CN1300117C - Microwave radiation synthesis of 1,3-substituted imidazole-2-thioketone - Google Patents

Abstract

The invention discloses a method for synthesizing 1,3-disubstituted imidazole-2-thione by microwave radiation. 1,3-disubstituted imidazolium salt and potassium thioacetate with an equivalent ratio of 1:1～3, synthesize 1,3-disubstituted imidazole-2-thione under microwave radiation conditions, and the power of microwave radiation is 50～ 300W, microwave radiation reaction time is 2-20 minutes, the reaction formula is: where R ₁ = alkyl (C _1-4 ), benzyl, R ₂ = alkyl (C _1-4 ), benzyl, allyl , hydroxyethyl, acetoxyethyl, X=Cl, Br, BF ₄ , PF ₆ . Compared with the existing method, the present invention has the following advantages: 1. The reaction speed is greatly improved by microwave radiation, and the reaction time is usually 2 to 20 minutes; 2. The reaction operation is simple and convenient, without removing water; 3. The post-reaction treatment is simple, Only need to dissolve and extract, filter, wash and concentrate, and the purity of the crude product is greater than 80%; 4. The reaction does not require organic solvents and is pollution-free.

Description

Method for synthesizing 1,3-disubstituted imidazole-2-thiones by microwave irradiation

technical field

The invention relates to a method for synthesizing 1,3-disubstituted imidazole-2-thione by microwave radiation.

Background technique

Imidazole-2-thione is a class of important compounds widely used in medicine and chemical industry, such as 1-methylimidazole-2-thione ( ^Methimazole ) can be used for the treatment of thyroid secretion disorders; some imidazole-2-thione Medicines are also used to treat arthritis. In addition, imidazole thione has antioxidant and flame retardant functions, such as benzimidazole thione can be used as rubber antioxidant; 1,3-dialkylimidazole-2-thione can be used as a catalyst for the synthesis of epoxy resin and can significantly improve properties of the resin. Arduengo applied for a patent (USP5,104,993) for the synthesis of 1,3-dialkylimidazolium-2-thiones in 1992. This synthesis method is in the presence of potassium carbonate, with 1,3-alkylimidazolium salt and Sulfur is used as a raw material to synthesize 1,3-dialkylimidazole-2-thione, the reaction time is long (24-48 hours) and anhydrous is required, and methanol is highly toxic.

Contents of the invention

The object of the present invention is to provide a method for synthesizing 1,3-disubstituted imidazole-2-thiones by microwave radiation

1,3-disubstituted imidazolium salt and potassium thioacetate with an equivalent ratio of 1:1～3, synthesize 1,3-disubstituted imidazole-2-thione under microwave radiation conditions, and the power of microwave radiation is 50～ 300W, microwave radiation reaction time is 2 to 20 minutes, the reaction formula is:

Wherein R ₁ = C _1-4 alkyl, benzyl, R ₂ = C _1-4 alkyl, benzyl, allyl, acetoxyethyl, X = Cl, Br, BF ₄ , PF ₆ .

Compared with existing methods, the present invention has the following advantages:

1. Use microwave radiation to greatly increase the reaction speed, usually the reaction time is 2 to 20 minutes;

2. The reaction is easy to operate and does not need to remove water;

3. The post-reaction treatment is simple, only need to dissolve and extract, filter, wash and concentrate, and the purity of the crude product is greater than 80%;

4. The reaction does not require organic solvents and is pollution-free.

Detailed ways

The following examples will help to understand the present invention, but are not limited to the content of the present invention:

Embodiment 1 1, the synthesis of 3 dimethylimidazoles-2-thione

Mix 10 mmol 1,3-dimethylimidazole chloride and 11 mmol potassium thioacetate in a 20 ml single-necked bottle evenly, install a reflux condenser, and react under 150W power microwave radiation for 5 minutes, naturally After cooling to room temperature, the reaction mixture was dissolved with 50 ml of ethyl acetate-water (volume ratio 1:1), placed in a separatory funnel, and the organic phase was separated, dried with anhydrous potassium sulfate for 2 hours, concentrated, and washed with silica gel. Column chromatography (eluent: n-hexane: ethyl acetate = 2:1) gave 998 mg of 1,3-dimethylimidazole-2-thione with a yield of 75%.

¹ HNMR (500MHz, CDCl ₃ ): δ=3.60(s, 6H), 6.71(s, 2H);

¹³ CNMR (500MHz, CDCl ₃ ): δ=34.56, 117.55, 162.12;

IR (cm ^-1 ) 2957, 1445, 1230, 1045;

MS ([M+H] ⁺ ): 128.8;

Example 2 Synthesis of 1,3-dimethylimidazole-2-thione

The reaction steps are the same as in Example 1, except that 1,3-dimethylimidazole bromide is used as the raw material to obtain the product with a yield of 78%.

Example 3 Synthesis of 1,3-dimethylimidazole-2-thione

The reaction steps are the same as in Example 1, except that 1,3-dimethylimidazolium tetrafluoroborate is used as the raw material to obtain the product with a yield of 79%.

Example 4 Synthesis of 1,3-dimethylimidazole-2-thione

The reaction steps are the same as in Example 1, except that the product was reacted under 100W power microwave radiation for 8 minutes, and the yield was 82%.

Example 5 Synthesis of 1-butyl-3-methylimidazole-2-thione

The reaction steps are the same as in Example 1, except that 1-butyl-3-methylimidazole bromide is used as the raw material to obtain the product with a yield of 78%.

¹ HNMR (500MHz, CDCl ₃ ): δ=0.96(t, 3H), 1.38(m, 2H), 1.75(m, 2H), 3.61(s, 3H), 4.03(t, 2H), 6.71(dd, 2H);

¹³ CNMR (500MHz, CDCl ₃ ): 13.74, 19.82, 31.02, 35.10, 47.83, 116.63, 117.74, 161.72

IR (cm ^-1 ) 2958, 2933, 1568, 1462, 1414;

MS ([M+H] ⁺ ): 170.8;

Example 6 Synthesis of 1-butyl-3-methylimidazole-2-thione

The reaction steps are the same as in Example 5, except that 1-butyl-3-methylimidazolium hexafluorophosphate is used as the raw material, and the product is reacted under 120W power microwave radiation for 6 minutes to obtain the product with a yield of 82%.

Example 7 Synthesis of 1-butyl-3-methylimidazole-2-thione

The reaction steps were the same as in Example 6, except that 15 mmoles of potassium thioacetate was used, and the product was reacted under 120W power microwave radiation for 6 minutes to obtain the product with a yield of 85%.

Example 8 Synthesis of 1-allyl-3-methylimidazole-2-thione

The reaction steps are the same as in Example 1, except that 1-allyl-3-methylimidazole bromide is used as the raw material to obtain the product with a yield of 72%.

¹ HNMR (500MHz, CDCl ₃ ): δ=3.62(s, 3H), 4.68(d, 2H), 5.25(m, 2H), 5.93(m, 1H), 6.70(dd, 2H);

¹³ CNMR (500MHz, CDCl ₃ ): 35.30, 50.36, 116.39, 117.99, 119.23, 132.06, 162.62;

IR (cm ^-1 ): 2925, 1568, 1459, 1398;

MS ([M+H] ⁺ ): 154.7;

Example 9 Synthesis of 1-benzyl-3-methylimidazole-2-thione

The reaction steps are the same as in Example 1, except that 1-benzyl-3-methylimidazole bromide is used as the raw material to obtain the product with a yield of 82%.

¹ HNMR (500MHz, CDCl ₃ ): δ=3.63(s, 3H), 5.24(s, 2H), 6.60(dd, 2H);

¹³ CNMR (500MHz, CDCl ₃ ): 35.39, 51.50, 116.49, 118.14, 128.28, 128.44, 129.00, 136.02, 162.50;

IR (cm ^-1 ): 3137, 1455, 1409, 1393;

MS ([M+H] ⁺ ): 204.8;

Example 10 Synthesis of 1-acetoxyethyl-3-methylimidazole-2-thione

The reaction steps are the same as in Example 1, except that 1-acetoxyethyl-3-methylimidazole bromide is used as the raw material to obtain the product with a yield of 81%.

¹ HNMR (500MHz, CDCl ₃ ): δ=1.30(t, 3H), 3.62(s, 3H), 4.25(m, 2H), 4.87(s, 2H), 6.74(dd, 2H);

¹³ CNMR (500MHz, CDCl ₃ ): 14.22, 35.42, 48.78, 61.97, 117.43, 118.08, 163.83, 167.57;

IR (cm ^-1 ): 2987, 1732, 1570, 1425, 1403, 1389;

MS ([M+H] ⁺ ): 200.8

Claims (4)

1. one kind synthetic 1, the method of 3-disubstituted imidazole-2-thioketones, it is characterized in that equivalence ratio be 1: 1～3 1,3-disubstituted imidazole salt and thioacetic acid potassium, synthesize 1 under the microwave radiation condition, 3-disubstituted imidazole-2-thioketones, the power of microwave radiation are 50～300W, the microwave radiation reaction times is 2～20 minutes, and reaction formula is:

R wherein ₁=C _1～4Alkyl, benzyl, R ₂=C _1～4Alkyl, benzyl, allyl group, acetyl oxygen ethyl, X=Cl, Br, BF ₄, PF ₆

2. according to claim 1 a kind of synthetic 1, the method for 3-disubstituted imidazole-2-thioketones, the power that it is characterized in that said microwave radiation is 50～200W.

3. according to claim 1 a kind of synthetic 1, the method for 3-disubstituted imidazole-2-thioketones is characterized in that the said microwave radiation reaction times is 2～10 minutes.

4. according to claim 1 a kind of synthetic 1, the method for 3-disubstituted imidazole-2-thioketones is characterized in that 1, and the equivalence ratio of 3-disubstituted imidazole salt and thioacetic acid potassium is 1: 1～2.