DD151164A5 - PROCESS FOR THE PREPARATION OF PYRAZOLES - Google Patents

Abstract

Preparation of Pyrazoles by Reaction of 1,3-Dicarbonyl Compounds with Hydrazines and Different Acid at a pH between 0 and 6.9. The producible by the process of the invention pyrazoles are valuable starting materials for the production of dyes, pesticides and pharmaceuticals.

Description

22 1 4 47-4-

Process for the preparation of pyrazoles Field of application of the invention

The invention relates to a novel process for the preparation of pyrazoles by reacting 1,3-dicarbonyl compounds with hydrazines and substoichiometric acid at a pH of between 0 and 6.9.

Characteristic of the known technical solutions

It is known from Rodd, Chemistry of Carbon Compounds, Vol. IVa (Elsevier, N.Y., 1957) * pages 246 to 249, numerous syntheses of the pyrazoles, e.g. by reacting hydrazines with 1,3-dicarbonyl compounds, dehydration of hydrazones of β-keto esters, cyclization of hydrazones of α-cyanoketones, reaction of aldehyde phenylhydrazones with β-ketoesters in the presence of zinc chloride, condensation of α-halohydrazones with sodium keto compounds or of diazo compounds with acetylene derivatives. The more important synthetic routes lead via the reaction of derivatives of 1,3-dicarbonyl compounds with hydrazine or · hydrazine derivatives in acidic, aqueous solution or with salts of hydrazine or of hydrazine derivatives to dilute aqueous solutions of pyrazole salts. Thus, J.A.C.S., Vol. 71 (1949), page 3 997, shows the stoichiometric reaction of 1: 3> 3-tetraethoxypropane with hydrazine dihydrochloride in a water / ethanol mixture. The solution is then evaporated, the residue taken up with water and released from the solution by sodium bicarbonate, the pyrazole from its salt. The mixture is filtered, the flock material thoroughly washed with ether and the ether filtrate used to extract the aqueous filtrate.

uWB / BL 'J

- 2 - O. Z. 0050/03

22 1 A 4 7

Since, in these syntheses, salts of the hydrazine (or its derivatives) are believed to be in solution, it is unavoidable, after use, e.g. inorganic bases to produce stöchio raetrische amounts of waste salts. When disposed of on an industrial scale, these salts lead to

considerable sewage and environmental problems. According to the aforementioned working method (J.A.C.S., loc.cit.), For example, more than 2 kg of common salt are released per kg of pyrazole produced

 10

It has now been found that pyrazoles of the formula

12 3

in which the individual radicals R, R and R 'may be identical or different and each represent a hydrogen atom, an aliphatic, araliphatic or aromatic radical

p, R is also a halogen atom, the radical -CN or the radical

-0-R, R ^ also for the remainder 0

»J · -C-R stands,

, R is an aliphatic, araliphatic or aromatic radical, is advantageously obtained by reacting 1,3-dicarbonyl compounds with hydrazines in the presence of water and acid, if 1,3-dicarbony! Compounds of the formula

0 R ² O

1 "'" 1

^ R-CCCR ^x II,

1 2

wherein R and R have the abovementioned meaning, with hydrazines of the formula. ·

- 3 -. Ο.Ζ. 0050/033894

wherein R ^- ^ has the abovementioned meaning, in the presence of less than 2 equivalents of acid per mole of hydrazine III at a temperature of -10 to + 100 ⁰ C, wherein the pH of the reaction mixture during the reaction between 0 and 6.9 is.

It has furthermore been found that the process according to the invention is advantageously carried out by reacting the proportion of pyrazole I in the form of the pyrazole salt with additional hydrazine III to give free pyrazole I in the reaction mixture.

Object of the invention

Explanation of the essence of the invention

In view of the state of the art, the process according to the invention surprisingly provides, in a simpler and more economical way, pyrazoles in better yield and purity. Significant amounts of acid and accordingly costly neutralization and sewage treatment operations are saved. The process is more environmentally friendly. All these advantageous results are surprising in view of the state of the art. With regard to the known processes, one had to expect reduced conversions, yields and the formation of heterogeneous mixtures of starting and final base and their salts.

The starting material II is mixed with the starting material III in stoichiometric amount or with an excess of a component. Nenten with respect to the other, preferably reacted with a ratio of 0.1 to 1.5, in particular from 0.9 to 1.1 moles of starting material III per mole of starting material II.

Preferred starting materials II and III and accordingly

- 4 - O.Z. ΟΟ5Ο / Ο33894

Preferred end products I are those in whose formulas the ^Ί

12 '3 individual radicals R, R and Vr may be identical or different and each represent a hydrogen atom, an alkyl radical having 1 to 18, preferably 1 to β carbon atoms, an aralkyl radical or alkylaryl radical having 7 to 12 carbon atoms

2 men, a phenyl radical, a naphthyl radical, R is also a bromine atom or chlorine atom, the radical -CN or the radical

4 3

-0-R, R ^ also for the remainder 0

I! H

C is -R, R is an alkyl radical having 1 to 18, preferably 1 to 6 carbon atoms, an aralkyl radical or alkylaryl radical having 7 to 12 carbon atoms, a phenyl radical or a naphthyl radical. The radicals mentioned can still be protected by groups which are inert under the reaction conditions, e.g. Alkyl groups having 1 to 3 carbon atoms, cyano groups, be substituted.

In general, instead of 1,3-dicarbonyl compounds II, substances which form such 1,3-dicarbonyl compounds II under the reaction conditions will be used. Mostly bisacetals, monoacetals, bisacylals and monoacylals are used. Appropriately come substances of the formula

6 2 S R R ^ R ^

R ° -C-C-C-R ^ IV

t 1 y

HHH

1 'S

or R-C = C-C-R- 'V,

R ² r5

or R ^X -C = C - C - R ⁵ VI, H. "H

- 5 - O. Z. OO5O / O33894

22 14 47

'"wherein each of R ^ and R ^Ί the may be the same or different and each is the radical -OR or the radical O'.

* »O-C-R, the two radicals R together also denote a 5 oxo group, a radical R 1 also denotes a halogen atom,

12 4

Suitably a chlorine atom, may be, R, R and R have the aforementioned general and preferred meanings, into consideration.

The reaction can be represented by the following formulas in the case of using Iil * 3i3-tetramethoxypropane and hydrazine:

OCH ₃ OCH ₃

CH ₃ OC-CH ₂ -C-OCH ₃ + H ₂ N-NH ₅ > (| I + 4CH ₃ OH.

HH "S ^T>

Examples of suitable starting materials II are unsubstituted or methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, benzyl, phenyl, chloro, cyano -, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, tert-butoxy, benzoxy, phenoxy group in α-position substituted tetramethoxy, tetraethoxy, tetrapropoxy , Tetraisopropoxy, tetrabutoxy, tetraisobutoxy, tetra-sec-butoxy, tetratert.-butoxy- (1,1,3,3 ) -propanes, 3,3-dimethoxy, 3> 3-diethoxy, 3,3-dipropoxy, ^, 3-diisopropoxy, 3,3-dibutoxy, 3,3-diisobutoxy, 3,3-di-tert-butoxy, 3i-3-di-sec-butoxypropionaldehydes, 1 , 1-dimethoxy, 1,1-diethoxy, 1,1-dipropoxy, 1,1-diisopropoxy, 1,1-dibutoxy, 1,1-diisobutoxy, 1,1-di-sec-. butoxy, 1,1-diisobutoxy, 1,1-di-tert-butoxy-propanals; homologous β-oxo-butanals unsubstituted or substituted in the abovementioned manner, β-oxo-pentanals, β-oxo-hexanals, β-oxo-heptanals, β-oxo

22 1A 47

/ "octanale; in α-position to two carbonyl groups unsubsti-" ^{1-substituted} or substituted in the aforementioned manner pentane-2,4-dione, hexane-2, 4-dione, heptane-2, 4-dione, octane ^, ^ - dione, heptane-3,5-dione, octane-3>5-dione; correspondingly unsubstituted or substituted in the α-position, 1,1-acetalated, in α, β-position unsaturated butenals, pentenals, hexenals; 1,1-acetalized propargyl aldehydes and homologous α, β-position unsaturated butynals, pentinals, hexinals. ,

Preference is given to 1,1,3,3-tetramethoxypropane, 1,1,3,3-tetraethoxypropane, 1,1'-O-tetraisobutoxypropane, 1,1,3,3-tetraisopropoxypropane, 1,1,3,3-tetrabutoxypropane, 1,1,3,3-Tetrapropoxypropan.

As hydrazines III are, for example: hydrazine, by methyl, ethyl, propyl, isopropyl, butyl, sec-butyl _e, tert. Butyl, isobutyl, benzyl, phenyl, acetyl, benzoyl, phenylacetyl group substituted hydrazines.

Instead of the hydrazines IiI, these hydrazines III forming substances can also be used under the reaction conditions, z-.B. the hydrazine hydrates; Salts of hydrazines such as the sulfates or disulfonates, e.g. the dibenzene sulfonates; Hydrazones, e.g. with formaldehyde, acetaldehyde, together with amines such as ethylamine. In the case of salts, the total amount of free and hydrazine-bound acid is always less than 2 equivalents of acid per mole of hydrazine.

The reaction is conducted at a temperature of -10 to +100, preferably from 0 to 100 ⁰ C, in particular from 30 to 70 ⁰ C, under atmospheric or unte.r pressure, continuously or discontinuously. If appropriate, inert organic solvents are added under the reaction conditions. Suitable solvents are, for example: aromatic hydrocarbons, for example toluene, ethylbenzene, o-,

. ·. R: -. ··. · ·. - 7 - O.Z. ΟΟ5Ο / Ο33894

2 2 1 A 4 7

Ίπ-, p-xylene, isopropylbenzene, methylnaphthalene; ^{Halogenohydrocarbons} , in particular chlorinated hydrocarbons, for example tetrachlorethylene, 1,1,2,2- or 1,1,1,2-tetrachloroethane, allyl chloride, dichloropropane, methylene chloride, dichlorodbutane, carbon tetrachloride, 1,1,1- or 1,1 , 2-trichloroethane, trichlorethylene, pentachloroethane, 1,2-dichloroethane, 1,1-dichloroethane, n-propyl chloride, 1,2-cis-dichloroethylene, n-butyl, 2, J> - and iso-butyl chloride, chlorobenzene, o-, p- and m-dichlorobenzene, o-, m-, p-chlorotoluene, 1,2,4-trichlorobenzene; Ethers, for example ethyl propyl ether, methyl tert-butyl ether, n-butyl ethyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, diisopropyl ether, cyclohexyl ether} ether, diethyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane; Alkanols and cycloalkanols such as ethanol, methanol, n-butanol, isobutanol, tert-butanol, glycol, n-propanol, isopropanol, amyl alcohol, cyclohexanol, 2-methyl-4-pentanol, Äthylenglykolraonoäthyläther, 2-ethylhexanol, methyl glycol, especially those with 1 to 4 carbon atoms; aliphatic or cycloaliphatic carbon-hydrogens, for example, heptane, pinane, nonane, petroleum fractions boiling within a range from 70 to 190 ⁰ C., cyclohexane, methylcyclohexane, decalin, Petrläther, hexane, ligroin, 2,2,4-trimethylpentane, 2,2, 3-trimethylpentane, 2,3 * 3-trimethylpentane, octane; and corresponding mixtures.

The solvent is expediently used in an amount of from 400 to 10 000 percent by weight, preferably from 100 to 500 percent by weight, based on starting material II.

Always water, suitably used in an amount of 1 to 70, advantageously from 1 to 10 moles of water, based on hydrazine III. It will be beneficial along with a. other reaction components, e.g. supplied with the acid and / or the starting material III, the starting mixture.

- 8 - 'Ο.Ζ.0050 / 033894'

2 14 4 7

^r The reaction is in the presence of less than 2 Äquivalen- ^"1 th acid, advantageously in an amount from 0.05 to 1.9 * in particular from 0.25 to 1.25 equivalents · acid with respect to 1 mole of starting material III, Inorganic or organic acids may be used Instead of monobasic acids, equivalent amounts of polybasic acids may be used, for example, the following acids are suitable: inorganic acids such as hydrogen chloride, hydrogen bromide, sulfuric acid, phosphoric acid, sulfonic acids such as benzene- and p-toluenesulfonic acid; Boron-containing acids such as boric acid, borofluoric acid, aliphatic carboxylic acids such as chloroacetic acid, dichloroacetic acid, trichloroacetic acid, oxalic acid, formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, glycolic acid, α- or β-chloropropionic acid or mixtures thereof. mixed with each other and / or with an L solvents, in particular water. Preference is given to hydrochloric acid. The pH of the reaction is between 0 and 6.9, preferably from 0.5 to 4, in particular from 0.9 to 2.5 ×.

The reaction can be carried out as follows: A mixture of hydrazine III, acid and water is brought to the reaction pH and then at the same time further starting materials III and starting material II, optionally together with water and / or organic solvent added so that the reaction -pH is always adhered to. Advantageously, an addition temperature of -10 to + 60 ° C and addition times of 5 to J> 0 minutes. The total reaction time is advantageously 0.1 to 12 hours. It is found to be a significant advantage of the process according to the invention that only minimal amounts of acid equivalents, based on the hydrazine derivative, have to be added in total. From the . Reaction mixture, the end product in a conventional manner, eg

by neutralization and extraction of the Geraischs and De-

-9- O. Z. 0050/033894

Extraction of the extract, to be separated. The neutralization may be carried out in a discontinuous manner, e.g. be carried out by an inorganic base, wherein according to the invention only as much salt is obtained as by-product, as corresponds to the reduced acid used. However, in particular in the case of a continuous procedure, the release of the pyrazoles I takes place according to the invention by adding the corresponding hydrazine III to the reaction mixture, with pH values of from 6 to 10 advantageously being set before the extraction. As shown in the following formula scheme using the example of the pyrazole, reusable hydrazine salt is recovered in solution:

(^ N x HCl + H ₂ N-NH ₂ XH ₂ O-> ^ \ + H ₂ N-NH ₂ x HCl + H ₂ OHH

Losses of acid equivalents advantageously occur only insofar as they occur in * distillation and extraction processes by transfer from the aqueous phase. The release of the end product I by additional hydrazine is advantageously carried out at 0 to 4o ° C. In the above manner, the resulting hydrazine salt solution can be reused in any repeated reactions, which is an essential and surprising advantage of the process.

The pyrazoles I which can be prepared by the process of the invention are valuable starting materials for the preparation of dyes, crop protection agents and pharmaceuticals. Regarding the use, reference is made to the aforementioned publications.

The parts given in the following examples mean parts by weight. The parts by weight relate to the volume parts as kilograms to liters.

22 1 4 Λ7

^r Implementation examples .

Example 1 .

In a stirred apparatus, 320 parts of water and 20 parts (0.4 mol) of hydrazine hydrate are introduced and placed at 4O ⁰ C by addition of 59 parts of aqueous, 36 weight percent hydrochloric acid (0.5 mol) to pH 1. In the course of 2 1/2 hours from three storage vessels at the same time (392 parts by volume) 380 parts (7.6 mol) of hydrazine hydrate, 354 parts aqueous, 36 weight percent hydrochloric acid (3 * 54 mol) and 1 312 parts (8 mol) 1 , 1,3,3-Tetramethoxypropane added in portions so that a pH of 2 to 3 is maintained. (43 to 55 ° C without cooling). The feed rate of the 1,1,3,3-tetramethoxypropane is kept constant at 540 parts per hour volra and the Hydrazinzulauf adjusted to 153 parts per hour. The pH is regulated by adding hydrochloric acid. After a stirring time of 7 hours, the mixture is adjusted to pH 8 by addition of 320 parts (4 mol) of NaOH and then distilled off 1 553 parts of methanol / water mixture at 20 mbar / 50 ° C in 2 1/2 hours. The residue is stirred with 2,000 parts by volume of methylene chloride and filtered with suction. The filtered material is obtained 250 parts of NaCl and from the Piltrat after distillation 445 parts (82% of theory) of pyrazole, bp 60 to 70 ⁰ C (0.3 mbar).

Example 2

a) 12.9 parts (0.258 mol) of hydrazine hydrate are placed in a stirred apparatus with pH electrode and neutralized with 50.6 parts of aqueous hydrochloric acid (O, 5O6 mol) with cooling. It falls out first hydrazine hydrochloride. Now at 45 to 50 ⁰ C 1,1,3 * 3-tetramethoxypropane and other hydrazine hydrate are added simultaneously so that

• ·. , .-. ·· - Ii - o.z. 0050/033894

22 1 4 47

^r maintaining a pH of 1 to 2, namely 20 minutes, 82 parts (0.5 mole) 1,1,3,3-tetramethoxypropane and 15.5 parts (0.31 mol) of hydrazine hydrate. After completion of the addition, the pH is 1. The mixture is stirred at 22 ⁰ C for 2 hours.

b) 120 parts by volume (= 3/4) of this solution are now adjusted to pH 6.8 to 7.2 with 20.6 parts by volume (0.426 mol) of hydrazine hydrate and then extracted with 2 × 200 volumes of CHpCl ₂ . (Hydrazinhydratphase / extract). Distillation of the extract gives 23.2 parts of pyrazole (85 % of theory) of bp 60 to 70 ° C / 0, l mbar). ,

c) Now, the remaining quarter, namely 40 parts by volume of the reaction solution obtained in Example 2a) (pH: 1), and presented for 20 minutes analogously to Example 2a with 6l, 5 parts (0.375 mol) of 1,1,3,3-tetramethoxypropane and the aqueous hydrazine hydrate phase (pH 6.9 to 7.2) extracted in b) is added. It turns back to a pH of 1 to 2. After a further 2 hours, the mixture is worked up in the same way as in Example 2b). After distillation, 21.45 parts (0.36 mol) of pyrazole (corresponding to 84 # yield) of boiling point 60 to 7O ⁰ C (o, l mbar).

d) This procedure c) is repeated in a further 10 reactions. A pH of the reaction mixture of 1.6 to 1.7 is still obtained in the 10th passage and the same results as in Example 2c).

Claims (1)

^ claims
1. A process for the preparation of pyrazoles of the formula 12 3 wherein the individual radicals R, R and R ^ may be identical or different and each represent a hydrogen atom, an aliphatic, araliphatic or aromatic 2
R, R is also a halogen atom, the radical -CN 4 3 or the radical -O-R, R ^ is also the radical 0 "4 4
-CR, R 'is an aliphatic, araliphatic or aromatic radical, by reaction of 1,3-dicarbony! Compounds with. Hydrazines in the presence of water and acid, characterized in that 1,3-dicarbonyl compounds of the formula OR ² O RCCCR ¹ II, .H 1 2
wherein R and R have the abovementioned meaning, with hydrazines of the formula III, · wherein R has the abovementioned meaning, in the presence of less than 2 equivalents of acid per mole of hydrazine III at a temperature of -10 to + 100 ⁰ C, wherein the pH of the reaction mixture during the reaction is between 0 and 6.9 , - 13 - O.Z. ^r 2. The method according to .Punkt 1, characterized in that reacting in the reaction mixture, the proportion of pyrazole I in the form of the pyrazole salt with additional hydrazine III to free pyrazole I. · 5