CN115161673A - Electrochemical method for synthesizing benzoxazine through thiocyanide - Google Patents

Electrochemical method for synthesizing benzoxazine through thiocyanide Download PDF

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CN115161673A
CN115161673A CN202210977816.4A CN202210977816A CN115161673A CN 115161673 A CN115161673 A CN 115161673A CN 202210977816 A CN202210977816 A CN 202210977816A CN 115161673 A CN115161673 A CN 115161673A
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黄申林
钱沈城
郑煜
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Nanjing Forestry University
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    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
    • C25B3/00—Electrolytic production of organic compounds
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    • C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
    • C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
    • C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D265/16—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with only hydrogen or carbon atoms directly attached in positions 2 and 4
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
    • C25B3/00—Electrolytic production of organic compounds
    • C25B3/01—Products
    • C25B3/05—Heterocyclic compounds
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
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Abstract

The invention discloses an electrochemical method for synthesizing benzoxazine through thiocyanide, which comprises the steps of adding raw materials of enamine ketone compounds, ammonium thiocyanate, trifluoroacetic acid and acetonitrile into a reaction bottle, using graphite as a positive electrode and platinum as a negative electrode, stirring at the rotation speed of 400-1200rpm for 1-10 hours at room temperature under the condition of the current of 10 mA. After the reaction is finished, concentrating the reaction solution, and separating by column chromatography to obtain the target product. The invention provides an electrochemical method for synthesizing benzoxazine through thiocyanide, the whole reaction successfully avoids the use of equivalent oxidant, and the method has the advantages of easily available raw materials, simple and convenient operation, wide application range and environmental friendliness. The reaction product can be used for further synthesis of skeleton molecules of various natural products, and has wide application prospect.

Description

Electrochemical method for synthesizing benzoxazine through thiocyanide
Technical Field
The invention relates to the technical field of chemistry, in particular to an electrochemical method for synthesizing benzoxazine through thiocyanide.
Background
Nitrogen and oxygen containing heterocyclic compounds are important structures in medicine, pesticides and functional molecules. Benzoxazines are an important class of active molecular frameworks and are widely found in a variety of biologically active molecules, such as bactericides and etivulvoxine. However, the synthesis of these compounds usually requires complex substrates and harsh reaction conditions. Among the various inorganic sulfur salts, thiocyanate has proven to be one of the most efficient and versatile sulfurizing agents for the synthesis of various sulfur-containing compounds, and also a key intermediate for the synthesis of pharmaceuticals and other sulfur-containing organic compounds. On the other hand, electrochemistry shows its advantages and environmentally friendly properties in the synthesis of organic compounds in place of traditional oxidants.
Therefore, it is still necessary to develop a new efficient serial thiocyanization reaction by using an electrochemical synthesis technology to construct various SCN-containing benzoxazine compounds.
Disclosure of Invention
This section is for the purpose of summarizing some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. In this section, as well as in the abstract and the title of the invention of this application, simplifications or omissions may be made to avoid obscuring the purpose of the section, the abstract and the title, and such simplifications or omissions are not intended to limit the scope of the invention.
The invention provides an electrochemical method for synthesizing benzoxazine through thiocyanization, which comprises the following steps:
adding raw materials of enamine ketone compounds, ammonium thiocyanate, trifluoroacetic acid and acetonitrile into a reaction bottle, using graphite as a positive electrode and platinum as a negative electrode, stirring at the rotation speed of 400-1200rpm for 1-10 hours at room temperature under the condition that the current is 10 mA. After the reaction is finished, concentrating the reaction solution, and then carrying out column chromatography separation to obtain the target product.
As a preferred scheme of the synthetic method for preparing the benzoxazine, the method comprises the following steps: the structural general formula of the raw material enamine ketone compound is shown as the following formula:
Figure BSA0000281368030000011
wherein R is 1 Groups include, but are not limited to, various halogens, ester groups, alkyl groups, methoxy groups, and the like; r 2 Groups include, but are not limited to, various phenyl, substituted phenyl, alkyl, and the like; r 3 Groups include, but are not limited to, phenyl, substituted phenyl(including mono-substituted phenyl as well as poly-substituted phenyl, substituents including but not limited to halogen, ester, alkyl, methoxy, etc.), thiophene, furan, and various alkyl groups, etc.
As a preferred scheme of the synthetic method for preparing the benzoxazine, the method comprises the following steps: the thiocyanate includes, but is not limited to, one or more of ammonium thiocyanate, potassium thiocyanate, and sodium thiocyanate.
As a preferred scheme of the synthetic method for preparing the benzoxazine, the method comprises the following steps: as a preferred scheme of the synthetic method for preparing the benzoxazine, the method comprises the following steps: the product thiocyanide benzoxazine has the following structural formula:
Figure BSA0000281368030000021
wherein R is 1 Groups include, but are not limited to, various halogens, ester groups, alkyl groups, methoxy groups, and the like; r 2 Groups include, but are not limited to, various phenyl, substituted phenyl, alkyl, and the like; r 3 Groups include, but are not limited to, phenyl, substituted phenyl (including mono-substituted phenyl as well as poly-substituted phenyl, substituents including, but not limited to, halogen, ester, alkyl, methoxy, and the like), thiophene, furan, and various alkyl groups, and the like.
The invention has the beneficial effects that:
(1) The invention adopts an electrochemical method to synthesize thiocyanide benzoxazine, and avoids the steps of using equivalent oxidant and treating reaction waste material difficultly.
(2) The raw materials needed by the reaction are cheap, the operation is simple and convenient, the application range is wide, and the method is environment-friendly.
(3) The reaction product has a thiocyanate group, can be used for further modification and derivation, and has a wide application prospect.
(4) The product structure skeleton has good biological activity, and is convenient for further application and exploration.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the description below are only some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to the drawings without inventive labor. Wherein:
FIG. 1 is a nuclear magnetic spectrum H of the compound of example 1.
FIG. 2 is a C-NMR spectrum of the compound of example 1.
FIG. 3 is a nuclear magnetic spectrum H of the compound of example 2.
FIG. 4 is a C-NMR spectrum of the compound of example 2.
FIG. 5 is a nuclear magnetic spectrum H of the compound of example 3.
FIG. 6 is a C-NMR spectrum of a compound of example 3.
FIG. 7 is a nuclear magnetic spectrum H of the compound of example 4.
FIG. 8 is a nuclear magnetic spectrum C of the compound of example 4.
Detailed Description
In order to make the aforementioned objects, features and advantages of the present invention more comprehensible, specific embodiments thereof are described in detail below with reference to examples of the specification.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, however, the present invention may be practiced otherwise than as specifically described herein, and it will be appreciated by those skilled in the art that the present invention may be practiced without departing from the spirit and scope of the present invention and that the present invention is not limited by the specific embodiments disclosed below.
Furthermore, the references herein to "one embodiment" or "an embodiment" refer to a particular feature, structure, or characteristic that may be included in at least one implementation of the present invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.
Example 1
Figure BSA0000281368030000031
0.2mmol of N- (2- (prop-1-en-2-yl) phenyl) benzamide, 0.8mmol of ammonium thiocyanate, 0.4mmol of trifluoroacetic acid and 6mL of acetonitrile were put into a pre-dried 10mL reaction flask, and the mixture was stirred at 600rpm for 5 hours at room temperature with a graphite electrode as a positive electrode and a platinum electrode as a negative electrode while adjusting the current to 10 mA. After the reaction is finished, concentrating the reaction solution, adjusting the rotating speed to 90rpm, the temperature to 40 ℃, the vacuum to 0.095Mpa, and the processing time to 4min; and then carrying out column chromatography separation to obtain benzoxazine, wherein 200-300-mesh column chromatography silica gel is adopted, an eluant is petroleum ether and ethyl acetate = 8: 2, the purity of the product is 98% by HPLC analysis, and the product purity is extremely high from the aspects of nuclear magnetic spectrum appearance, signals, noise and the like.
1 H NMR(600MHz，CDCl 3 )δ8.19-8.15(m，2H)，7.56-7.50(m，1H)，7.47(t，J＝7.5Hz，2H)，7.42-7.35(m，2H)，7.26(td，J＝7.4，1.6Hz，1H)，7.14(dd，J＝7.6，0.8Hz，1H)，3.59(d，J＝13.9Hz，1H)，3.46(d，J＝13.9Hz，1H)，1.92(s，3H).
13 C NMR(150MHz，CDCl 3 )δ155.4，138.8，132.0，131.9，130.1，128.5，128.1，127.4，126.5，126.1，123.0，112.3，79.1，44.5，25.9.
Example 2
Figure BSA0000281368030000041
0.2mmol of 4-methoxy-N- (2- (prop-1-en-2-yl) phenyl) benzamide, 0.8mmol of ammonium thiocyanate, 0.4mmol of trifluoroacetic acid and 6mL of acetonitrile were added to a pre-dried 10mL reaction flask, and the mixture was stirred at 600rpm at room temperature for 5 hours with a graphite electrode as a positive electrode and a platinum electrode as a negative electrode and with a current of 10mA adjusted. After the reaction is finished, concentrating the reaction solution, adjusting the rotating speed to 90rpm, the temperature to 40 ℃, the vacuum to 0.095Mpa, and the processing time to 4min; and then carrying out column chromatography separation to obtain benzoxazine, wherein 200-300-mesh column chromatography silica gel is adopted, an eluant is petroleum ether and ethyl acetate = 8: 2, the purity of the product is 98% by HPLC analysis, and the product purity is extremely high from the aspects of nuclear magnetic spectrum appearance, signals, noise and the like.
1 H NMR(600MHz，CDCl 3 )δ8.12(d，J＝8.9Hz，1H)，7.37(td，J＝7.8，1.2Hz，1H)，7.33(dd，J＝7.7，1.0Hz，1H)，7.22(td，J＝7.5，1.3Hz，1H)，7.12(dd，J＝7.6，0.8Hz，1H)，6.96(d，J＝8.9Hz，1H)，3.86(s，3H)，3.57(d，J＝13.8Hz，1H)，3.43(d，J＝13.8Hz，1H)，1.90(s，3H).
13 C NMR(150MHz，CDCl 3 )δ163.8，156.4，140.0，130.83，130.80，127.7，127.2，126.5，125.1，123.7，114.6，113.1，79.3，55.9，44.6，25.8.
Example 3
Figure BSA0000281368030000051
0.2mmol of 4-cyano-N- (2- (prop-1-en-2-yl) phenyl) benzamide, 0.8mmol of ammonium thiocyanate, 0.4mmol of trifluoroacetic acid and 6mL of acetonitrile were added to a pre-dried 10mL reaction flask, and the mixture was stirred at 600rpm at room temperature for 5 hours with a graphite electrode as a positive electrode and a platinum electrode as a negative electrode and with a current of 10mA adjusted. After the reaction is finished, concentrating the reaction solution, adjusting the rotating speed to 90rpm, the temperature to 40 ℃, the vacuum to 0.095Mpa, and the processing time to 4min; and then carrying out column chromatography separation to obtain benzoxazine, wherein 200-300-mesh column chromatography silica gel is adopted, an eluant is petroleum ether and ethyl acetate = 8: 2, the purity of the product is 98% by HPLC analysis, and the product purity is extremely high from the aspects of nuclear magnetic spectrum appearance, signals, noise and the like.
1 H NMR(600MHz，CDCl 3 )δ8.28(d，J＝8.4Hz，2H)，7.74(d，J＝8.3Hz，2H)，7.41(t，J＝7.5Hz，1H)，7.37(d，J＝7.2Hz，1H)，7.31(t，J＝7.4Hz，1H)，7.14(d，J＝7.6Hz，1H)，3.58(d，J＝14.1Hz，1H)，3.45(d，J＝14.1Hz，1H)，1.92(s，3H).
13 C NMR(150MHz，CDCl 3 )δ153.5，138.1，136.1，132.2，130.3，128.5，128.3，126.5，126.2，123.1，118.5，115.O，112.0，79.8，44.7，26.4.
HRMS(ESI)calcd for C 18 H 14 N 3 OS[M+H] + 320.0852，found 320.0857.
Example 4
Figure BSA0000281368030000052
0.2mmol of N- (2- (prop-1-en-2-yl) phenyl) pivaloyl amide, 0.8mmol of ammonium thiocyanate, 0.4mmol of trifluoroacetic acid and 6mL of acetonitrile were charged into a pre-dried 10mL reaction flask, and the flask was stirred at 600rpm for 5 hours at room temperature with a graphite electrode as the positive electrode and a platinum electrode as the negative electrode and with a current of 10mA adjusted. After the reaction is finished, concentrating the reaction solution, adjusting the rotating speed to 90rpm, the temperature to 40 ℃, the vacuum to 0.095Mpa, and the processing time to 4min; and then carrying out column chromatography separation to obtain benzoxazine, wherein 200-300-mesh column chromatography silica gel is adopted, an eluant is petroleum ether and ethyl acetate = 8: 2, the purity of the product is 98% by HPLC analysis, and the product purity is extremely high from the aspects of nuclear magnetic spectrum appearance, signals, noise and the like.
1 H NMR(600MHz，CDCl 3 )δ7.32(td，J＝7.8，1.3Hz，1H)，7.23-7.18(m，2H)，7.04(dd，J＝7.6，1.1Hz，1H)，3.53(d，J＝13.6Hz，1H)，3.42(d，J＝13.6Hz，1H)，1.74(s，3H)，1.28(s，9H).
13 C NMR(150MHz，CDCl 3 )δ166.5，138.6，129.8，127.0，125.9，125.7，122.7，112.4，78.19，44.4，37.5，27.6，26.2.
The invention provides an electrochemical method for synthesizing benzoxazine through thiocyanide, the whole reaction successfully avoids the use of equivalent oxidant, and the method has the advantages of easily available raw materials, simple and convenient operation, wide application range and environmental friendliness. The reaction product can be used for further synthesis of skeleton molecules of various natural products, and has wide application prospect.
It should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.

Claims (4)

1. An electrochemical method for synthesizing benzoxazine by thiocyanization is characterized by comprising the following steps:
adding raw materials of enamine ketone compounds, ammonium thiocyanate, trifluoroacetic acid and acetonitrile into a reaction bottle, using graphite as a positive electrode and platinum as a negative electrode, stirring at the rotation speed of 400-1200rpm for 1-10 hours at room temperature under the condition that the current is 10 mA. After the reaction is finished, concentrating the reaction solution, and then carrying out column chromatography separation to obtain the target product.
2. The process of benzoxazine according to claim 1, wherein: the structural general formula of the used raw material enamine ketone compound is shown as the following formula:
Figure FSA0000281368020000011
wherein R is 1 Groups include, but are not limited to, various halogens, ester groups, alkyl groups, methoxy groups, and the like; r is 2 Groups include, but are not limited to, various phenyl, substituted phenyl, alkyl, and the like; r 3 Groups include, but are not limited to, phenyl, substituted phenyl (including mono-substituted phenyl as well as poly-substituted phenyl, substituents including, but not limited to, halogen, ester, alkyl, methoxy, and the like), thiophene, furan, and various alkyl groups, and the like.
3. A thiocyanided benzoxazine characterized by comprising a compound of the formula:
Figure FSA0000281368020000012
whereinR 1 Groups include, but are not limited to, various halogens, ester groups, alkyl groups, methoxy groups, and the like; r 2 Groups include, but are not limited to, various phenyl, substituted phenyl, alkyl, and the like; r 3 Groups include, but are not limited to, phenyl, substituted phenyl (including mono-substituted phenyl as well as poly-substituted phenyl, substituents including, but not limited to, halogen, ester, alkyl, methoxy, and the like), thiophene, furan, and various alkyl groups, and the like.
4. The process for the synthesis of benzoxazines as claimed in claim 1, wherein: the thiocyanate includes, but is not limited to, one or more of ammonium thiocyanate, potassium thiocyanate, and sodium thiocyanate.
CN202210977816.4A 2022-08-15 2022-08-15 Electrochemical method for synthesizing benzoxazine through thiocyanide Pending CN115161673A (en)

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