CN106986800B - A kind of preparation method of β-carbonyl thioether - Google Patents
A kind of preparation method of β-carbonyl thioether Download PDFInfo
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- CN106986800B CN106986800B CN201710264250.XA CN201710264250A CN106986800B CN 106986800 B CN106986800 B CN 106986800B CN 201710264250 A CN201710264250 A CN 201710264250A CN 106986800 B CN106986800 B CN 106986800B
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- phenyl
- preparation
- mercaptan
- cyclosubstituted
- virtue
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/22—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and doubly-bound oxygen atoms bound to the same carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
Abstract
The invention discloses a kind of β-carbonyl thioether preparation methods.The preparation method carries out concatenated Meyer-Schuster rearrangement reaction and Isosorbide-5-Nitrae-addition reaction under acid effect, to realize β-carbonyl thioether one pot process using the cyclosubstituted propilolic alcohol of virtue and mercaptan as raw material.Preparation method maximum output of the invention has many advantages, such as easy to operate and 100% atom economy up to 99%, provides a kind of completely new synthetic method for the building of β-carbonyl thio-ether type compounds.
Description
Technical field
The present invention relates to technical field of organic synthesis, specifically, are related to a kind of preparation method of β-carbonyl thioether.
Background technique
β-carbonyl thioether is the important skeleton of one of organic synthesis, is important organic synthesis intermediate, and it is very
It is easy to be changed into α, alpha, beta-unsaturated ketone.Some β-carbonyl thioether can make fragrance, the synthesis of natural products and drug, beverage,
Foods and cosmetics field is all widely used.There is following two about its chemical synthesis process at present
Route one: under the conditions of water and diethylamine, with α, alpha, beta-unsaturated ketone and mercaptan are the Michael's addition of starting material
It reacts (Tetrahedron Letters.2012,53,4405-4408).Its synthetic route is as follows:
Route two:, using p-methyl benzenesulfonic acid as catalyst, α, alpha, beta-unsaturated ketone and alkyl sodium (potassium) thiosulfate are the addition of raw material
It reacts (Rsc Adv.2015,5,27107-27111).Its synthetic route is as follows:
Summary of the invention
For overcome the deficiencies in the prior art, a kind of completely new, former it is an object of the invention to be provided for β-carbonyl thioether
Son is utilized as 100% preparation method.
Technical solution of the present invention is specifically described as follows.
A kind of preparation method of β-carbonyl thioether, β-carbonyl thioether 3 is by the cyclosubstituted propilolic alcohol 1 of virtue, mercaptan 2 and acid molten
Back flow reaction obtains in agent；Its reaction equation is as follows:
Wherein:
R in the cyclosubstituted propilolic alcohol 1 of virtue1For phenyl, naphthalene, thienyl, pyridyl group, furyl or pyrroles
Base；
The acid is trifluoromethanesulfonic acid, trifluoroacetic acid, trifluoromethanesulfonic acid iron, trifluoromethanesulfonic acid ferrous iron, trifluoromethanesulfonic acid
Bismuth, copper trifluoromethanesulfcomposite, silver trifluoromethanesulfonate or trifluoromethanesulfonic acid scandium；
R in the mercaptan 22For benzyl, phenyl or alkyl.
R in the present invention, in the cyclosubstituted propilolic alcohol 1 of virtue1Selected from 4- fluoro-phenyl, the chloro- phenyl of 4-, the bromo- benzene of 4-
Base, phenyl, 4- methylphenyl, 4- phenyl-phenyl, 4- methoxyl group-phenyl, 3- methoxyl group-phenyl or 2- methoxyl group-phenyl
In any one.
R in the present invention, in the mercaptan 22Selected to trifluoromethyl benzyl, to luorobenzyl, p-chlorobenzyl, to bromobenzyl
Base, benzyl, to methylbenzyl, to methoxy-benzyl, phenyl, p-methylphenyl, to ethylphenyl, allyl, ethyl, propyl,
Any one in tert-butyl or isopentyl.
In the present invention, solvent is appointed in dioxane, dichloroethanes, benzotrifluoride, toluene, benzene or glycol dimethyl ether
It is one or more of.
In the present invention, the molar ratio of the cyclosubstituted propilolic alcohol 1 of virtue, mercaptan 2 and acid is 1:(1.1~1.2): (0.13~
0.16)；The cyclosubstituted propilolic alcohol 1 of virtue and be 1:5~1:10mmol/mL with the feed ratio of solvent.
Compared to the prior art, the beneficial effects of the present invention are:
Through acid catalysis Meyer- occurs for a kind of β-carbonyl thioether preparation method of the invention, i.e., fragrant cyclosubstituted propilolic alcohol
Then Schuster rearrangement reaction occurs Isosorbide-5-Nitrae-addition reaction with sulfur alcohol compound and obtains target product β-carbonyl thioether.It should
The raw material propargyl alcohol of method is easy to get, and reaction process is easy to operate, and side reaction is few, 100% atom utilization.One kind of the invention
β-carbonyl thioether preparation method provides a completely new synthetic method for the synthesis of β-carbonyl thio-ether type compounds.
Specific embodiment
Acid used in various embodiments of the present invention, mercaptan, dioxane, dichloroethanes, benzotrifluoride, toluene, benzene, second two
Diethylene glycol dimethyl ether, ethyl acetate, petroleum ether and anhydrous sodium sulfate are traditional Chinese medicines reagent.Equipment used in various embodiments of the present invention and
The information of manufacturer is as follows:
Blender are as follows: the Shanghai Pu Mei Ying MYPII-2 constant temperature blender with magnetic force；
Water circulating pump are as follows: Shanghai Yu Kang recycles multiplex vavuum pump SHB-IIIA；
Rotary Evaporators are as follows: Shanghai Yu Kang Rotary Evaporators W.S 206B；
Oil pump are as follows: Shanghai Yu Kang 2XZ-2 type rotary-vane vaccum pump；
Preparative HPLC are as follows: Shimadzu LC-20A.
Experimental procedure:
A kind of preparation method of β-carbonyl thioether, specifically comprises the following steps:
It is sequentially added in a 15mL tube sealing propilolic alcohol (2mmol), solvent (10-20mL), sour (0.3mmol) and mercaptan
(2.4mmol), is reacted under reflux conditions, is monitored and is reacted by TLC, is added after propilolic alcohol fully reacting into reaction solution
Enter 20mL water, the extraction of 50mL ethyl acetate be added, resulting organic phase is washed with saturated sodium-chloride, after anhydrous sodium sulfate is dry in
It is concentrated on Rotary Evaporators, obtained concentrate obtains β-carbonyl thioether by column chromatographic purifying；
Embodiment 1
3- Benzylsulfanyl -1- phenyl -1- acetone, yield: 99%, propilolic alcohol, solvent, acid and mercaptan sample-adding situation are benzene
Propilolic alcohol (2mmol), dioxane (15mL), trifluoromethanesulfonic acid iron (0.3mmol) and benzyl mercaptan (2.4mmol)；1H NMR
(500MHz,CDCl3) δ 2.86 (t, J=7.0Hz, 2H), 3.20 (t, J=7.0Hz, 2H), 3.80 (s, 2H), 7.26 (t, J=
7.0Hz, 1H), 7.37-7.32 (m, 4H), 7.47 (t, J=7.0Hz, 2H), 7.58 (t, J=7.0Hz, 1H), 7.91 (d, J=
7.0Hz,2H).
Embodiment 2
3- Benzylsulfanyl -1- naphthalene -1- acetone, yield 98%, propilolic alcohol, solvent, acid and mercaptan sample-adding situation are 3-
(2- naphthalene) -2- propine -1- alcohol (2mmol), benzotrifluoride (10mL), trifluoromethanesulfonic acid ferrous iron (0.3mmol) and benzyl mercaptan
(2.4mmol)；1H NMR(500MHz,CDCl3) δ 2.80 (t, J=9.0Hz, 2H), 3.19 (t, J=9.0Hz, 2H), 3.69 (s,
2H),7.16-7.13(m,1H),7.26-7.19(m,4H),7.51-7.43(m,2H),7.77-7.75(m,2H),7.88-7.82
(m,2H),8.26(s,1H).
Embodiment 3
3- (benzylthio) -1- (3- thienyl) -1- acetone, yield 81%, propilolic alcohol, solvent, acid and mercaptan are loaded situation
For 3- (2- thienyl) -2- propine -1- alcohol (2mmol), glycol dimethyl ether (20mL), Bismuth triflate (0.3mmol) and
Benzyl mercaptan (2.4mmol)；1H NMR(500MHz,CDCl3) δ 2.81 (t, J=9.0Hz, 2H), 3.06 (t, J=9.0Hz, 2H),
3.76(s,2H),7.25-7.24(m,1H),7.33-7.29(m,5H),7.50-7.48(m,1H),7.95-7.94(m,1H).
Embodiment 4
3- (3- methyl-butylthio) -1- phenyl -1- acetone, yield 98%, propilolic alcohol, solvent, acid and mercaptan are loaded situation
For phenylpropyl alcohol alkynol (2mmol), benzene (15mL), copper trifluoromethanesulfcomposite (0.3mmol) and 3- methyl-1-butanethiol (2.4mmol)；1H
NMR(500MHz,CDCl3)δ0.91(s,3H),0.92(s,3H),1.53-1.48(m,2H),1.71-1.67(m,1H),2.60-
2.57 (m, 2H), 2.93 (t, J=7.5Hz, 2H), 3.28 (t, J=7.5Hz, 2H), 7.48 (t, J=8.0Hz, 2H), 7.58
(t, J=8.0Hz, 1H), 7.97 (d, J=8.0Hz, 2H)
The above is only the citing of embodiments of the present invention, it is noted that for the ordinary skill of the art
For personnel, without departing from the technical principles of the invention, several improvements and modifications can also be made, these improve and become
Type also should be regarded as protection scope of the present invention.
Claims (3)
1. a kind of β-carbonyl thioether preparation method, which is characterized in that β-carbonyl thioether 3 is by the cyclosubstituted propilolic alcohol 1 of virtue, mercaptan
2 obtain with sour back flow reaction in a solvent；Its reaction equation is as follows:
Wherein:
R in the cyclosubstituted propilolic alcohol 1 of virtue1For phenyl, 4- fluoro-phenyl, the chloro- phenyl of 4-, the bromo- phenyl of 4-, 4- methyl-
Phenyl, 4- phenyl-phenyl, 4- methoxyl group-phenyl, 3- methoxyl group-phenyl, 2- methoxyl group-phenyl, naphthalene, thienyl, pyridine
Base, furyl or pyrrole radicals；
The acid is trifluoromethanesulfonic acid iron, trifluoromethanesulfonic acid ferrous iron, Bismuth triflate or copper trifluoromethanesulfcomposite；
R in the mercaptan 22For benzyl, to trifluoromethyl benzyl, to luorobenzyl, p-chlorobenzyl, to bromobenzyl, to methyl benzyl
Base, to methoxy-benzyl, phenyl, p-methylphenyl, to ethylphenyl, allyl or alkyl.
2. preparation method according to claim 1, which is characterized in that solvent is selected from dioxane, dichloroethanes, fluoroform
It is any one or several in benzene, toluene, benzene or glycol dimethyl ether.
3. preparation method according to claim 1, which is characterized in that the cyclosubstituted propilolic alcohol 1 of virtue, mercaptan 2 and acid rub
You are than being 1:(1.1~1.2): (0.13~0.16)；The feed ratio of the cyclosubstituted propilolic alcohol 1 of virtue and solvent is 1:5~1:
10mmol/mL。
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107698469B (en) * | 2017-10-13 | 2020-10-02 | 上海应用技术大学 | Preparation method of alpha-halogenated-beta-aminoketone |
| CN109836410B (en) * | 2019-04-02 | 2021-07-23 | 上海应用技术大学 | (4, 6-diaryl-3, 4-dihydro-2H-thiopyran-3-yl) -aryl ketone and preparation |
| CN109912473B (en) * | 2019-04-02 | 2021-03-05 | 上海应用技术大学 | Preparation method of 2- ((sulfenyl) methyl) -1,3, 5-triaryl-1, 5-diketone |
| CN110483474B (en) * | 2019-08-26 | 2021-09-28 | 上海应用技术大学 | Preparation method of 2-methylene-1, 3, 5-triaryl-1, 5-pentanedione |
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Non-Patent Citations (5)
| Title |
|---|
| A General Procedure for the Synthesis of Enones via Gold-Catalyzed Meyer-Schuster Rearrangement of Propargylic Alcohols at Room Temperature;Matthew N. Pennell, 等;《J. Org. Chem.》;20110125;第76卷;1479–1482 |
| Gold- and Silver-Catalyzed Reactions of Propargylic Alcohols in the Presence of Protic Additives;Matthew N. Pennell, 等;《Chem. Eur. J.》;20120228;第18卷;4748 – 4758 |
| Kurt H. Meyer und Kurt Schueter: Umlagerung tertisrer Athinyl-carbinole in ungesiittigte Ketone.;K. H. Meyer, K. Schuster;《Chem. Ber.》;19221231;第55卷;819-823 |
| Synthesis of b-sulfanyl ketones via a tandem rearrangement-conjugate addition reaction catalyzed by a Re(V)-oxo complex;Alyson E. Garst, 等;《Tetrahedron Letters》;20121121;第54卷;459-461 |
| The Meyer–Schuster rearrangement for the synthesis of a,b-unsaturated carbonyl compounds;Douglas A. Engel 等;《Org. Biomol. Chem.》;20090914;第7卷;4149–4158 |
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