JPS62273966A - Novel triazole derivative production thereof - Google Patents

Abstract

NEW MATERIAL:A triazole derivative expressed by formula I (R1 and R2 are same or different and H, <=8C alkyl, aralkyl, alkenyl or allyl; X is Cl, Br or I). EXAMPLE:3-Bromo-5-n-propylamino-1,2,4-triazole. USE:A compound useful for physiological and chemical applications and further extremely useful as an intermediate derivable into various triazole compounds. PREPARATION:A 3,5-dihalosubstituted 1,2,4-triazole expressed by formula II (X1 and X2 are same or different Cl, Br or I) is reacted with an amine compound expressed by formula III in a solvent, e.g. N-methylpyrrolidone, etc., at 100-300 deg.C to afford the aimed compound expressed by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to Nanatsuba Ra! 11! The present invention also relates to l,2*4-triazole derivatives having mono-7-mino substitution or mono-7-substituted amine substitution, and a method for producing the same. More specifically, the general formula ([I] represented by rL[
Regulation 1, 2.4 - IJ 7sol derivatives and their #
j2i method − is also υ].

BACKGROUND OF THE INVENTION Hitherto, 8 triazoles have been useful compounds for physiological and chemical applications such as the synthesis of IIM, and a large number of derivatives have been synthesized.

For example, one or two σ) hydrogen atoms of triazole are chlorine,
British Patent No. 112394 describes the following triazole compound LIV) and the method for producing 7, which is like a conjugate and has 10 genes.
It is described in No. 3 #4jta book. The above (IVI lidriazole compound is a 1,2,4-) lyazole with salt IC or bromine in the presence of an alkali at -lO to 100°C.
It is synthesized by reaction at a temperature of .

10,000, heptanoamino** or diamino-substituted triazole KyGI may be used, for example, by organic synthesis (O
rganic 5ynthesis) Volume ■W495
Page (1955) R3-7 Minnow 1.2.4-) A method of synthesizing lyazole is described. This method, as shown in the reaction formula LV below, is a method in which charcoal is added to quanidine charcoal salt and heated, and it is possible to obtain the desired purpose with a single southern yield.
It is J-Noh.

Furthermore, a method for synthesizing a triazole substituted with diamino or triazole represented by the following general formula (Vl) is described in the British Special Publication! F No. 1157256
1 described in the specification of No. 1, and the method described in LL.
, and/; or corresponds to a compound where R2 is a halogen atom).

100°C to 271)'C with a nucleophilic reagent (e.g. amines), methanol, and a high-boiling alcohol.

This is a method in which the reaction is carried out in a catalyst such as N,N-dimethylformide or N-methylpyrrolidone. That is,
In this method, a monohalo compound (formula (V
In l), when R3 or Kojima corresponds to a compound in which any one of n is a halogen atom (°C), a monosubstituted triazole is @-substituted, and a dihalo compound (T5
When the iJ notation (corresponding to a compound in which R5 and & are both halogen atoms in Vll) is used, a di-converted tri7zole can be obtained as a mercury. However, this light a1
flea; There is no mention.

Purpose of the Invention The present inventor has conducted research to provide a monohalo-m-substituted monoamino-substituted triazole that is useful in itself and can be derived into extremely lidriazole derivatives, and a useful method for synthesizing the same, resulting in the present invention. be.

Structure of the Invention According to the research conducted by the present inventors, the object of the present invention is achieved by providing a novel triazole h4 represented by the following general formula Lu1l).

Furthermore, according to Misfire 8Avc, 3,5-dihejrjt$1.2-4-triazole represented by the following general formula (13) is combined with an amine compound represented by the following general formula [11] by N-methylpyrrolidone, dioxane, etc. and Q, -(MCh, CH,09OQ.

(Here, Q and Tsuru are the same or different and represent a water-based atom or an alkyl To having 1 to 5 carbon atoms, but Ql and Q are simultaneously VC water atoms and cannot be selected from the group consisting of At least some kind of bathing.

The present invention provides a method for producing a novel trin'zole enzyme represented by the general formula ([1)] by reacting at a temperature in the range of 100 to 100°C. From the 3,5-dihalo-1,2,4-)su7zole of the former i1e formula flll.

Monoamino-substituted Q&/triazole derivatives of formula Lnl) are obtained in fair yields.

Hereinafter, the special triazole of the present invention and its manufacturing method will be explained in detail.

The novel triazole conductor in the present invention has the following general formula [
It is represented by 1111.

In the general formula [111], X is a chlorine atom, a bromine atom or an iodine X atom, preferably a cyclosulfate atom f or a bromine atom, and particularly preferably an A atom.

R526 is the same or different and is a hydrogen atom.

Furkyl group, alkenyl group having 8 or less subatomic atoms.

It represents a 7ralkyl group or a 7lyl group. Both R5 and R, 4 are water-based atoms, or any one of -1 is a water-based atom, and 6I) is preferred. If R5 and bird are not water X atoms,
A fulkyl group is more preferable than an aral, fulkenyl, or 7lyl group.

The above-mentioned furkyl group may be either 1 minute or direct (and preferably has 5 or less carbon atoms. Examples of such alkyl groups include methyl group, ethyl group+n
-Pupil 1m r n-butyl jh + n 7
Todoroki is mentioned.

In addition, the alkenyl group may have at least 2 or less carbon atoms and may be branched.
iA's i) may be used.

Preferably, it has 5 or less carbon atoms, such as vinyl group, 7! I -ruji (-C)110H=CH1)
+ ) l Liroux etc.

The above-mentioned 7ralkyl group has 8 or less carbon atoms, and includes, for example, a benzyl group or a benzyl group substituted with a halogen, a hydroxyl group, or the like. Also, the 7ril 1
As phenyl group or methyl crystal, methoxy JI5
I8-gen, hydroxyl group! A phenyl group substituted with a schifno+thiomethyl group or the like can be mentioned as an example.

The triazole compound of the general formula (Ill) of the present invention is not only useful in itself, but also extremely valuable as an intermediate that can be used in various triazole compounds as shown in the following. be.

That is, the following formula [■'' Rv OC-
C(C00Rs)t・・・・・・・・・・・・
... [■] R1 [However, an island? R, l R, represents a low M furkyl group.

] It is possible to react with the flufukidimethylene malon ester which is expressed in [4] to form a compound having a tri-7zolopyrimidine skeleton.

In addition, the following formula [■] ^-0-C=C-COOR, ......
... [■] A compound having a tri7zolopyrimidine skeleton can be obtained by reacting with a fusifoxy-substituted acrylic ester derivative represented by a bird.

According to the vcL of the present invention, the 3.5-
Dihalo-substituted 112.4-triazole and general formula [11]
An amine compound of N-methylpyridone, dioxane and formula Q1-07C)I,CH,0+Q.

(Here, Q and Q are the same or different and represent a hydrogen atom or a full molar crystal having 1 to 5 carbon atoms, but Q and Q are not hydrogen atoms at the same time.) (The reaction is carried out in a solvent at a temperature of 100 to 300°C, preferably 110 to 280°C, especially 120 to 250°C.) Therefore, E, the yield of the desired new triazole conductor (llf ) can be obtained.

The above general formula [! ] As the dihalo-substituted 1,2,4-triazole, the following compounds can be mentioned as specific examples.

CI-a) CI-b) CI-c) L
ld) (I-e) The above circles Ll-a) and (1-b) are preferred, and CI-b] is particularly preferred.

Further, as the amine compound of the general formula (11), an amine corresponding to the same one as defined in the general formula (till) by R3 and Peng is used.The amine compound (u) is
0.1 to 20 mol per 17 mol of the triazole [I],
Preferably 0.5 to 15 mol.

In particular, the ratio of 1 to 1 θ is used.

Is it possible to carry out the reaction of the present invention in a solvent specified in IIJ, together with temperature conditions? It is expensive to selectively obtain high yields, and fHI is described in British Patent No. 3.157.
．． Similar reaction in methanol'PN, N-dimethylformamide, as published in No. 256 Mingxian! When carried out, a diamino-substituted triazole can be obtained in high yield, but the triazole compound targeted by the present invention cannot be obtained.

Specific examples of IL solvents used in the present invention include N-methylpyridone, dioxane, and ethylene glycol methyl ether.

Examples include diethylene glycol diethyl ether, diethylene glycol dipropyl ether, diethylene glycol dimethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, and the like.

These solvents are the triazole (I) 11
It is preferable to use it in the range of 0.1 to 100 parts per volume, and preferably 0.5 to 5003111 parts.

In the reaction of the present invention, the reaction time is within the above-mentioned range, and may be relatively short at high reaction temperatures (and relatively long at low reaction temperatures. Generally, from 1 minute to
BLi at about 200°C for 100 hours, preferably 5 minutes to 5 hours, e.g. 3 hours at a reaction temperature of about 160'C.
At this temperature, 0.5 hours is sufficient.

As described above, according to the present invention, the desired 7) 8t' 1I-substituted noamino-substituted triazole (In) can be easily obtained in high yield.

The present invention will be described in detail below with reference to Examples.

Reference Example 1 3,5-dibudim 11214 used as starting material
)! +Azole was synthesized by Hisanoyoshi.A four-tube flask with a stirring device of 21 was equipped with a cooling tube, a thermometer, and a dropping funnel for C100ILt. This and water (71
487) and sodium hydroxide (85,74#”)tt
I prepared it. Cool to 18°C with ice and stir while stirring 1.2.
4) Add 7sol (5051) and dissolve it, then add bromine (75
) was slowly added dropwise over 3 hours. At the next meeting, yellow crystals precipitated.

After the dropwise addition, after stirring for about 15 minutes, add ms+acid (60d
) and returned to the chamber to filter out the solid yellow product. 76.6N of pale yellow crystalline material was obtained.

Water (3UOU) 2111t, 100'C
After Ijtfi, the temperature was returned to 70°C and heated once. A pale yellow or white target product 55j+ was obtained. This melting point is 205
The temperature was between 207°C and 207°C.

Reference Example 2 A four-way SOO flask equipped with a stirring device similar to Reference Example 1 and -J was equipped with a thermometer and a 9-dropping funnel. 3.5-Sifumino-1,2,4-triazole 9.9I was dissolved in concentrated hydrochloric acid 20
It was dissolved in G-. While keeping the temperature below 10°C, a pottery was made using a solution prepared by dissolving sodium sulfite 211 in 50 cc of water for about 30 minutes.

- It reacted violently at the same time as under control, and turned orange after the end of under control. After stirring at below 5°C for about 20 minutes.

From now on it will be heated in the bath until refluxed. After approximately 10 minutes and 7 lux, the liquid was removed under reduced pressure. 6
When the IA solution was cooled to 8° C./130 kettle, a precipitate was determined. Ether 80 at, 2 times extraction 1 and 10.4
A yellow crystalline product of II was obtained.

Example 1 Synthesis; 3.5 dibσm1,214)su7sol40. as starting material. lJ Oj' and n-propylamine 31.7
II (molar ratio) 2j, 1) to Geo-V 7 words [310-
The mixture was then placed in a 500-liter Kitan Electric M stirring autoclave and reacted at 160° C. for 3 hours. The pressure at this time was 5ky/d'. After the reaction was completed, the reaction product was transferred to a 500114 eggplant flask, and a light brown crystalline substance was obtained using a bathing machine. Add this to 2o water
After adding Om and refluxing, let it cool to 70°C and filter it through a and f to obtain the target object. After vacuum drying, 23 liters of the target product was obtained. Examples 2 to 14 and Comparative Examples 1 to 3 Using the same titanium autoclave as in Example 1, reactions were carried out by changing the starting materials or reaction conditions.

Objective: Hydrogen flame plate gas chromatograph G manufactured by Shimadzu Corporation
Analysis was performed using C-7A under the following conditions.

The results are shown in Tables 1 and 2. The data of the obtained triazole derivative from Company M are shown in Table 3 below.

Analysis conditions Table 2 The h group data of the target compound were as follows.

Table 3 IR was measured by Nugol@.

N　M　R42ds　D　M　SO　with a solvent.

Claims (1)

[Claims] 1. A novel triazole derivative represented by the following general formula [III]. ▲There are mathematical formulas, chemical formulas, tables, etc.▼……………………〔I
II] [However, R_1 and R_2 in the formula are the same or different,
Indicates a hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, or an allyl group having 8 or less carbon atoms. X represents a chlorine atom, a bromine atom or an iodine atom. ] 2. The following general formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼……………………[I
] However, in the formula, X_1 and X_2 are the same or different,
Indicates a chlorine, bromine or iodine atom. 3,5-dihalo-substituted 1,2,4-triazole represented by and the following general formula [II] ▲There are numerical formulas, chemical formulas, tables, etc.▼……………………[I
I] [However, R_1 and R_2 in the formula are the same or different,
Indicates a hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, or an allyl group having 8 or less carbon atoms. ] The amine compound represented by N-methylpyrrolidone, dioxane and the formula Q_1-O-(CH_2CH_2
O) Selected from the group consisting of_2-Q_2 (where Q_1 and Q_2 are the same or different and represent a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, but Q_1 and Q_2 are not hydrogen atoms at the same time) in at least one solvent;
The following general formula [III], which is characterized by reacting at a temperature in the range of 100 to 300°C ▲There are mathematical formulas, chemical formulas, tables, etc.▼……………………[I
II] [However, in the formula, R_1 and R_2 are the same as defined above, and X represents a chlorine atom, a bromine atom, or an iodine atom. ] A method for producing a novel triazole derivative represented by: