WO2014089729A1

WO2014089729A1 - 1-substituted-4-bromo-2h-1,2,3-triazole derivative and preparation method therefor

Info

Publication number: WO2014089729A1
Application number: PCT/CN2012/001705
Authority: WO
Inventors: 江岳恒; 阙利民; 蔡彤�
Original assignee: 雅本化学股份有限公司
Priority date: 2012-12-14
Filing date: 2012-12-14
Publication date: 2014-06-19

Abstract

Disclosed are a 1-substituted-4-bromo-2H-1,2,3-triazole derivative and a preparation method therefor. The disclosed 1-substituted-4-bromo-2H-1,2,3-triazole derivative has a structure as represented by formula (I), where R expresses either an alkyl, an aryl, an aralkyl, a cycloalkyl, a cycloalkylalkyl, a heteroaryl, a heteroarylalkyl or a heterocycloalkyl, and X expresses either chlorine or iodine. The preparation method of the present invention is simple and easy, and acquires a high compound yield.

Description

TECHNICAL FIELD The present invention relates to a 1-substituted-4-bromo-2H-1,2,3-triazole An azole derivative and a preparation method thereof.

Say

Background technique

The 1-substituted-4-bromo-2H-1,2,3-triazole derivatives are a new class of compounds with great developmental value. Triazole-based compounds have a wide range of potential applications, and are important intermediates for many drugs, herbicides, and insecticides. They are also the major pharmacophores in many drug molecules. SUMMARY OF THE INVENTION An object of the present invention is to provide a novel 1-substituted-4-bromo-2H-1,2,3-triazole derivative and a process for the preparation thereof. In order to achieve the above object, the technical scheme adopted by the present invention is as follows: A 1-substituted-4-bromo-2H-1,2,3-triazole derivative having the structure represented by the following formula I: xH ^{Br cl} >=( ^Br '>=( ^Br

κ Ν ^κ Ν ^κ Ν

Formula I Formula IV Formula IV wherein R represents a fluorenyl group, an aryl group, an aryl fluorenyl group, a cyclodecyl group, a cyclodecyl fluorenyl group, a heteroaryl group, a heteroaryl fluorenyl group or a heterocyclic fluorenyl group; X represents chlorine or iodine . When X is chlorine, the 1-substituted-4-bromo-2H-1,2,3-triazole derivative is 1-substituted-4-bromo-5-chloro-lH-1 represented by formula III 2,3-trinitrogen frustration; when X is iodine, the 1-substituted-4-bromo-2H-1,2,3-triazole derivative is 1-substituted-4- represented by formula IV Bromo-5-iodo-lH-1,2,3-triazole. The 1-substituted-4-bromo-2H-1,2,3-triazole derivatives disclosed in the present invention are prepared by the following steps: 1) Dissolving the compound of the following formula II in the first organic solvent, cooling to -78 to 0 ° C, adding the Grignard reagent, and stirring for 0.5 to 2 hours.

Wherein R represents a fluorenyl group, an aryl group, an aryl fluorenyl group, a cyclodecyl group, a cyclodecyl fluorenyl group, a heteroaryl group, a heteroaryl fluorenyl group or a heterocyclic fluorenyl group;

2) introducing chlorine gas or adding chlorinating agent, or adding iodine, stirring for 5 to 30 minutes, heating to room temperature, quenching with saturated aqueous ammonium chloride solution or hydrochloric acid solution, and extracting with a second organic solvent;

3) The extract obtained in the step 2) is dried and concentrated to dryness under reduced pressure, and the obtained concentrate is recrystallized to obtain the 1-substituted-4-bromo-2H-1,2,3-triazole derivative.

In the step 1) of the embodiment of the present invention, the mass to volume ratio of the compound of the formula II to the first organic solvent is 1: 2 to 20; the molar ratio of the compound of the formula II to the Grignard reagent is 1: 0.8-1.5, preferably 1: 0.8-1.2; the first organic solvent is diethyl ether, tetrahydrofuran, 1,4-dioxane or methyltetrahydrofuran; the Grignard reagent is isopropyl magnesium chloride or different Propyl magnesium chloride-lithium chloride complex.

The isopropylmagnesium chloride or the isopropylmagnesium chloride-lithium chloride complex of the present invention is a tetrahydrofuran solution, a 2-methyltetrahydrofuran solution or a diethyl ether solution of different molar concentrations, and the commercially available concentration is usually 1.0 to 2.0 mol/ Rise.

In the step 2) of the embodiment of the present invention, the molar ratio of the compound of the formula II to chlorine, chlorinating agent or iodine is 1:1 to 10, preferably 1:2 to 5; the chlorinating agent Including N-chlorosuccinimide and 1,3-dichloro-5,5-dimethylhydantoin; the second organic solvent is one or more of a fatty acid ester or an ether. a mixture of ratios, wherein the fatty acid esters include ethyl formate, propyl formate, butyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, isopropyl acetate, isobutyl acetate, pentane acetate Ester, isoamyl acetate, methyl propionate, ethyl propionate, propyl propionate, butyl propionate and amyl propionate, ethers including diethyl ether, propyl ether, diisopropyl ether and methyl tert-butyl ether .

In step 3) of the embodiment of the present invention, drying step with anhydrous sodium sulfate or anhydrous magnesium sulfate Step 2) The obtained extract, the recrystallization comprises the following steps: adding the concentrate to the solvent at a mass to volume ratio of 1: 1 to 100, stirring at -20 to 50 ° C for 0.5 to 24 hours, filtering, and vacuum drying to obtain The 1-substituted-4-bromo-2H-1,2,3-triazole derivative; the solvent is one of water, an alcohol, a fatty acid ester, a ketone, an ether, and a hydrocarbon or Mixing of two or more of any ratio, wherein the alcohol includes methanol, ethanol, n-propanol, isopropanol, n-butanol and t-butanol, and the fatty acid esters include ethyl formate, propyl formate, butyl formate, and acetic acid Ester, ethyl acetate, propyl acetate, butyl acetate, isopropyl acetate, isobutyl acetate, amyl acetate, isoamyl acetate, methyl propionate, ethyl propionate, propyl propionate, propionic acid Butyl ester and amyl propionate, ketones including acetone, 2-butanone, cyclopentanone and cyclohexanone, ethers including diethyl ether, propyl ether, diisopropyl ether, methyl tert-butyl ether and tetrahydrofuran, 1, 4 - Dioxane and petroleum ether, hydrocarbons include n-hexyl, cyclohexanyl, methylcyclohexanide and n-glyoxime.

The preparation of 1-substituted-4,5-dibromo-1H-1,2,3-triazole (Formula II) has been described in detail in the applicant's patent applications No. 201110166067.9 and No. 201210051904.8.

The reaction formula of the preparation method of the 1-substituted-4-bromo-2H-1,2,3-triazole derivative disclosed in the present invention is as follows:

^K NN type II type V type III type IV

The preparation method of the 1-substituted-4-bromo-2H-1,2,3-triazole derivative of the present invention is simple and easy, and the obtained compound has a high yield. BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be further illustrated by the following examples, but does not limit the scope of application of the present invention.

Example 1

r

3.0 g (12.45 mmol) of 1-methyl-4,5-dibromo-2H-1,2,3- Hydrogen furan was cooled to -15~0 ° C, and 7.47 ml (14.95 mmol) of 2.0 M isopropylmagnesium chloride tetrahydrofuran solution was slowly added dropwise over 30 minutes. After the addition is complete, continue stirring for 30 to 60 minutes. Chlorine gas is slowly introduced until the reaction liquid does not heat up. The reaction mixture was poured into 20 ml of aq.垸(1/3), heated to reflux for 1 hour, cooled to 0-10 ° C, stirring was continued for 1 hour, filtered, and dried at <40 ° C under vacuum. There was obtained 2.01 g of 1-methyl-4-bromo-5-chloro-2H-1,2,3-triazole solid in a yield of 82%. NMR (CDC1 ₃ , 400 MHz): δ 4.02 (s, 3H); ¹³ C NMR (CDC1 ₃ , 400 MHz): δ 125.9, 119.0, 35.9. Example 2

The procedure was the same as in Example 1, replacing 1-methyl-4,5-dibromo-2Η-1,2,3-triazole with 3.17 g (12.45 mmol) of 1-ethyl-4,5-dibromo -2H-1,2,3-triazole. There was obtained 2.33 g of 1-ethyl-4-bromo-5-chloro-2H-1,2,3-triazole solid in a yield of 89%. NMR (CDC1 ₃ , 400 MHz): δ 4.38 (q, J = 7.2 Hz, 2H), 1.51 (t, J = 7.2 Hz, 3H); ¹³ C NMR (CDC1 ₃ , 400 MHz) δ 124.9, 119.2, 44.9 , 14.5. Example 3

The procedure was the same as in Example 1. Substituting 1-methyl-4,5-dibromo-2Η-1,2,3-triazole to 3.35 g (12.45 mmol) 1-n-propyl-4,5-di Bromo-2H-1,2,3-triazole. There was obtained 1.58 g of 1-n-propyl-4-bromo-5-chloro-2H-1,2,3-triazole oil in a yield of 92%. NMR (CDC1 ₃ , 400 MHz): 5 4.31 (t, / = 7.2 Hz, 2H), 1.97-1.90 (m, 2H), 0.97 (t, / = 7.2 Hz, 3H); ¹³ C NMR (CDC1 ₃ , 400 MHz): δ 125.2, 119.1, 51.1, 22.7, 10.9.

The procedure was the same as in Example 1, replacing 1-methyl-4,5-dibromo-2H-1,2,3-triazole with 3.50 g (12.45 mmol) of 1-cyclopropylmethyl-4,5. -Dibromo-2H-1,2,3-triazole. There was obtained 2.71 g of 1-cyclopropylmethyl-4-bromo-5-chloro-2H-1,2,3-triazole oil in a yield of 92%. NMR (CDC1 ₃ , 400 MHz): δ 4.22 (d, J = 7.2 Hz, 2H), 1.40-1.32 (m, IH), 0.67 (m, 2H), 0.53 (m, 2H); ¹³ C NMR (CDC1 ₃ , 400 MHz): δ 124.9, 119.2, 54.3, 10.7, 4.3.

Example 5

The procedure was the same as in Example 1, replacing 1-methyl-4,5-dibromo-2Η-1,2,3-triazole with 3.67 g (12.45 mmol) of 1-cyclobutylmethyl-4,5-di. Bromo-2H-1,2,3-triazole. 2.84 g of 1-cyclobutylmethyl-4-bromo-5-chloro-2H-1,2,3-triazole oil was obtained in a yield of 91%. _{NMR (CDC1 3, 400 MHz)} : δ 4.36 (d, / = 7.2 Hz, 2H), 2.93-2.85 (m, IH), 2.12-2.06 (m, 2H), 1.96-1.82 (m, 4H); 13 C NMR (CDC1 ₃ , 400 MHz): δ 124.0, 117.9, 53.0, 33.7, 24.6, 16.9.

Example 6

The procedure was the same as in Example 1, replacing 1-methyl-4,5-dibromo-2Η-1,2,3-triazole with 3.67 g (12.45 mmol) of 1-cyclopentyl-4,5-di. Bromo-2H-1,2,3-triazole. 2.87 g of 1-cyclopentyl-4-bromo-5-chloro-2H-1,2,3-triazole oil was obtained in a yield of 92%. NMR (CDC1 ₃ , 400 MHz): δ 4.86-4.80 (m, IH), 2.21-2.16 (m, 4H), 1.99-1.95 (m, 2H), 1.79-1.74 (m, 2H); ¹³ C NMR ( CDC1 ₃ , 400 MHz): δ 124.8, 119.3, 61.3, 32.3, 24.4.

Example 7

The procedure was the same as in Example 1, replacing 1-methyl-4,5-dibromo-2H-1,2,3-triazole with 3.87 g (12.45 mmol) of 1-(tetrahydrofuran-3-methyl)- 4,5-Dibromo-2H-1,2,3-triazole, a saturated aqueous solution of ammonium chloride was replaced with a hydrochloric acid solution. 1-(tetrahydrofuran-3-methyl)-4-bromo-5-chloro-2H-1,2,3-triazole oil 3.05 g, yield 92% _3⁄4 NMR (CDC1 ₃ , 400 MHz): δ 4.33 (d, J = 7.6 Hz, 2H), 3.66 (dd, / = 4.8, 9.2 Hz, IH), 2.94-2.87 (m, IH), 2.12-2.03 (m, IH), 1.76-1.68 (m , IH); ¹³ C NMR (CDC1 ₃ , 400 MHz): δ 125.4, 119.3, 70.6, 67.5, 51.7, 39.0, 29.5. Example 8

The procedure was the same as in Example 1, replacing 1-methyl-4,5-dibromo-2H-1,2,3-triazole with 3.87 g (12.45 mmol) of 1-(4-tetrahydropyran). 4,5-Dibromo-2H-1,2,3-triazole. 1-(4-Tetrahydropyran)-4-bromo-5-chloro-2H-1,2,3-triazole solid 3.15 g was obtained in a yield of 95%. ^NMR (CDC1 ₃ , 400 MHz): δ 4.60-4.53 (m, IH), 4.15 (dt, / = 2.0, 10.0 Hz, 2H), 3.56 (dt, / = 2.0, 12.0 Hz, 2H), 2.36 ( Dq, J = 4.4, 12.0 Hz, 2H), 2.02 (dd, /= 2.0, 12.8 Hz, 2H); ¹³ C NMR (CDC1 ₃ , 400 MHz): δ 124.5, 119.5, 66.6, 57.0, 31.8. Example 9

^Br N, , .N ^c - ^l

NN was operated as in Example 1, replacing 1-methyl-4,5-dibromo-2H-1,2,3-triazole with 3.32 g (12.45 mmol) 1-allyl-4,5- Dibromo-2H-1,2,3-triazole. There was obtained 2.49 g of 1-allyl-4-bromo-5-chloro-2H-1,2,3-triazole oil in a yield of 90%. NMR (CDC1 ₃ , 400 MHz): δ 6.00-5.90 (m, IH), 5.36 (dd, /=0.4, 10.0 Hz, IH), 5.25 (dd, J = 0.4, 17.2 Hz, IH), 4.97 (dd , / = 1.6, 6.0 Hz, 2H); ¹³ C NMR (CDC1 ₃ , 400 MHz): δ 129.5, 125.5, 120.5, 119.4, 51.9. Example 10

The procedure was the same as in Example 1. Substituting 1-methyl-4,5-dibromo-2H-1,2,3-triazole to 4.12 g (12.45 mmol) 1-phenylethyl-4,5-di Bromo-2H-1,2,3-triazole. There was obtained 1.10 g of 1-phenylethyl-4-bromo-5-chloro-2H-1,2,3-triazole oil in a yield of 87%. ^ NMR (CDC1 ₃ , 400 MHz) : δ 7.32-7.24 (m, 3Η), 7.13 (d, / = 7.2 Hz, 2H), 4.56 (t, / = 7.6 Hz, 2H), 3.21 (t, J = 1.6 Hz, 2H); ¹³ C NMR (CDC1 ₃ , 400 MHz): δ 136.1, 128.9, 128.7, 127.4, 125.5, 119.1, 50.7, 35.8 o Example 11

The procedure was the same as in Example 1, replacing 1-methyl-4,5-dibromo-2H-1,2,3-triazole with 4.17 g (12.45 mmol) 1-p-fluorobenzyl-4,5. -Dibromo-2H-1,2,3-triazole. A solid of 1-p-fluorobenzyl-4-bromo-5-chloro-2H-1,2,3-triazole was obtained in an amount of 3.18 g, yield 88%. NMR (CDC1 ₃ , 400 MHz) : δ 7.33-7.26 (m, 2H), 7.06 (dd, / = 8.4, 8.8 Hz, 2H), 5.50 (s, 2H); ¹³ C NMR (CDC1 ₃ , 400 MHz) : δ 163.0 (d, J = 248.0 Hz), 130.0 (d, J = 9.0 Hz), 128.9 (d, / = 3.0 Hz), 125.3, 119.7, 116.2 (d, / = 21.0 Hz), 52.5.

Example 12

The procedure was the same as in Example 1, replacing 1-methyl-4,5-dibromo-2H-1,2,3-triazole with 4.17 g (12.45 mmol) 1-m-fluorobenzyl-4,5. -Dibromo-2H-1,2,3-triazole. Get 1-m-fluorobenzoate The base 4-bromo-5-chloro-2H-1,2,3-triazole solid was 2.98 g, and the yield was 83%. NMR (CDC1 ₃ , 400 MHz): δ 7.37-7.32 (m, 1H), 7.08 (d, /= 0.8 Hz, 1H), 7.06-7.03 (m, 1H), 6.99 (d, /=8.6 Hz, 1H ), 5.52 (s, 2H); ¹³ C NMR (CDC1 ₃ , 400 MHz): δ 163.0 (d, J = 247.0 Hz), 135.3 (d, J = 8.0 Hz), 130.9 (d, J = 8.0 Hz) , 125.5, 123.5 (d, J=3.0 Hz), 119.7, 116.1 (d, /=20.0 Hz), 115.0 (d, / = 22.0 Hz), 52.5 (d, J = 1.0 Hz). Example 13

The procedure was the same as in Example 1, replacing 1-methyl-4,5-dibromo-2H-1,2,3-triazole with 4.38 g (12.45 mmol) of 1-p-chlorobenzyl-4,5. -Dibromo-2H-1,2,3-triazole. A solid of 3.25 g of 1-p-chlorobenzyl-4-bromo-5-chloro-2H-1,2,3-triazole was obtained in a yield of 85%. NMR (CDC1 ₃ , 400 MHz): 57.35 (ABq, J = 8.0 Hz, 2H), 7.25 (ABq, J = 8.0 Hz, 2H), 5.50 (s, 2H); ¹³ C NMR (CDC1 ₃ , 400 MHz) : δ 135.1, 131.5, 129.4, 129.3, 125.4, 119.7, 52.5.

Example 14

The procedure was the same as in Example 1. Substituting 1-methyl-4,5-dibromo-2Η-1,2,3-triazole to 4.38 g (12.45 mmol) 1-m-chlorobenzyl-4,5 -Dibromo-2H-1,2,3-triazole. 1-7% of m-chlorobenzyl-4-bromo-5-chloro-2H-1,2,3-triazole solid was obtained in a yield of 83%. _3⁄4 NMR (CD ₃ COCD ₃ , 400 MHz): 57.4-7.41 (m, 3H), 7.31 (d, /=6.8Hz, 1H), 5.74 (s, 2H); ¹³ C NMR (CD ₃ COCD ₃ , 400 MHz): δ 137.4, 135.1, 131.6, 129.6, 128.8, 127.4, 125.8, 119.7, 52.9.

Example 15

The procedure was the same as in Example 1. Substituting 1-methyl-4,5-dibromo-2H-1,2,3-triazole to 4.93 g (12.45 mmol) 1-p-bromobenzyl-4,5 -Dibromo-2H-1,2,3-triazole. There was obtained 3.90 g of 1-p-bromobenzyl-4-bromo-5-chloro-2H-1,2,3-triazole solid in a yield of 89%. _3⁄4 NMR (CD ₃ COCD ₃ , 400 MHz): δ 7.60 (ABq, / = 8.4 Hz, 2H), 7.33 (ABq, J = 8.4 Hz, 2H), 5.71 (s, 2H); ¹³ C NMR (CD ₃ COCD ₃ , 400 MHz): δ 134.4, 132.9, 131.1, 130.9, 125.7, 119.7, 53.0.

Example 16

The procedure was the same as in Example 1, replacing 1-methyl-4,5-dibromo-2Η-1,2,3-triazole with 4.90 g (12.45 mmol) of 1-p-trifluoromethoxybenzyl. -4,5-Dibromo-2H-1,2,3-triazole. There was obtained 3.53 g of 1-trifluoromethoxybenzyl-4-bromo-5-chloro-2H-1,2,3-triazole solid in a yield of 83%. _3⁄4 NMR (CDC1 ₃ , 500 MHz): δ 7.35 (ABq, /= 8.5 Hz, 2H), 7.22 (ABq, / = 8.5 Hz _: 2H), 5.53 (s, 2H); ¹³ C NMR (CDC1 ₃ , 500 MHz): δ 149.6 (d, /= 2.0 Hz), 131.7, 129.7, 125.5, 121.5 (d, J = 1.0 Hz), 120.3 (q, J = 256.0 Hz), 119.7, 112.6, 52.3.

Example 17

The procedure was the same as in Example 1. Substituting 1-methyl-4,5-dibromo-2H-1,2,3-triazole to 3.95 g (12.45 mmol) 1-benzyl-4,5-dibromo -2H-1,2,3-triazole. There was obtained 2.88 g of 1-benzyl-4-bromo-5-chloro-2H-1,2,3-triazole oil in a yield of 85%. NMR (CDC1 ₃ , 500 MHz): δ 7.40-7.35 (m, 3H), 7.31-7.29 (m, 2H), 5.53 (s, 2H); ¹³ C NMR (CDC1 ₃ , 500 MHz): δ 133.1, 129.1 , 129.0, 128.0, 125.4, 119.6, 53.3.

Example 18

The procedure was the same as in Example 1, replacing 1-methyl-4,5-dibromo-2Η-1,2,3-triazole with 4.80 g (12.45 mmol) 1-p-trifluoromethylbenzyl- 4,5-Dibromo-2H-1,2,3-triazole. 1-1.8% trifluoromethylbenzyl-4-bromo-5-chloro-2H-1,2,3-triazole solid was obtained in a yield of 75%. _3⁄4 NMR (CDC1 ₃ , 500 MHz): δ 7.64 (ABq, /= 8.0 Hz, 2H), 7.41 (ABq, / = 8.0 Hz _: 2H), 5.59 (s, 2H); ¹³ C NMR (CDC1 ₃ , 500 MHz): δ 136.9 (d, J = 1.3 Hz), 131.3 (q, / = 32.6 Hz), 128.3, 126.2 (q, / = 3.9 Hz), 125.6, 123.7 (q, / = 270.6 Hz), 119.8, 52.5.

Example 19

The procedure was the same as in Example 1, replacing 1-methyl-4,5-dibromo-2H-1,2,3-triazole with 4.32 g (12.45 mmol) 1-p-methoxybenzyl-4 , 5-dibromo-2H-1,2,3-triazole. There was obtained 3.37 g of 1-p-methoxybenzyl-4-bromo-5-chloro-2H-1,2,3-triazole solid in a yield of 90%. NMR (CDC1 ₃ , 400 MHz): δ 7.31 (ABq, J = 8.8 Hz, 2H), 6.89 (ABq, J = 8.8 Hz, 2H), 5.41 (s, 2H), 3.80 (s, 3H); ¹³ C NMR (CDC1 ₃ , 400 MHz): δ 160.1, 137.3, 130.0, 125.9, 121.1, 114.3, 59.8, 55.

Example 20

Br

The procedure was the same as in Example 1, replacing 1-methyl-4,5-dibromo-2H-1,2,3-triazole with 4.30 g (12.45 mmol) 1-p-methylbenzyl-4. 5-Dibromo-2H-1,2,3-triazole. 1-0.3% of p-methoxybenzyl-4-bromo-5-chloro-2H-1,2,3-triazole solid was obtained in a yield of 88%. NMR (CDC1 ₃ , 400 MHz): δ 7.20 (ABq, J = 8.0 Hz, 2H), 7.16 (ABq, J = 8.0 Hz, 2H), 5.48 (s, 2H), 2.34 (s, 3H); ¹³ C NMR (CDC1 ₃ , 400 MHz): δ 139.0, 130.1, 129.8, 128.0, 125.3, 119.6, 53.1, 21.2. Example 21

r

The procedure was the same as in Example 1, replacing chlorine with 1.66 g (12.45 mmol) of N-chlorosuccinimide. There was obtained 1.67 g of 1-methyl-4-bromo-5-chloro-2H-1,2,3-triazole solid in a yield of 68%. _3⁄4 NMR (CDC1 ₃ , 400 MHz): δ 4.15 (s, 3H); ¹³ C NMR (CDC1 ₃ , 400 MHz): δ 137.0, 120.8, 43.1 o

Example 22 -

1.20 g (5.0 mmol) of 1-methyl-4,5-dibromo-2H-1,2,3-triazole was dissolved in 10 ml of tetrahydrofuran, cooled to -20~0 ° C, and slowly dripped in 30 minutes. 2.74 ml (5.18 mmol) of a 2.0 M solution of isopropylmagnesium chloride in tetrahydrofuran was added. After the addition is complete, continue stirring for 30 to 60 minutes. Solid iodine 1.26 g (5.0 mmol) was added and the reaction was continued for 30 minutes. The reaction mixture was diluted with EtOAc (EtOAc m. Solid was added to 10 ml of isopropanol / water (5 / 1), heated to reflux for 1 hour, cooled to 0 ~ 10 ° C, stirring was continued for 1 hour, filtered, and dried at <40 ° C under vacuum. 1-1.2 mg of 1-methyl-4-bromo-5-iodo-2H-1,2,3-triazole solid was obtained in a yield of 85%. ^NMR CDC, 400 MHz): 54.10 (s, 3H); ¹³ C NMR (CDC1 ₃ , 400 MHz): δ 131.6, 95.3, 43.7. The above is only the preferred embodiment of the present invention, and is not intended to limit the scope of the present invention; the invention is modified or equivalently substituted without departing from the spirit and scope of the invention. Within the scope of protection.

Claims

Claim

A 1-substituted-4-bromo-2H-1,2,3-triazole derivative 4 characterized by having the structure represented by the following formula I:

X Br

W

κ Ν

Formula I

Wherein R represents a fluorenyl group, an aryl group, an aryl fluorenyl group, a cyclodecyl group, a cyclodecyl fluorenyl group, a heteroaryl group, a heteroaryl fluorenyl group or a heterocyclic fluorenyl group; and X represents chlorine or iodine.

A method for producing a 1-substituted-4-bromo-2H-1,2,3-triazole derivative according to claim 1, wherein the method comprises the steps of:

1) Dissolving the compound of the following formula II in the first organic solvent, cooling to -78 to 0 ° C, adding the Grignard reagent, and stirring for 0.5 to 2 hours.

κ Ν

Formula II

The preparation method according to claim 2, wherein in the step 1), the mass to volume ratio of the compound of the formula II to the first organic solvent is 1:2-20.

The preparation method according to claim 3, wherein in the step 1), the molar ratio of the compound of the formula II to the Grignard reagent is 1: 0.8 to 1.5.

The method according to claim 4, wherein in step 1), the The first organic solvent is diethyl ether, tetrahydrofuran, 1,4-dioxane or methyltetrahydrofuran; the Grignard reagent is isopropylmagnesium chloride or isopropylmagnesium chloride-lithium chloride complex.

The preparation method according to claim 5, wherein in the step 2), the molar ratio of the compound of the formula II to chlorine gas, chlorinating agent or iodine is 1:1 to 10.

The preparation method according to claim 6, wherein the chlorinating agent comprises N-chlorosuccinimide and 1,3-dichloro-5,5-dimethylhydantoin.

The method according to claim 7, wherein in the step 2), the second organic solvent is one or a mixture of two or more of a fatty acid ester or an ether, wherein the fatty acid ester The classes include ethyl formate, propyl formate, butyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, isopropyl acetate, isobutyl acetate, amyl acetate, isoamyl acetate, C. Methyl ester, ethyl propionate, propyl propionate, butyl propionate and amyl propionate. Ethers include diethyl ether, propyl ether, diisopropyl ether and methyl tert-butyl ether.

The preparation method according to claim 8, wherein in the step 3), the recrystallization comprises the following steps: adding the concentrate to the solvent at a mass to volume ratio of 1:1 to 100, at -20 to 50 The mixture was stirred at ° C for 0.5 to 24 hours, filtered, and dried under vacuum to give the 1-substituted 4-bromo-2H-1,2,3-triazole derivative.

The preparation method according to claim 9, wherein the solvent is one or a mixture of two or more of water, an alcohol, a fatty acid ester, a ketone, an ether, and a hydrocarbon. Among them, alcohols include methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, and fatty acid esters include ethyl formate, propyl formate, butyl formate, methyl acetate, ethyl acetate, and acrylic acid. Ester, butyl acetate, isopropyl acetate, isobutyl acetate, amyl acetate, isoamyl acetate, methyl propionate, ethyl propionate, propyl propionate, butyl propionate and amyl propionate, Ketones include acetone, 2-butanone, cyclopentanone and cyclohexanone. Ethers include diethyl ether, propyl ether, diisopropyl ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane and petroleum ether. Hydrocarbons include n-hexyl, cyclohexanyl, methylcyclohexanide and n-glyoxime.