DK171706B1 - Epoxide and halohydrin compounds - Google Patents

Description

DK 171706 B1

The present invention relates to novel epoxide and halohydrin compounds useful as intermediates in the preparation of triazole compounds having fungicidal and plant growth regulating properties.

GB-A-1,529,818 discloses certain 1,2,4-triazole compounds which can be used in the preparation of antifungal agents for the control of fungal diseases in plants. The intermediates of the invention can be used to prepare compounds which, in relation thereto, constitute a selection invention, the compounds of this invention having unexpectedly more potent effects and surprisingly being effective against a greater number of diseases.

Such fungicidal compounds are described in DK Publication No. 157364.

The invention provides compounds of the general formula: / X, CH2-C-R1 (II) R2 or

20 OH

X-CHn-C-R1 (III), wherein X is a halogen atom, R1 is butyl or C1-8 cycloalkyl, and R2 is 2-chlorobenzyl; or R1 is phenyl substituted with one or more chlorine or fluorine atoms, and R2 is phenyl optionally substituted with fluorine, however, R2 is not phenyl when R1 is chloro-substituted phenyl.

2 DK 171706 B1

In particular, the invention provides the compounds defined above wherein R 1 is 2-chlorophenyl or 2-fluorophenyl and R 2 is 4-fluorophenyl; or R1 is 4-chlorophenyl, 4-fluorophenyl or 2-chloro-4-fluorophenyl, and R2 is 2-fluorophenyl.

A specific epoxide or oxirane compound of the invention has the formula: 0 Cl ch 2 -c- (j

V

F

Examples of triazole compounds useful as fungicides and which can be prepared using the oxirane and halohydrin intermediates of the present invention are shown in the following Table I.

The triazole compounds have the general formula:

OH

N-N-CH9-C- R1 3 DK 171706 B1

TABLE I

Compound R1 R2 Melting point # (° C) 20 t-Bu O-Cl-C6H4CH2- 74-75 5 27 p-Cl-C6H4- pF-C6H4- 154-155 29 pF-G6H4- pF-C6H4-170 -171 30 PF-C6H4- C6H5 "139-140 42 0-F-C6H4- C6H5" 126-128 44 p-Cl-C6H4- 0-F-C6H4- 144-145 10 45 0-Cl-C6H4-PF- C6H4- 115-116 46 pF-C6H4- 0-F-C6H4- 120-123 51 2,4-diCl-C6H3- pF-CgH4- 137-138 55 2,4-diCl-C6H3- oF-C6H4- 146 147 60 m-Cl-CgH4-pF-C6H4-190-193 15 252 p-Cl-CgH4-mF-CgH4-55-59 253 mF-CgH4-pF-CgH4-116-118 In the following Tables II, III and IV, physical data for the intermediates of the invention are presented against the end products prepared therefrom, which are previously discussed in Table I:

TABLE II

4 DK 171706 B1

End product_Intermediate products according to the invention

Compound No. in TABLE I Oxiran Chlorohydrin 5 20 Oil 27 Oil Oil 29 Oil 30 100-104 (0.1 mm Hg) 42 Oil 10 44 Oil 45 Oil 46 Oil 51 155-160 (0.5 mm Hg) 55 Oil 15 60 oil 252 oil 253 oil

TABLE III

The compound's Oxiran Chlorohydrin

20 in Table I

27 δ 3.20 (2H, dd) 6.86-7.98 (8H, m) 29 δ 3.20 (2H, s) δ 2.99 (1H, s) 4.01 6.70-7 , 80 (8H, m) (2H, s), 6.8-7.5 (8H, m) 45 δ 3.30 (2H, s) δ 3.51 (1H, s) 4.33 6.80-7 , 60 (8H, m) (2H, dd) 6.8-7.9 (8H, m) 46 δ 3.24 (2H, dd) δ 3.24 (1H, d) 4.3 6.80-7 , 60 (8H, m) (2H, m) 6.8-7.9 (8H, m) 51 δ 3.25 (2H, dd) Boiling point 155-160 6.8-7.6 (7H, m) (0.05 mm Hg) Nuclear magnetic resonance data are set forth in CDCl3. Chemical shifts are δ values (ppm down from TMS).

In the table, s means singlet, d doubled, dd double doubled and m multiplied.

TABLE IV

1.1-Bis (4-fluorophenyl) ethylene oxide 0-7 Physical Properties NMR Data Oil δ 3.22 (2H, s), 7.00 10 / L YY Γ II (4H, t), 7.30 (4H , dd) F ^ F ppm

The compounds of Table I can be prepared by reacting a compound of the invention of the general formula: CH2-C-R1 or X-CH2-C-R112-210, wherein R and R4 have the meanings defined above and X is a halogen atom (preferably a chlorine or bromine atom) with 1,2,4-triazole, either in the presence of an acid-binding agent 20 or in the form of one of its alkali metal salts in a suitable solvent. The oxirane or halohydrin compounds of the invention are suitably reacted at 20-100 ° C with the sodium salt of 1,2,4-triazole (the salt can be prepared by adding either sodium hydride or sodium methoxide to 1,2,4-triazole) in a suitable solvent. such as acetonitrile, methanol, ethanol or dimethylformamide. The product can be isolated by pouring the reaction mixture into water and recrystallizing the solid formed from a suitable solvent.

6 DK 171706 B1

The oxirane and halohydrin compounds of the invention can be prepared by reacting a compound of the general formula: X 0 -CH 2 -C-R1 or X-CH 2 -C-R2 wherein R1, R2 and X have the meanings defined above, respectively. a Grignard compound of the general formula: Y-Mg-R 2 or Y-Mg-R 1 wherein R 1 and R 2 have the meanings defined above, Y is a halogen atom (preferably chlorine, bromine or iodine) in a suitable solvent such as diethyl ether or tetrahydrofuran . A mixture of the oxirane and halohydrin compounds of the invention is generally obtained. When a ketone compound of the general formula set forth above, wherein R 1 is butyl or cycloalkyl, e.g. reaction, the oxirane compound generally dominates in the mixture. In contrast, when R 1 is substituted phenyl, the halohydrin compound generally dominates in the mixture.

The ketone compounds of the above formula can be prepared by methods described in the literature.

The oxirane compounds of the above general formulas wherein R 1 and R 2, which may be the same or different, are substituted phenyl, may also be prepared by reacting the appropriate benzophenone compound of the general formula: R 1 - CO - R 2 wherein R and R have the meanings defined above, with dimethyloxosulfonium methylide (Corey and Chaykovsky, JACS, 1965, 87, 1353-1364) or dimethylsulfonium methylide (Corey and Chaykovsky, JACS, 1962, 84, 3782) using in literature 7 DK 171706 B1 pure methods described.

The benzophenone compounds of the general formula shown can be prepared using the Friedel-Crafts reaction by reacting a substituted benzoyl chloride with the appropriate substituted benzene in the presence of a Lewis acid e.g. aluminum chloride,.

The oxirane compounds of the invention, wherein R 1 and R 2 have the meanings defined above, can also be prepared by reacting a β-hydroxyselenide compound of the general formula: R 1

CH7- See -CH2 - C -OH

Wherein R 1 and R 2 have the meanings defined above, with methyl iodide in potassium t-butoxide according to the method of Van Ende, Dumont and Krief, Angew. Chem. Int. Ed., 1975, 14, 700.

The β-hydroxyselenide compound can be prepared by treating the diselenide with the appropriate ketone in the presence of butyllithium.

The triazole compounds listed in Table I are, as mentioned, fungicidal especially effective against the diseases:

Piricularia oryzae on rice,

Puccinia recondita, Puccinia striiformis and other 25 wheat wheat rust, Puccinia hordei, Puccinia striiformis and other barley rust and rust on other host plants e.g. coffee, apples, vegetables and ornamental plants,

Plasmopara viticola on wine,

Erysiphe graminis (powdery mildew) on barley and wheat and other powdery mildew forms on various hosts such as Sphaerotheca fuliginea on cucumber,

Podosphaera leucotricha on apples and Uncinula necator on wine, Helminthosporium spp. and Rhynchosporium spp. on cereals, 5 Cercospoa arachidicola on peanuts and other Cercospora forms of e.g. sugar beet, bananas and soybeans,

Botrytis cinerea (gray mold) on tomatoes, strawberries, wine and other hosts,

Phytophthora infestans (potato mold) on tomatoes, 10 Venturia inaequalis (scab) on apples.

Some of the compounds have also shown a broad spectrum activity against fungi in vitro. They are effective against various post-harvest diseases of fruit (eg Penicillium digatatum and italicum on oranges and Gloeosporium musarum on bananas).

15 Some of the compounds also act as dressing agents against: Fusarium spp., Septoria spp., Tilletia spp. (i.e. wheat stink fire, which is a seed-borne disease on wheat), Ustilago spp., Helminthosporium spp. on cereals, Rhizoctonia solani on cotton and Corticium sasakii on rice.

20 The compounds may move mid-point seeking in the plant tissue. In addition, the compounds may be volatile enough to be active in the vapor phase against fungi on the plant.

The compounds can be used as such for fungicidal purposes, but are most conveniently formulated into agents for such use.

The following example illustrates the invention as well as the use of the intermediate of the invention for the preparation of a triazole fungicide as set forth in Table I.

Claims (5)

X-CH2-C-R1 (III) wherein X is halogen; R 1 is butyl or C 3-6 cycloalkyl and R 2 is 2-chlorobenzyl; or R 1 is phenyl substituted with one or more chlorine or fluorine atoms and R 2 is phenyl optionally substituted with fluorine, however R 2 is not phenyl when R 1 is chloro-substituted phenyl. Epoxide or halohydrin according to claim 1, characterized in that R 1 is 2-chlorophenyl or 2-fluorophenyl and R 2 is 4-fluorophenyl; or R1 is 4-chlorophenyl, 4-fluorophenyl or 2-chloro-4-fluorophenyl, and R2 is 2-fluorophenyl. A compound according to claim 1, characterized in that it has the formula: 0 Cl Ch2-C- Φ 20 F