NL8200338A - Antiparasitic 2-benzimidazolylcarbanates prepn. - from substd. 1,2-diamino-benzenes and isothioureas - Google Patents

Abstract

2-Benzimidazolyl carbamates of formula (I): (where R is 1-4C alkyl; R1 is -SO2R2, -SOR2, -SCN, -SR2, -OR5 or M'(CH2)nMR7; M and M1 are O, S, SO or SO2; R7 is 1-4C alkyl or aryl; n = 1-4; R2 is 1-4C alkyl, 3-7C cycloalkyl, 3-6C alkenyl or alkynyl; aralkyl or aryl; R5 is lower alkenyl, lower alkynyl or aralkyl) possess broad-spectrum anthelmintic activity. They are also active as fungicides for plant treatment.

Description

tm ~ - N.0. 30576 1

A method of preparing or manufacturing anthelmintically active pharmaceutical preparations and fungicidal preparations and a method of preparing anthelmintic and fungicidal 2-alkoxy-carbonylamino-benzimidazole derivatives.

The present invention relates to a process for the preparation or manufacture of anthelmintically active pharmaceutical preparations, in which a 2-alkoxycarbonylamino-benzimidazole derivative is brought into a form suitable for therapeutic use, and for the preparation of fungicidal preparations, in which a 2- alkoxycarbonylamino-benzimidazole derivative mixes with a carrier.

Such a method is known. For example, U.S. Pat. No. 3,574,845 discloses anthelmintically active 2-alkoxycarbonyl-aminobenzimidazole derivatives which contain in the benzene core one or two alkyl, alkoxy, trifluoromethyl, amino, hydroxy, nitro, alkyl mercapto, alkylamino, may contain dialkylamino, cyano, acylamino, carboxyl, carbalkoxy, N-alkylcarbamoyl or NN-dialkylcarbamoyl groups, or halogen atoms as substituents. Israeli Patent 27006 corresponding to this U.S. Patent shows that within the large group of imidazoyl-2-carbamic acid esters described therein, the 5 (6) -n-butylimidazolyl-carbamic acid methyl ester (Parbendazole) exhibits the best activity, while 5 (6) alkoxy compounds also exhibit good activity, although the methoxy compound has less activity than the butoxy and propoxy compounds. Furthermore, U.S. Pat. No. 3,010,968 discloses a fungicidal activity of 2-alkoxycarbonyl-aminobenzimidazole derivatives, which contain in the benzene core 1, 2 or 3 halogen atoms, alkyl and / or alkoxy groups and additionally a chlorine atom or a nitro, methyl or ethyl group as substituents may contain 25.

It has now been found that the new compounds of formula I of the formula sheet and salts thereof, in which formula R represents an alkyl group having 1 to 4 carbon atoms, R have a residue -SR 2 in position 5 (6) or -R represents where R represents an alkenyl, alkynyl-30 or aralkyl radical exhibit excellent anthelmintic and fungicidal activity.

The alkyl groups of 1-4 carbon atoms include straight or branched chain alkyl groups, therefore primary, secondary and 8200338

a

2 tertiary alkyl groups. Typical examples of these alkyl groups are, for example, methyl, ethyl, n.propyl, isopropyl, n.butyl, isobutyl, tert.butyl, n.amyl, n.hexyl groups and the like.

The term "alkenyl group" denotes an unsaturated hydrocarbon radical having 5-6 carbon atoms and one double bond between two carbon atoms, provided that the double bond cannot be present on the α-carbon atoms. Typical examples of the alkenyl groups are, for example, the 2-propenyl, 2-butenyl, 3-butenyl groups and the like. The term "alkynyl group" denotes an unsaturated hydrocarbon radical having 3-6 carbon atoms and one triple bond between two carbon atoms, provided that also the triple bond cannot be present on the α-carbon atom. Typical examples of alkynyl groups are, for example, 2-propynyl, 2-butynyl, 3-butynyl groups and the like. An alkenyl or alkynyl-15 group of the radical R may be optionally substituted by one or more halogen atoms. The term "halogen atom" designates an iodine, bromine, chlorine or fluorine atom. The term "aralkyl group" refers to an alkyl group substituted by an aryl group, such as, for example, the benzyl or phenethyl group. They may optionally be substituted by one or more halogen atoms, alkyl and / or alkoxy groups.

The compounds of the invention and the non-toxic salts thereof, which are formed with pharmaceutically acceptable inorganic or or organic acids bases, have a broad spectrum activity against mammalian and human parasites, ie both adult and immature parasitic forms, such as, for example, of genera Trichostronglylus, Haemonchus,

Ostertagia, Cooperia, Nematodirus and Stronglyoides and more particularly against, for example, Nematospiroides dubius, Hymenolepis 30 nana, Syphacia obvelata and / or Aspiculuria tetraptera. In particular, the compounds appear to have high activity against various helminth infections of the intestinal tract of economically important animals, which is associated with low systemic toxicity of the host animal.

The compounds of the invention are also useful as fungicides, in particular as systemic fungicides for controlling fungal diseases in plants, which are of economic interest.

8200338 "3

The anthelmintic activity of the compounds of formula 1 and their salts can be determined as follows.

Four young male Swiss-Webster mice (16-20 g) are artificially infected with 200 larvae of Mematospiroides dubius 5 and Hymenolepis nana, as well as naturally infected with 15-40 larvae of Syphacia. obvelata and Aspiculuris tetraptera. The drug is administered in a commercially available rat / mouse diet at the indicated doses from day 1 to day 18. Infection is accomplished on day 0. The animals are sacrificed on day 18 and the parasites remaining in the entire small intestine, the cecum and the colon are counted and classified by species. The mean number of each parasite species in each treated group is compared to the mean number left in the control group. This equation is expressed as a percent reduction compared to the parasites in the control group.

The following table lists the values found for compounds of formula 1 along with those of the corresponding 5 (6) -n.-butyl compound (Parbendazole).

20 R1 Dose Nd Hn So At _ (ppm) _ _ _ HCHC-CH2-S- 250 100 0 100 100 125 98 0 100 100 62.5 63 0 98 46 25 31 0 0 68 0 HCHC-CH2-0- 125 89 85 100 100 62 70 0 100 100 C1-CH = CH-CH2-0- 125 100 0 100 100 62 84 0 100 100 nO, Hq 30 (parbendazole) 500 .100 100 100 100 250 100 69 100 100 125 59 0 100 100 62.5 0 0 100 0

Nd = Nematospiroides dubius So = Syphacia obvelata 35 Hn = Hymenolepis nana At = Aspiculuris tetraptera 8200338 4

According to the invention, in the method defined in the first paragraph of this description, an active ingredient is used

compound of formula 1 or a salt thereof, in which formula R

an alkyl group having 1-4 carbon atoms and R represents a -OR or -SR moiety located at 2 2 2 5 position 5 (6), wherein R represents an alkenyl, alkynyl or aralkyl moiety.

The term "non-toxic salts" as used herein. of the invention relates to pharmaceutically acceptable salts of the compounds of the invention which do not have an adverse effect on the fungicidal or anthelmintic properties of the base compound, such as the salts commonly used in the present field. These non-toxic salts include, for example, salts of inorganic acids, such as, for example, sulfuric acid, sulfonic acid, sulfamic acid, nitric acid, phosphoric acid, hydrochloric acid and the like, and salts of organic acids, such as, for example, acetic acid, citric acid, lactic acid, palmitic acid, tartaric acid , succinic acid, maleic acid, benzoic acid and the like.

The compositions are prepared in known manner, and may contain conventional auxiliaries and excipients as anti-fungal agents in plants.

The helminth-active pharmaceutical preparations may be mixtures of animal feeds or animal feed components with the active substance. It is also possible to prepare or manufacture other preparations for oral administration, such as filled gelatin capsules, tablets, pills, suspensions and the like. In general, the active substance is mixed with a solid or liquid carrier. Examples of solid carriers are corn starch, terra alba, lactose, sucrose, calcium phosphate, gelatin, stearic acid, agar and pectin. Examples of suitable liquid carriers are arachis oil, sesame oil and water.

The invention also relates to a process for the preparation of 2-alkoxycarbonylamino-benzimidazole derivatives with anthelmintic and fungicidal activity, which are suitable for use in the above-mentioned process for the preparation of pharmaceutical and fungicidal preparations, characterized in that compounds of the formula I are and salts thereof, in which formula R represents an alkyl group of 1-4 carbon atoms and R represents a group in position 5 (6) 8200338 5 2 2 2 -SR or -OR, wherein R represents an alkenyl, alkynyl- or aralkyl residue, prepared in a manner known for the synthesis of analogous compounds.

In general, the compounds of the invention can be prepared from benzene starting materials having nitro and amino or acylamino (eg acetamido) substituents at adjacent positions of the benzene core (eg positions 1 and 2) and 1 the desired moiety R (or a radical which can be reacted to form the desired radical R) in position 4 or 5 of the benzene core (i.e. in the position which later in the benzimidazole compound to be prepared is position 5 or 5). Will be 6). The nitro group is reduced to an amino group to obtain a benzene derivative with amino groups in positions 1 and 2.

The diamino compound is then reacted with a 1,3-bis-15 (alkoxycarbonyl) S-alkylisothiourea to yield the corresponding benzimidazole 2-carbamate derivative substituted in position 5 (6).

The functional residue in position 4 or 5 of the benzene used as starting material can be, for example, the thiocyanato group 20, which can be converted into the residue 2 -SR according to known reactions.

A synthesis which may serve to illustrate these steps is illustrated by the reaction scheme of Figure 2, wherein R has the above meaning.

A suitable starting material for the synthesis of the figure is the 1-acetamido 2-nitro 4-thiocyanatobenzene (of the formula 2) which can be prepared according to the method of F. Challenger and A.T. Peters, J. Chem. Soc., 1364 (1928). Other starting materials are, for example, 1-amino 2-nitro 4-thiocyanatobenzene, 1-acetamido 4-hydroxy 2-nitrobenzene and 1-amino 4-hydroxy 2-nitrobenzene.

The conversion of the acylamino group -NHAC of the compound of formula 2, for example an acetamido group, into an amino group, as explained for example by reaction step IV, can be carried out by the compound of formula 2 with a strong acid, such as hydrochloric acid or treat a strong base such as sodium hydroxide, potassium hydroxide, potassium carbonate or sodium carbonate in aqueous methanol for about 1/4 to about 24 hours at a temperature from about 20 ° C to about 100 ° C.

8200338 6

The reduction of the nitro group of the compound of formula 4 to an arano group, as illustrated by reaction step VI, can be carried out by various techniques. For example, the nitro group can be catalytically reduced using hydrogen in the presence of a palladium / charcoal catalyst. This conversion is performed in an inert solvent, such as methanol, over a period of about 1 to about 2 hours at a temperature of about 0 ° C-35 ° C and generally at about room temperature. Other suitable inert solvents are ethyl acetate, acetic acid and ethanol.

According to another suitable reduction technique, the nitro compound is treated with iron powder and ferrous salt, such as ferrous sulfate or ferrous chloride, in aqueous methanol, the mixture being refluxed under neutral conditions for about 1-6 hours. Other suitable reaction mediums are acetic acid and concentrated hydrochloric acid, while other suitable metals can also be used, such as zinc.

According to another reduction technique, the compounds of formula 4 are treated with stannous chloride in concentrated hydrochloric acid at a temperature within the range of about -20 ° C to about + 100 ° C, generally at room temperature, with a reaction period of about 1 to about 6 hours is applied. An excess of stannous chloride should be used as the reactant, generally about 5 parts by weight per part by weight of the starting compound.

The reduction can also be carried out with sodium dithionite (sodium hydrosulfite) in alkaline aqueous methanol by refluxing for 10 minutes to 6 hours.

The diamino compounds illustrated by formula 5 are converted to the corresponding benzimidazole 2-carbamate compounds according to reaction stage VII by the diamino compound with a 1,3-bis (alkoxycarbonyl) S-alkylisothiourea, for example 1,3-bis (methoxy-carbonyl) S-methylisothiourea or 1,3- bis (ethoxycarbonyl) S-methyl isothiourea in an aqueous alcoholic medium, for example aqueous methanol or aqueous ethanol, at a temperature within the range of about room temperature to the temperature, the reaction medium being refluxed, with a reaction time of about one to about 6 hours is used. The reaction medium is preferably acidified to a pH of about 8200335 about 4-6 with, for example, a sufficient amount of i (e.g. 1-2 moles) acetic acid. About 1-2 moles, generally about 1.1 moles, of the isothiourea reaction component are used per mole of the diamino compound of formula 5.

The conversion of the thiocyanato group of the starting material 1-acetamidp 2-nitro 4-thiocyanatobenzene into a group 2 -SR simultaneously with the conversion of the acetamido group m an amino group, as indicated by reaction step III, can be carried out by the thiocyanato compound ( for example, treating the compound of formula 2) with an R-halide, in dimethylformamide or an alcoholic medium, such as methanol or ethanol, in the presence of a base, such as potassium hydroxide, sodium hydroxide, potassium carbonate or sodium carbonate. The conversion is carried out at a temperature from about 10 ° C to about 50 ° C, generally at about room temperature, over a period of about 1/4 to about 12 hours, with a major molar ratio of the major reactants is used. The conversion is preferably carried out in isopropanol or dimethylformamide. Optionally, the thiocyanato group can be converted to the -SR group without changing the acetamido group, as will be explained to the. by reaction step I by treating the starting material 1-acetamido 2-nitro 4-thio-cyanatobenzene at room temperature with sodium borohydride in dimethylformamide for about 1/4 to about 2 hours, followed by treatment with the R halide under the conditions described above. The same reaction for entering the 2 -SR group can be applied to 1-amino 2-nitro 4-thiocyanatobenzene (see step V).

2

Compounds having the substituent -OR in position 5 (6) can be prepared by reacting 1-acetamido 4-hydroxy 2-nitro-benzene with an alkenyl halide (such as 1-bromopropene- (2)), an alkynyl halide (such as 1 -bromopropyn- (2)), or an aralkyl halide (such as benzyl bromide), etc. and then carry out the other steps as necessary and in the manner described above to obtain the desired compound.

Examples of the compounds of the invention corresponding to formula 1 include the following compounds: 8 2 0 0 3 3 6 * v ^ 8 5 (6) - (prop-2-en-1-ylthio) 2 -methoxycarbonylaminobenzimidazole; mp 201-2Q1.5 ° C.

5 (6) - (prop-2-yn-1-ylthio) 2-methoxycarbonylaminobenzimidazole; mp 212-212.5 ° C.

These compounds are presently preferred because they exhibit substantial activity against the above-mentioned helminths.

Another representative compound within the scope of the invention is, for example, 5 (6) -phenethylthio 2-methoxy-10-carbonylaminobenziraidazole.

Preparation instructions 1.

175 g of S-methylisothiouronium sulfate in 1 liter of water are cooled to a temperature of 0 ° C, followed by the addition of 162.5 g of methyl chloroformate, followed by the addition of a solution of 250 g of potassium hydroxide in 750 ml of water at a temperature of 0-5 ° C. The crude product is extracted with benzene, the benzene extract is dried and evaporated and the residue is recrystallized from methanol. The 1,3-bis (methoxy-carbonyl) S-methylisothiourea is obtained in this way.

Similarly, by replacing the methyl chloroformate with ethyl chloroformate, propyl chloroformate and butyl chloroformate, the 1,3-bis (ethoxycarbonyl) S-methyl isothiourea, 1,3-bis (propoxycarbonyl) S-methyl isothiourea, and the 1,3-bis (butoxycarbonyl) S- methyl isothiourea.

25 Preparation instructions 2.

2.37 g of 1-acetamido 2-nitro 4-thiocyanatobenzene in 10 ml of dimethylformamide are treated under nitrogen with 0.38 g of sodium borohydride at a temperature of 20-25 ° C. After one hour, 2.4 ml of benzyl bromide are added, the mixture is allowed to stand for 2 hours, then diluted with water and filtered, the residue is washed with cyclohexane and recrystallized from methanol to give 1-acetamido 2 nitro 4-benzylthiobenzene.

Example I.

5.85 g of 1-amino 2-nitro-4-thiocyanatobenzene are treated in

20 ml of dimethylformamide under a nitrogen atmosphere with 1.14 g of sodium borohydride at a temperature of not more than 30 ° C. The mixture is left for one hour at a temperature of 15-20 ° C

8200338 9 and then treated with 5 ml of propargyl bromide at a temperature of 20-25 ° C. After a further 3 hours, water is added and the crude product is extracted with chloroform.

The dried chloroform solution is passed through a silica gel color 5 to remove a small amount of polar material.

The pure 1-amino 2-nitro 4- (prop-2-yn-1-ylthio) benzene is obtained from the eluate.

4.8 g of 1-amino 2-nitro 4- (prop-2-yn-1-ylthio) -benzene in 14 ml of concentrated hydrochloric acid are treated with a solution of 24 g of 10-stannous chloride in 14 ml of concentrated hydrochloric acid at a temperature of 20 -30 ° C. After about 30 minutes, the mixture is neutralized with a saturated potassium bicarbonate solution and chloroform is added. The mixture is filtered, then the chloroform phase is separated, dried and evaporated to give the 1,2-diamino 4- (prop-2-yn-1-ylthio) benzene. Overall yield 75%.

4.0 g of 1,2-diamino 4- (prop-2-yn-1-ylthio) benzene in 25 ml of ethanol and 25 ml of water are then treated with 4.9 g of 1,3-bis (methoxy-carbonyl) S-methylisothiourea and 1 .5 ml of acetic acid, the mixture being refluxed for 3 hours. The mixture is then cooled and the 5 (6) - (prop-2-yn-1-ylthio) 2-methoxycarbonylaminobenzimidazole isolated by filtration.

Recrystallization can be carried out from methanol / chloroform. Mp 212-212.5 ° C; yield of last stage: 92%.

By replacing the propargyl bromide with 2-propenyl bromide, 2-butenyl bromide, 3-butenyl bromide, 2-pentenyl bromide, 2-hexenyl bromide, 2-butynyl bromide, 3-butynyl bromide, 2-pentynyl bromide or 2-hexynyl bromide, the same is obtained corresponding 5 (6) -alkenylthio- and 5 (6) -alkynylthio 2-methoxycarbonylaminobenzimida-30 sole compounds including the 5 (6) - (prop-2-en-1-ylthio) 2-methoxycarbonylaminobenzimidazole (melting point 201-201, 5 ° C).

Similarly, using 1,2-diamino 4-alkenyl-thiobenzene or 1,2-diamino 4-alkynylthiobenzene compounds prepared according to this example and replacing the 1,3-bis (methoxycarbonyl) 35 S-methyl isothiourea with 1,3-bis (ethoxycarbonyl ) S-methylisothiourea, 1,3-bis (propoxycarbonyl) S-methylisothiourea or 1,3-bis (butoxycarbonyl) S-methylisothiourea, the corresponding 5 (6) -alkenylthio- and 5 (6) -alkynylthio-2-alkoxycarbonylaminobenzimidazole compounds, wherein R represents an ethyl, propyl or 8200338 '10 butyl group.

Example II,

1.0 g of 1-acetamido 2-nitro 4-benzylthiobenzene prepared according to Preparation Procedure 2 are treated with 2 rals of a 5 N sodium hydroxide solution and 6 ml of ethanol on a steam bath for 15 minutes. The mixture is diluted with water and the 1-amino 2-nitro 4-benzylthiobenzene filtered off.

Then 0.9 g of 1-amino 2-nitro-4-benzylthiobenzene in 5 ml of concentrated hydrochloric acid are treated for a very short period on the steam bath with 4.5 g of stannous chloride. The mixture is cooled and the liquid is decanted from the resulting gummy material, which is then washed with 5 ml of cold 6N hydrochloric acid. By treatment of the gummy material with a potassium bicarbonate solution, the 1,2-diamino-4-benzylthiobenzene is obtained, which is isolated by extraction with chloroform and purified by recrystallization from cyclohexane. In the same manner as described in the regulation of the third paragraph of Example I, the 5 (6) -benzylthio 2-methoxycarbonylaminobenzimida sole is also prepared. Melting point 196 ° C, with decomposition.

By replacing the benzyl bromide, as used in preparation 2, with p-chlorobenzyl bromide, p-methylbenzyl bromide and p-methoxybenzyl bromide, the corresponding 1,2-diamino 4- (substituted benzylthio) -benzene and 5 are obtained in the same manner. (6) - (substituted benzylthio) 2-methoxycarbonyl-25 aminobenzimidazole compounds. By the 1,2-diamino 4- (substituted benzylthio) benzene compounds prepared in this manner with 1,3-bis (ethoxycarbonyl) S-methylisothiourea, 1,3-bis (propoxy-carbonyl) S-methylisothiourea or 1,3-bis (butoxycarbonyl) S-methylisothiourea instead of reacting with 1,3-bis (methoxycarbonyl) S-methyl-30 isothiourea, the corresponding 5 (6) - (substituted benzylthio) 2-alkoxycarbonylaminobenzimida sole compounds are prepared, wherein R is an ethyl, propyl or butyl group proposes.

Example III.

A mixture of 2.94 g of 1-acetamido 4-hydroxy 2-nitrobenzene, 5.13 g of benzyl bromide and 4.2 g of anhydrous potassium carbonate is refluxed overnight in acetone and then stirred, then the excess benzyl bromide 8200338 * J5-11 is removed in vacuo, water is added and the product is extracted with dichloromethane to give the 1-acetamido 4-benzyloxy 2-nitrobenzene.

The 1-acetamido 4-benzyloxy-2-nitro-5-benzene thus obtained is treated with sodium hydroxide in methanol, briefly heated on a steam bath for about 15 minutes, until the conversion is complete, then diluted with water and extracted with dichloromethane, whereby the 1-amino 4-benzyloxy-2-nitrobenzene is obtained.

10. 2.44 g of 1-amino 4-benzyloxy-2-nitrobenzene are stirred in 100 ml of methanol and 100 ml of 20% hydrochloric acid at room temperature with 1.0 g of iron powder. After 2 hours, the mixture is poured into an excess of ammonia, the residue is extracted with chloroform, the extract is filtered under nitrogen, dried over magnesium sulphate, filtered again and evaporated to give the 1,2-diamino-4-benzyloxybenzene. .

5 g of 1,2-diamino-4-benzyl-oxybenzene, 5 g of 1,3-bis (methoxycarbonyl) S-methylthiourea and 1.8 g of acetic acid are dissolved in 50 ml of ethanol and 50 ml of water and the solution is refluxed for 3 hours. . The mixture is cooled and the 5 (6) -benzyloxy-2-raethoxycarbonylaminobenzimidazole is filtered and washed with methanol. Melting point 230 ° C, with decomposition; yield 70% for entire process.

By replacing the benzyl bromide with p-chlorobenzyl chloride, p-methylbenzyl bromide and p-methoxybenzyl bromide, the corresponding 1,2-diamino 4-substituted benzyl oxybenzene and 2-methoxycarbonylamino 5 (6)-substituted benzyloxy-benzimidazole compounds are likewise obtained. By the 1,2-diamino-4-substituted benzyloxybenzene compounds prepared in this manner with 1,3-bis (ethoxy-30 carbonyl) S-methyl isothiourea, 1,3-bis (propoxycarbonyl) S-methyl isothiourea or 1,3-bis (butoxycarbonyl) S-methyl isothiourea instead of the reaction with the 1,3-bis (methoxycarbonyl) S-methylisothiourea, the corresponding 2-alkoxy-carbonylamino-5 (6) -substituted benzyloxybenzimidazole compounds are obtained, wherein R represents the ethyl, propyl or butyl group.

Example IV.

1-Acetamido 4-hydroxy 2-nitrobenzene is treated with the alkenyl or alkynyl halides of Example I under the conditions described in Example III (or similar or analogous conditions 8200338), with the corresponding 5 (6) -alkenyloxy- 2-alkoxycarbonylaminobenzimidazoles, including 5 (6) - (prop-2-en-1-yloxy) -2-methoxycarbonylaminobenzimidazole (Melting point 21 ° C, under decomposition) and corresponding 5 (6) -alkynyloxy 2-5 alkoxycarbonylaminobenzimidazoles.

Example V.

A soaking powder is prepared with the following composition: 5 (6) - (prop-2-en-1-ylthio) -2-methoxycarbonyl-. aminobenzimidazole 30% 10 "Carbowax" 6000 "40%" Myrj "52 (polyoxyl (40) stearate; a product of Atlas Chemical Co.) 30%

A soaking liquid is prepared by mixing 25 g of this powder with 1 l of water, after which an appropriate amount thereof (depending inter alia on the weight of the animal and the frequency of administration) is administered to the animal to be treated.

8200338

Claims (3)

13 * Ί V \ CONCLUSIONS. A method for the preparation or manufacture of anthelmintically active pharmaceutical preparations, in which a 2-alkoxycarbonyl-amino-benzimidazole derivative is brought into a form suitable for therapeutic use, and for the preparation of fungicidal preparations, wherein a 2-alkoxycarbonylamino-benzimidazole derivative is mixed with a carrier, characterized in that the active substance used is a compound of the formula 1 or a salt thereof, in which formula R is an alkyl group containing 1 to 4 carbonatoraes and R is a residue located at 2 2 2 position 5 (6) - SR or -OR, wherein R 10 represents an alkenyl, alkynyl or aralkyl radical. 2. Process for the preparation of 2-alkoxycarbonylamino-benzimidazole derivatives with anthelmintic and fungicidal activity suitable for use in the process according to claim 1, characterized in that compounds of formula 1 and salts thereof, in which formula R an alkyl group having 1 to 4 carbon atoms and R 1 represents a 2 2 moiety located in position 5 (6), -SR or 0R, wherein 2 R represents an alkenyl, alkynyl or aralkyl moiety, prepared in a manner known for the synthesis of analogous compounds . 3. Process according to claim 2, characterized in that a 1,2-diamino 5 (6) -R-benzene is reacted with a 1,3-bis- (alkoxycarbonyl) -S-alkylisothiourea. 8200338> * '- f'