CN109053631A - One kind passing through the synthetic method of isothiocyanates and 2- Sulfonylalkyl phenol synthesis benzo [1,3] oxazines -2- thioketones - Google Patents

One kind passing through the synthetic method of isothiocyanates and 2- Sulfonylalkyl phenol synthesis benzo [1,3] oxazines -2- thioketones Download PDF

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CN109053631A
CN109053631A CN201810980752.7A CN201810980752A CN109053631A CN 109053631 A CN109053631 A CN 109053631A CN 201810980752 A CN201810980752 A CN 201810980752A CN 109053631 A CN109053631 A CN 109053631A
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phenol
sulfonylalkyl
synthetic method
isothiocyanates
phenyl
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CN109053631B (en
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于丽萍
于世涛
肖建
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Qingdao University of Science and Technology
Qingdao Agricultural University
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Qingdao University of Science and Technology
Qingdao Agricultural University
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D279/00Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/041,3-Thiazines; Hydrogenated 1,3-thiazines
    • C07D279/081,3-Thiazines; Hydrogenated 1,3-thiazines condensed with carbocyclic rings or ring systems

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Abstract

The present invention has developed a kind of synthetic method that 2- Sulfonylalkyl phenol synthesis benzo [1,3] oxazines -2- thioketones is utilized under weak basic condition.Using 2- Sulfonylalkyl phenol and isothiocyanates as substrate, polyfunctional group benzo [1,3] oxazines -2- thioketones of nitrogen, oxygen, thia ring structure is contained using one-step synthesis method, expands the application of isothiocyanates and the reaction method of o-QMs.Synthetic method provided by the invention can react at room temperature, and reaction condition is mild, and substrate universality is good, be not necessarily to catalyst, but alkaline reagent simple and easy to get, easy to operate, economical and efficient;The reactivity of the method for the present invention is high, and yield is up to 92%, and raw material conversion is complete;Convenient product separation, and react with green economy, it is environmentally friendly.

Description

One kind passing through isothiocyanates and 2- Sulfonylalkyl phenol synthesis benzo [1,3] oxazines- The synthetic method of 2- thioketones
Technical field
The invention belongs to chemosynthesis technical fields, and the present invention relates to one kind to pass through isothiocyanates and 2- Sulfonylalkyl benzene The synthetic method of phenol synthesis benzo [1,3] oxazines -2- thioketones.
Background technique
Heterocyclic compound becomes the hot spot of drug research field research and development due to extensive bioactivity, wherein oxazines- 2- thioketones belong to it is a kind of containing nitrogen, oxygen, sulfur heteroatom polycyclic compound, such compound have anticancer, antitumor, analgesia, The bioactivity such as desinsection and sterilization.For example, the synthetic progestin Tanaproget of on-steroidal, it is clinical to enter the second phase in 2010 Test, future possibly serve for effective contraceptive.
But at present for the synthetic method of oxazines -2- thioketones, including the use of corresponding oxazines -2- ketone be substrate and Lawesson reagent carries out substitution reaction (Bioorg.Med.Chem.Lett.2003,13,1313-1316), or utilizes organolithium It is catalyzed phenyl isothiocyanate and carries out intramolecular nucleophilic displacement of fluorine (New J.Chem., 2017,41,7824-7835).
2015, Kazuhiro Kobayashi et al. utilized 2- (1- alkylisothiocyanate) phenol, in temperate condition Lower carry out intramolecular cyclization generates benzoxazine -2- thioketones (Heterocycles, 2016,93,63-74).Although the reaction can It effectively to synthesize benzoxazine -2- thioketones, but is carried out for the ease of reaction, and the synthetic strategy of intramolecular cyclization is taken to lead Cause substrate relatively limited;And substrate 2- (1- alkylisothiocyanate) phenol is complicated for operation by five step synthesis processes.
Isothiocyanates may participate in various organic reactions, special for synthesizing a plurality of types of sulfur-bearings, nitrogen, the compound of oxygen It is heterocyclic compound.It is located at the electrophilicity that the C in-N=C=S has height in isothiocyanic acid ester molecule, can be sent out with nucleopilic reagent Raw nucleophilic addition.Such as in above-mentioned synthetic schemes, intramolecular nucleophilic addition cyclization occurs for isothiocyanate group.Due to The classical reaction pattern of isothiocyanates is confined to nucleophilic addition, and be applied to the natural products containing glycosyl heterocycle and its Analog it is fully synthetic, limit isothiocyanates in the development of drug chemical field.
O-quinone methides (o-QMs) are a kind of transient state, the very high reactive intermediate of reactivity, and there are two types of typical for it Existence form: diradical substance or polarization amphoteric ion.But asymmetric [4+2] cycloaddition of catalysis that o-QMs is participated in is anti- It answers difficult point to be not only in that its of short duration service life, further includes that catalyst and o-QMs effect too weak are not enough to promote reaction.And And at present in a variety of generting machanisms of o-QMs, Lewis acid andAcid catalysis substituent group leave away operating method simplicity, answer With in extensive range, but the o-QMs precursor containing acid-sensitive functional group (such as phenolic hydroxyl group) is not particularly suited for these acidic catalysts. Therefore, under neutral or weak basic condition, elimination reaction will be carried out containing the compound of the groups such as hydroxyl and generate o-QMs, it can be with Effectively expand the synthetic reaction type that o-QMs is participated in.
Therefore, in order to realize efficiently synthesizing for benzoxazine -2- thione compounds, and isothiocyanates and o- are expanded The application of the reaction method of QMs needs a kind of strategy of new benzo [1,3] oxazines -2- thione compounds synthesis conversion.
Summary of the invention
The purpose of the present invention is to provide pass through isothiocyanates and 2- Sulfonylalkyl phenol synthesis benzo [1,3] oxazines- The synthetic method of 2- thioketones.Operation of the present invention is simple and practical, and yield is good, and reacts with green economy, environmentally friendly.
Synthetic method provided by the present invention, specifically:
2- Sulfonylalkyl phenol and isothiocyanates, under alkaline reagent effect, reaction generates the benzo [1,3] and dislikes Piperazine -2- thioketones.
Above-mentioned benzo [1,3] oxazines -2- thioketones is compound shown in formula I:
In formula I, dotted line indicates optional singly-bound;
R1In methyl, methoxyl group, halogen any one;And
R2、R3It is each independently selected from C1-C3Alkyl, phenethyl, phenyl, trifluoromethyl, cyano-phenyl, halogen take For phenyl, C1-C3Alkyl-substituted phenyl, C1-C3Any one in alkoxy substituted phenyl.
Above-mentioned 2- Sulfonylalkyl phenol is compound shown in formula II, and above-mentioned isothiocyanates is compound shown in formula III:
In formula II, formula III, dotted line indicates optional singly-bound;
R1In methyl, methoxyl group, halogen any one;And
R2、R3It is each independently selected from C1-C3Alkyl, phenethyl, phenyl, trifluoromethyl, cyano-phenyl, halogen take For phenyl, C1-C3Alkyl-substituted phenyl, C1-C3Any one in alkoxy substituted phenyl.
Above-mentioned alkaline reagent be cesium carbonate, potassium carbonate, triethylamine, 11 carbon -7- alkene of 1,8- diazabicylo [5.4.0], Any one in tetramethylguanidine.
Above-mentioned reaction carries out in a solvent, and solvent is methylene chloride, tetrahydrofuran, any one in dioxanes.
The molar ratio of above-mentioned 2- Sulfonylalkyl phenol and isothiocyanates is 2:3.
The molar ratio of above-mentioned alkaline reagent and 2- Sulfonylalkyl phenol is 2.5:1;The dosage of the solvent is every mole of 2- Sulfonylalkyl phenol adds 10L solvent.
Above-mentioned reaction carries out under the conditions of 25 DEG C.
The above-mentioned reaction time is 1-16h.
The present invention provides one kind and passes through isothiocyanates and 2- Sulfonylalkyl phenol synthesis benzo [1,3] oxazines -2- thioketones Synthetic method, specifically includes the following steps:
2- Sulfonylalkyl phenol 0.2mmol is added in 2mL solvent, then to isothiocyanates is added in solvent 0.3mmol and alkaline reagent 0.5mmol;Control system temperature is 25 DEG C of room temperature, lasting to stir, by chromatographic sheet point sample with Track is reacted to raw material fully reacting;
After reacting 12h, using reaction product in silica gel post separation solution, by obtaining product after concentrated by rotary evaporation.
Compound of the present invention can exist in the form of one or more kinds of stereoisomers.Various isomers packets Include enantiomter, diastereoisomer, geometric isomer.These isomers include the mixture of these isomers in this hair In bright protection scope.
Technical solution of the present invention achieves as follows the utility model has the advantages that under alkaline condition, and 2- Sulfonylalkyl phenol is sloughed to first With isothiocyanates [4+2] cycloaddition reaction occurs for benzenesulfonyl in-situ preparation o-QMs.The reaction is strong because of isothiocyanates The difficult of inverse electrical requirements hetero Diels Alder reaction occurs for short of electricity subsystem, but undergoes a kind of series connection cyclisation anti- It answers.Since the property of isothiocyanates is influenced the product very big, different substituents cause reaction acquisition different by substituent effect, And not it is only benzo [1,3] oxazines -2- thioketones.It is specifically expressed as follows: firstly, 2- Sulfonylalkyl phenol sloughs tolysulfonyl Base in-situ preparation o-QMs, then the short of electricity center carbon of the oxygen atom attack isothiocyanates of o-QMs, forms the mistake of two kinds of resonance State amphoteric ion TS2 and TS2 ' is crossed, when R is methoxyl group, methyl, fluorine, chlorine, bromine and trifluoromethyl substituted-phenyl, with the shape of TS2 Formula generates product 3;When R is p-nitrophenyl, product 4 is generated in the form of TS2 ';When R is to cyano-phenyl, two kinds of shapes Formula exists to arrive mix products.But when R is ester group, o-QMs is not undergone, but phenolic hydroxyl group is directly as nucleophilic Reagent carries out addition reaction to isothiocyanates, generates product 5.
The present invention has developed one kind and has utilized 2- Sulfonylalkyl phenol synthesis benzo [1,3] oxazines -2- under weak basic condition The synthetic method of thioketones.Using 2- Sulfonylalkyl phenol and isothiocyanates as substrate, using one-step synthesis method contain nitrogen, Polyfunctional group benzo [1,3] oxazines -2- thioketones of oxygen, thia ring structure.This method reaction substrate is conveniently easy to get, substrate universality It is good, and the position of substrate substituent group does not influence reaction yield significantly.Alkaline reagent is simple and easy to get, easy to operate, economical Efficiently;Reactivity is higher, and raw material conversion is complete;Convenient product separation, and react with green economy, it is environmentally friendly.
Specific embodiment
The specific embodiment provided by following embodiment carries out further specifically above content of the invention It is bright, for the technical staff of this research field, this should not be interpreted as the above-mentioned theme of the present invention range be only limitted to it is following Example;The techniques implemented on the basis of the foregoing are all within the scope of the present invention.
Experimental method used in following example is conventional method unless otherwise specified;Institute in following embodiments Reagent, material, instrument etc., are commercially available unless otherwise specified.
Embodiment 1
2- (α-phenyl p-toluenesulfonyl) phenol of 0.2mmol is taken in reaction flask, to sequentially add 2mL solvent, 0.3mmol phenyl isothiocyanate finally adds 0.5mmol alkaline reagent.It is 25 DEG C of control system temperature, lasting to stir, pass through The tracking of chromatographic sheet point sample is reacted to raw material fully reacting.
To after the reaction was completed, be isolated and purified using silicagel column, product after purification is rotated into obtain target product.
Using above-mentioned reaction equation, 10 groups of parallel test groups are set up, different alkaline reagents, solvent and reaction time are used. Alkaline reagent is respectively cesium carbonate Cs2CO3, potassium carbonate K2CO3, 11 carbon of triethylamine TEA, 1,8- diazabicylo [5.4.0]- 7- alkene DBU, tetramethylguanidine TMG.Solvent is respectively methylene chloride DCM, tetrahydrofuran THF, dioxanes Dioxane.Test group tool Alkaline reagent, solvent type and the concentration that body uses are as shown in table 1:
1. 2- of table (α-phenyl p-toluenesulfonyl) phenol and phenyl isothiocyanate reaction yield table
Serial number Alkaline reagent Solvent Reaction time (h) Yield (%)
1 Cs2CO3 DCM 12 92
2 Cs2CO3 Dioxane 12 86
3 Cs2CO3 THF 12 79
4 TEA DCM 12 63
5 DBU DCM 12 54
6 TMG DCM 12 62
7 K2CO3 DCM 12 75
8 Cs2CO3 DCM 1 19
9 Cs2CO3 DCM 8 72
10 Cs2CO3 DCM 16 80
Note: yield is separation yield.
According to the above parallel test interpretation of result, reduction or increase reaction time will lead to the reduction of reactant yield, anti- Answer middle selection metal salt reagent and organic alkali agents that can obtain higher purpose product yield.
Embodiment 2
According to the operating procedure and reagent dosage of embodiment 1, in reaction system, 2- (α-phenyl p-toluenesulfonyl) phenol It is reacted respectively with 4- cyano-phenyl isothiocyanates, 4- nitro phenylisothiocyanate, different sulphur cyanato- Ethyl formate, alkaline reagent For dosage 0.5mmol cesium carbonate, solvent is made with 2mL DCM, is persistently stirred to react at a temperature of 25 DEG C, reaction was completed by 12h.
According to the above test result analysis, one of reaction raw materials are the isothiocyanates with different electrical substituent groups, instead Its different addition product that carried out what [4+2] cycloaddition obtained from o-QMs during answering, benzo [1,3] oxazines -2- thioketones Yield can significantly reduce.
In the following example 3-16, according to the operating procedure of embodiment 1, in reaction system, raw material 1- Sulfonylalkyl phenol It is respectively 0.2mmol, 0.3mmol with isothiocyanates, alkaline reagent is dosage 0.5mmol cesium carbonate, is made with 2mL DCM molten Agent is persistently stirred to react at a temperature of 25 DEG C, and by 12h, reaction was completed.
Embodiment 3
Raw material: 2- (α-phenyl p-toluenesulfonyl) phenol, phenyl isothiocyanate
Product: chemical formula: C20H15NOS
Molecular weight: 318.4126
Structural formula:
Yield: 92%
1H NMR(500MHz,CDCl3) δ 7.39-7.31 (m, 8H), 7.21-7.14 (m, 3H), 7.04 (d, J=7.1Hz, 3H),5.69(s,1H).13C NMR(125MHz,CDCl3) δ=182.9,147.9,143.8,140.2,129.6,129.5, 129.2,128.9,128.5,127.6,127.4,126.2,125.5,121.8,116.5,67.1.HRMS(ESI)Calcd for C20H15NOS[M+H]+:318.4121,Found:318.4126.
Embodiment 4
Raw material: 4- methyl -2- (α-phenyl p-toluenesulfonyl) phenol, phenyl isothiocyanate
Product: chemical formula: C21H17NOS
Molecular weight: 332.4386
Structural formula:
Yield: 81%
1H NMR(500MHz,CDCl3)δ7.39–7.30(m,6H),7.21-7.15(m,4H),7.02(s,2H),6.81 (s,1H),5.63(s,1H),2.28(s,3H).13C NMR(125MHz,CDCl3) δ=183.1,146.0,143.9,140.3, 135.3,130.2,129.5,129.2,128.9,128.4,127.6,127.4,126.3,121.4,116.2,67.2, 20.8.HRMS(ESI)Calcdfor C21H17NOS[M+H]+:332.4381,Found:332.4386.
Embodiment 5
Raw material: 2- methoxyl group -6- (α-phenyl p-toluenesulfonyl) phenol, phenyl isothiocyanate
Product: chemical formula: C21H17NO2S
Molecular weight: 348.4386
Structural formula:
Yield: 62%
1H NMR(500MHz,CDCl3)δ7.31-7.26(m,6H),7.20(s,2H),7.08–7.02(m,3H),6.90 (d, J=8.0Hz, 1H), 6.58 (d, J=7.6Hz, 1H), 5.65 (s, 1H), 3.94 (s, 3H)13C NMR(125MHz, CDCl3) δ=182.5,147.0,143.8,140.1,137.6,129.4,129.1,128.8,128.3,12 7.5,127.2, 125.5,122.8,117.0,111.5,66.9,56.0.HRMS(ESI)Calcd for C21H17NO2S[M+H]+:348.4381, Found:348.4386.
Embodiment 6
Raw material: the chloro- 2- of 4- (α-phenyl p-toluenesulfonyl) phenol, phenyl isothiocyanate
Product: chemical formula: C20H14ClNOS
Molecular weight: 352.8577
Structural formula:
Yield: 71%
1H NMR(500MHz,CDCl3) δ 7.39-7.30 (m, 7H), 7.26 (d, J=3.2Hz, 1H), 7.16 (dd, J= 6.5,3.0Hz, 2H), 7.00 (d, J=2.2Hz, 3H), 5.62 (s, 1H)13C NMR(125MHz,CDCl3) δ=182.4, 146.4,143.6,139.5,130.5,129.7,129.6,129.4,129.2,128.6,127.5,127.3,126.0, 123.3,118.0,66.7.HRMS(ESI)Calcd for C20H14ClNOS[M+H]+:352.8572,Found:352.8577.
Embodiment 7
Raw material: 2- (α-aminomethyl phenyl p-toluenesulfonyl) phenol, phenyl isothiocyanate
Product: chemical formula: C21H17NOS
Molecular weight: 332.4392
Structural formula:
Yield: 83%
1H NMR(500MHz,CDCl3) δ 7.38-7.28 (m, 5H), 7.21-7.10 (m, 3H), 7.02 (d, J=7.2Hz, 3H), 6.96 (d, J=8.7Hz, 2H), 5.62 (s, 1H), 2.29 (s, 3H) .HRMS (ESI) Calcd for C21H17NOS[M+ H]+:332.4387,Found:332.4392.
Embodiment 8
Raw material: 2- (α-is to benzyloxy p-toluenesulfonyl) phenol, phenyl isothiocyanate
Product: chemical formula: C21H17NO2S
Molecular weight: 348.4386
Structural formula:
Yield: 86%
1H NMR(500MHz,CDCl3) δ 7.32-7.14 (m, 5H), 7.04 (t, J=7.2Hz, 1H), 6.96 (d, J= 8.7Hz, 2H), 6.90 (d, J=7.7Hz, 3H), 6.72 (d, J=8.6Hz, 2H), 5.55 (s, 1H), 3.67 (s, 3H) .HRMS (ESI)Calcd for C21H17NO2S[M+H]+:348.4381,Found:348.4386.
Embodiment 9
Raw material: 2- (α-o-methyl-phenyl p-toluenesulfonyl) phenol, phenyl isothiocyanate
Product: chemical formula: C21H17NOS
Molecular weight: 332.4392
Structural formula:
Yield: 71%
1H NMR(500MHz,CDCl3)δ7.36–7.28(m,5H),7.24–7.14(m,4H),7.14–7.02(m,3H), 6.90 (d, J=7.6Hz, 1H), 6.05 (s, 1H), 1.97 (s, 3H) .HRMS (ESI) Calcd for C21H17NOS[M+H]+: 332.4387,Found:332.4392.
Embodiment 10
Raw material: 2- (α-phenyl p-toluenesulfonyl) phenol, to Tolueneisothiocyanate
Product: chemical formula: C21H17NOS
Molecular weight: 332.4392
Structural formula:
Yield: 83%
1H NMR(500MHz,CDCl3) δ 7.38-7.27 (m, 5H), 7.22-7.09 (m, 5H), 7.01 (d, J=7.5Hz, 1H), 6.89 (d, J=7.0Hz, 2H), 5.65 (s, 1H), 2.34 (s, 3H)13C NMR(125MHz,CDCl3) δ=183.0, 147.9,141.3,140.3,138.5,130.2,129.5,129.2,128.9,127.4,127.2,126.2,125.4, 121.8,116.5,67.1,21.2.HRMS(ESI)Calcd for C21H17NOS[M+H]+:332.4387,Found: 332.4392.
Embodiment 11
Raw material: 2- (α-phenyl p-toluenesulfonyl) phenol, Tolueneisothiocyanate
Product: chemical formula: C21H17NOS
Molecular weight: 332.4392
Structural formula:
Yield: 73%
1H NMR(500MHz,CDCl3) δ 7.29-7.17 (m, 6H), 7.17-7.02 (m, 5H), 6.94 (d, J=7.3Hz, 1H), 6.74 (d, J=34.9Hz, 2H), 5.58 (s, 1H), 2.20 (s, 3H)13C NMR(125MHz,CDCl3) δ=182.8, 147.9,143.7,140.2,139.6,129.5,129.2,129.2,129.1,128.8,127.8,127.3,126.1, 125.4,124.6,121.8,116.4,67.0,21.2.HRMS(ESI)Calcd for C21H17NOS[M+H]+:332.4387, Found:332.4392.
Embodiment 12
Raw material: 2- (α-phenyl p-toluenesulfonyl) phenol, 4- methoxyphenyl isothiocyanates
Product: chemical formula: C21H17NO2S
Molecular weight: 348.4386
Structural formula:
Yield: 74%
1H NMR(500MHz,CDCl3) δ 7.39-7.28 (m, 5H), 7.21-7.11 (m, 3H), 7.01 (d, J=7.2Hz, 1H), 6.92 (s, 2H), 6.83 (d, J=8.7Hz, 2H), 5.64 (s, 1H), 3.79 (s, 3H)13C NMR(125MHz,CDCl3) δ=183.2,159.1,147.9,140.3,136.7,129.5,129.2,128.9,128.6,12 7.5,126.2,125.4, 121.8,116.5,114.6,67.3,55.4.HRMS(ESI)Calcd for C21H17NO2S[M+H]+:348.4381,Found: 348.4386.
Embodiment 13
Raw material: 2- (α-phenyl p-toluenesulfonyl) phenol, 4- fluorophenylisothiocyanate
Product: chemical formula: C20H14FNOS
Molecular weight: 336.4031
Structural formula:
Yield: 85%
1H NMR(500MHz,CDCl3) δ 7.39-7.29 (m, 5H), 7.17-7.14 (m, 3H), 7.01 (d, J=7.8Hz, 5H),5.64(s,1H).13C NMR(125MHz,CDCl3) δ=183.0,161.9 (d, J=249.1Hz), 147.7,139.7 (d, J=2.5Hz), 139.6,129.6,129.5 (d, J=7.0Hz), 129.2,129.0,127.4,126.2,125.5, 121.5,116.6,116.4,67.1.HRMS(ESI)Calcd for C20H14FNOS[M+H]+:336.4026,Found: 336.4031.
Embodiment 14
Raw material: 2- (α-phenyl p-toluenesulfonyl) phenol, 4- chlorophenyl isothiocyanate
Product: chemical formula: C20H14ClNOS
Molecular weight: 352.8577
Structural formula:
Yield: 94%
1H NMR(500MHz,CDCl3) δ 7.38-7.29 (m, 7H), 7.17-7.13 (m, 3H), 7.01 (d, J=7.6Hz, 1H), 6.95 (d, J=7.5Hz, 2H), 5.63 (s, 1H)13C NMR(125MHz,CDCl3) δ=182.9,147.8,142.2, 139.9,134.3,129.8,129.7,129.3,129.1,127.4,126.3,125.6,121.5,116.5,67.1.HRMS (ESI)Calcd forC20H14ClNOS[M+H]+:352.8572,Found:352.8577.
Embodiment 15
Raw material: 2- (α-phenyl p-toluenesulfonyl) phenol, 4- bromophenyl isothiocyanates
Product: chemical formula: C20H14BrNOS
Molecular weight: 397.3087
Structural formula:
Yield: 81%
1H NMR(500MHz,CDCl3) δ 7.47 (d, J=7.9Hz, 2H), 7.40-7.27 (m, 5H), 7.24-7.12 (m, 3H), 7.03 (d, J=7.5Hz, 1H), 6.90 (d, J=6.8Hz, 2H), 5.65 (s, 1H)13C NMR(125MHz,CDCl3)δ =182.8,147.7,142.7,139.8,132.8,129.7,129.4,129.3,129.1,12 7.3,126.2,125.6, 122.4,121.4,116.4,67.0.HRMS(ESI)Calcd for C20H14BrNOS[M+H]+:397.3082,Found: 397.3087.
Embodiment 16
Raw material: 2- (α-phenyl p-toluenesulfonyl) phenol, benzyl isothiocyanate
Product: chemical formula: C21H17NOS
Molecular weight: 332.4392
Structural formula:
Yield: 73%
1H NMR(500MHz,CDCl3) δ 7.40-7.31 (m, 6H), 7.30-7.20 (m, 4H), 7.05 (t, J=7.6Hz, 1H), 6.90 (d, J=7.2Hz, 1H), 6.32 (d, J=15.1Hz, 1H), 5.34 (s, 1H), 4.10 (d, J=15.2Hz, 1H) .13CNMR(125MHz,CDCl3) δ=183.6,147.6,140.0,134.6,129.5,129.4,129.0,128.3,128.2, 126.9,126.4,126.3,126.3,125.3,116.3,61.2,56.2.HRMS(ESI)Calcd for C21H17NOS[M+ H]+:332.4387,Found:332.4392.
The above described is only a preferred embodiment of the present invention, being not that the invention has other forms of limitations, appoint What those skilled in the art changed or be modified as possibly also with the technology contents of the disclosure above equivalent variations etc. Imitate embodiment.But without departing from the technical solutions of the present invention, according to the technical essence of the invention to above embodiments institute Any simple modification, equivalent variations and the remodeling made, still fall within the protection scope of technical solution of the present invention.

Claims (9)

1. one kind passes through the synthetic method of isothiocyanates and 2- Sulfonylalkyl phenol synthesis benzo [1,3] oxazines -2- thioketones, It is characterized in that:
2- Sulfonylalkyl phenol and isothiocyanates, under alkaline reagent effect, reaction generates benzo [1, the 3] oxazines -2- Thioketones.
2. synthetic method according to claim 1, it is characterised in that:
Benzo [1,3] oxazines -2- thioketones is compound shown in formula I:
In formula I, dotted line indicates optional singly-bound;
R1In methyl, methoxyl group, halogen any one;And
R2、R3It is each independently selected from C1-C3It is alkyl, phenethyl, phenyl, trifluoromethyl, cyano-phenyl, halogen-substituted Base, C1-C3Alkyl-substituted phenyl, C1-C3Any one in alkoxy substituted phenyl.
3. synthetic method according to claim 1 or 2, it is characterised in that:
The 2- Sulfonylalkyl phenol is compound shown in formula II, and the isothiocyanates is compound shown in formula III:
In formula II, formula III, dotted line indicates optional singly-bound;
R1In methyl, methoxyl group, halogen any one;And
R2、R3It is each independently selected from C1-C3It is alkyl, phenethyl, phenyl, trifluoromethyl, cyano-phenyl, halogen-substituted Base, C1-C3Alkyl-substituted phenyl, C1-C3Any one in alkoxy substituted phenyl.
4. synthetic method according to claim 3, it is characterised in that: the alkaline reagent is cesium carbonate, potassium carbonate, three second Amine, 11 carbon -7- alkene of 1,8- diazabicylo [5.4.0], any one in tetramethylguanidine.
5. synthetic method according to claim 4, it is characterised in that: the reaction carries out in a solvent, and solvent is dichloro Methane, tetrahydrofuran, any one in dioxanes.
6. synthetic method according to claim 5, it is characterised in that: the 2- Sulfonylalkyl phenol and isothiocyanates Molar ratio is 2:3.
7. synthetic method according to claim 6, it is characterised in that: the alkaline reagent rubs with 2- Sulfonylalkyl phenol You are than being 2.5:1;The dosage of the solvent is that every mole of 2- Sulfonylalkyl phenol adds 10L solvent.
8. synthetic method according to claim 7, it is characterised in that: the reaction carries out under the conditions of 25 DEG C.
9. synthetic method according to claim 1-8, it is characterised in that: specifically includes the following steps:
2- Sulfonylalkyl phenol 0.2mmol is added in 2mL solvent, then to addition isothiocyanates 0.3mmol in solvent With alkaline reagent 0.5mmol;Control system temperature is 25 DEG C of room temperature, lasting to stir, and is tracked and is reacted by chromatographic sheet point sample To raw material fully reacting;
After reacting 12h, using reaction product in silica gel post separation solution, by obtaining product after concentrated by rotary evaporation.
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