DE19826669B4 - Process for the preparation of pyrazoles - Google Patents

Abstract

wobei R¹ bis R⁴ Wasserstoff, ggf. substituierte Alkyl-, Aryl-, Aralkyl- oder Cycloalkyl-Reste mit 1 bis 16 C-Atomen bedeuten, durch Oxidation aus den entsprechenden Pyrazolinen, dadurch gekennzeichnet, daß man die Pyrazoline oder die in situ aus α,β-ungesättigten Carbonylverbindungen und den Hydrazinderivaten hergestellten Pyrazoline mit einem Oxidationsmittel ausgewählt aus der Gruppe Wasserstoffperoxid, Peroxodisulfat, tert.-Butylhydroperoxid, Salpetersäure, Stickstofftetraoxid, Chlor oder Hypochlorit in Gegenwart von Iod und/oder eines Iodids oder einer Iod und/oder Iodid freisetzenden Verbindung bei 50 bis 120 °C umsetzt.Process for the preparation of pyrazole or its derivatives of general formula I.

where R ¹ to R ^{4 are} hydrogen, optionally substituted alkyl, aryl, aralkyl or cycloalkyl radicals having 1 to 16 carbon atoms, by oxidation from the corresponding pyrazolines, characterized in that the pyrazolines or in situ from pyrazolines prepared from α, β-unsaturated carbonyl compounds and the hydrazine derivatives with an oxidizing agent selected from the group of hydrogen peroxide, peroxodisulfate, tert-butyl hydroperoxide, nitric acid, nitrogen tetraoxide, chlorine or hypochlorite in the presence of iodine and / or an iodide or an iodine and / or Iodide releasing compound at 50 to 120 ° C.

Description

The The present invention relates to a process for the preparation of Pyrazole or its derivatives by oxidation from the corresponding Pyrazolines.

Pyrazole derivatives are used as nitrification inhibitors and as precursors for plant protection products, Dyes or polymers used. In several review articles are numerous Synthetic routes to pyrazoles described, for. In "The Chemistry of Heterocyclic Compounds" Vol. 22, Chapter 3 and 5 or in "Houben-Weyl, Methods of Organic Chemistry ", Vol. E8b, pp. 408-703.

3-methylpyrazole is according to DE-OS 41 37 011 starting from hydrazine and diacetylene from cracked gas available. However, this requires the presence of suitable gap gas systems and is associated with high investment.

It is known, pyrazoline with chlorine or hypochlorite (EP-PS 48 373) in water or aromatics to oxidize. According to DE-PS 31 22 261 also leads the Chlorination of an α, β-unsaturated Carbonyl compound over the subsequent reaction with hydrazine to pyrazoles, wherein the simultaneous neutralization of the resulting hydrochloric acid as reaction-critical is specified. The emergence of chlorinated by-products, which Environmental protection not he wishes can not be ruled out in this procedure.

In DE-OS 30 29 160 is the dehydrogenation of pyrazolines with sulfur or selenium at about 110 ° C in organic solvents described as a by-product of quantitatively highly toxic sulfuric or hydrogen selenide is formed.

Out EP-A 290 991 discloses a process which uses sulfur only as Catalyst and nitroaromatics such as nitrobenzene in excess as an oxidizing agent starts. The pure isolation of pyrazoles by this method is very difficult because of the usual extractive or distillative Workup the product only with difficulty from nitrobenzene or its Subsequent product aniline can be separated.

The in DE-OS 36 03 376 described electrochemical oxidation of Pyrazolines in the presence of alkali halides often results only in low yields and selectivities to the corresponding pyrazoles.

The Dehydrogenation of pyrazolines in the gas phase to platinum or palladium catalysts disclosed in DE-OS 32 09 148. As a disadvantage of this method the comparatively high technical requirements have to be considered.

According to the process of DE-OS 30 35 394 is formed in the thermal treatment of Pyrazolinsulfonsäuren pyrazole. At the same time quantitatively reduced alkyl or arylsulfinic RSO ₂ H are formed, which must be disposed of or worked up consuming.

From EP-PS 162 247 a process is known, according to which the production of pyrazoles from pyrazolines by oxidation with hydrogen peroxide or organic hydroperoxides succeed. Unsatisfactory, however, are the achievable yields and selectivities. Thus, 3 (5) -methylpyrazole could be obtained in only 40 to 60% yield even when using pure 3- or 5-methylpyrazoline as the starting compound and the peracetic acid, which is expensive compared to hydrogen peroxide but known to be more selective. In addition, 10 to 14% methylpyrazoline are not reacted. When hydrogen peroxide is used, a safety-relevant residual content of 4 to 6% H ₂ O ₂ remains.

Finally is also the preparation of pyrazoles with sulfuric acid in the presence of iodine or iodine compounds known (EP-A 402 722, EP-A 474 037, WO 95/06 036, DE-OS 195 00th 838). In these processes, sulfur dioxide is always in stoichiometric Quantities formed as sulfuric acid not just as a solvent, but also acts as an oxidizing agent.

The disadvantages of the known methods can be summarized as follows:
The methods often run only with moderate yields and selectivities (DE-PS 31 22 261, DE-OS 36 03 376, EP-PS 162 247) and / or are technically difficult to carry out (DE-OS 32 09 148, DE-PS 31st 22 261, DE-OS 36 03 376), require expensive oxidizing agents or catalysts (EP-A 290 991, DE-OS 32 09 148), or they are associated with the formation of toxic by-products (DE-OS 30 29 160, EP- A 290 991, DE-OS 30 35 394, EP-A 402 722, EP-A 474 037, WO 95/06 036, DE-OS 195 00 838).

wobei R¹ bis R⁴ Wasserstoff, ggf. substituierte Alkyl-, Aryl-, Aralkyl- oder Cycloalkyl-Reste mit 1 bis 16 C-Atomen bedeuten, durch Oxidation aus den entsprechenden Pyrazolinen zu entwickeln, welches die genannten Nachteile entsprechend dem Stand der Technik nicht aufweist, sondern in technisch einfacher Weise die Herstellung von Pyrazolen in hoher Ausbeute und Selektivität ermöglicht.The present invention was therefore based on the object, a process for the preparation of pyrazole or its derivatives of general formula I.

wherein R ¹ to R ^{4 are} hydrogen, optionally substituted alkyl, aryl, aralkyl or cycloalkyl radicals having 1 to 16 carbon atoms, to develop by oxidation from the corresponding pyrazolines, which disadvantages mentioned in the prior art does not have, but in a simple manner, the production of pyrazoles in high yield and selectivity allows.

These Task was inventively characterized solved, that he the pyrazolines or in situ from α, β-unsaturated carbonyl compounds and the hydrazine derivatives produced pyrazolines with an oxidizing agent selected from the group of hydrogen peroxide, peroxodisulfate, tert-butyl hydroperoxide, Nitric acid, Nitrogen tetraoxide, chlorine or hypochlorite in the presence of iodine and / or an iodide or an iodine and / or iodide releasing Compound at 50 to 120 ° C implements.

It this has surprisingly shown that one produce the corresponding pyrazoles in high yield and good selectivity can.

zu den entsprechenden Pyrazol-Derivaten umgesetzt.In the method according to the present invention, therefore, pyrazolines of the general formula II

converted to the corresponding pyrazole derivatives.

R ¹ to R ⁴ in formula II are hydrogen, alkyl, aryl, aralkyl or cycloalkyl radicals having 1 to 16 carbon atoms, which may be identical or different and substituted or interconnected. Suitable aryl groups are optionally substituted radicals such as, for example, phenyl, naphthyl, pyridyl, furyl, thiophenyl, pyrrolyl, imidazolyl or pyrazolyl radicals. Substituents may be, for example, halogen, nitro, oxoalkyl or sulfenylalkyl groups.

When Oxidizing agent according to the invention hydrogen peroxide, peroxodisulfate, tert-butyl hydroperoxide, nitric acid, nitrogen tetraoxide, chlorine or hypochlorite used. As peroxodisulfate is preferably Sodium, potassium or ammonium peroxodisulfate used while Hydrogen peroxide is preferably used in the form of a 30 to 70% hydrogen peroxide solution. The iodates or periodates are preferably in the form of their sodium or potassium salts for use. The molar ratio of oxidizing agent used to pyrazoline or hydrazine derivative can be varied, but it has proven to be particularly beneficial proved this ratio to values between 1: 2 and 2: 1, preferably between 1: 1 and 1.3: 1, adjust. According to one preferred embodiment becomes the method according to the invention at 90 to 105 ° C carried out in sulfuric acid medium, the concentration the sulfuric acid used between 50 and 100%, preferably between 70 and 97%, and that molar ratio sulfuric acid to hydrazine or pyrazoline derivative between 1: 3 and 5: 1, preferably between 1: 1 and 3: 1, can lie.

It is not crucial, first of all Hydrazine hydrate or a hydrazine derivative with the α, β-unsaturated carbonyl compound reacted and this mixture is added to the sulfuric acid. One can also first to prepare the pyrazoline derivative, optionally isolated from this mixture and then into the sulfuric acid is entered or the submitted sulfuric acid Hydrazinkomponente and the α, β-unsaturated carbonyl compound give.

It is to be regarded as essential to the invention that the oxidation in the presence of iodine and / or an iodide, such as. As sodium iodide or potassium iodide, or an iodine and / or iodide releasing compound takes place. As iodine and / or iodide-releasing compounds are in principle all substances to be able to understand, under the specified reaction conditions Release iodine or iodide, for example hydrogen iodide, iodates, Periodates or organic iodine compounds, such as methyl iodide. Preferably becomes a mixture of sodium or potassium iodide and elemental iodine used. The amount of iodine used or the iodine or iodide releasing Connections is generally 0.01 to 10 mol%, preferably 0.2 to 2 mol% (based on the pyrazoline used or the α, β-unsaturated carbonyl compound).

in the Difference to the known methods according to the state of Technique in which stoichiometric Sulfur dioxide is formed as sulfuric acid also acts as an oxidant acts, produced by the method according to the invention is not expensive and expensive sulfur dioxide to be disposed of.

The reaction temperatures are also well below the recommended according to the prior art reaction temperatures. In order to achieve high yields of 125 to 155 ° C must be used in the prior art, while according to the inventive reaction temperatures below 120 ° C are sufficient to complete the conversion. By these comparatively moderate conditions, the process is also easier, since during the oxidation step no distillative aqueous, with aggressive Substances such as hydrogen iodide or sulfur dioxide polluted vapors is necessary.

According to the present Procedure falls the product is usually in such high purity that the Neutralization and phase separation obtained organic phase in usually can be distilled directly. This can be the technical consuming extraction including workup of the required solvent may be omitted. That bothers you in the organic phase contained water for further use, can it is easily separated by distillation. Contains the water thus separated Still pyrazole derivatives, it may be appropriate in the manufacturing process to be led back, for example, prior to the addition of the oxidizing agent or the neutralization.

With Help of the method is it is possible Pyrazole or its derivatives in high yields of 80 to 90% wherein the content of unreacted pyrazoline is <2 wt .-%. Furthermore after the implementation, no residual content of safety-related questionable hydrogen peroxide, so that the process in technical be carried out in a simple manner can.

The Invention will be explained in more detail below by embodiments.

example 1

3 (5) -Methylpyrazol

154 g (2.20 mol) of crotonaldehyde are cooled to 121 g (2.42 mol) of hydrazine hydrate dripped. 490 g of sulfuric acid (80 %). Then 1.9 g of iodine and 1.1 g of sodium iodide are added and the suspension is heated. Subsequently be while 2 h 163 g (2.40 mol) of hydrogen peroxide solution (50%) was added dropwise, wherein the reaction temperature is about 100 ° C is. After cooling becomes the solution neutralized with 1 270 g of sodium hydroxide solution (26%). The upper organic Phase is separated and fractionally distilled at 108 ° C / 50 mbar. You get 161 g of 3-methylpyrazole (89% yield) with> 99% purity (GC).

Example 2

3 (5) -Methylpyrazol

28 g (0.40 mol) of freshly distilled methyl vinyl ketone are added cooling to 22 g (0.44 mol) of hydrazine hydrate was added dropwise. This mixture is under cooling to 82 g conc. sulfuric acid dripped. Then, 0, 7 g of sodium iodide are added and the suspension heated. Subsequently be while 2 h 54 g (0.48 mol) of hydrogen peroxide solution (30%) was added dropwise, wherein the reaction temperature is maintained at about 100 ° C. After that will 15 minutes. stirred at 100 ° C. To cooling down becomes the solution neutralized with 264 g of sodium hydroxide solution (25%). Subsequently, will extracted with dichloromethane, the organic phase with sodium sulfate dried, freed from the solvent and the residue at 108 ° C / 50 mbar distilled. You get 29 g of 3-methylpyrazole (88% yield) with> 99% purity (GC).

Example 3

3 (5) -Methylpyrazol

28 g (0.40 mol) of crotonaldehyde, while cooling, becomes 22 g (0.44 mol) of hydrazine hydrate dripped. This mixture is concentrated with cooling to 82 g. Sulfuric acid added dropwise. Then 0.7 g of sodium iodide are added and the suspension is heated. Then be while 2 h 46 g (0.48 mol) of nitric acid (65%) was added dropwise, with the reaction temperature maintained at about 100 ° C. becomes. After that, 30 min. at 10 ° C stirred. After cooling becomes the solution neutralized with 264 g of sodium hydroxide solution (25%). Subsequently, will extracted with dichloromethane, the organic phase with sodium sulfate dried, from the solvent freed and the residue at 108 ° C / 50 mbar distilled. You get 26 g of 3-methylpyrazole (80% yield) with> 99% purity (GC).

Example 4

3 (5) -Methylpyrazol

35 g (0.50 mol) of crotonaldehyde are added to 25 g (0.50 mol) of hydrazine hydrate with cooling getropf. This mixture is concentrated with cooling to 60 g. Sulfuric acid added dropwise. Then 0.4 g of iodine and 0.3 g of sodium iodide are added and the suspension is heated. Subsequently, will while 165 min. a solution of 120 g (0.53 mol) of ammonium peroxodisulfate in 200 g of water is added dropwise, wherein the reaction temperature is maintained at about 95 ° C. After that will be 105 minute at 95 ° C stirred. After cooling becomes the solution neutralized with 330 g of sodium hydroxide solution (25%). Subsequently, will extracted with dichloromethane, the organic phase with sodium sulfate dried, from the solvent freed and the residue at 108 ° C / 50 mbar distilled. You get 35 g of 3-methylpyrazole (86% yield) with> 99% purity (GC).

Example 5

3,4-dimethylpyrazole

28 g (0.40 mol) of Tiglinaldehyd be under Cooling to 22 g (0.44 mol) of hydrazine hydrate added dropwise. This mixture is concentrated with cooling to 82 g. Sulfuric acid added dropwise. Then 0.7 g of sodium iodide are added and the suspension is heated. Subsequently, 54 g (0.48 mol) of hydrogen peroxide solution (30%) are added dropwise during 2 h, with the reaction temperature being maintained at about 100 ° C. After that 15 min. stirred at 100 ° C. After cooling, the solution is neutralized with 264 g of sodium hydroxide solution (25%). It is then extracted with dichloromethane, the organic phase dried with sodium sulfate, freed from the solvent and the residue is distilled at 111 ° C / 14 mbar. This gives 34 g of 3,4-dimethylpyrazole (87% yield) with> 99% purity (GC).

Example 6

4-methylpyrazole

154 g (2.20 mol) of methacrolein are cooled to 121 g (2.42 mol) of hydrazine hydrate dripped. 490 g of sulfuric acid (80 %). Then 1.9 g of iodine and 1.1 g of sodium iodide are added and the suspension is heated. Subsequently be while 2 h 163 g (2.40 mol) of hydrogen peroxide solution (50%) was added dropwise, wherein the reaction temperature is about 100 ° C is. After cooling becomes the solution neutralized with 1270 g of sodium hydroxide solution (26%). The upper organic Phase is separated and fractionally distilled at 100 ° C / 24 mbar. You get 146 g of 4-methylpyrazole (81% yield) with> 99% purity (GC).

Example 7

3-phenylpyrazole

291 g (2.20 mol) of cinnamic aldehyde are cooled to 121 g (2.42 mol) of hydrazine hydrate dripped. 490 g of sulfuric acid (80 %). Then 1.9 g of iodine and 1.1 g of sodium iodide are added and the suspension is heated. Subsequently be while 2 h 163 g (2.40 mol) of hydrogen peroxide solution (50%) was added dropwise, wherein the reaction temperature is about 100 ° C is. After cooling becomes the solution neutralized with 1270 g of sodium hydroxide solution (26%). It is three times with Extracted methylene chloride. The organic phase is dried, from the solvent freed and at 150 ° C / 0.1 Mbar fractionated distilled. This gives 211 g of 3-phenylpyrazole (73 % Yield) with> 99 % Purity (GC).

Example 8

3 (5) -Methylpyrazol

28 g (0.40 mol) of 5-methylpyrazoline are added with cooling to 110 g of sulfuric acid (75 %). Then 0.7 g of sodium iodide are added and the suspension heated. Subsequently be while 2 h 45 g (0.40 mol) of hydrogen peroxide solution (30%) was added dropwise, wherein the reaction temperature is maintained at about 100 ° C. After that will 15 minutes. at 100 ° C stirred. After cooling becomes the solution neutralized with 264 g of sodium hydroxide solution (25%). Subsequently, will extracted with dichloromethane, the organic phase with sodium sulfate dried, from the solvent free and the residue at 108 ° C / 50 mbar distilled. You get 30 g of 3-methylpyrazole (91% yield) with> 99% purity (GC).

Claims (12)

Process for the preparation of pyrazole or its derivatives of general formula I.

where R ¹ to R ^{4 are} hydrogen, optionally substituted alkyl, aryl, aralkyl or cycloalkyl radicals having 1 to 16 carbon atoms, by oxidation from the corresponding pyrazolines, characterized in that the pyrazolines or in situ from pyrazolines prepared from α, β-unsaturated carbonyl compounds and the hydrazine derivatives with an oxidizing agent selected from the group of hydrogen peroxide, peroxodisulfate, tert-butyl hydroperoxide, nitric acid, nitrogen tetraoxide, chlorine or hypochlorite in the presence of iodine and / or an iodide or an iodine and / or Iodide releasing compound at 50 to 120 ° C. Method according to claim 1, characterized in that that he the oxidation is carried out at 90 to 110 ° C. Process according to claims 1 and 2, characterized that he as oxidizing agent uses a 30 to 70% hydrogen peroxide solution. Process according to claims 1 and 2, characterized that he used as the oxidizing agent sodium, potassium or ammonium peroxodisulfate. Process according to claims 1 to 4, characterized that he 0.01 to 10 mol% of iodine or iodide or an iodine or iodide releasing Compound based on pyrazoline or α, β-unsaturated carbonyl compound used. Process according to claims 1 to 5, as characterized in that one uses as iodide sodium iodide or potassium iodide. Process according to claims 1 to 6, characterized that he as iodine or iodide releasing compound selected from a compound the group of hydrogen iodide, iodates, periodates or organic iodine compounds such as methyl iodide used. Process according to claims 1 to 6, characterized that he as iodine or iodide releasing compound, a mixture of sodium or Potassium iodide and elemental iodine. Process according to claims 1 to 8, characterized that he the reaction in the presence of 50 to 100%, preferably 70 to 97%, sulfuric acid performs. Process according to claims 1 to 9, characterized that he the molar ratio of sulfuric acid to pyrazoline derivative to 1: 3 to 5: 1, especially 1: 1 to 3: 1, sets. Process according to claims 1 to 10, characterized that he the molar ratio of oxidant to hydrazine or pyrazoline derivative between 1: 2 and 2: 1, preferred between 1: 1 and 1.3: 1. Process according to claims 1 to 11, characterized that he the reaction mixture neutralized after the reaction, if necessary with an organic solvent extracted, and the organic phase, optionally after removal of the solvent, distilled.