HU209237B - Fungicidal composition comprising quinazolinone derivative as active ingredient and process for producing the active ingredient - Google Patents

Abstract

Quinazoline fungicide has formula (I) where R1 and R2 are independently: H, halo, alkyl-, nitro-, amino-, alkylamino dialkylamino, alkoxy or alkyl sulphonyl-amino, or 1-3 carbon alkylene-dioxy; Z1 and Z2 are H or halo or alkyl; Z is halo, alkoxy-, phenoxy-, amino-, alkylamino-, benzylamino-, thiocyanate, mercapto-, alkylthio-, phenylalkylthio, alkylsulphonyl-thio or OH; and W is OH, amino-, alkyl-methylene-amino, alkoxycarbonylamino, aminocarbonylphenyl or halo or pyrazol-4-yl or oxazol-4-yl.

Description

FIELD OF THE INVENTION The present invention relates to fungicidal compositions containing quinazolinone derivatives as active ingredients. The invention further relates to a process for the preparation of the active ingredients of the compositions.

The fungicidal compositions of the present invention contain as active ingredients the 4 (3H) -quinazolinone derivatives of the formula (I) or their agriculturally useful salts -

R ¹ is hydrogen, nitro, amino or C 1-4 alkylsulfonylamino,

R ² is hydrogen, or

R ¹ and R ^{2 taken} together are C 1 -C 2 alkylenedioxy groups bonded to two adjacent carbon atoms of the benzene ring,

Z ¹ is hydrogen, halogen or C 1-4 alkyl,

Z is halogen, phenyl (C 1-4 alkyl) thio, thiocyanato or morpholino; and

W is amino, (C1-C8-alkoxy) -carbonylamino, fufurylideneimino, phenyl-phenylcarbonyl-amino optionally substituted on the phenyl moiety, or one or two (C1-C4) -alkyl optionally substituted 1-pyrrolyl, 4-pyrazolyl or 4-isoxazyl.

Among the compounds of formula I, a

2- (fluoromethyl) -3-amino-4 (3H) -quinazolinone [Zh. Obsch. Khim. 34 (9), 2965-2969 (1964)], which is prepared by reacting 2- (fluoromethyl) -3,1-benzoxazin4 (4H) -one with ammonia at reflux, followed by 2- (fluoro- methyl) -4 (3H) -quinazolinone is reacted with hydrazine hydrate at reflux; 3-amino-2- (1-chloroethyl) -4 (3H) quinazolinone prepared in a similar manner is also known (Indian J. Chem. Sec. B (10) 981).

In the literature, 2- (hydroxymethyl) -3-amino-4 (3H) -quinazolinone, structurally related to the compounds of formula (I) [J. Org. Chem., 29 (3), 582-584 (1964)], in which N- (chloroacetyl) anthranilic acid is reacted with H-CO-N (CH ₃ ) ₂ and the resulting cyclic compound is reacted with hydrazine hydrate under reflux. ; and many representatives of the 2-alkyl-3-aryl-4 (3H) -quinazolinones have been described as having therapeutic activity. Of these, the

2-methyl-3- (o-tolyl) -4 (3H) -quinazolinone [J. Ind. Chem. Soc., 28, 344 (1951)] known as methaqualon and used in clinical practice as a central nervous system agent. 2- (fluoromethyl) -3- (o-tolyl) -6-amino-4 (3H) -quinazolinone [J. Med. Chem. 20, 379] are used in medicine as a muscle relaxant. Fungicidal 4 (3H) -quinazolinone derivatives have not yet been reported in the literature.

Further compounds of formula I are new.

In our studies we have found that the compounds of the formula I and their agriculturally useful salts have a strong fungicidal activity against plant fungal pests. A particular advantage of the compounds is that they are systemic. Accordingly, agrochemical compositions comprising the compounds of formula (I) or their agriculturally useful salts are useful for preventing or treating fungal infections in plants.

Among the compounds of formula (I), those derivatives have a very beneficial fungicidal activity, wherein W is a group attached to the nitrogen atom of the quinazoline ring through a nitrogen atom. Particularly advantageous examples of the latter compounds are those compounds wherein W represents an amino or furfurylidene amino group and the group -CHZ'Z contains at least one halogen atom.

The compositions of the invention may contain, in addition to the active ingredient of formula (I) or an agriculturally acceptable salt thereof, a carrier or diluent, and optionally one or more known agricultural excipients, such as surfactants, suspending agents, tackifiers, preservatives and the like. The compositions of the present invention preferably contain at least 0.001% by weight of the active compound of formula (I), optionally in the form of a salt.

Carriers or diluents in the compositions of the present invention may be solid or liquid, for example, water, liquid hydrocarbons, alcohols, glycols, talc, clay minerals, silica gel, calcium carbonate, calcium phosphate, magnesium oxide, calcium oxide and dolomite. Suitable surfactants include both ionic (such as anionic and cationic) and nonionic surfactants, and mixtures thereof. Exemplary suspending agents include swellable clay minerals (such as bentonite) and carboxymethylcellulose.

The compositions of the invention may be in the form of solid compositions (such as dusts, wettable powders or granules) and liquid compositions (such as solutions, emulsions, suspensions, emulsifiable concentrates and suspension concentrates). Liquid formulations are usually marketed as concentrates having a high active ingredient content (up to 95% by weight) and the concentrates are diluted with water to the desired final active ingredient content immediately before use.

The compositions of the invention include any portion of the plant (such as foliage, stem, branches, roots, bark or fruit), seeds or propagating material, soil, and spaces for storing or transporting plants or plant parts, or containers (such as storage racks, crates, etc.) can be handled. The compositions may be applied, for example, by spraying, spraying, spraying, injection, brushing, or the like in a suitable manner. If desired, other biologically active substances, such as fungicidal, insecticidal, plant growth regulating or similar compounds having the same activity as the compounds of formula (I), may be included in the compositions of the invention.

And / or rodenticidal active substances.

The compounds of formula (I) may be prepared by any of the known methods of preparation of related quinazolinone derivatives. In addition, novel methods for the preparation of compounds of formula I have been developed to provide compounds of formula I more readily and / or in higher yields than known methods. Suitable methods for the preparation of compounds of formula I are described below.

a) For preparing compounds of formula (I) wherein R ^1, R ^2, Z ¹ and Z are defined as above and W is other than furanyl imino benzoxazinone of formula as defined above, (Π) derivative (V ), wherein R ¹ , R ² , Z ¹ and Z are as defined above, W 'is the same as W above, except for the fufurilideneimino group, and the resulting compound of formula (I) general formula

Z is halogen, optionally converted to a compound of formula (I) as defined above with the exception of halogen, and / or ₂ ) W (C 1 -C 8) alkoxy-carbonylamino, optionally wherein W is amino is converted to the compound by acid treatment or thermal treatment.

The compounds of formula (II) are prepared under the conditions described for the preparation of related quinazolinone derivatives [J. Ind. Chem. Soc. 60,610-611 (1983): Monatsch. Chem. 90: 846-857 (1959); Acta Chem. Scand. Ser. B. 34 (9), 637-642 (1980); J. Org. Chem. 50 (16): 2926-2929 (1985); J. Pract. Chem. 31 (3-4) 140-148 (1966); Tr: Nauchnoissled. Khim. -Farm. Inst. 1972 (8), 127-127] can be reacted with compounds of formula (V). The reaction conditions are described in detail in the Examples.

In the case of products having the formula -CHZ'Z instead of C2-C5 alkyl, the

The hydrogen atom attached to the C-1 position can be replaced by a halogen atom by known methods (e.g. N-bromosuccinimide treatment). However, the compounds of formula (I) containing the bromomethyl group in the 2-position can also be prepared by a new method we have developed

b) for the preparation of compounds wherein R ¹ , R ² and W in formula I are as defined above, Z ^{1 is} hydrogen and Z is bromo, 2-methylquinazolinone of formula VI, in which R ¹ , R ² and W are reacted with cyanogen bromide as described above.

The Z in the halogen atom may be replaced by another Z group by reacting compounds of formula I wherein Z represents a halogen atom, and R ¹ , R ² , Z ¹ and W represent a salt or a basic salt of the above compounds Z ' reaction with a compound of formula Z "-H, wherein Z" except Z is the same as Z.

c) Compounds of formula I for the preparation of compounds of formula I wherein R ¹ , R ² , Z ¹ and Z are as defined above and W is a furfurylidene imino group; 1-pyrrolyl optionally substituted with C 1 -C 4 alkyl, where W is amino.

C0 furfural, or c ₂₎ 1,4-butanedione derivative (XII), wherein, R ³ and R ⁴ is hydrogen or C1-4 alkyl; and the resulting compound of formula (I) wherein Z is halogen is optionally converted to a compound of formula (I) other than halogen.

d) For the preparation of compounds of formula (I) wherein R ¹ , R ² , Z ¹ and Z are as defined above and W is amino or (C 1 -C 8) alkoxy) carbonylamino, dj) (VII) reacting a 2- (2-aminobenzoyl) carbazonic acid ester derivative of the general formula (VIII) with an alpha-haloalkane carboxylic acid halide (VIII), or d ₂ ) 2- [2- (acylamino) - (IX) the benzoyl] -carbazidic acid ester derivative is thermally cyclized in the formulas (VII) to (IX) wherein R ¹ , R ² and Z ¹ are as defined above, Z 'and Hal are halogen and Alk is C 1 -C 8 alkyl; optionally converting a compound of formula (I), wherein Z is as defined above, except halogen, and / or optionally converting the resulting compound to an acidic or thermal compound of formula (I); represents an amino group, or

e) converting R ¹ , Z and / or W present in a compound of formula I into another R ¹ , Z and / or W in a known manner; and, if desired, converting the compound obtained by any of the preceding processes into an acid addition salt by treatment with an appropriate acid.

The invention is further illustrated by the following non-limiting examples.

Example 1

Preparation of N- [2- (Chloromethyl) -4 (3H) -quinazolinon-3-yl] -carbamic acid tert-butyl ester

A mixture of 2- (chloromethyl) -3,1-benzoxazin-4 (4H) -one, ten times the amount of benzene and 1.2 equivalents of the carboxylic acid tert-butyl ester was heated under reflux for 1 hour. After cooling, the precipitated crystalline material is filtered off, washed with ether and dried. The title compound was obtained in 80% yield; 180 DEG C. (dec.).

The starting material 2- (chloromethyl) 3,1-benzoxazin-4 (4H) -one was prepared by

237 Β (Chloroacetylamino) -benzoic acid (Compound prepared by reaction of 2-aminobenzoic acid and chloroacetyl chloride in benzene with boiling; m.p. 185 ° C) in 10-15 times of acetic anhydride for 30-40 minutes. The solution is evaporated under reduced pressure. The yellow crystalline 2- (chloromethyl) -3,1-benzoxazin-4 (4H) -one is obtained in 88% yield; 95 DEG C. (recrystallized from a mixture of benzene and pentane).

Example 2

Preparation of N- [2- (Chloromethyl) -6,7-methylenedioxy-4 (3H) -quinazolinon-3-yl] -carbamic acid tert-butyl ester

The procedure described in Example 1 was followed except that 2- (chloromethyl) -6,7-methylenedioxy-3,1-benzoxazin-4 (4H) -one (Example 1, paragraph 2) m.p. 148 ° C). The title compound was obtained in 90% yield; 178 DEG C. (dec.).

Example 3

Preparation of N- [2- (Chloromethyl) -6-nitro-4 (3H) -quinazolinon-3-yl] -carbamic acid tert-butyl ester

The procedure described in Example 1 was followed except that starting from 2-chloromethyl-6-nitro-3,1-benzoxazin-4 (4H) -one. The title compound was obtained in 88% yield; 178 DEG C. (dec.).

The starting material, 2- (chloromethyl) -6-nitro-3,1-benzoxazin-4 (4H) -one, was prepared by nitration of 2-chloroacetylamino) benzoic acid with concentrated nitric acid, followed by (chloroacetylamino) -5-nitrobenzoic acid (m.p. 226-227 ° C) was boiled in acetic anhydride as described in Example 1 (2).

Example 4

Preparation of 3-Amino-2- (chloromethyl) -4 (3H) -quinazolinone

A mixture of N- [2- (chloromethyl) -4 (3H) -quinazolinon-3-yl] -carbamic acid tert-butyl ester prepared in Example 1 and 5 times acetic acid was heated to reflux. The solvent was evaporated, the residue was triturated with methanol, and the precipitated solid was filtered off and washed with ether. The title compound was obtained in 70% yield; 158 'C (crystallized from ethanol).

Example 5

Preparation of 3-Amino-2- (chloromethyl) -6,7-methylenedioxy-4 (3H) quinazolinone

The procedure described in Example 4 was followed except that N- [2- (chloromethyl) -6,7- (methylenedioxy) -4 (3H) -quinazolinon-3-yl] -carbamic acid tert-butyl ester was let's start. The title compound was obtained in 80% yield; m.p. 208 'C (recrystallized from butanol).

Example 6

Preparation of 3-Amino-2- (chloromethyl) -6-nitro-4 (3H) -quinazolinone

The procedure described in Example 4 was repeated except that the starting material was N- [2- (chloromethyl) -6-nitro-4 (3H) -quinazolinon-3-yl] -carbamic acid tert-butyl ester. The title compound was obtained in 78% yield; 151-152 ° C (recrystallized from butanol).

Example 7

Preparation of 3-Amino-2- (chloromethyl) -6-nitro-4 (3H) -quinazolinone

10.3 g of N- [2- (chloromethyl) -6-nitro-4 (3H) -quinazolinon-3-yl] -carbamic acid tert-butyl ester are heated at 180-182 ° C for 2 minutes under argon. . After the effervescence of the melt has ceased, it is poured into a frit, rubbed with butanol, and the solid is filtered off. The filtered solid was recrystallized several times from n-butanol. 4.0 g (57%) of the title compound are obtained, which is identical to the compound prepared in Example 6.

Example 8

Preparation of N- [2- (Bromomethyl) -4 (3H) -quinazolinon-3-yl] -carbamic acid tert-butyl ester

3.4 g of 2- (bromomethyl) -4 (4H) -3,1-benzoxazinone,

A mixture of 2.1 g of tert-butyl carbazide acid and 30 ml of benzene was stirred for 1 hour at room temperature. During this time, the suspension gradually thickens. The suspension is refluxed for 1 hour under a water separating pad; in the meantime the suspension becomes a homogeneous solution. The reaction mixture was cooled, the solid by-product precipitated was removed by filtration and the filtrate was chromatographed. Kieselgel G 60 silica gel was used as the adsorbent and dichloromethane-acetone (10: 1) was used as eluent. Three fractions of eluate were separated. Concentration of the individual eluate fractions afforded the title compound (2.56 g, 51%) and unidentified by-products (0.15 g and 0.33 g). After recrystallization from benzene, the title compound melts at 180181C.

Infrared Spectral Band (KBr): 3250,

2990.1760.1680 cm ¹ .

The starting material 2- (bromomethyl) -4 (4H) -1,3-benzoxazinone (m.p. 106-107 ° C) was prepared in a manner similar to that described in Example 1, except that in the first step, bromoacetyl chloride is used as the reagent instead of chloroacetyl chloride.

Example 9

Preparation of N- [2- (Bromomethyl) -6,7-methylenedioxy-4 (3H) -quinazolinon-3-yl] -carbamic acid tert-butyl ester

The procedure described in Example 8 was followed except that 4.3 g of 2- (bromomethyl) -6,7- (methylenedioxy) -4 (4H) -3,1-benzoxazinone and 2.2 g of carbazolic acid were obtained. starting from tert-butyl ester. 1.0 g of the title compound are obtained; 179-180 ° C (after recrystallization from benzene).

Infrared Spectral Band (KBr): 3150,

2985,1750,1685,1275,1035 cm ¹ .

The starting material used is 2- (bromomethyl) 4

HU 209 237 Β

6,7-methylenedioxy-4 (4H) -3,1-benzoxazinone is prepared by reacting 6- (bromoacetylamino) piperonyl acid (6-amino-piperonyl acid with bromoacetyl chloride); 220-221 ° C) and acetic anhydride was refluxed for 1 hour, then the reaction mixture was evaporated and the residue was purified by chromatography on Kieselgel G 60 silica gel. Elution is carried out with dichloromethane. 2- (Bromomethyl) -6,7-methylenedioxy-4 (4H) -3,1-benzoxazinone was obtained in 95% yield; mp 140-141 ° C.

Infrared Spectral Band (KBr): 1760,

1295.1040 cm ¹ .

Example 10

Preparation of N- [2- (Bromomethyl) -6-methyl-4 (3H) -quinazolinon-3-yl] -carbamic acid tert-butyl ester 5 g of 2- (bromoacetylamino) -5-nitrobenzoic acid [A compound prepared by nitration of concentrated nitric acid with 2-bromoacetylamino) benzoic acid; 206-207 ° C (after recrystallization from dioxane)] and 50 ml of acetic anhydride are refluxed for 1 hour. The initial suspension forms a homogeneous solution upon boiling. The reaction mixture was cooled, the solvent was evaporated under reduced pressure and the solid residue was triturated with pentane, filtered and air dried.

A mixture of 2- (bromomethyl) -6-nitro-4 (4H) -3,1-benzoxazinone, 2.4 g of tert-butyl ester of carbazolic acid and 20 ml of benzene was stirred at room temperature for 1 hour. The suspension gradually thickens. The reaction mixture is then heated under reflux for 1 hour. The mixture forms a homogeneous solution during boiling, which forms a yellow precipitate at the end of boiling. The precipitate was filtered off, washed with ether and air-dried. 3.6 g (55%) of the title compound are obtained; mp 168-169 ° C. After recrystallization from isopropanol, the product melts at 170-171 ° C.

Infrared Spectral Band (KBr): 3185,

2990.1760, 1710, 1520, 1350 cm ^1st

Example 11

Preparation of 3-Amino-2- (bromomethyl) -4 (3H) -quinazolinone

The procedure described in Example 4 was repeated except that N- [2- (bromomethyl) -4 (3H) -quinazolinon-3-yl] -carbamic acid tert-butyl ester was used and ten times the amount of acetic acid was used. . 0.44 g (56%) of the title compound is obtained; mp 176-177 ° C. Infrared Spectral Band (KBr): 3310,

3280 (shoulder), 3210.1670 cm ^1st

Example 12

Preparation of 3-Amino-2- (bromomethyl) -6,7-methylenedioxy-4 (3H) quinazolinone

The procedure described in Example 4, except that N- [2- (bromomethyl) -6,7- (methylenedioxy) -4 (3H) -quinazolinon-3-yl] -carbamic acid tert-butyl ester was obtained. start with 10 times the amount of acetic acid. The title compound was obtained in 67% yield; mp 181-182 ° C.

Infrared Spectral Band (KBr): 3320,

3270, 3200 (shoulder), 1660.1275, 1035 cm ^1st

Example 13

Preparation of 3-Amino-2- (bromomethyl) -6-nitro-4 (3H) -quinazolinone

The procedure described in Example 4 was repeated except that N- [2- (bromomethyl) -6-nitro-4 (3H) -quinazolinon-3-yl] -carbamic acid tert-butyl ester was used. and seven times the amount of acetic acid. The title compound was obtained in 76% yield; mp 144-145 ° C. The product sample, after recrystallization from n-butanol, m.p. 151-152 ° C. Infrared Spectral Band (KBr): 3320,

3280 (shoulder), 3220, 1695, 1520, 1350 cm -1.

Example 14

Preparation of 2- (chloromethyl) -3- (3,5-dimethyl-4-pyrazolyl) -4 (3H) -quinazolinone

A mixture of 2.95-chloromethyl-4 (4H) -3,1-benzoxazinone (1.95 g), 4-amino-3,5-dimethylpyrazole (1.22 g) and dioxane (40 ml) was stirred at room temperature for 16 hours. The solvent was evaporated from the reaction mixture and the residue was purified by chromatography. Kieselgel G silica gel was used as the adsorbent and dichloromethane-acetone (7: 3) was used as eluent. 1.93 g (67%) of the title compound are obtained; mp 192 ° C.

Example 75

Preparation of 2- (chloromethyl) -6,7-methylenedioxy-3- (3,5-dimethyl-4-isoxazolyl) -4 (3H) -quinazolinone

12.8 g of 2- (chloromethyl) -6,7-methylenedioxy-4 (4H) 3,1-benzoxazinone, 6.6 g of 4-amino-3,5-dimethylisoxazole and 130 ml of The slurry of anhydrous benzene was stirred at room temperature for 4 hours and then refluxed for 4 hours. During boiling, the suspension first forms a homogeneous solution and then crystallizes out. The reaction mixture was cooled and the precipitated crystalline material was filtered off. The filtrate was evaporated and the resulting solid residue was combined with the crystalline material obtained above. The crude product obtained is purified by chromatography; Kieselgel G silica gel was used as adsorbent and dichloromethane as eluent. 11.6 g (65%) of the title compound are obtained; mp 225-227 ° C.

Example 76

Preparation of 2- (chloromethyl) -3- (3,5-dimethyl-4-isoxazolyl) -6-nitro4 (3H) -quinazolinone

A suspension of 6.4 g of 4-amino-3,5-dimethylisoxazole and 13.1 g of (2-chloromethyl) -6-nitro-4 (4H) -3,1-benzoxazinone in 100 ml of anhydrous benzene was heated at room temperature for half an hour. stirred. The slurry is first converted into a foam and then the ointment decomposes into a crystalline material. This mixture is refluxed for half an hour and then allowed to cool. The activated burgundy solid is filtered off, dried and recrystallized from benzene with activated carbon clarification. 14.4 g (75.2%) of the title compound are obtained; mp 207-208 ° C.

HU 209 237 Β

Example 17

- Preparation of (chloromethyl) -3- (3,5-dimethyl-4-pyrazolyl) -6-nitro4 (3H) -quinazolinone

A suspension of 2.40 g of 2- (chloromethyl) -6-nitro-4 (4H) -3,1-benzoxazinone and 1.11 g of 4-amino-3,5-dimethylpyrazole in 25 ml of benzene was added for 16 hours. stirring at room temperature. Meanwhile, a homogeneous solution is formed from the suspension and crystalline material begins to precipitate. The benzene was evaporated and the solid residue was triturated with dichloromethane, filtered, dried and recrystallized from n-butanol. 1.55 g (46%) of the title compound are obtained; mp 242 ° C.

Example 18

Preparation of 2- (chloromethyl) -3- (3,5-dimethyl-4-pyrazolyl) -6,7-methylenedioxy-4 (3H) -quinazolinone 3.85 g of 4-amino-3,5 A suspension of dimethylpyrazole and 7.89 g of 2-chloromethyl-6,7-methylenedioxy-4 (4H) -3,1-benzoxazinone in 150 ml of anhydrous dioxane is stirred for 4 hours at room temperature. Meanwhile, the suspension forms a homogeneous solution. The reaction mixture was allowed to stand overnight, the little solid was filtered off, and the filtrate was refluxed for 1 hour and the solvent was evaporated. The resulting solid residue was recrystallized from methanol. 7.5 g (68%) of the title compound are obtained; mp: 206-206 'C.

Example 19

Preparation of N- [2- (Chloromethyl) -4 (3H) -quinazolinon-3-yl] -carbamic acid ethyl ester

A mixture of 9.7 g of 2- (chloromethyl) -4 (4H) -3,1-benzoxazinone, 5.7 g of ethyl carboxylic acid and 80 ml of benzene was stirred at room temperature for 10 minutes, and then the mixture was removed to remove water. boil. The resulting solution was evaporated and the solid residue was triturated with a little ether. 7.4 g (54%) of the title compound are obtained; mp 148 ° C.

Example 20

Preparation of N- [2- (Bromomethyl) -4 (3H) -quinazolinon-3-yl] -carbamic acid ethyl ester

13.0 g of 2- (bromomethyl) -4 (4H) -3,1-benzoxazinone and

A solution of 6.2 g of the carboxylic acid ethyl ester in 50 ml of benzene is heated under reflux for 1 hour. The solution was evaporated and the residue was purified by chromatography. Kieselgel G, silica gel, 10: 1 dichloromethane-acetone (9.0 g, 51%) was used as adsorbent. 143 ° C (after recrystallization from ethanol).

Example 21

Preparation of N- [2- (Chloromethyl) -6-nitro-4 (3H) -quinazolinon-3-yl] -carbamic acid ethyl ester

A mixture of 2.4 g of 2- (chloromethyl) -6-nitro-4 (4H) -3,1-benzoxazinone, 1.14 g of ethyl carboxylic acid and 25 ml of benzene is stirred at room temperature. The initially homogeneous solution becomes a thick paste within a few minutes. The resulting suspension is refluxed and the solvent evaporated. The solid residue was purified by chromatography; Kieselgel G silica gel adsorbent, dichloromethane-acetone (10: 0.5 v / v) was used as the adsorbent. 2.16 g (66.4%) of the title compound are obtained; mp 146-147 ° C.

Example 22

Preparation of 3-Amino-2- (dichloromethyl) -4 (3H) -quinazolinone

To a mixture of 6.2 g of 2- (dichloromethyl) -4 (4H) -3,1-benzoxazinone and 30 ml of anhydrous methanol is added 1.8 ml of 98% pure hydrazine hydrate at room temperature. After stirring for 1 hour at room temperature, boron trifluoride diethyl etherate (0.1 ml) was added and the resulting mixture was refluxed for 1.5 hours. The reaction mixture was cooled, and the precipitated solid was filtered and washed with ethanol (2 x 5 mL) and diethyl ether. 5.2 g of the title compound are obtained; mp 117-120 'C.

Example 23

Preparation of 3-Amino-2- (bromomethyl) -4 (3H) -quinazolinone A solution of g-3-amino-2-methyl-4 (3H) -quinazolinone and 21.2 g of bromocyanide in 350 ml of ethanol for 5 hours. boil. The resulting hydrogen cyanide is neutralized in an aqueous base trap. After boiling for about 1 hour, a precipitate begins to form. After refluxing for 5 hours, the precipitate formed is filtered off hot and washed with cold ethanol. The title compound was obtained in 60% yield; mp 176-177 ° C.

Example 24

Preparation of 2- (chloromethyl) -3- (2,5-dimethyl-1-pyrrolyl) -4 (311) -quinazolinone g of 3-amino-2- (chloromethyl) -4 (3H) -quinazolinone and A mixture of 2.5 ml of hexanedione (1.5 ml) was stirred for 1.5 hours under an argon bath at 150 ° C. The excess 2,5-hexanedione is then evaporated under reduced pressure and the oily residue is crystallized by trituration with ether. The blue crystalline material was purified by chromatography; Kieselgel G silica gel was used as adsorbent and dichloromethane as eluent. 8.2 g (66.4%) of the title compound are obtained; 132-133 ° C.

Example 25

Preparation of 2- (bromomethyl) -3-furfurylideneimino-4 (3H) -quinazolinone

A solution of 3-amino-2- (bromomethyl) -4 (3H) -quinazolinone (2.5 g) in freshly distilled furfural (5 ml) in ethanol (20 ml) was heated to reflux for 2 hours and then cooled. The precipitated crystals are filtered off and washed twice with 5 ml of cold ethanol and then with diethyl ether. 2.3 g of the title compound are obtained; 197-200 'C (recrystallized from ethyl acetate).

Example 26 Preparation of (+) - 2- (1-Bromoethyl) -3- (furfurylideneimino) -4 (3H) quinazolinone g 3-amino-2- (1-bromoethyl) -4 (3H) -quinazolinone and

A solution of freshly distilled furfural in 30 ml of ethanol was refluxed for 1 hour and the reaction mixture was cooled. The precipitated crystalline material is filtered off and washed twice with 5 ml of cold ethanol and then with diethyl ether. 3.6 g of the title compound are obtained; mp 172-173 ° C.

Example 27

Preparation of 2- (dichloromethyl) -3-furfurylideneimino-4 (3H) -quinazolinone g of 3-amino-2- (1-bromoethyl) -4 (3H) -quinazolinone and 5 ml of freshly distilled furfural A solution of ethanol (30 ml) was heated to reflux for 1 hour and the reaction mixture was cooled. The precipitated crystalline material is filtered off and washed twice with 5 ml of cold ethanol and then with diethyl ether. 3.6 g of the title compound are obtained; mp 172-173 ° C.

Example 27

Preparation of 2- (dichloromethyl) -3-furfurylideneimino-4 (3H) -quinazolinone g of 3-amino-2- (dichloromethyl) -4 (3H) -quinazolinone and 10 ml of freshly distilled furfural 80 ml ethanol solution was refluxed for 6 hours and the reaction mixture was cooled. The precipitated crystalline material is filtered off and washed twice with 15 ml of cold ethanol and then with diethyl ether. 12 g of the title compound are obtained; 161-163 ° C (recrystallized from ethyl acetate).

Example 28

Preparation of N- [2- (Bromomethyl) -6,7-methylenedioxy-4 (3H) -quinazolinon-3-yl] -carbamic acid tert-butyl ester

To a suspension of 5.9 g of 2- (6-amino-piperonyloyl) -carboxylic acid tert-butyl ester and 2.2 g of sodium carbonate in 120 ml of anhydrous dioxane are added 3.3 g of bromoacetyl chloride under ice-cooling with stirring. so that dioxane does not freeze. The cooling bath was removed and the reaction mixture was stirred for 3 hours. After cooling again, 3.3 g of bromoacetyl chloride were added dropwise, the cooling bath was removed and stirring continued for 3 hours. The suspension obtained is evaporated under reduced pressure. To the residue was added dichloromethane (60 mL) and the dichloromethane solution was washed with water (3 x 20 mL). The organic phase is dried over magnesium sulfate, filtered and the filtrate is evaporated. The white crystalline residue is suspended in ether, filtered, washed with ether and finally air-dried. 5.8 g (73%) of the title compound are obtained; m.p. 190 'C.

Infrared Spectral Band (KBr): 3150,

2985, 1750, 1685, 1275, 1035 cm -1.

The 2- (6-aminopiperonyl) carbazonic acid tert-butyl ester (also known as 2- [2-amino-4,5-methylenedioxy) benzoyl] carbazolic acid tert-butyl ester was used as starting material. is prepared as follows:

A solution of 4.22 g of 2-nitro-4,5-methylenedioxybenzoic acid and 5 ml of thionyl chloride in 15 ml of dioxane is refluxed for 1 hour and the volatiles are evaporated. The residue was dissolved in dichloromethane (10 ml) and this solution was treated with 2.64 g of tert-butyl ester of carbazide and

Add 3.1 ml of triethylamine in 10 ml of dichloromethane at -5 ° C. After addition of the acid chloride solution, which takes about 1.5 hours, the reaction mixture was stirred for half an hour at room temperature, washed with water (3 x 10 ml), dried over magnesium sulfate, filtered and the solvent was evaporated from the filtrate. The solid residue was triturated with benzene (20 mL) and the solid filtered. 5.6 g (82%) of 2- [2-nitro-4,5-methylenedioxy-benzoyl] carboxylic acid tert-butyl ester are obtained; mp 143 'C.

To a solution of the above compound (g) in ethanol (1000 ml) was added 5 g of 10% palladium on charcoal and the reaction mixture was stirred under hydrogen atmosphere until hydrogen consumption ceased. The catalyst was filtered off and the filtrate was evaporated. The residue was triturated with ether, filtered and the solid dried. 2- [2-Amino-4,5-methylenedioxy-benzoyl] carbazolic acid tert-butyl ester (50 g, 80%) is obtained; mp: 182 'C.

Example 29

Preparation of 3-Amino-2- (chloromethyl) -6,7-methylenedioxy-4 (3H) quinazolinone g 2- [2- (chloroacetylamino) -4,5- (methylenedioxy) ) Benzoyl] -carbazidic acid tert-butyl ester is melted at 180-190 ° C. The material foams, foams, and then solidifies. The solid was cooled, pulverized in ethanol with ethanol, filtered, and recrystallized from 50-60 volumes of butanol. 3 g (87.8%) of the title compound are obtained; mp: 208 'C.

The 2- (2- (chloroacetylamino) -4,5-methylenedioxy-benzoyl) -carboxylic acid tert-butyl ester used as starting material was prepared as follows:

To a suspension of 2- [2-amino-4,5-methylenedioxy-benzoyl] -carboxylic acid tert-butyl ester (g) in sodium carbonate (29.55 g) in dry dioxane (1200 ml) was added chloroform (24.2 ml) under ice-cooling. -acetyl chloride is added dropwise at such a rate that the mixture does not freeze. It takes about 45 minutes to add the reagent. After the addition of the reagent, the mixture was stirred at room temperature for one hour and allowed to stand overnight. The precipitated solid was filtered off, washed with dioxane and water and dried.

2- [2- (Chloroacetylamino) -4,5-methylenedioxy-benzoyl] -carbazolic acid tert-butyl ester (35.5 g, 37.5%) is obtained; mp: 187 'C. An additional 20.6 g (21.8%) of the same compound can be isolated by evaporation of the organic filtrate and purification of the residue.

Example 30

Preparation of 2- (fluoromethyl) -3- (2,5-dimethyl-1-pyrrolyl) -4 (3H) -quinazolinone

A mixture of 15.35 g of 2- (chloromethyl) -3- (2,5-dimethyl-pyrrolyl) -4 (3H) -quinazolinone, 9.2 g of potassium fluoride and 15 ml of ethylene glycol was heated at 165 ° C for 2 hours. stir in a bath. The mixture was cooled, transferred to a shaking funnel with water (100 mL) and dichloromethane (30 mL), shaken vigorously, and the layers separated. The aqueous layer was extracted with dichloromethane (2 x 30 mL). The organic layers were combined, dried over magnesium sulfate,

Filter and evaporate the filtrate. The residue was purified by chromatography; Kieselgel G silica gel was used as the adsorbent and dichloromethane-hexane (7: 3) was used as eluent. 4.5 g (31.5%) of the title compound are obtained; 89-90 ° C (recrystallized from a mixture of benzene and pentane).

Example 31

Preparation of 2- (fluoromethyl) -6,7-methylenedioxy-3- (3,5-dimethyl-4-isoxazolyl) -4 (3H) -quinazolinone

6.7 g of 2- (chloromethyl) -6,7-methylenedioxy-3- (3,5-dimethyl-4-isoxazolyl) -4 (3H) -quinazolinone, 3.8 g of potassium fluoride and of ethylene glycol was stirred in a 165 'Cos bath for 2 hours. The mixture was cooled, suspended in water (100 mL) and extracted with dichloromethane (2 x 50 mL). The organic layers were combined, washed with water (2 x 30 mL), dried over magnesium sulfate, filtered and the filtrate was evaporated. The residue was recrystallized from ethanol (80 mL). 4.03 g (63.6%) of the title compound are obtained; mp 192194 'C.

Example 32

Preparation of 2- (fluoromethyl) -3- (3,5-dimethyl-4-pyrazolyl) -4 (3H) quinazolinone

The procedure described in Example 30 was followed except that it was started from 2- (chloromethyl) -3- (3,5-dimethyl-4-pyrazolyl) -4 (3H) -quinazolinone. The title compound was obtained in 35.5% yield; m.p. 187 'C (recrystallized from ethyl acetate).

Example 33

Preparation of 3-amino-2- (thiocyanato-methyl) -4 (3H) -quinazolinone g-3-amino-2- (bromomethyl) -4 (3H) -quinazolinone,

A mixture of 2.9 g of potassium rhodanide and 40 ml of ethanol is refluxed for half an hour. The solution was filtered hot and the filtrate cooled. The crystals which formed during cooling were filtered off and washed with ethanol (5 ml) and diethyl ether (5 ml). 3.9 g of the title compound are obtained; 152-155 ° C (recrystallized from ethanol).

Example 34

Preparation of N- [2- (Dichloromethyl) -4 (3H) -quinazolinon-3-yl] -N '- (3-chlorophenyl) urea

To a solution of 3-amino-2- (dichloromethyl) -4 (3H) -quinazolinone (7.5 g) in dimethylformamide (5 ml) was added dropwise 3 ml of 3-chlorophenyl isocyanate at room temperature. The reaction mixture was stirred at room temperature for 6 hours and then poured into ice water (200 g). The precipitated crystals were filtered off and washed with water (2 x 10 mL) followed by cold acetic acid. 7.5 g of the title compound are obtained; m.p. 247-249 'C (recrystallized from acetic acid).

Example 35

Preparation of 2- (Morpholinomethyl) -3-amino-6,7-methylenedioxy-4 (3H) -quinazolinone g 2- (chloromethyl) -3-amino-6,7-methylenedioxy A mixture of 4 (3H) -quinazolinone and 250 ml of morpholine was stirred for 3 hours at room temperature. The precipitated crystalline material is filtered off, washed with water and dried. 14.7 g (72%) of the title compound are obtained; mp 226 'C (recrystallized from butanol).

Example 36

Preparation of N- [2- (Morpholinomethyl) -6-nitro-4 (3H) -quinazolinon-3-yl] -carbamic acid ethyl ester

A solution of 20.3 g of ethyl N- [2- (chloromethyl) -6-nitro-4 (3H) -quinazolinon-3-yl] -carbamic acid in 50 ml of dichloromethane at 0 ° C. Morpholine (5 ml) was added. The cooling bath was removed and the mixture was stirred for 1 hour. The precipitated solid is filtered off, washed with water, dried and finally recrystallized from 60 ml of ethanol. 22.0 g (92.5%) of the title compound are obtained; mp: 148'C.

Example 37

Preparation of N- [2- (Benzylthiomethyl) -4 (3H) -quinazolinon-3-yl] -carbamic acid ethyl ester

Sodium salt of benzyl mercaptan (1.41 ml) was prepared in sodium hydroxide in dioxane, and 9.3 g of ethyl N- [2- (morpholinomethyl) -4 (3H) -quinazolinon-3-yl] -carbamic acid were added to the resulting suspension. After stirring for 2 hours at room temperature, the volatiles were evaporated. The solid residue was washed with water and dried. Yield: 9.3 g (76%); mp 128-129 ° C.

Example 38

Preparation of N- [2- (Morpholinomethyl) -6- (methanesulfonylamino) -4 (3H) -quinazolinon-3-yl] -carbamic acid ethyl ester

To a mixture of 9.8 g of N- [2- (morpholinomethyl) -6-amino-4 (3H) -quinazolinon-3-yl] -carbamic acid ethyl acetate in 80 ml of anhydrous pyridine at 2.4 ° C of methanesulfonyl chloride was added. The cooling bath was removed and the reaction mixture was stirred for 1 hour. The volatiles were evaporated, the solid residue was triturated with water, and the resulting crystalline material was filtered off and dried. The crude product (11.6 g) was recrystallized from 100 ml of n-butanol. 10.0 g (83%) of the title compound are obtained; mp: 213 'C.

Example 39

Preparation of Emulsifiable Concentrate 2 parts by weight of 2-bromomethyl-3-amino-4 (3H) -quinazolinone are mixed with 70 parts by weight of xylene and a homogeneous solution is prepared with gentle heating. To the solution was added 5 parts by weight of sodium dioctylsulfosuccinate and 3 parts by weight of polyoxyethylene sorbitan monolaurate and the resulting mixture was filtered. An emulsifiable concentrate containing 20% by weight of the active ingredient is obtained, which can be formulated in water-diluting emulsions for spraying.

Example 40

Preparation of Dusts 3 parts by weight of 3-amino-2- (bromomethyl) -6-nitro4 (3H) -quinazolinone are homogenized in a Z-arm blender with 30 parts by weight of kaolin. For a homogeneous mixture

While stirring, 2 parts by weight of sulfite waste water powder are added. The powder mixture is homogenized, then ground in a fine mill to a grain size of 20-30 micrometres, and finally homogenized with 58 parts by weight of fine talc powder. A powder containing 10% by weight of active ingredient is obtained which can be used directly in agriculture for protection against fungal pests.

Example 41

Preparation of wettable powder formulation 50 parts of 2- (1-chloroethyl) -3-amino-4 (3H) -quinazolinone are mixed with 40 parts by weight of bentonite, 5 parts by weight of cresol-formaldehyde condensate dispersant and 5 parts by weight of fatty alcohol sulphate powder. micrometer to average particle size. The resulting meal is homogenized. A wettable powder formulation containing 50% by weight of the active ingredient is obtained which can be formulated as a stable suspension in aqueous dilution for spray application.

Example 42

Examination of the fungicidal activity of the preparations The following active substances were included in the studies:

1: 2- (Bromomethyl) -3-amino-4 (3H) -quinazolinone 2: 2- (Trifluoromethyl) -3-amino-4 (3H) -quinazolinone 3: 2- (1-Bromoethyl) ) -3-Amino-4 (3H) -quinazolinone 4: 2- (dichloromethyl) -3-amino-4 (3H) -quinazolinone 5: 2- (chloromethyl) -3- (furfurylideneamino) -4 (3H) -quinazolinone

6: 2- (1-Bromoethyl) -3- (furfurylideneamino) -4 (3H) -quinazolinone

7: 2- (Isothiocyanato-methyl) -3-amino-4 (3H) -quinazolinone The activity of the preparations was tested against the following fungal pests:

AS: Venturia inaequalis

GDM: Plasmopara viticola

PB: Botrytis cinerea

RB: Pyricularia oryzae

SBC: Cerocospora beticola

TLB: Photophthora infestans

WLR: Puccinia recondita

WPM: Erysiphe graminis

PSDCHE: Pseudeocercosporella herpotrichoides PYTHUL: Pythium ultimum RHIZSO: Rhizoctonia solani FUSOXC: Fusarium oxysporum

The fungicidal activity of the formulations (inhibition of infection or mycelial development) was characterized by a number scale from 0 to 9, where each figure was as follows:

0: 0% inhibition

1: 1-14% inhibition

2: 15-29% inhibition

3: 30-44% inhibition

4: 45-59% inhibition

5: 60-74% inhibition

6: 75-89% inhibition

7: 90-95% inhibition

8: 96-99% inhibition

9: 100% inhibition

In vivo studies were performed as follows:

Spray broths containing 400, 100 and 25 ppm of active compounds were sprayed onto the leaves of plants. The plants were allowed to dry for 1-2 hours after spraying and the plants were infected with a spore suspension of the fungus to be tested. The plants were then placed in favorable conditions for the development of infection and kept under such conditions until evaluation. The degree of infection control was evaluated after 5-14 days, depending on the environmental conditions and the species of fungal pest. The observed results are reported in Table I below.

In vivo studies were performed as follows:

The wells of the culture plates containing the fungal species to be examined were filled into the wells of the cell culture plates. Acetone solutions containing 25, 10 and 1 ppm of the active compounds were prepared and aliquots of the solutions were added to the wells. Plates were incubated for 3-5 days and growth inhibition was evaluated. The observed results are shown in Table II. in Table.

Table I

Serial number of compound Degree of infection control DIG GDM PB SBC WLR TLB 400 100 25 400 100 25 400 100 25 400 100 25 400 100 25 400 100 25 First 9 8 4 9 9 7 7 8 0 9 5 0 8 6 0 2 0 0 Second 4 0 0 4 4 3 4 0 0 0 0 0 0 0 0 7 0 0 Third 8 8 0 8 6 5 7 0 2 0 0 0 5 6 0 6 0 0 4th 0 0 0 2 2 0 7 2 0 3 0 0 0 0 0 0 0 0 5th 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 6th 4 0 0 2 0 0 4 0 0 0 0 0 0 0 0 0 0 0 7th 7 4 6 5 2 2 8 2 0 5 0 0 0 0 0 0 0 0

HU 209 237 Β

II. spreadsheet

Serial number of compound Degree of inhibition of growth PSDCHE PYTHUt RHIZSO FUSOXC 25 10 1 25 10 1 25 10 1 25 10 1 First 9 0 0 9 9 0 0 0 0 9 0 0 Second 0 0 0 0 0 0 5 5 0 0 0 0 Third 0 0 0 7 3 0 3 0 0 0 0 0 4th 0 0 0 0 0 0 5 0 0 0 0 0 7th 0 0 0 5 0 0 3 0 0 0 0 0

The systemic activity of 2- (bromomethyl) -3-amino-4 (3H) -quinazolinone (Compound 1), which proved to be extremely effective in screening assays, was investigated by the following experiments:

Experiment A:

AIII. The formulations containing the active compounds of Table 1 are sprayed transversely to the upper leaf surface of the test plants in a 1 cm wide band. Plants 25 were placed under a waterproof tent. After 24 hours, the active ingredient was allowed to be absorbed and spread by the plants, and the plants were infected with a spore suspension of Botrytis cinerea and maintained under favorable conditions for the development of infection. After 4 days, the degree of infection was determined in the treated band, in the proximal region from the treated band to the apical (distal) region of the treated band. The results, which are the average of three experiments, are shown in Table III. See Table 35.

III. spreadsheet

agent quantity (Ppm) Degree of infection control Proximal range In the treated lane In the distal range 1000 6.3 9.0 7.6 750 2.6 8.0 6.3 500 1.7 6.7 6.7 250 0.0 0.0 1.0

Experiment B:

The active substance to be examined is shown in Table IV. in the amounts given in Table II. After 3 days, the rice plants were infected with a spore suspension of Pyricularia 55 oryzae, and the infected plants were maintained under favorable conditions for the development of infection. The results were evaluated after 10 days and shown in Table IV. in Table. 60

ARC. spreadsheet

Ingredient Quantity kg / ha Degree of infection control 10 6.7 5 0 2.5 2.3

The results of both studies demonstrate systemic activity of the compound.

Laboratory tests:

Examination of spore germination inhibition by Helminthosporium sativum fungal spores:

The experiments were performed on a spray of the compound of the invention in WP, FW, EC forms at a dilution of 10, 100, 1000 mg / ml using a double control. aqueous, k _f = a dummy "form" measures the effect of forming agents.

0.1 ml of a spore suspension (distilled from an aqueous suspension) was added to a diluted slide in a sterile petri dish and incubated for 1 day at room temperature and the number of germinated and non-germinated spores counted under a microscope. Rating based on the average of four repetitions k os ₀ is 100% germination was calculated taking the extent of the% of inhibition of germination.

Table 1

Example Form * 0 ppm 10 ppm 100 ppm 1000 ppm 12 41st (WP) 5% 30% 80% 100% 12 39th (EC) 8% 65% 98% 100% 13 39th 12% 68% 100% 100% 15 41st 4% 85% 100% 100% 16 39th 6% 92% 100% 100% 22 39th 8% 46% 78% 90% 30 39th 10% 68% 96% 96% 33 41st 6% 45% 82% 100%

* kf

HU 209 237 Β

Fungal Colon Growth Inhibition Test:

Phytopathogenic fungi and bacteria examined:

As: Aspergilus niger

Bo: Botrytis cinerea 5

Mu: Mucor globosum Ni: Nigrospora orizae Ph: Phythophtora inf.

Ve: Venturia inequalis

Fu: Fusarium oxysporum 10

Er: Tsar Ervinia.

Ag: Agrobact. sp.

An agar sterile medium for the growth of fungi and bacteria is prepared and then sprayed in a sterile inoculum with the formulations of the active compounds of the invention and sprayed with a 0.1% and 1% spray on a fine spray device. After drying, the medium is inoculated with the stock culture, after incubation evaluated against the non-sprayed active compound and

The average of 4 fold replicates is considered as 50% partial (R), above 80% total inhibition (T).

Table 2

Example Form Dig Bo Mu Ni Ph ve Grass Er Branch 12 (41) 0.1% T T T T T T T R T 1.0% T T T T T T T T T 13 (39) 1.0% T R R T R R - - - 16 (39) 0.1% T T R T T R R - R 1.0% T T R T T T T - R 30 (39) 0.1% T T T T - R T R R 32 (41) 1.0% T R R T T T R - T 38 (41) 1.0% T T T T R R T - -

PATENT CLAIMS

Claims (5)

CLAIMS 1. A fungicidal composition comprising up to 95% by weight as active ingredient of a 4 (3H) -quinazolinone derivative of the formula (I) or an agriculturally useful salt thereof, wherein R ¹ is hydrogen, nitro, amino or C 1-4 alkylsulfonylamino, R ² is hydrogen, or R ¹ and R ^{2 taken} together are C 1 -C 2 alkylenedioxy groups bonded to two adjacent carbon atoms of the benzene ring, Z ¹ is hydrogen, halogen or C 1-4 alkyl, Z is halogen, phenyl (C 1-4 alkyl) thio, thiocyanato or morpholino, and W is amino, (C 1 -C 8) alkoxy-carbonylamino, furfurylideneamino, phenyl-phenylcarbonylamino optionally substituted on the phenyl moiety or one or two (C 1 -C 4) alkyl optionally substituted 1-pyrrolyl, 4-pyrazolyl or 4-isoxazolyl, together with solid and / or liquid, mineral and / or organic carriers, and optionally other agriculturally useful excipients, preferably ionic and / or nonionic surfactants. Composition according to claim 1, characterized in that it contains at least 0.001% by weight of the active ingredient of the formula (I). Composition according to claim 1 or 2, characterized in that it contains an active ingredient of the formula I in which W represents an amino or furfurylideneimino group and the group -CHZ'Z contains at least one halogen atom. . 4. Composition according to any one of claims 1 to 3, characterized in that it contains 2- (bromomethyl) -3-amino-4 (3H) -quinazolinone as active ingredient. 5. A process for the preparation of 4 (3H) -quinazolinone derivatives of the formula I and their agriculturally useful salts R * is hydrogen, nitro, amino or C 1-4 alkylsulfonylamino, R ² is hydrogen, or R ¹ and R ^{2 taken} together are C 1 -C 2 alkylenedioxy groups bonded to two adjacent carbon atoms of the benzene ring, Z ¹ is hydrogen, halogen or C 1-4 alkyl, Z is halogen, phenyl (C 1-4 alkyl) thio, thiocyanato, or morpholino, and W is amino, (C 1 -C 8) alkoxycarbonylamino-furfurylideneimino, phenyl-phenylcarbonylamino optionally substituted on the phenyl moiety or 1-pyrrolyl optionally substituted with one or two C 1 -C 4 alkyl groups -, 4-pyrazolyl or 4-isoxazolyl group, with the proviso that when R ^1, R ² and Z ¹ is hydrogen and Z is fluorine, or when R ¹ and R ² is hydrogen, ^Z1 is methyl, and Z is chlorine, W is other than amino, characterized in that HU 209 237 Β a) for compounds of formula (I) wherein R ^1, R ^2, Z ¹ and Z are as stated above and W is other than furanyl imino group stated above, (II), benzoxazinone derivative With an amino compound of formula (V) - wherein R ¹ , R ² , Z ¹ and Z are as defined herein, W 'is as defined for W with the exception of furfurylideneimino, and the resulting a compound of formula (I) a) Z is halogen, optionally converted to a compound of formula I wherein Z is other than halogen and / or ₂ ) W is (C 1 -C 8) alkoxy-carbonylamino, if desired Converting W into an amino-containing compound by acidic or thermal treatment; obsession preparing b) a compound of formula (I) wherein R ^1, R ² and W have the meanings stated above and Z ¹ is hydrogen and Z is bromo, (VI), 2-methyl-quinazolinone derivative of the formula: - wherein R ¹ , R ² and W are as defined above - is reacted with cyanogen bromide; obsession c) for the preparation of compounds wherein R ¹ , R ² , Z ¹ and Z are as defined in formula I and W is a furfurylideneimino group or W is optionally substituted with one or two C 1 -C 4 alkyl groups; is a pyrrolyl group, wherein W is an amino group of a compound of formula I wherein z is furfural, or c ₂ ) a 1,4-butanedione derivative of formula XII wherein R ³ and R ^{4 are} hydrogen or C 1 -C 4 alkyl; and the resulting compound of formula (I) wherein Z is halogen is optionally converted to a compound of formula (I) other than halogen; obsession d) for the preparation of compounds wherein R ¹ , R ² , Z ¹ and Z are as defined in formula I and W is amino or C 1-8 alkoxy) carbonylamino, dj) reacting a 2- (2-aminobenzoyl) carbazolic acid ester derivative of formula (VIII) with an alpha-haloalkanoic acid carboxylic acid halide of formula (VIII), or d ₂ ) 2- [2- (acylamino) of formula (IX) the benzoyl] -carbazidic acid ester derivative is thermally cyclized; in formulas VII to IX, R ¹ , R ² and Z ¹ are the halogen atoms Z 'and Hal and Alk are C 1 -C 8 alkyl groups, and optionally converting the resulting compound to a compound of formula (I) other than halogen and / or converting the resulting compound to an acidic or thermal reaction of the compound of formula (I) or W represents an amino group; e) converting R ¹ , Z and / or W present in a compound of formula I into another R ¹ , Z and / or W in a known manner; and, if desired, converting the compound obtained by any of the preceding processes into an acid addition salt by treatment with an appropriate acid.