阅读说明：本技术 （1-乙烯基）氨磺酰氟衍生物及其制备方法和应用 ((1-vinyl) sulfamoyl fluoride derivative and preparation method and application thereof ) 是由 黄立梁 冯煌迪 白雪莹 卿斌 周鹏宇 于 2021-10-15 设计创作，主要内容包括：本发明公开了(1-乙烯基)氨磺酰氟衍生物及其制备方法和应用,属于有机合成化学领域。该衍生物具有如式所示的通式结构,R独立地选自芳香族或杂芳族或脂肪烃的单取代或二取代邻位、间位或对位上的苯基、甲基、乙基、丁基、戊基、甲氧基、氟、氯、溴、硝基或氰基。本发明中(1-乙烯基)氨磺酰氟衍生物含有磺酰氟官能团(RSO-(2)F),具有独特的稳定性和活性,可作为中间体或氟交换试剂用于合成含氟化合物或含磺酰化合物,合成方法简便,产率和原子经济性高,在有机合成、材料科学、化学生物学和药物发现等方面具有广阔的应用前景。(The invention discloses a (1-vinyl) sulfamoyl fluoride derivative and a preparation method and application thereof, belonging to the field of organic synthetic chemistry. The derivatives have the formula The general structure is shown, R is independently selected from phenyl, methyl, ethyl, butyl, pentyl, methoxy, fluorine, chlorine, bromine, nitro or cyano on mono-substituted or di-substituted ortho-, meta-or para-position of aromatic or heteroaromatic or aliphatic hydrocarbon. (1-vinyl) sulfamoyl fluoride derivatives of the present inventionThe organisms contain sulfonyl fluoride functional groups (RSO) 2 F) The method has unique stability and activity, can be used as an intermediate or a fluorine exchange reagent for synthesizing fluorine-containing compounds or sulfonyl-containing compounds, has simple and convenient synthesis method and high yield and atom economy, and has wide application prospect in the aspects of organic synthesis, material science, chemical biology, drug discovery and the like.)

1. A (1-vinyl) sulfamoyl fluoride derivative has a general formula shown as (I):

r is independently selected from phenyl, methyl, ethyl, butyl, pentyl, methoxy, fluoro, chloro, bromo, nitro or cyano in the ortho, meta or para position of an aromatic or heteroaromatic or aliphatic hydrocarbon.

2. The (1-vinyl) sulfamoyl fluoride derivative according to claim 1, which is selected from the general structures shown in any one of (ii):

R¹independently selected from mono-or di-substituted methyl, ethyl, methoxy, fluoro, chloro, bromo, nitro, cyano or alkyl on an aromatic or heteroaromatic aromatic ring;

m is an integer from 0 to 12 and n is an integer from 1 to 8.

3. The (1-vinyl) sulfamoyl fluoride derivative according to claim 1 or 2, characterized by being selected from compounds of any one of the following structures 2a to 2 b':

4. a process for the preparation of a (1-vinyl) sulfamoyl fluoride derivative according to any one of claims 1 to 3, characterized in that the synthetic route is represented by formula (III):

wherein R is independently selected from phenyl, methyl, ethyl, butyl, pentyl, methoxy, fluoro, chloro, bromo, nitro or cyano in the mono-or di-substituted ortho-, meta-or para-position of an aromatic or heteroaromatic or aliphatic hydrocarbon;

comprises the step of dissolving alkyne, lithium ammonium salt and quaternary ammonium salt in a solvent and then stirring for 2-24 hours at the temperature of 20-100 ℃.

5. The method for producing the (1-vinyl) sulfamoyl fluoride derivative according to claim 4, wherein the quaternary ammonium salt is one or a combination of two or more selected from benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydrogensulfate, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, and tetrabutylammonium tetrafluoroborate.

6. The method for producing the (1-vinyl) sulfamoyl fluoride derivative according to claim 4, wherein the solvent is one or a combination of two or more selected from dichloromethane, chloroform, 1, 2-dichloroethane, tetrahydrofuran, acetonitrile, toluene, and chlorobenzene.

7. The process for the preparation of the (1-vinyl) sulfamoyl fluoride derivative according to any one of claims 4 to 6, wherein the synthetic route is represented by formula (IV):

wherein R is¹Independently selected from mono-or di-substituted methyl, ethyl, methoxy, fluoro, chloro, bromo, nitro, cyano or alkyl on an aromatic or heteroaromatic aromatic ring, m is selected from an integer from 0 to 12, n is selected from an integer from 1 to 8;

the method comprises the steps of dissolving alkyne, lithium ammonium salt and tetrabutylammonium tetrafluoroborate in a solvent, and stirring for 2-24 hours at 20-100 ℃.

8. Use of the (1-vinyl) sulfamoyl fluoride derivative of any one of claims 1 to 3 for the synthesis of fluorine-containing compounds or sulfonyl-containing compounds.

9. Use according to claim 8, wherein the fluorine-containing compound comprises fluorosulfate and sulfamoyl fluoride, and/or the sulfonyl-containing compound comprises sulfonamide, sulfonate and sulfone;

the (1-vinyl) sulfamoyl fluoride derivative is used as an intermediate or a fluorine exchange reagent.

10. Use of a (1-vinyl) sulfamoyl fluoride derivative as claimed in any one of claims 1 to 3 as a selective fluorinating agent in the deoxofluorination¹⁸F radiolabelling.

Technical Field

The invention relates to the field of organic synthetic chemistry, in particular to a (1-vinyl) sulfamoyl fluoride derivative and a preparation method and application thereof.

Background

Hexavalent sulfur fluoride exchange chemistry is one of the most recent and most powerful click chemistry reactions, and is centered on the relative stability of the sulfur fluoride bond and its ability to undergo defluorination by nucleophilic substitution under specific conditions. In organic synthesis, sulfonyl fluorides in place of sulfonyl chlorides have long been recognized as versatile precursors for the synthesis of sulfonyl-containing compounds, including sulfonamides, sulfonates, and sulfones. In addition, sulfonyl fluorides have been used as a new class of selective fluorinating agents for deoxofluorination and¹⁸f radiolabeling, most recently fluorosulfonyl azide (FSO)₂N₃) Have proven to be excellent diazo transfer reagents for the synthesis of azides from primary amines. In materials science, sulfonyl fluorides have been used to synthesize compounds with a unique-SO₂Polymers of bonds, which are an important complement to classical synthetic polymers having carbon-carbon or carbon-heteroatom bonds. Furthermore, due to the orthogonal reactivity of Sufexable groups, -SO₂The F moiety has been used as a reactive handle in the side chain, allowing facile pre-assembly onto monomers for post-polymerization modification of polymers. In the biological sciences, sulfonyl fluorides have been used as privileged covalent probes and inhibitors in chemical biology and drug discovery that have been shown to covalently modify various amino acid residues of enzyme binding sites, including context-specific serine, threonine, lysine, tyrosine, cysteine and histidine residues. The SuFEx reaction has unique characteristics relative to the widely used copper-catalyzed alkyne-azide cycloaddition (CuAAC). First, the SuFEx reaction is usually studied under metal-free conditions for click chemistry in biological systems of particular interest for application programs. Second, the SuFEx reaction produces nucleophiles that are linked to a variety of different groups, from silyl ethers, alcohols, amines to carbon nucleophiles, creating different functions through S-FAnd (4) molecule exchange. Third, with the defined terminal alkyne and azide functionalities requiring multiple steps to install into a substrate for CuAAC reactions, the SuFExable handle is a common native functionality hub that is generally more flexible and easier to incorporate by union through discrete connectives, such as SO₂F₂And SOF₄. These features of the SuFEx reaction will allow it to find a wider range of applications in the fields of chemical biology and medicine.

Disclosure of Invention

A first object of the present invention is to provide a (1-vinyl) sulfamoyl fluoride derivative represented by the general formula (I).

Another object of the present invention is to provide a process for producing a (1-vinyl) sulfamoyl fluoride derivative represented by the above general formula (I).

Still another object of the present invention is to provide use of the (1-vinyl) sulfamoyl fluoride derivative represented by the above general formula (I) for synthesizing a fluorine-containing compound or a sulfonyl-containing compound.

The above object of the present invention is achieved by the following technical solutions:

the invention provides a (1-vinyl) sulfamoyl fluoride derivative, which has a general formula shown as (I):

r is independently selected from phenyl, methyl, ethyl, butyl, pentyl, methoxy, fluoro, chloro, bromo, nitro or cyano in the ortho, meta or para position of an aromatic or heteroaromatic or aliphatic hydrocarbon.

Preferably, the (1-vinyl) sulfamoyl fluoride derivative is selected from the general structures shown in any one of (ii):

R¹independently selected from mono-or di-substituted methyl, ethyl, methoxy, fluoro, chloro, bromo, nitro on aromatic or heteroaromatic aromatic ringsAlkyl, cyano or alkyl;

m is an integer from 0 to 12 and n is an integer from 1 to 8.

Preferably, the (1-vinyl) sulfamoyl fluoride derivative is selected from compounds of any one of the following structures 2a to 2 b':

the invention provides a preparation method of a (1-vinyl) sulfamoyl fluoride derivative shown as a general formula (I), wherein a synthetic route is shown as a formula (III) below:

wherein R is independently selected from phenyl, methyl, ethyl, butyl, pentyl, methoxy, fluoro, chloro, bromo, nitro or cyano in the mono-or di-substituted ortho-, meta-or para-position of an aromatic or heteroaromatic or aliphatic hydrocarbon;

the preparation method comprises the steps of dissolving alkyne, lithium ammonium salt and quaternary ammonium salt in a solvent, and stirring for 2-24 hours at 20-100 ℃.

Preferably, the quaternary ammonium salt is selected from one or more of benzyltriethylammonium chloride (TEBA), tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate (TBAB), trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride or tetrabutylammonium tetrafluoroborate.

Preferably, the solvent is one or more of dichloromethane, chloroform, 1, 2-dichloroethane, tetrahydrofuran, acetonitrile, toluene or chlorobenzene.

Preferably, the (1-vinyl) sulfamoyl fluoride derivative represented by the general formula (II) is prepared by a synthetic route represented by the following formula (IV):

wherein R is¹Independently selected from mono-or di-substituted methyl, ethyl, methoxy, fluoro, chloro, bromo, nitro, cyano or alkyl on an aromatic or heteroaromatic aromatic ring, m is selected from an integer from 0 to 12, n is selected from an integer from 1 to 8;

the preparation method comprises the steps of dissolving alkyne, lithium ammonium salt and tetrabutylammonium tetrafluoroborate in a solvent, and stirring for 2-24 hours at the temperature of 20-100 ℃.

The invention provides application of any one of the (1-vinyl) sulfamoyl fluoride derivatives in synthesis of fluorine-containing compounds or sulfonyl-containing compounds.

Preferably, the fluorine-containing compounds include fluorosulfate and sulfamoyl fluoride, and the sulfonyl-containing compounds include sulfonamides, sulfonates, and sulfones.

Preferably, the (1-vinyl) sulfamoyl fluoride derivative acts as an intermediate or fluorine exchange reagent.

The invention provides the use of any one of the (1-vinyl) sulfamoyl fluoride derivatives as selective fluorinating agents in deoxofluorination¹⁸F radiolabelling.

Compared with the prior art, the invention has the beneficial effects that:

the invention utilizes simple addition reaction to synthesize the (1-vinyl) sulfamoyl fluoride derivative, has simple and convenient synthesis method, high yield and high atom economy, and provides a new way for synthesizing fluorine-sulfur exchange compounds in the fields of organic synthesis and pharmaceutical chemistry.

The (1-vinyl) sulfamoyl fluoride derivative of the present invention contains a sulfonyl fluoride functional group (RSO)₂F) The fluorine-containing compound has unique stability and activity, can be used as an intermediate or a fluorine exchange reagent for synthesizing fluorine-containing compounds such as fluorosulfate and sulfonamide fluoride or sulfonyl-containing compounds such as sulfonamide and sulfonate sulfone, and has wide application prospects in the aspects of organic synthesis, material science, chemico-biology, drug discovery and the like.

Drawings

Other features, objects and advantages of the invention will become more apparent upon reading of the detailed description of non-limiting embodiments with reference to the following drawings:

FIG. 1 shows nuclear magnetism of 2a in example 1¹H NMR。

FIG. 2 shows nuclear magnetism of 2b in example 1¹H NMR。

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention are clearly and completely described below with reference to the drawings of the embodiments of the present invention. It is to be understood that the embodiments described are only a few embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the described embodiments of the invention without any inventive step, are within the scope of protection of the invention.

Example 1

The synthesis of formula III is prepared according to the following formula:

the preparation method comprises the following steps: dissolving alkyne (10mmol) and lithium ammonium salt (1.5equiv) in 30ml of solvent, adding tetrabutyl tetrafluoroborate (0.5equiv), stirring in a reaction bottle at 20-100 ℃ for 12h, cooling to room temperature, extracting and separating by using ethyl acetate, drying an organic phase by using anhydrous sodium sulfate, filtering, spin-drying, and carrying out column chromatography separation to obtain a light yellow viscous product.

In example 1, (1-vinyl) sulfamoyl fluoride derivatives represented by the formula (2a-2 b'), substituent selection, yield and nuclear magnetism were prepared in accordance with the above-mentioned method¹The H NMR data are shown in Table 1.

TABLE 1