CN107151237B - A kind of 3- sulfuryl cumarin and preparation method thereof - Google Patents
A kind of 3- sulfuryl cumarin and preparation method thereof Download PDFInfo
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- CN107151237B CN107151237B CN201710339751.XA CN201710339751A CN107151237B CN 107151237 B CN107151237 B CN 107151237B CN 201710339751 A CN201710339751 A CN 201710339751A CN 107151237 B CN107151237 B CN 107151237B
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- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
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Abstract
The invention discloses a kind of 3- sulfuryl cumarin and preparation method thereof, the method for the present invention is that in organic solvent, arylamine, phenylpropiolic acid phenyl ester are reacted with sodium formaldehyde sulfoxylate, and 3- sulfuryl coumarin compound, the structure warp of such compound is made1H NMR、13The methods of C NMR, HRMS are characterized and are confirmed.The method of the present invention is reacted in a mild condition, using sodium formaldehyde sulfoxylate as sulfur dioxide source, is directly realized sulfonylating reaction, is constructed 3- sulfuryl coumarin compound；This conversion reaction raw material is simple and easy to get, and avoids the use of sulfonic acid chloride in prior synthesizing method, is applicable to fairly large preparation, has extraordinary application prospect.
Description
Technical field
The invention belongs to cumarin technical fields more particularly to a kind of 3- sulfuryl cumarin and preparation method thereof.
Background technique
Coumarin compound plays an important role in fields such as medicine, dyestuff, materials.Coumarin skeleton is common miscellaneous
One of ring structure is widely present among a variety of natural products and drug molecule with significant bioactivity.For example, from plant
The Calanolide A extracted in diversiform-leaved poplar paulownia shows extraordinary HIV-1 reverse transcriptase inhibitory activity, is a kind of potential anti-
AIDS-treating medicine；Coumarin kind compound warfarin (Wafarin) is a kind of anti-coagulants for being widely used in clinical medicine；Rue
In umbelliferone, angelica lactone in aesculetin and Radix Angelicae Pubescentis in the bark of ash etc. all has coumarin skeleton；Work
The fluorescent coumarin dye of industry includes disperse yellow 184, disperse yellow 232, solvent red 196 and disperse red 277 etc..Its derivative
It is also used as the fields such as fluorescence probe, semiconductor material, optical switch material and bio-imaging.Due to Coumarins chemical combination
Object is extensive with these and important role, the new structure and its completely new synthetic method for developing coumarin skeleton have very big
Demand.
Sulfuryl segment is also widely present in many natural products and drug molecule, these compounds in clinical medicine and
It has been widely used in Chemical Manufacture.The method of traditional synthesis sulfone compound relate generally to sulfur-containing compound such as thiophenol,
The oxidation of mercaptan and thioether；And sulfinate and electrophilic reagent carry out substitution reaction.The method of oxidation needs to use some strong
Oxidant and sulfur-bearing regent have the smell of stench, are unfavorable for operating with.In addition, sulfinate derives from corresponding sulphur
Acyl chlorides, and needed in the preparation process of sulfonic acid chloride using some strong chlorination reagents.In order to overcome these disadvantages, using industrial
Cheap and easily-available, simple and stable, easy to operate sulfur dioxide substitute has been applied it to as sulfur dioxide source
It will become very valuable in machine synthesis.
Based on this, the present invention is reacted using arylamine, phenylpropiolic acid phenyl ester with sodium formaldehyde sulfoxylate.Reaction experience aryl sulfonyl is free
Base then carries out addition and intramolecular cyclization, the migration of further occurrence ester group and aromatisation to alkynyl in phenylpropiolic acid phenyl ester,
3- sulfuryl cumarin is made, to provide a kind of new technology for efficiently synthesizing 3- sulfuryl cumarin.
Summary of the invention
The technical problem to be solved by the invention is to provide a kind of 3- sulfuryl cumarins and preparation method thereof.
In order to solve the above technical problems, the present invention adopts the following technical scheme: a kind of 3- sulfuryl cumarin, general structure I
Shown in one kind 3- sulfuryl coumarin derivative:
Wherein, Ar is phenyl, the aromatic substituent containing electron-donating group or electron-withdrawing group；Preferably, described to contain
The aromatic substituent of electron-donating group is p-methylphenyl, p-methoxyphenyl, o-methyl-phenyl, o-methoxyphenyl, first
Base phenyl or m-methoxyphenyl；The aromatic substituent containing electron-withdrawing group is rubigan, p-fluorophenyl, to bromine
Phenyl, p-nitrophenyl, Chloro-O-Phenyl, o-fluorophenyl, o-bromophenyl, chlorphenyl, fluorophenyl or m-bromophenyl.
R1 is H, electron-donating group or electron-withdrawing group；Preferably, the electron-donating group be methyl, ethyl, tert-butyl,
Normal-butyl or methoxyl group；The electron-withdrawing group is chlorine, fluorine, bromine, ester group, acetyl group or trifluoromethyl.
R2 is aromatic substituent or alkyl containing electron-donating group or electron-withdrawing group；Preferably, described to contain power supply
The aromatic substituent of subbase group is p-methylphenyl, p-methoxyphenyl, o-methyl-phenyl, o-methoxyphenyl, methylbenzene
Base or m-methoxyphenyl；Aromatic substituent containing electron-withdrawing group is rubigan, p-fluorophenyl, p-bromophenyl, right
Nitrobenzophenone, p-trifluoromethyl phenyl, to acetylphenyl, Chloro-O-Phenyl, o-fluorophenyl, o-bromophenyl, chlorphenyl, fluorine
Phenyl or m-bromophenyl；Alkyl is methyl, ethyl, n-propyl or normal-butyl.
The preparation method of 3- sulfuryl cumarin provided by the invention is anti-using arylamine, phenylpropiolic acid phenyl ester and sodium formaldehyde sulfoxylate
It answers.Reaction experience aryl sulfonyl free radical, then carries out addition and intramolecular cyclization to alkynyl in phenylpropiolic acid phenyl ester, into
Ester group migration and aromatisation occur for one step, efficiently synthesize 3- sulfuryl cumarin.Specifically, the method for the present invention is in organic solvent
In, arylamine, phenylpropiolic acid phenyl ester are reacted with sodium formaldehyde sulfoxylate at 70~80 DEG C.Reaction experience aryl sulfonyl free radical, it is then right
Alkynyl carries out addition and intramolecular cyclization, the migration of further occurrence ester group and aromatisation in phenylpropiolic acid phenyl ester, and 3- sulfone is made
Butylcoumariii 1, reaction equation are as follows:
A kind of preparation method of 3- sulfuryl cumarin, comprising the following steps:
Step 1: sequentially added in reaction tube arylamine, boron trifluoride ether solution,tBuONO and organic solvent, In
Inert nitrogen gas or argon gas protection under, in 70~80 DEG C stirring 0.5-1.0 hours；
Step 2: being added phenylpropiolic acid phenyl ester and sodium formaldehyde sulfoxylate, 70~80 DEG C stirring 5.0-6.0 hours；It has been detected to TLC
Full response；Step 3: after reaction solution washing, ethyl acetate extraction, column chromatography for separation after extract liquor concentration obtains corresponding 3- sulfone
Butylcoumariii.
Preferably, the organic solvent in the step 1 is one in 1,2- dichloroethanes, Isosorbide-5-Nitrae-dioxane or toluene
Kind or two or more mixtures.
Preferably, with phenylpropiolic acid phenyl ester for 1.0 equivalents, arylamine dosage is 1.2-1.5 equivalent, preferably 1.5 equivalents.It hangs
White piece of dosage is 1.5-2.0 equivalent, preferably 1.6 equivalents.tThe dosage of BuONO is 1.6-2.0 equivalent, and preferably 1.8 work as
Amount；The dosage of boron trifluoride ether solution is 1.4-1.6 equivalent, preferably 1.5 equivalents.
Compared with prior art, present invention reaction is under the conditions of simple as mild as a dove, using sodium formaldehyde sulfoxylate as dioxy
Change sulphur source, is directly realized sulfonylating reaction, constructs 3- sulfuryl coumarin compound；This conversion reaction raw material is simply easy
, and the use of sulfonic acid chloride in prior synthesizing method is avoided, it is applicable to fairly large preparation, there is extraordinary application
Prospect.
Specific embodiment
Below by way of specific embodiment, invention is further described in detail, but not as a limitation of the invention.
Embodiment 1
A kind of 3- sulfuryl cumarin, structural formula are as follows:
The preparation method comprises the following steps: sequentially adding 1.5 equivalent of arylamine, 1,2- dichloroethanes 1.5mL, tBuONO1.8 in reaction tube
Equivalent, 1.5 equivalent of boron trifluoride ether solution stir 10 minutes under inert nitrogen gas or argon gas protection in 0 DEG C；Then
Phenylpropiolic acid phenyl ester 0.2mmol, 1.6 equivalent of sodium formaldehyde sulfoxylate and 1,2- dichloroethanes 2.0mL, in 70~80 DEG C of stirring 5.0- is added
6.0 hours, until TLC detection reaction completely.After reaction solution washing, ethyl acetate extraction, column chromatography for separation after extract liquor concentration is obtained
To corresponding 3- sulfuryl cumarin Ia, reaction yield 83%.
The structure of the compound passes through1H NMR、13The methods of C NMR, HRMS are characterized and are confirmed:1H NMR(400MHz,
CDCl3) δ 7.95 (d, J=8.9Hz, 2H), 7.56-7.58 (m, 3H), 7.32-7.34 (m, 2H), 7.14 (s, 1H), 6.95-
7.00 (m, 3H), 6.88 (d, J=8.3,1H), 3.86 (s, 3H), 2.44 (s, 3H)；13C NMR(100MHz,CDCl3)δ
163.7,158.8,155.9,153.8,146.5,132.9,131.7,131.5,129.5,129.0,128.0,127.3,
126.0,125.1,117.8,116.7,113.7,55.6,21.8；HRMS(ESI)calcd for C22H17O5S:393.0791(M
+H+),found:393.0793。
Embodiment 2
A kind of 3- sulfuryl cumarin, structural formula are
The preparation method comprises the following steps: sequentially adding arylamine (1.5 equivalent), 1,2- dichloroethanes (1.5mL), tBuONO in reaction tube
(1.8 equivalent), boron trifluoride ether solution (1.5 equivalent) stirs 10 points in 0 DEG C under inert nitrogen gas or argon gas protection
Clock；Then it is added phenylpropiolic acid phenyl ester (0.2mmol), sodium formaldehyde sulfoxylate (1.6 equivalent) and 1,2- dichloroethanes (2.0mL), 70~
80 DEG C stirring 5.0-6.0 hours, until TLC detection completely reaction.After reaction solution washing, ethyl acetate extraction, after extract liquor concentration
Column chromatography for separation obtains corresponding 3- sulfuryl cumarin Ib, reaction yield 84.5%.
The structure of the compound passes through1H NMR、13The methods of C NMR, HRMS are characterized and are confirmed:1H NMR(400MHz,
CDCl3) δ 7.94 (d, J=8.6Hz, 2H), 7.58-7.89 (m, 3H), 7.47 (d, J=8.6Hz, 2H), 7.32-7.34 (m,
2H), 7.16 (s, 1H), 7.02 (d, J=8.2Hz, 1H), 6.90-6.92 (d, J=8.1Hz, 1H), 2.46 (s, 3H)；13C NMR
(100MHz,CDCl3)δ159.9,155.8,147.1,140.2,138.7,132.5,130.6,129.6,129.2,128.8,
127.3,126.2,124.2,117.7,116.8,21.8；HRMS(ESI)calcd for C22H16ClO4S:411.0452(M+H+),found:411.0441。
Embodiment 3
A kind of 3- sulfuryl cumarin, structural formula are
The preparation method comprises the following steps: sequentially adding arylamine (1.5 equivalent), 1,2- dichloroethanes (1.5mL), tBuONO in reaction tube
(1.8 equivalent), boron trifluoride ether solution (1.5 equivalent) stirs 10 points in 0 DEG C under inert nitrogen gas or argon gas protection
Clock；Then it is added phenylpropiolic acid phenyl ester (0.2mmol), sodium formaldehyde sulfoxylate (1.6 equivalent) and 1,2- dichloroethanes (2.0mL), 70~
80 DEG C stirring 5.0-6.0 hours, until TLC detection completely reaction.After reaction solution washing, ethyl acetate extraction, after extract liquor concentration
Column chromatography for separation obtains corresponding 3- sulfuryl cumarin Ic, reaction yield 85%.
The structure of the compound passes through1H NMR、13The methods of C NMR, HRMS are characterized and are confirmed:1H NMR(400MHz,
CDCl3) δ 7.87 (d, J=8.7Hz, 2H), 7.64 (d, J=8.7Hz, 2H), 7.58-7.59 (m, 3H), 7.32-7.34 (m,
2H), 7.17 (s, 1H), 7.02 (d, J=8.3Hz, 1H), 6.91 (d, J=8.3Hz, 1H), 2.46 (s, 3H)；13C NMR
(100MHz,CDCl3)δ159.9,155.8,154.0,147.1,139.3,132.5,131.8,130.7,129.6,129.2,
128.9,128.1,127.3,126.2,124.2 117.7,116.9,21.8；HRMS(ESI)calcd for C22H16BrO4S:
454.9947(M+H+),found:454.9943。
Compared with prior art, present invention reaction is under the conditions of simple as mild as a dove, using sodium formaldehyde sulfoxylate as dioxy
Change sulphur source, is directly realized sulfonylating reaction, constructs 3- sulfuryl coumarin compound；This conversion reaction raw material is simply easy
, and the use of sulfonic acid chloride in prior synthesizing method is avoided, it is applicable to fairly large preparation, there is extraordinary application
Prospect.
The foregoing description of the disclosed embodiments enables those skilled in the art to implement or use the present invention.
Various modifications to these embodiments will be readily apparent to those skilled in the art, as defined herein
General Principle can be realized in other embodiments without departing from the spirit or scope of the present invention.Therefore, of the invention
It is not intended to be limited to the embodiments shown herein, and is to fit to and the principles and novel features disclosed herein phase one
The widest scope of cause.
Claims (4)
1. a kind of preparation method of 3- sulfuryl cumarin shown in formula (3), which is characterized in that reaction equation are as follows:
Wherein, Ar is phenyl, p-methylphenyl, p-methoxyphenyl, o-methyl-phenyl, o-methoxyphenyl, aminomethyl phenyl
Or m-methoxyphenyl, rubigan, p-fluorophenyl, p-bromophenyl, p-nitrophenyl, Chloro-O-Phenyl, o-fluorophenyl, adjacent bromine
Phenyl, chlorphenyl, fluorophenyl or m-bromophenyl；
R1For H, methyl, ethyl, tert-butyl, normal-butyl or methoxyl group, chlorine, fluorine, bromine, acetyl group or trifluoromethyl；
R2For p-methylphenyl, p-methoxyphenyl, o-methyl-phenyl, o-methoxyphenyl, aminomethyl phenyl or meta-methoxy
Phenyl, rubigan, p-fluorophenyl, p-bromophenyl, p-nitrophenyl, p-trifluoromethyl phenyl, to acetylphenyl, adjacent chlorobenzene
Base, o-fluorophenyl, o-bromophenyl, chlorphenyl, fluorophenyl or m-bromophenyl；
Including following preparation step:
Step 1: sequentially added in reaction tube arylamine shown in formula (1), boron trifluoride ether solution,tBuONO and organic molten
Agent, inert nitrogen gas or argon gas protection under, in 70~80 DEG C stirring 0.5-1.0 hours；
Step 2: being added phenylpropiolic acid phenyl ester derivative and sodium formaldehyde sulfoxylate shown in formula (2), small in 70~80 DEG C of stirring 5.0-6.0
When；Reaction completely is detected to TLC；
Step 3: after reaction solution washing, ethyl acetate extraction, column chromatography for separation after extract liquor concentration obtains phase shown in formula (3)
The 3- sulfuryl cumarin answered.
2. the preparation method of 3- sulfuryl cumarin shown in formula (3) according to claim 1, it is characterised in that: the step
Organic solvent in rapid one is the mixture of one or more of 1,2- dichloroethanes or Isosorbide-5-Nitrae-dioxane or toluene.
3. the preparation method of 3- sulfuryl cumarin shown in formula (3) according to claim 1, it is characterised in that: with formula (2)
Shown in phenylpropiolic acid phenyl ester derivative be 1.0 equivalents, arylamine dosage shown in formula (1) is 1.2-1.5 equivalent；The use of sodium formaldehyde sulfoxylate
Amount is 1.5-2.0 equivalent；tThe dosage of BuONO is 1.6-2.0 equivalent；The dosage of boron trifluoride ether solution is worked as 1.4-1.6
Amount.
4. the preparation method of 3- sulfuryl cumarin shown in formula (3) according to claim 3, it is characterised in that: with formula (2)
Shown in phenylpropiolic acid phenyl ester derivative be 1.0 equivalents, arylamine dosage shown in formula (1) is 1.5 equivalents；The dosage of sodium formaldehyde sulfoxylate is
1.6 equivalent；tThe dosage of BuONO is 1.8 equivalents；The dosage of boron trifluoride ether solution is 1.5 equivalents.
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Non-Patent Citations (3)
| Title |
|---|
| Direct and metal-free arylsulfonylation of alkynes with sulfonylhydrazides for the construction of 3-sulfonated coumarins;Wei Wei et al.;《Chem. Commun.》;20141107;第51卷;768-771 * |
| Generation of Sulfonyl Radicals from Aryldiazonium Tetrafluoroborates and Sulfur Dioxide: The Synthesis of 3-Sulfonated Coumarins;Danqing Zheng et al.;《Angew. Chem. Int. Ed.》;20161231;第55卷;11925-11929 * |
| Visible-light initiated oxidative cyclization of phenyl propiolates with sulfinic acids to coumarin derivatives under metal-free conditions;Wenchao Yang et al.;《Chem. Commun.》;20150313;第51卷;7520-7523 * |
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