CN112479958B - Preparation method of hydroxy aliphatic selenocyanate derivative - Google Patents
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- CN112479958B CN112479958B CN202011360001.9A CN202011360001A CN112479958B CN 112479958 B CN112479958 B CN 112479958B CN 202011360001 A CN202011360001 A CN 202011360001A CN 112479958 B CN112479958 B CN 112479958B
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- C07C391/00—Compounds containing selenium
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- C—CHEMISTRY; METALLURGY
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- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- C—CHEMISTRY; METALLURGY
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- C07C2601/14—The ring being saturated
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Abstract
The invention discloses a reaction for constructing hydroxy aliphatic selenocyanate by epoxy derivatives, elemental selenium and TMSCN under the condition of no metal and no additive. The new strategy has the advantages of no metal participation, no additive promotion, wide substrate range and good functional group compatibility, and provides an efficient and green approach for the preparation of various hydroxy aliphatic selenocyanates in a highly concise manner.
Description
Technical Field
The application belongs to the technical field of organic selenium chemistry, and particularly relates to a preparation method of a hydroxy aliphatic selenocyanate derivative.
Background
The hydroxy aliphatic selenocyanate derivatives have great application value (Eur.J.Org.chem.2006, 22,4979-4988, synth Commun.2016,46,831-868 Synth Commun.2016,46, 1397-1416.), and the compounds can be used as a very useful intermediate in synthesis and can be used for synthesizing a series of products with very application value, such as hydroxy aliphatic selenocyanate and the like (chem.Rev.2015, 115, 3564-3614; synthesis.1996,6,669-686 curr.chem.1997,190,1-85 Org.Lett.2020,22, 3339-3344.. The method is extremely widely applied to the fields of synthesis of a plurality of biological molecules, research of new materials, drug molecules and the like (chem.Soc.Rev.2012, 41, 643-665.). The synthesis and properties of such compounds have therefore been of increasing interest to organic synthetic chemists of the relevant art since the last century. After extensive studies on efficient insertion of elemental selenium, similar to the work of the predecessors and our group of topics (adv. Synth. Call.2018, 360, 4336-4340.), the inventors wanted to use epoxy derivatives with elemental selenium, TMSCN, to obtain good yields by ring opening under mild conditions and to be compatible with a wide range of functional groups. Finally, a high-efficiency strategy which is convenient and feasible, easy to operate, high in yield, green and environment-friendly and capable of constructing the hydroxy aliphatic selenocyanate in one step is obtained.
Disclosure of Invention
The invention aims to provide a preparation method of a hydroxy aliphatic selenocyanate derivative, the method is used for constructing the epoxy derivative, elemental selenium and TMSCN to obtain the hydroxy selenocyanate under the conditions of no metal and no additive, the method has the advantages of no participation of a metal catalyst, no need of promotion of an additive, wide substrate range and good functional group compatibility, and provides an efficient and green way for the preparation of various hydroxy aliphatic selenocyanates in a highly concise mode.
The invention provides a preparation method of a hydroxyl aliphatic selenocyanate derivative, which comprises the following steps:
sequentially adding an epoxy compound shown in formula I, selenium powder, TMSCN and an organic solvent into a reactor provided with a magnetic stirrer, then replacing the atmosphere in the reactor with an inert atmosphere, heating and stirring for reaction, diluting a reaction mixture with diethyl ether after the reaction is finished, filtering through a silica gel pad, decompressing and concentrating filtrate, and then purifying residues through silica gel flash chromatography to obtain a hydroxy aliphatic selenocyanate compound shown in formula II; the reaction formula is as follows:
in the above reaction formula, n =0,1 or 2.
R 1 ，R 2 ，R 3 Represents substituents on the bonded ring, independently of one another, selected from hydrogen and C 1-20 Alkyl radical, C 1-20 Haloalkyl, C 6-20 Aryl radical, C 3-20 Cycloalkyl radical, C 6-20 aryl-C 1-20 An alkyl group; or two adjacent (R) 1 /R 2 ，R 2 /R 2 ，R 2 /R 3 ，R 1 /R 3 ) The substituents being linked to each other and forming, together with the carbon atom linking the two substituents, a saturated or unsaturated five-to seven-membered carbonAnd (4) a ring.
Preferably, R when n =0 1 And R 3 One of which is not hydrogen.
Herein, said C 1-20 Alkyl (including C as referred to in each of the above groups) 1-20 Alkyl moieties) may be selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, and the like. Said C is 6-20 Aryl (including C as referred to in each of the above groups) 6-20 Structural part of aryl) can be selected from phenyl, naphthyl, anthryl, phenanthryl. Said C is 3-20 Cycloalkyl groups may be selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and the like. The saturated or unsaturated five-to seven-membered carbocyclic ring is selected from cyclopentane, cyclohexane, benzene rings, and the like.
Most preferably, R when n =0 1 Represents chloromethyl or phenyl, R 3 Represents hydrogen; or R 1 And R 3 Are linked to each other and form, together with the carbon atoms linking the two substituents, a cyclopentane, cyclohexane or benzene ring structure.
When n =1 or 2, R 1 ，R 2 ，R 3 Are all selected from hydrogen.
According to the preparation method of the present invention, the organic solvent is selected from any one of methanol, ethanol, isopropanol, DMSO, DMF, THF, meCN, and toluene, and is most preferably isopropanol.
According to the preparation method of the invention, the reaction temperature of the heating and stirring reaction is 60-120 ℃, preferably 80-100 ℃, and most preferably 90 ℃. The reaction time of the heating stirring reaction is 4 to 48 hours, preferably 12 to 24 hours, and most preferably 24 hours.
According to the preparation method, the feeding molar ratio of the epoxy compound shown in the formula I, the selenium powder and the TMSCN is 1: (2-5) and (1-3). Preferably, the charging molar ratio of the epoxy compound shown in the formula I, the selenium powder and the TMSCN is 1:3:2.
In the above-described production method according to the present invention, the reaction atmosphere for the heating and stirring reaction is not particularly limited, and may be an inert atmosphere, an air atmosphere, or an oxygen atmosphere, and is preferably an inert atmosphere. The inert atmosphere is a nitrogen atmosphere or an argon atmosphere, and preferably a nitrogen atmosphere.
The method of the invention achieves the following beneficial effects:
the invention reports a synthesis strategy for obtaining the hydroxy selenocyanate by constructing the epoxy derivative, the elemental selenium and the TMSCN under the conditions of no metal and no additive for the first time, the synthesis strategy has the advantages of no participation of a metal catalyst, no promotion of an additive, wide substrate range and good functional group compatibility, and an efficient and green synthesis way is provided for the preparation of various hydroxy aliphatic selenocyanates in a highly concise manner.
Detailed Description
The present invention will be described in further detail with reference to specific examples. In the text, unless otherwise specified, all methods employed are conventional in the art, and the reagents used are commercially available from conventional sources and/or are prepared by known organic synthesis methods.
Examples 1-13 optimization of reaction conditions
The epoxycyclohexane shown in the formula 1a is used as a template substrate, and the optimal reaction conditions are screened out.
Wherein the reaction operation of example 1 is as follows:
a10 mL pressure tube containing stirring magnetons was charged with 1a epoxycyclohexane (0.5 mmol), selenium powder (3.0 equiv,1.5 mmol), TMSCN (2.0 equiv,1.0 mmol) and isopropanol (2 mL). The reaction mixture was stirred at 90 ℃ for 24 hours under nitrogen. After the reaction was complete, the reaction mixture was diluted with 10mL of diethyl ether, filtered through a pad of silica gel and concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel to give the pure target product of formula 2 a. Yellow liquid (136mg, 83% yield), etOAc/PE =1/5. 1 H NMR(400MHz,CDCl 3 ):δ3.62-3.57(m,1H),3.30-3.24(m,1H),2.73(s,1H),2.37-2.34(m,1H),2.13-2.10(m,1H),1.82-1.75(m,3H),1.39-1.28(m,3H)； 13 C NMR(125MHz,CDCl 3 ):δ101.3,73.9,54.0,35.8,34.1,26.7,24.2。
In substantial agreement with the method of example 1, only the reaction conditions shown in Table 1 were changed to examine the effect of the reaction on the yield of the objective product under different conditions, and the results are shown in Table 1.
Table 1 is as follows:
the experimental results show that the template reaction shows different reactivities in various solvents, and in the case of isopropanol as a solvent, the target product is obtained in a yield of 83% without any additive. Finally, considering economic and efficient factors, isopropanol is selected as a reaction solvent, and the reaction is carried out for 24 hours at 90 ℃ under the protection of nitrogen, wherein the optimal condition is.
Example 14
A10 mL pressure tube containing stirring magnetons was charged with epoxycyclopentane (0.5 mmol) as represented by formula 1b, selenium powder (3.0 equiv,1.5 mmol), TMSCN (2.0 equiv,1.0 mmol) and isopropanol (2 mL). The reaction mixture was stirred at 90 ℃ for 24 hours under nitrogen. After the reaction was complete, the reaction mixture was diluted with 10mL of diethyl ether, filtered through a pad of silica gel and concentrated under reduced pressure. The residue is then purified by flash chromatography on silica gel to give the pure target product of formula 2 b. Colorless liquid (73 mg, 76% yield), etOAc/PE =1/5. 1 H NMR(400MHz,CDCl 3 ):δ4.35-4.31(m,1H),3.52(q,J＝5.2Hz,1H),2.95(d,J＝2.8Hz,1H),2.38-2.31(m,1H),2.11-2.06(m,1H),1.89-1.75(m,3H),1.69-1.63(m,1H)； 13 C NMR(125MHz,CDCl 3 ):δ101.6,79.1,51.4,32.7,31.4,22.0.。
Example 15
A10 mL pressure tube containing a stirring magneton was charged with monochloromethyloxirane (0.5 mmol) as shown in formula 1c, selenium powder (3.0 equiv,1.5 mmol), TMSCN (2.0 equiv,1.0 mmol) and isopropanol (2 mL). The reaction mixture was stirred at 90 ℃ for 24 hours under nitrogen. After the reaction was complete, the reaction mixture was diluted with 10mL of diethyl ether, filtered through a pad of silica gel and concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel to give the pure target product of formula 2 c. Yellow liquid (68 mg, 80% yield), etOAc/PE =1/5. 1 H NMR(400MHz,CDCl 3 ):δ4.20(s,1H),3.71-3.65(m,2H),3.34(dd,J＝10.0,3.6Hz,1H),3.24(dd,J＝9.6,6.0Hz,1H),3.14(d,J＝2.8Hz,1H)； 13 C NMR(125MHz,CDCl 3 ):δ101.8,70.1,47.7,32.9。
Example 16
A10 mL pressure tube containing stirring magnetons was charged with phenyloxirane (0.5 mmol) as shown in formula 1d, selenium powder (3.0 equiv,1.5 mmol), TMSCN (2.0 equiv,1.0 mmol) and isopropanol (2 mL). The reaction mixture was stirred at 90 ℃ for 24 hours under nitrogen. After the reaction was complete, the reaction mixture was diluted with 10mL of diethyl ether, filtered through a pad of silica gel and concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel to give the pure target product of formula 2 d. Colorless liquid (59 mg, 52% yield), etOAc/PE =1/5. 1 H NMR(400MHz,CDCl 3 ):δ7.40-7.36(m,5H),4.82(t,J＝7.2Hz,1H),4.23-4.20(m,2H),2.77(s,1H)； 13 C NMR(125MHz,CDCl 3 ):δ136.3,129.3,129.2,128.1,102.0,65.4,52.6。
Example 17
A10 mL pressure tube containing stirring magnetons was charged with oxetane (0.5 mmol) as shown in formula 1e, selenium powder (3.0 equiv,1.5 mmol), TMSCN (2.0 equiv,1.0 mmol) and isopropanol (2 mL). The reaction mixture was stirred at 90 ℃ for 24 hours under nitrogen. After the reaction was complete, the reaction mixture was diluted with 10mL of diethyl ether, filtered through a pad of silica gel and concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel to give the pure target product of formula 2 e. Colorless liquid (29 mg, 35% yield), etOAc/PE =1/2. 1 H NMR(400MHz,CDCl 3 ):δ3.80(s,2H),3.24-3.21(m,2H),2.17-2.11(m,2H),1.98(s,1H)； 13 C NMR(125MHz,CDCl 3 ):δ102.6,61.1,32.7,26.6。
Example 18
A10 mL pressure tube equipped with a stirring magneton was charged with formula 1f (2 mL), selenium powder (1.5 mmol) and TMSCN (1.0 mmol). The reaction mixture was stirred at 120 ℃ for 24 hours under nitrogen. After the reaction was complete, the reaction mixture was diluted with 10mL of diethyl ether, filtered through a pad of silica gel and concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel to give the pure target product of formula 2 f. Yellow liquid (48 mg, 54% yield), etOAc/PE =1/5. 1 H NMR(400MHz,CDCl 3 ):δ3.70(t,J＝4.8Hz,2H),3.10(t,J＝6.0Hz,2H),2.05-1.99(m,2H),1.80(s,1H),1.74-1.69(m,2H)； 13 C NMR(125MHz,CDCl 3 ):δ101.7,61.8,31.8,29.5,27.6。
The embodiments described above are only preferred embodiments of the inventors determined after extensive experimental screening and are not exhaustive of the possible implementations of the invention. Any obvious modifications to the present invention, which do not depart from the synthetic route of the present invention, should be construed as being included within the scope of the present invention as set forth in the appended claims.
Claims (10)
1. A preparation method of a hydroxy aliphatic selenocyanate derivative is characterized by comprising the following steps:
sequentially adding the epoxy compound shown in the formula I, selenium powder, TMSCN and an organic solvent into a reactor provided with a magnetic stirrer, heating and stirring for reaction, diluting a reaction mixture with diethyl ether after the reaction is finished, filtering through a silica gel pad, concentrating filtrate under reduced pressure, and purifying residues through silica gel flash chromatography to obtain the hydroxy aliphatic selenocyanate compound shown in the formula II; the reaction formula is as follows:
in the above reaction formula, n =0,1 or 2;
R 1 ，R 2 ，R 3 represents substituents on the bonded ring, independently of one another, selected from hydrogen and C 1-20 Alkyl radical, C 1-20 Haloalkyl, C 6-20 Aryl radical, C 3-20 Cycloalkyl, C 6-20 aryl-C 1-20 An alkyl group; or two adjacent substituents are linked to each other and form, together with the carbon atom linking the two substituents, a saturated or unsaturated five-to seven-membered carbocyclic ring.
2. The method according to claim 1, wherein R is R when n =0 1 And R 3 One of which is not hydrogen.
3. The method according to claim 1, wherein R is R when n =0 1 Represents chloromethyl or phenyl, R 3 Represents hydrogen; or R 1 And R 3 Are linked to each other and form, together with the carbon atoms linking the two substituents, a cyclopentane, cyclohexane or benzene ring structure;
when n =1 or 2, R 1 ，R 2 ，R 3 Are all selected from hydrogen.
4. The method according to any one of claims 1 to 3, wherein the organic solvent is selected from the group consisting of methanol, ethanol, isopropanol, DMSO, DMF, THF, meCN, and toluene.
5. The method according to claim 4, wherein the organic solvent is isopropyl alcohol.
6. The process according to any one of claims 1 to 3, wherein the reaction temperature of the heating and stirring reaction is 60 to 120 ℃; the reaction time of the heating stirring reaction is 4-48h.
7. The preparation method according to claim 6, wherein the reaction temperature of the heating stirring reaction is 80-100 ℃; the reaction time of the heating stirring reaction is 12-24h.
8. The method according to claim 7, wherein the reaction temperature of the heating and stirring reaction is 90 ℃; the reaction time of the heating stirring reaction is 24h.
9. The preparation method according to any one of claims 1 to 3, wherein the epoxy compound represented by formula I, the selenium powder and the TMSCN are fed in a molar ratio of 1: (2-5) and (1-3).
10. The preparation method according to claim 9, wherein the feeding molar ratio of the epoxy compound shown in formula I, the selenium powder and the TMSCN is 1:3:2.
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Non-Patent Citations (4)
| Title |
|---|
| Catalystand Additive-Free SelectiveRing-Opening Selenocyanationof Heterocycleswith Elemental Selenium and TMSCN;Li-Guo Lu，等;《Adv. Synth.Catal.》;20210129;第363卷;1346–1351 * |
| Reaction of trimethylsilyl isoselenocyanate with oxiranes and oxetane;Kazuaki sukata;《Bull. Chem. Soc. Jpn.》;19900331;第63卷;825-828 * |
| Silver-Catalyzed One-Pot Three-Component Selective Synthesis of b-Hydroxy Selenides;Tao Leng,等;《Adv. Synth. Catal.》;20181008;第360卷;4336–4340 * |
| Spaltungsreaktionen des trimethylsilylcyanids durch epoxyde carbonsaurechloride, chlorkohlensaureester und sulfenylchloride;Werner Lidy，等;《Tetrahedron Letters》;19731231(第17期);1449-1450 * |
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