CN104803895B - A kind of method for preparing sulfinic acid ester as raw material with benzenesulfonylmethyl isonitrile - Google Patents

Abstract

The invention relates to a method for preparing sulfinic acid ester by using benzenesulfonylmethyl isonitrile as raw material, and the compound has potential anti-leukemia activity through preliminary biological activity test. The structural formula of the prepared sulfinic ester compounds is shown in the figure, wherein Ar ¹ and Ar ² are aryl groups, etc.; R ¹ is a hydrogen atom, an alkyl group, etc. Preparation method: benzyl alcohol compound, benzenesulfonylmethyl isonitrile compound, catalyst and additive are stirred in nitromethane solvent at room temperature for 1 day. After the reaction was completed, water and ethyl acetate were added to the reaction system. After extraction, solvent drying, concentration, and column chromatography purification, the sulfinic acid ester compounds were obtained with a yield of 42-71%. The catalyst is bismuth tribromide, etc.; the additive is acetic acid, etc.

Description

A kind of method using benzenesulfonylmethyl isonitrile as raw material to prepare sulfinic acid ester

technical field

The invention relates to a method for preparing sulfinate by using benzenesulfonylmethyl isonitrile as raw material.

Background technique

Sulfinate compounds are key organic synthesis intermediates and have important uses in the fields of synthetic chemistry and medicinal chemistry ( J. Org. Chem . 1987, 52 , 2598; Tetrahedron Lett . 1991, 47 , 9167; Tetrahedron 1999, 55 , 2311; Mol. Cryst. Liq. Cryst . 2001, 356 , 371; Tetrahedron Lett . 2006, 47 , 2717 ; Chem . Eur. J . 2011, 17 , 10417 ; . Int. Ed. 2014, 53 , 9851; Angew. Chem. Int. Ed. 2014, 53 , 4404 ; Nat. Protoc . 2013, 8 , 1042; Org. Biomol. Chem . 2014, 4, 4286; Chem. Commun . 2014, 50 , 11533). For example, sulfinate compounds are important molecular fragments of drugs, and its representative compound, decantate, is a low-toxic, non-systemic, and low-residue organosulfuride developed in 1964 by the U.S. Lilailu Company. Acaricides ( Can. J. Plant Sci . 1966, 46 , 521; J. Agr. Food Chem . 1971, 19 , 894; Pesticides 1981, 15 , 22). There are three main methods for the synthesis of sulfinic acid ester compounds: 1) dehydration of alcohol compounds and sulfinic acid compounds under the action of dehydrating agent DCC to generate sulfinic acid ester compounds ( Tetrahedron Lett . 2006, 47 , 2717); 2 ) Alcohol compounds and sulfonyl chloride compounds generate sulfinate compounds under alkaline/reducing conditions ( J. Org. Chem . 1987, 52 , 2598); 3) Alcohol compounds and sulfinyl nitrile compounds Under alkaline conditions, sulfinate compounds are generated ( Tetrahedron Lett . 1991, 47 , 9167). The invention uses benzenesulfonylmethyl isonitrile compounds and alcohol compounds as raw materials to prepare sulfinate compounds under mild acidic conditions.

Contents of the invention

The object of the present invention is to provide a kind of method that takes benzenesulfonylmethyl isonitrile as raw material to prepare sulfinate.

In order to achieve the above object, the structure of the sulfinic acid ester compound provided by the present invention is as shown in Figure 1:

Fig. 1 is the general structure diagram of target compound sulfinic acid ester compound

Wherein: Ar ¹ and Ar ² are aryl groups, etc.; R ¹ is a hydrogen atom, an alkyl group, etc.

The main steps of the preparation method provided by the invention are: stirring benzyl alcohol compounds, benzenesulfonylmethyl isonitrile compounds, catalysts and additives in a nitromethane solvent at room temperature for 1 day. After the reaction was completed, water and ethyl acetate were added to the reaction system. After extraction, solvent drying, concentration, and column chromatography purification, the sulfinic acid ester compounds were obtained with a yield of 42-71%. The obtained compound was confirmed by nuclear magnetic resonance spectrum ( ¹ H-NMR and ¹³ C-NMR) and infrared spectrum, with high resolution and correct structure.

The substituted or unsubstituted benzyl alcohol compounds and benzenesulfonylmethyl isonitrile compounds used in the present invention can be purchased directly from the market.

The catalyzer that the present invention adopts is bismuth tribromide etc., and catalyst consumption is 0.1 equivalent;

The additive that the present invention adopts is acetic acid etc., and consumption is 1 equivalent;

The organic solvent that the present invention adopts is nitromethane etc.;

The eluent used in the column chromatography of the present invention is sherwood oil or alkane etc.

Description of drawings

Fig. 1 is the general structure diagram of target compound sulfinic acid ester compound; Fig. 2 is the general reaction diagram of preparing sulfinic acid ester type compound with benzenesulfonyl methyl isonitrile as raw material.

detailed description

Its reaction process is shown in Figure 2:

Fig. 2 is the general reaction diagram of preparing sulfinic acid ester compound with benzenesulfonyl methyl isonitrile as raw material

Wherein: Ar ¹ and Ar ² are aryl groups, etc.; R ¹ is a hydrogen atom, an alkyl group, etc.

Specific preparation method example: 0.2 mmol 3,5-difluorobenzyl alcohol, 0.3 mmol p-toluenesulfonylmethyl isonitrile, 0.02 mmol bismuth tribromide (catalyst), 0.2 mmol acetic acid (additive) and 1 ml of nitromethane was mixed together and the reaction was stirred well at room temperature for 24 hours. After the reaction was completed, 5 milliliters of water and 10 milliliters of ethyl acetate were added to the reaction system, shaken, and the organic phase was separated from the inorganic phase. The aqueous phase was extracted three times with ethyl acetate (3 × 10 mL). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 40 mg of 3,5-difluorobenzyl p-toluenesulfinate with a yield of 70%. Colorless liquid; ¹ H NMR (400 MHz, CDCl ₃ ) delta 7.63 (d, J = 8.0 Hz, 2H),7.35 (d, J = 8.0 Hz, 2H), 6.78–6.70 (m, 3H ), 4.95 (d, J = 12.3 Hz, 1H), 4.49(d, J = 12.3 Hz, 1H), 2.44 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) delta162.9 (dd, J _CF = 330.2, 16.7 Hz, 1C), 143.3, 141.2, 139.6 (t, J _CF = 12.2 Hz, 1C), 129.8, 125.3, 110.8 (dd, J _CF = 23.0, 10.8 Hz, 1C), 103.6 (t, J _CF = 33.4Hz, 1C), 63.6, 21.5; Infrared Spectrum FTIR (film): 1629, 1599, 1464, 1368, 1323, 1137,1119, 946, 854, 813, 759, 673 cm ^-1 . HRMS (ESI) m/z: Calcd forC ₁₄ H ₁₂ F ₂ NaO ₂ S[M+Na] ⁺ : 305.0418. Found: 305.0416.

Claims (1)

1. a kind of preparation method of sulfinic acid ester type compound shown in formula I, has main steps that：

A) 1 equivalent benzalcohol derivatives and 1.5 different nitrile compounds of equivalent benzenesulfonylmethyl are added to reaction tube In, 0.1 the catalyst bismuth tribromide and 1 equivalent additive acetic acid of equivalent are added, it is subsequently adding a little solvent nitro first Alkane, reacts 1 day under ambient temperature；

I

Wherein Ar¹And Ar²It is aryl；R is hydrogen atom, alkyl；

B) after reaction terminates, water and ethyl acetate, ethyl acetate extraction, anhydrous sodium sulfate drying, mistake are added to reaction system Filter, concentration；

C) column chromatography for separation, eluant, eluent is petroleum ether or alkane, obtains sulfinic acid ester type compound.