examples show that the reaction of alkyl isothiocyanate with phenyl isothiocyanate containing a halogen atom can give the corresponding asymmetric 1, 3-disubstituted thiourea for 1h.
The invention takes isothiocyanate as raw material to prepare a series of 1, 3-disubstituted thiourea; in the invention, the 1, 3-disubstituted thiourea is simply and efficiently synthesized by taking the isothiocyanate as a raw material, and the reaction raw material is simple and easy to obtain, convenient to operate and high in yield.
In the description herein, references to the description of the term "one embodiment," "some embodiments," "an example," "a specific example," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, various embodiments or examples described in this specification can be combined and combined by those skilled in the art.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein. Any reference sign in a claim should not be construed as limiting the claim concerned.
Furthermore, it should be understood that although the present description refers to embodiments, not every embodiment may contain only a single embodiment, and such description is for clarity only, and those skilled in the art should integrate the description, and the embodiments may be combined as appropriate to form other embodiments understood by those skilled in the art.
Claims (8)
1. A synthetic method of 1, 3-disubstituted thiourea is characterized in that isothiocyanate is used as a reaction substrate and is dissolved by a solvent under an alkaline condition to generate an amine intermediate, and the amine intermediate and the isothiocyanate undergo a condensation reaction under the alkaline condition to prepare the 1, 3-disubstituted thiourea; the method comprises the following steps:
in the air atmosphere, 0.2-0.4mmol of phenyl isothiocyanate and 0.2-0.4mmol of dimethylaminopyridine are magnetically stirred in water for 8-10h at the temperature of 90-100 ℃, TLC is used for monitoring the reaction process till complete reaction, ethyl acetate is added for extraction, anhydrous sodium sulfate is used for drying, the solvent is dried by decompression and spin drying, and then pure diphenylthiourea is obtained by column chromatography separation.
2. The method for synthesizing 1, 3-disubstituted thiourea according to claim 1, wherein the isothiocyanate is any one of phenyl isothiocyanate, ethyl isothiocyanate, 4-methoxyphenyl isothiocyanate, p-tolyl isothiocyanate, m-tolyl isothiocyanate, 4-chlorophenyl isothiocyanate.
3. The method for synthesizing 1, 3-disubstituted thiourea according to claim 1, wherein the solvent is water.
4. The method for synthesizing 1, 3-disubstituted thiourea according to claim 1, wherein the base is dimethylaminopyridine.
5. The method for synthesizing 1, 3-disubstituted thiourea according to claim 1, wherein the temperature of the condensation reaction is 90-100 ℃.
6. The method for synthesizing 1, 3-disubstituted thiourea according to claim 1, characterized in that the specific method comprises the following steps:
in the air atmosphere, 0.4mmol of phenyl isothiocyanate and 0.4mmol of dimethylaminopyridine are magnetically stirred in water at 100 ℃ for 10 hours, TLC is used for monitoring the reaction process till complete reaction, ethyl acetate is added for extraction, anhydrous sodium sulfate is used for drying, the solvent is dried by decompression and spinning, and then column chromatography is carried out to obtain pure diphenylthiourea 3a, wherein the separation yield is as follows: and 90 percent.
7. The method for synthesizing 1, 3-disubstituted thiourea according to claim 1, characterized in that the specific method comprises the following steps:
in the air atmosphere, 0.4mmol of p-methyl phenyl isothiocyanate and 0.4mmol of dimethylaminopyridine are magnetically stirred in water for 10 hours at the temperature of 100 ℃, TLC is used for monitoring the reaction process till the complete reaction, ethyl acetate is added for extraction, anhydrous sodium sulfate is used for drying, the solvent is dried in a rotary manner under reduced pressure, and then the pure 1, 3-bis (4-methylphenyl) thiourea 3c is obtained through column chromatography separation, wherein the separation yield is as follows: 89 percent.
8. The method for synthesizing 1, 3-disubstituted thiourea according to claim 1, characterized in that the specific method comprises the following steps:
in the air atmosphere, 0.2mmol of ethyl isothiocyanate, 0.2mmol of m-toluyl isothiocyanate and 0.4mmol of dimethylaminopyridine are magnetically stirred in water at 100 ℃ for 10 hours, TLC is used for monitoring the reaction process till complete reaction, ethyl acetate is added for extraction, anhydrous sodium sulfate is dried, the solvent is dried in a rotary manner under reduced pressure, and then 3g of pure 1-ethyl-3- (3-methylphenyl) -2-thiourea is obtained through column chromatography separation, wherein the separation yield is as follows: 72 percent.
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| CN101525310A (en) * | 2009-04-21 | 2009-09-09 | 大连凯飞精细化工有限公司 | Method for compounding 1-benzoyl-3-(2-oxhydryl-1, 1-dimethylethyl) thiourea |
| CN101531622A (en) * | 2009-04-29 | 2009-09-16 | 淮阴师范学院 | Microwave synthesis method for 1-benzoyl-3-substituted phenylthiourea |
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| CN113444024A (en) * | 2021-07-07 | 2021-09-28 | 安徽师范大学 | Method for synthesizing polysubstituted ureas, thioureas, chiral ureas and thioureas compounds without catalyst and solvent |
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