CN102485715A

CN102485715A - Synthesizing technology of triazole derivative

Info

Publication number: CN102485715A
Application number: CN2010105713596A
Authority: CN
Inventors: 刘志敏
Original assignee: Individual
Current assignee: Individual
Priority date: 2010-12-03
Filing date: 2010-12-03
Publication date: 2012-06-06

Abstract

The invention belongs to the field of medicine processing, and specifically relates to a synthesizing technology of a triazole derivative. The synthesizing technology provided by the invention is advantaged in that: the raw materials are easy to obtain, the time consumption is low, the condition is mild, and the yield is high. A technical scheme adopted by the invention comprises steps that: methanamide is added into a four-port flask provided with a stirrer, a constant-temperature dropping funnel, a distillation apparatus and a tail gas absorbing apparatus; methanamide is heated to a temperature of 175-190 DEG C; hydrazine hydrate is dropped into methanamide, wherein a molar ratio of methanamide to hydrazine hydrate is 1:1.1-1:2; the dropping is finished in 0.5-2.5h; emitted ammonia gas is delivered into an absorbing bottle to be absorbed, wherein the absorbing bottle contains 20-30% H2SO4; when dropping is finished, the temperature is maintained for 0.5-2.5h; the materials are cooled; when a large amount of crystals are precipitated, the materials are subject to pump filtration, such that a crude product is obtained; the crude product is washed by using ethyl acetate, such that a target product 1H-1,2,4-triazole is obtained. A yield is calculated, and a melting point is detected.

Description

The synthesis technique of triazole derivative

Technical field

The invention belongs to the medicine manufacture field, more particularly, relate to the synthesis technique of triazole derivative.

Background technology

1H-1,2, the 4-triazole is important medicine, agricultural chemicals, dyestuff intermediate.Especially at field of medicaments, the triazole pharmacophore has lower toxicity and demonstrates multiple biological activity than imidazoles, like antimycotic, antibiotic, tuberculosis, antiviral etc.1H-1,2,4-triazole and verivate thereof have become drug research and one of hot of research and development and emphasis in recent years.

At present, synthetic 1H-1,2, the 4-triazole mainly contains four kinds of methods:

(1) by formyl hydrazine and formamide preparation, this method raw material is more expensive, is solvent with excessive methane amide mostly, and aftertreatment need remove methane amide under reduced pressure, and operation is very complicated, reduces productive rate greatly if handle bad meeting;

(2) by formic acid, Hydrazine Hydrate 80, three kinds of feedstock production of methane amide, this method selects for use raw material more, adopts two-tube feed way strict to feed rate, divides two-stage reaction, and technology is comparatively complicated, and the production cycle is longer;

(3) in formic acid, feed ammonia earlier, generate ammonium formiate, drip Hydrazine Hydrate 80 again, it is two phase reaction that this method the first step feeds ammonia, severe reaction conditions, and long reaction time, operation is complicated;

(4) by the preparation of methane amide and Hydrazine Hydrate 80, this method is simple and convenient, and productive rate is higher, the reaction times length be 4.5～5h, and need spend the night and to be crystallized separating out such as leave standstill, the production cycle is longer.

Summary of the invention

The present invention is exactly to the problems referred to above, provides that a kind of raw material is easy to get, the synthesis technique of weak point consuming time, mild condition, triazole derivative that productive rate is high.

In order to realize above-mentioned purpose of the present invention; The present invention adopts following technical scheme, and process step is: in the four-hole boiling flask that whisking appliance, constant pressure funnel, water distilling apparatus and device for absorbing tail gas are housed, add methane amide, be heated to 175～190 ℃; Drip Hydrazine Hydrate 80; The mol ratio of methane amide and Hydrazine Hydrate 80 is 1: 1.1～1: 2, and 0.5～2.5h drips off, with the ammonia of overflowing absorption bottle (interior Sheng 20% 1 30%H that induces one ₂SO ₄) absorb; After dropwising, insulation 0.5～2.5h; Cooling, separate out a large amount of crystal after, suction filtration, thick product, with ETHYLE ACETATE washing, obtain title product 1H-1,2, the 4-triazole is calculated productive rate, surveys fusing point.

Reaction equation is:

Beneficial effect of the present invention:

1. the present invention is simple to operate, has saved post-processing step;

2. reaction conditions of the present invention is gentle, weak point consuming time;

3. productive rate of the present invention is 82.35%.

Embodiment

Process step of the present invention is: in the four-hole boiling flask that whisking appliance, constant pressure funnel, water distilling apparatus and device for absorbing tail gas are housed, add methane amide; Be heated to 175～190 ℃; Drip Hydrazine Hydrate 80; The mol ratio of 1/3 methane amide and Hydrazine Hydrate 80 is 1: 1.1～1: 2, and 0.5～2.5h drips off, with the ammonia of overflowing absorption bottle (interior Sheng 20% 1 30%H that induces one ₂SO ₄) absorb; After dropwising, insulation 0.5～2.5h; Cooling, separate out a large amount of crystal after, suction filtration, thick product, with ETHYLE ACETATE washing, obtain title product 1H-1,2, the 4-triazole is calculated productive rate, surveys fusing point.

Reaction equation is:

The present invention selects the mol ratio, temperature of reaction, dropping time, soaking time of 1/3 methane amide and Hydrazine Hydrate 80 as 1H-1, and 2, the influence factor of 4-triazole synthetic yield, visible table 1, table 2, table 3, table 4.

Table 1 mol ratio is to the influence of productive rate

Mol ratio	1∶1.1	1∶1.3	1∶1.5	1∶1.7	1∶2
						Productive rate/%	65.23	76.61	82.35	79.39	77.45

Table 2 temperature of reaction is to the influence of productive rate

Temperature of reaction/℃	175	180	185	190
					Productive rate/%	47.39	70.17	82.35	75.26

The table 3 dropping time is to the influence of productive rate

Dropping time/h	0.5	1.0	1.5	2.0	2.5
						Productive rate/%	70.43	82.35	81.15	80.34	81.21

Table 4 soaking time is to the influence of productive rate

Soaking time/h	0.5	1.0	1.5	2.0	2.5
						Productive rate/%	82.35	80.57	79.63	78.85	78.52

As a kind of preferred version, process step of the present invention is: the mol ratio of 1/3 methane amide and Hydrazine Hydrate 80 is 1: 1.5, and promptly the mol ratio of methane amide and Hydrazine Hydrate 80 is 2: 1, and the dropping time of Hydrazine Hydrate 80 is 1h; Reaction times is 1.5h, and temperature of reaction is 185 ℃; Soaking time is 0.5h.

Claims

1. the synthesis technique of triazole derivative is characterized in that, the present invention adopts following technical scheme; Process step is: in the four-hole boiling flask that whisking appliance, constant pressure funnel, water distilling apparatus and device for absorbing tail gas are housed, add methane amide; Be heated to 175～190 ℃, drip Hydrazine Hydrate 80, the mol ratio of methane amide and Hydrazine Hydrate 80 is 1: 1.1～1: 2; 0.5～2.5h drips off, with the ammonia of overflowing absorption bottle (interior Sheng 20% 1 30%H that induces one ₂SO ₄) absorb; After dropwising, insulation 0.5～2.5h; Cooling, separate out a large amount of crystal after, suction filtration, thick product, with ETHYLE ACETATE washing, obtain title product 1H-1,2, the 4-triazole is calculated productive rate, surveys fusing point.

Reaction equation is:

2. the synthesis technique of triazole derivative according to claim 1; It is characterized in that; Process step of the present invention is: the mol ratio of 1/3 methane amide and Hydrazine Hydrate 80 is 1: 1.5, and promptly the mol ratio of methane amide and Hydrazine Hydrate 80 is 2: 1, and the dropping time of Hydrazine Hydrate 80 is 1h.

3. the synthesis technique of triazole derivative according to claim 1 is characterized in that, process step of the present invention is: the reaction times is 1.5h, and temperature of reaction is 185 ℃.

4. the synthesis technique of triazole derivative according to claim 1 is characterized in that, process step of the present invention is: soaking time is 0.5h.