DE2047464A1 - Process for the preparation of substituted phenyl 1,3,4-oxdiazoles - Google Patents

Description

F Λ R Ii ¥ ERKEHOE C HS Ύ Λ G formerly Meistor Lucius & UrLining ¹

Az .: 'Hoe 7O / F

Date: ² 5 September

Dr. KM / Brd "

Process for the preparation of substituted phenyl-1,3> 4-oxdiazoles

It is known to use substituted 1,3> 4-oxdiazoles on the following Way to manufacture.

a) The thermal splitting off of hydrazine and water results in BcHzoylhydraziden at 250-3OO ° C 2,5-diaryl-1,3> 4-oxdiazoles

N-N 250-300 ° C

2 C ₆ H CO-NH-NH ₂ > C ₆ H ₅ -C P-CgH + H ₃ O + HgN-NH ₂

(Elderfield, Heterocyclic Compounds, Volume 7 »Pages 5% 5-526).

b) The withdrawal of water from asymmetric diacylhydrazides by means of phosphorus pentoxide, phosphorus pentachloride, phosphorus oxychloride, thionyl chloride, tin chloride or other dehydrating agents Medium leads to asymmetrically substituted 1,3 »^ - oxdiazoles.

N- N

Ii-CO · NHNH'COR ' ^: > | | j

-H ₂ O RC C-R '

^ 0 ^ (Elderfield, op. Cit., Volume 7, page 527).

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c) The preparation of 2-haloalkyl-5-aryl-1,3 »'t-oxdiazoles in the above way and by reaction of Halogenacyliinidoäthem with benzoyl hydrazides according to the equation

.HCl

+ H NNHCAr

N- N

Hal (CH) -C / J-Ar + NH. Cl + RAW \ /

C / J-Ar +
\ /

where η = 1 to h is described in English patent specification No. 1.161.802.

The most economical of the above, for the Preparation of haloalkyl-1,3 »4-oxdiazoles useful Method requires acyl-haloacylhydrazide as starting material, those made from acylhydrazines and relatively expensive halo-acyl chlorides or anhydrides awkward ways must be isolated.

A process for the preparation of ^ -Piienyl-1, 3, h oxdiazoles of the general formula I has now been established

N N

Il Il

R ₁ CCR ₂

⁰
found, in which R 1 is a singly halogenated alkyl radical with _{1, 2, 3} or h carbon atoms, preferably brominated or in particular chlorinated methyl or ethyl groups, and R "denotes a phenyl radical which is replaced by one or more halogen atoms, preferably by chlorine or Bromine, in particular by chlorine, or by alkyl or alkoxy groups with 1, 2, 3 or k C atoms, preferably with 1 or 2 C atoms, can be substituted

2098U / 1783

is characterized in that one halocarboxylic acids of the general Formula II with carboxylic acid hydrazide !! of the general formula III, in which R and R have the meaning given above, in one inert solvents in the presence of inorganic acid halidesii Reacts at temperatures of 60 - 15O C.

The reaction proceeds according to the following equation:

₀ NN

+ II N NH-C> R C P-Rp

¹ ^ OH ^ R ₂ .- 2 H ₂ O \ ₀ /

(II '(III) (I)

The preferred reaction temperatures are those between 80 ° C. and 1 ° C.; It is particularly favorable to work at the boiling point of the solvent used.

The reactants halocarboxylic acid and carboxylic acid hydrazide are expediently used in approximately equimolar amounts. The inorganic acid halide used according to the invention is added at least in the amount sufficient to d \ s at to bind water to be split off the condensation; an excess of up to $ 30, based on the water to be split off can be beneficial.

The amount of inert solvent depends on the Solubility of the organic reaction partners. She "amounts to expediently between 0.3 and 5 liters, advantageously between 0.5 and 2 liters, per mole of an organic reactant.

8AD ORIGINAL

A 2098U / 1783 -

To carry out the reaction, all reaction parts can be used zuaiinnoi submitted and with stirring to reaction temperature be heated. But it can also hydrazide and halocarboxylic acid presented with solvent and the inorganic acid halide. optionally also in an inert solvent dissolved, added at reaction temperature, this addition can take place in a time between 0.1 and 15 hours, advantageous in 1 to. 5 hours happened. The reaction ends when the evolution of hydrogen halide ceases recognize; the total reaction time can be between 2 and 20 hours be.

The condensation proceeds with elimination of water. The acid halide used as a condensing agent is used in the relevant inorganic acid and hydrogen halide, decomposed. The hydrogen halide escapes from the reaction mixture gaseous and is expediently discharged via a reflux condenser.

The following halocarboxylic acids of the general formula II are particularly suitable as starting materials: chloroacetic acid, 0C -chloropropi.onic acid, ί ^ -chloro-n-butyric acid, ^ / ■ -chloro-iso-butyric acid, Q \ -chloro-n-valeric acid, CA -Chloroiso-valeric acid.

Particularly suitable carboxylic acid hydrazides of the general formula III are the following into consideration:

Benzoic acid hydrazide, in the 2,3> or ^ 4 position of the benzene ring Benzoesävirehydrazide, 2,3- and substituted by chlorine 3, ^ - dichlorobenzoic acid hydrazide, 2-methyl-benzoic acid hydrazide, 2-ethylbenzoic acid hydrazide, 3 ~ and ^ -methoxy-benzoic acid hydrazide, 3- and 4-ethoxy-benzoic acid hydrazide.

BAO ORIGINAL

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2098U / 1783

All solvents which are inert towards the coalition partners can be used as solvents, for example lower halogenated, in particular chlorinated, aliphatics such as trichloroethane, trichlorethylene, tetrachlorethylene, carbon tetrachloride, and also aromatics such as benzene or substituted benzenes such as toluene, xylene, cumene, chlorobenzene or dichlorobenzene. Preferred solvents are benzene, toluene, chlorobenzene and xylene. . .

As water-binding or water-releasing inorganic acid halides phosphorus trichloride or phosphorus oxychloride are preferred; furthermore are also thionyl chloride, phosphorus penta-ί chlorld, as well as corresponding bromine compounds can be used.

The chemical course of the manufacturing process according to the invention is surprising. One would have expected that the very reactive halogen atom of the halocarboxylic acid would react with the strongly basic amino group of the carboxylic acid hydrazides. However, this is not the case, or only to a very minor extent, so that the ^ -henyl-1,3 »^ - oxdiazoles can be obtained in mostly good yield and high purity by this process. In addition, the process according to the invention has the advantage of inexpensive starting materials and relatively low reaction temperatures, so that decomposition and secondary reactions can largely be avoided.

The 5-phenyl-1,3> 4-oxdiazoles prepared by the process of this invention are valuable intermediates for Manufacture of pesticides and pharmaceuticals.

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2098 H / 1783 ' _{BA0 0R1G1NAL}

So you can ζ. B. by reaction with 0,0-dialkyl -ditliiophosphorsäure or with their salts of the general formula IV, in which X is hydrogen, an alkali metal or cleis ammonium radical and in which R and R are alkyl radicals with "[- k carbon atoms, in dithiophosphoric acid esters of the general formula V , in which the substituents have the meanings given above and η is 1, 2, 3 or h . This reaction is represented by the following scheme:

N N R ^ O S N-N

) PS- (CH ₂ J _n (Jl _R

R θ '* ⁿ ^ ^K

(IV) (Ia) (V)

Draw the 0,0-dialkyl-dithiophosphoric acid esters thus obtained are particularly characterized by good insecticidal and acaricidal properties (cf. German patent application P 19 6-3 672.7).

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2098H / 1783

Example 1: 2-chloromethyl-5-phenyl-1 »3-4-oxdiazole

68 g (g, 5 mol) Beiizoesäurehydrazid, 47.2 g (0.5 mol) and ChI oressigsäure k8 g Pliosphortrichlorid h are heated in 400 ml of benzene hours under reflux. Crystal from the benzene solution! After decanting of dex "precipitated phosphorous acid, the 2-chlorometh.yl-5-ph.enyl-1,3> 4-oxdiazole separates out as a colorless powder.

The yield is 1.5 g (74.5% of theory) of 2-chloromethyl-5-phenyl-1,3,4-oxdiazole of m.p. 106-108 ° C.

CH C3N 0 M 194 -5 ^{calc; : N 1} ^ ^{C1 18} ' ² C ₉ H ₇ ClN ₂ UM 19 ^, 5 _fm . ν -1 ^, 2 Cl 18.0

Example 2: 2-chloromethyl-5- (3-chlorophenyl) -1,3 »^ - oxdiazole

170 g (1 mol) of 3-chlorobenzoic acid hydrazide, 9 ^, 5 S (1 mol) of chloroacetic acid and 96 g of phosphorus trichloride are refluxed in 800 ml of benzene for 15 hours. The benzene is separated from the phosphorous acid. Upon concentration of the solution of 2-chloromethyl-5- (3-chi orphenyl) -1, 3,4-oxadiazol colorless in the form of crystals, melting at 182 g 60 (79.5 $> of theory...) - 62 C obtain.

CH Cl N 0 V ₂₂ Q t ^ ·: N 12.2 Cl 31.0

C ₉ H ₆ Cl ₂ N ₂ OM 229 _{ger <: N 11> 9} ei 30.8

Example 3; 2-chloromethyl-5- (3,4-dichlorophenyl) -1,3,4-oxdiazole

A suspension of 103 g of 3 »4-dichlorobenzoic acid hydrazide in 500 ml of toluene is mixed with a solution of 95 S chloroacetic acid in 400 ml of toluene at 60 ° C. while stirring. After adding 55 g of phosphorus oxy chloi-id, the reaction mixture is boiled under reflux for 5 hours. The organic phase is decanted from the precipitated phosphoric acid while hot and cooled while stirring.

209814/1783

A 8-

The 2-chloromethyl 1-3- (3> Ί-dichlorophonyl) 1,3,4-oxdiazole in white crystals with a melting point of 121-122 ° C. In this way and by concentrating the mother liquor, a total of 164 g (63.5 $ of theory) 2-chloromethyl-3- (3, ^ - diclilorplienyl) -1, 3, 'l-oxdiazo .: obtain.

ρ H π TJ η M 961 * calc.r N 10.6 Gl kO, h C ₉ H ₅ Cl ₃ N ₂ OM 263.5 · found _# . _{N 10> 4 C1 hOfO}

Example h : 2-chloromethyl-3- (3 ~ ' ^ne thoxyphenyl) -1,3 »4-oxdiazole

127 S 3-methoxybenzoic acid hydrazide (0.7 ^ 5 mol) are suspended in 300 ml of benzene, and a solution of 72.3 S chloroacetic acid, dissolved in 300 ml of benzene, is added. The mixture is heated to 80 ° C. and 3 ^, 7 S PCI «are added dropwise with stirring. When the evolution of HCl subsides, a further 36.7 g of PCI are added dropwise. After 8 hours, the benzene solution is decanted hot from the precipitated phosphorous acid and cooled with stirring. The colorless crystals which have separated out are filtered off with suction and the mother liquor is concentrated obtain.

CH ClN 0 M 224 5 ^ber * ^{: C 53} '° ^{H 4} ' ^{8 C1} G ₁₀ H ₉ ClN ₂ UM 2245

Example 5: 2-chloromethyl-5- (4-ethoxyphenyl) -1,3,4-oxdiazole

159 g of 4-ethoxy-benzoic acid hydrazide (0.88 mol) are suspended in 35Ο ml of benzene and a solution of 83.5 g of chloroacetic acid dissolved in 35Ο ml of benzene is added. 7 g of PCI are added dropwise and the mixture is heated to 80 ° C. After completion of HCl evolution further k 0.7 g PCI are added dropwise.

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20981 U / 1783

ν -9-

K; I 1 5 ~ j stund according heating au Γ 80 C% v ^r ird the Reaktionsgeiiiisch wi e et aiifgearbeiI in Example 4.

The yield is 141 g (67 '; o d. TIi.) 2-Chlormef, hyl-5- (4-ethoxyphenyl) -1 , 3,4-oxdiazo 1., mp 77-79 ° C.

_M, 0 Calcd .: C 55, 4 II 4.61 Cl 14.75 ^{M 2JB 'J} _e ef .: C 55.7 H 4.7 Cl 14.8

At game 6; 2-Chloroethyl-5 ~ (2-methyl-phenyl) -1, 3, 4-oxdiazole

75 S of 2-methylbenzoic acid hydrazide (0.5 mol) are suspended in 200 ml of benzene, and a solution of 47.3 S (0 »5 mol) of chloroacetic acid in 200 ml of benzene is added. To this end, 24 g of PC1 “are added dropwise at 80 ° C. twice. 'After 9 hours, the benzene solution of precipitated phosphorous acid is decanted while hot, cooled and extracted with sodium bicarbonate. After the benzene has been distilled off, 98 g (94% of theory) of 2-chloromethyl-5- (2-methyl-phenyl) -1,3 »4-oxdiazole remain as a colorless oil which solidifies at room temperature and shows the following analytical data.

ρ w PIW η μ pn «ς u« r. : C 57.6 H 4.3 N 13 >>

C ₁₀ H ₉ ClN ₂ OM 208.5 Found: C 57.6 H 5.2 N 10.7

Example 7: 2-β-chloroethyl-5-phenyl-1,3,4-oxdiazole

68 g (0.5 mol) of benzoic acid hydrazide and 54 g (0.5 mol) 2-chloro-propionic acid are heated to 80 ° C. in 300 ml of xylene and 46 g (0.34 mol) of phosphorus trichloride were added. To

3-hour heating to 120 C results in the evolution of hydrogen chloride completed. The xylene solution is fractionally distilled

The yield is 57 g of 2 - <? F -Chlorathyl-5 ~ ph.en.yl-1, 3, 4-oxdiuzole with a boiling point of _{0 Q} : 108 - 112 ° C (55 1 ° d · Th.)

ο Tt PiW η μ onR ς bor .: N 13.4 Cl 17.0

C ₁₀ H ₉ ClN ₂ OM 208.5 found _# . _{N 13> 6 C1 17> 0}

209 8 U / 1783

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Claims (1)

-IQ- Claim: Method of making 5-phony .1 -1, 3 > Ί-oxdiazoles der general formula I. N N R ₁ - C CR ₀ ¹ \ / ² _v in which R is a singly halogenated alkyl radical with 1, 2, 3 and h carbon atoms and R is a phenyl radical which is substituted by one or more halogen atoms or by alkyl or alkoxy groups with 1, 2, 3 or VC atoms can, characterized in that halocarboxylic acids of the general formula II R ₁ - c (U) \OH
with carboxylic acid hydrazides of the general formula III HN in which R ₁ and R have the abovementioned meaning, in an inert solvent in the presence of inorganic Säurehaiogenxden at temperatures of 60 - 150 C are reacted. 2098U / 1783