DD282914A5 - PROCESS FOR THE PREPARATION OF (2-THIENYL-METHYL) -THIOMAN DERIVATIVES - Google Patents

Abstract

The invention relates to a process for the preparation of (2-thienylmethyl) thiourea derivatives of general formula I, (wherein A ind 1 is hydrogen, C 1-14 alkyl or C 4-8 cycloalkyl; A ind 2 C ind 3-10 alkenyl, C ind 3-10 alkenyl, C ind 4-8 cycloalkyl, phenyl C 1-4 alkyl, phenyl C 2-4 alkenyl, optionally substituted by one or more C 1-4 alkoxy, C 1-4 alkyl and / or hydroxy group (s) substituted phenyl; naphthyl; optionally C 1-4 alkyl is substituted pyridyl or furfuryl; X is a valence bond or a group -CO-, with the proviso that if X is a valence bond, A ind 2 is other than phenyl). The compounds according to the invention can be used as feed supplement due to their weight-increasing and feed-enhancing properties. Formula I {2- (thienylmethyl) thiourea derivative preparation; Feed additive; Effect, weight increasing}

Description

Field of application of the invention

The invention relates to a process for the preparation of novel (2-thienylmethyl) thiourea derivatives and feed compounds containing these compounds, FuUermittelkonzentrate and feed, in particular with the feed conversion and weight-increasing effect.

Characteristic of the known state of the art

European Patent Publication No. 0207358 discloses weight-increasing compounds for various species of animals (domestic animals, game, reptiles, hobby animals). a ^ -Thienyl-methyl-thiourea described. However, the patent does not contain a specific indication of the effect on any animal species.

U.S. Patent Nos. 4,207,191 and 4,313,885 disclose (2-furfuryl) thiourea derivatives which exert a weight-increasing effect on lamb, pork and chicks.

Object of the invention

The compounds according to the invention are superior to the already known derivatives in their weight-increasing activity. They have neither antibiotic nor mutagenic effects.

Explanation of the essence of the invention

The invention has for its object to provide a process for the preparation of novel (2-thienyl-methyl) -thiourea derivatives with over the prior art superior Beifuttermittelwirkung to provide and containing these compounds feed, feed concentrates and feed.

The above has surprisingly been achieved by the invention. The invention thus provides a process for the preparation of novel (2-thienvl-methyl) thiourea derivatives of the general formula I.

I i

^Λ 1

-CH ₀ -NH-CNXA ₀ (I),

A, hydrogen, C ₁ ^ alkyl or C ₄ ^ cycloalkyl;

A ₂ Ci-IO alkyl, C ₃ -I ₀ alkenyl, C _t - _e cycloalkyl, phenyl-Ci ^ alkyl, phenyl-C ^ alkenyl; optionally phenyl substituted by one or more C 1-4 -alkoxy, C 1-4 -alkyl and / or hydroxy group (s); naphthyl; optionally C ₁ ^ alkyl

substituted pyridyl or furfuryl; X represents a valence bond or a group -CO-; with the bond that if X is a valence bond, A _{2 is} different from phenyl.

By the term "alkyl group" is meant straight-chain or branched saturated aliphatic hydrocarbon groups having the specified number of carbon atoms (eg, methyl, ethyl, tert-butyl, η-butyl, n-decyl, etc.) The term "alkoxy group" refers to straight-chain or branched alkyl ether groups having the specified number of carbon atoms (eg, methoxy, ethoxy, tert-butoxy, etc.). The term "alkenyl group" refers to straight-chain or branched olephinically unsaturated aliphatic groups having the specified number of carbon atoms (eg, allyl, methallyl, butenyl, etc.). "Phenylalkyl group" means alkyl groups substituted by a phenyl group and having the specified carbon atom number (for example, benzyl, .beta.-phenylethyl, 4-phenylbutyl, etc.). The term "phenylalkenyl group" refers to alkenyl groups substituted by a phenyl group as defined above (e.g., phenylvinyi, phenylpropenyl, etc.) Advantageous representatives of the compounds of general formula I are the following derivatives: N-benzoyl-N '- (2 -thienyl-methyl) -thiourea; N-benzyl-N '- (2-thienyl-methyl) -thiourea; N- (p-methoxy-benzoyl) -N' - (2-thienyl-methyl) -thiourea; N- Cyclohexyl-N '- (2-thienyl-methyl) -thiourea; N- (2,6-dimethyl-phenyl) -N' - (2-thienyl-methyl) -thiourea; N- (β-phenyl-acryloyl) - N '- thiourea (2-thienyl-methyl).

A particularly advantageous member of the compounds of general formula I is N, N-dicyclohexyl-N '- (2-thienyl-methyl) thiourea.

According to the invention, the compounds of general formula I are prepared by a) for the preparation of compounds of general formula I wherein X is a valence bond and A ₁ and A _{2 have} the above meaning, ai) an isothiocyanate of the general formula II

A ₂ -NCS (II)

with 2-thienyl-amine of the formula III

U.

reacted; or a ₂ )! 2-thienylmethyl) isothiocyanate of the formula V

CH ₂ -NCG (V)

with an amine of the general formula VI

NH

reacted; or

b) for the preparation of compounds of general formula I, wherein X represents a group -CO- and is hydrogen;

t> i) 2-thier, yl-amine dei formula III with an acyl isothiocyanate of the general formula IV

A ₂ -CO-NCS (IV)

reacted; or b ₂ ) N- (2-thionylmethyl) thiourea of formula VII

ΙΓΊ1

CH ₀ -NH-C-NH,

with a carboxylic acid of general formula VIII

A ₂ -COOH (VIII)

or a reactive derivative thereof (in which formulas Ai, A ₂ and X have the above meaning).

According to process variant a,), an isothiocyanate of the general formula II is reacted with 2-thienylamine of the formula Hi. The starting materials are preferably used in equimolar Memge. The reaction can be advantageously carried out in an inert solvent. Suitable reaction medium are inert solvents (eg, ethanol, gasoline, ether, dichloromethane, tetrahydrofuran, etc.). One can special. ', Advantageously in gasoline or ethanol work. The reaction may be carried out at room temperature at a temperature between O ⁰ C and 10O ⁰ C, preferably. The resulting compounds of general formula I can be isolated from the reaction mixture by filtration and / or evaporation.

According to process variant a ₂ ), an amine of general formula VI is reacted with (2-thienyl-ethyl) -isothiocyanate of general formula V. As the reaction medium, the enumerated in the procedure a,) solvents - advantageously gasoline or ethanol - serve. The reaction may preferably be carried out at room temperature. The resulting compounds of general formula I can be isolated by filtration and / or concentration. According to the process variant b |), an acyl isothiocyanate of the general formula IV is reacted with (2-thienylmethyl) amine of the formula III. The reaction may be carried out in a suitable inert solvent, preferably in acetone. The reaction can be carried out with heating, at a temperature between 4O ⁰ C and the boiling point of the Raassgemisches; you can preferably work at the boiling point. The resulting compound of general formula I can, for. B. be isolated so that the reaction mixture is poured into the water.

According to an advantageous embodiment of this process variant, the acyl isoihiocyanate of the general formula IV is prepared by reacting ammonium thiocyanate and the corresponding acid halide - in particular acid chloride and reacted in situ with the (2-thienyl-methyl) -amine of the formula III.

According to the process variant (b ₂ ), the (2-thienylmethyl) thiourea of the formula VII is reacted with a carboxylic acid of the general formula VIII or a reactive derivative thereof. Suitable acid derivatives are first and foremost the corresponding acid halides, preferably acid chlorides. The acylation may be carried out in a suitable organic solvent (eg acetonitrile, methylene chloride, aromatic hydrocarbons, preferably gasoline). The reaction may be carried out under heating, between 4O ⁰ C and the boiling point of the reaction mixture, reaction is carried out conveniently at the boiling point of the reaction mixture.

The starting materials of general formula II, III, Vl and VIII are commercial products. The starting materials of the general formula II can be prepared according to Houben-Weyl: Methods of Organic Chemistry IX, pages 867-878. Di 9 Preparation of the acyl isothiocyanates of the general formula IV is carried out according to the method described in Houben-Weyl: Methods of Organic Chemistry IX, pages 878-879.

The (2-thienylmethyl) isothiocyanate of the formula V can be prepared in an analogous manner to J. Chem. Soc. Perkin I. (1976) page 139.

The (2-thienylmethyl) -thiourea of the formula VII can be prepared by the method described in Houben-Weyl: Methods of Organic Chemistry Vol. 84, 484-505, Georg Thieme Verlag 1983.

The compounds of general formula I exert on valuable animals - especially pig, poultry, ruminants, especially on lamb and chicks - a valuable weight-increasing effect, which is associated with a favorable feed conversion improvement

 The above effect of the compounds of the invention is demonstrated by the following test experiments.

1) Try on lambs

This trial is performed on roast lambs with a feeding time of 40 days. The animals receive a Futtor of the following composition:

Composition of the food premix Quantity, Gow% component 70.0 corn scrap 24.0 Lucerne flour II. Class 3.0 urea 0.5 feed lime 1.0 Monocalcium phosphate 0.5 Crystalline sodium sulfate 0.5 food salt 0.5 Lamb Premix XIX (Phylaxia)

100.0

The test compound is the standarden granules in a concentration of 50 ppm admixed The animals of the control group received a feed premix above ammensetzung 7, but without the active ingredient.

As lambs only separated Hungarian Marino bucks are used. Each group consists of 12 lambs and for each treatment 3 groups are used. During the 40-day trial period, the lambs are weighed individually five times, at the beginning of the experiments and every 10th day (for the last time on the 40th day), always at the same time. In the evaluations, the actual weights are given, whereby koine deductions were made. The amount of food eaten is determined in each decade and group.

The results are summarized in Table 1, with weight gain and feed conversion given as the average of three trials.

Tcbelln 1

treatment g% control Example 4 Example 5 Example 3 example 1 Example 2 Examples Average daily weight gain kg / kg% 254.3 100 237.9 113.6 283.9 112.0 279.6 110.3 266.7 105.2 275.2 108.2 276.2 108.9 Specific feed consumption 3.95 100 3.57 90.4 3.57 90.4 3.66 92.7 3.79 95.9 3.72 94.9 3.68 93.2

It is apparent from the above results that the compounds of the general formula I substantially improve the feed utilization, that is to say the feed conversion. 1 kg weight gain can be achieved with a significantly lower feed amount.

The compounds of the general formula I according to the invention do not exert any antibiotic effect and are therefore free of the disadvantages occurring when the antibiotics are used.

A very important advantage of the compounds of general formula II is that they show no mutagenic effect.

This fact stelii in animal breeding is a significant advantage, because several representatives of the known weight gain-enhancing agent because of their mutagenic effect as Futerzusatz only in limited quantities or even not at all can be used.

2) Try on chicks

The experiments are carried out on broiler chickens. The results obtained are shown in Table II.

tables

Age of 28 days

active substance Can mg / kg feed Living weight g Deviation from the control g% 106.7 103.9 100.0 Example 12 Zinc bacitracin control 50 20 0 827 796 775 CM T- in co I + + Age of 42 days 106.3 103.9 100.0 Example No. 12 Zinc bacitracin control 50 20 0 1545 1510 1454 + 91 + 56 Age of 49 days 108.4 102.9 100.0 Example No. 12 Zinc bacitracin control 50 20 0 1979 1878 1825 + 154 + 53

-6- 282 014

At the age of 49 days, the control group can save 2.3% of food (calculated on 1 kg of live weight). The feed additives according to the invention may be present as preparations.

The feed additives, feed concentrates and feedstuffs according to the invention may contain as carriers any substance of plant or animal origin which is used for feeding. Appropriate vehicles are wheat semolina, barley, rye, oatmeal, rice bran, wheat bran, soybean meal, corn seedling meal, bone meal, alfalfa meal, soybean meal, meat meal and fish meal and their mixtures. Particularly advantageous carrier substances are fiber-free green plant feed concentrates with increased protein content, for example VEPEX *.

As auxiliaries, the feed additives, feed concentrates and feedstuffs according to the invention may advantageously contain wetting agents, antioxidants, starches, mineral substances and / or sorbic acid. The wetting agents may be, for example, non-toxic oils, advantageously soybean, corn and / or mineral oil. As advantageous wetting agents, the various alkylene glycols have also been found. The starch may advantageously be corn, wheat and / or potato starch. The mineral substances may be, for example, silica, calcium carbonate and / or dicalcium phosphate.

The active substance content of the preparations according to the invention can vary within wide limits. Thus, the active ingredient content of the feedstuffs according to the invention, feed concentrates and feedstuffs is generally from 0.0001 to 85% by weight. The feed concentrates according to the invention may expediently contain about 5 to 85% by weight, advantageously 5 to 80% by weight, preferably about 10 to 80% by weight, in particular 20 to 50% by weight, of the compound according to the invention. The content of the inventive ready-to-use diluted feedstuff in the active substance according to the invention may usefully be about 0.0001 to 0.04% by weight, in particular 0.001 to 0.01% by weight.

The feed additives and feed concentrates according to the invention may also contain conventional vitamins, for example vitamins A, B ₂ , B ₃ , B ₅ , B ₁₂ , E and / or K, and / or trace elements, for example manganese, iron, zinc, copper and / or iodine. The feed concentrates according to the invention can be used after their dilution for feeding animals; By contrast, with the feeds according to the invention, the animals can be fed directly.

The feeds of the invention may be used to feed various farm animals, such as pigs, sheep, cattle and poultry, especially the former

 The invention will be explained in more detail with reference to the following examples.

embodiments

example 1

N-Benzoy'-N '- (2-thlf> ny methyl!) -Thiohainstoff

To a hot solution of 38.08 g (0.5 mol) of ammonium thiocyanate and 500 ml of acetone, 70.08 g (0.5 mol) of benzoyl chloride are added dropwise with stirring at the boiling point within 10 minutes. White crystals are eliminated.

To the resulting suspension is added dropwise a hot solution of 56.6 g (0.5 mol) of 2-thienylamine and 300 ml of acetone, after which the reaction is heated to boiling for a further 20 minutes. The reaction mixture is cooled, poured into 4 liters of ice-cold water, the precipitated crystals are filtered and washed with water. Are obtained in the form of beige colored crystals 103,8g of the title compound, yield 75.1%, m.p .: 118-119 ⁰ C. (methanol).

Example 2

N-benzyl-N'-U-thienyl-methyD-thiourea

To an emulsion of 73.56 g (0.65 mole) of 2-thienylamine and 500 ml of gasoline, 97.0 g (0.65 mole) of benzyl isothiocyanate are added dropwise with stirring. The reaction mixture is stirred at room temperature for 4 hours, then filtered and washed with petrol. There are obtained 153.75 g of the title compounds, yield 89.6%, F.: 108-109 ⁰ C (from methanol).

Example 3

N- (p-methoxy-benzoyl) -N '- (2-thiDnyl-methyl) thiourea

38.08 g (0.5 mol) of ammonium thiocyanate, 85.3 g (0.5 mol) of anisoyl chloride and 56.6 g (0.5 mol) of 2-thienyl-amine are reacted in an analogous manner, for example 1. There are obtained 118.5 g of the titled compound, yield 77.3%, mp .: 124-125 ° C (from a 3: 1 mixture of methanol and benzene).

Example 4

N-cyclohexyl-N '- (2-thienyl-meihyl) thiourea

82.46 g (0.7 mol) of 2-thienyl-amine and 98.86 g (0.7 mol) of cyclohexyl isothiocyanate are reacted in an analogous manner to Example 2. There are obtained 171.6 g of the title compound, yield 96.4%, F.: 112-113 ⁰ C (from methanol).

Example 5

N- (2,6-dimethyl-phenyl) -N '- (2-thienyl-methyl) -thloharnstoff

A solution of 15.5 g (0.1 mol) of (2-thienylmethyl) isothiocyanate in 200 ml of benzene is stirred at room temperature while stirring a solution of 12.1 g (0.1 mol) of 2,6-dimethylaniline and 100 ml of gasoline added dropwise. The reaction mixture is stirred for 4 hours, the precipitated crystals are filtered and washed with petrol. There are 22,55g of the title compound are obtained, yield 81.7%, m.p .: 147-148 ⁰ C.

Examples

N- (β-phenyl-akryloyl) -N '- (2-thienyl-methyl) -thiourea 76.1 g (1 mol) ammonium rhodanide, 166.6 g (1 mol) cinnamic acid chloride and 113.2 g (1 mol) 2- Vhionyl-amine are reacted in analogy to Example 1. 210 g of the title compound are obtained, yield 69.5%, mp. 181-182 ⁰ C (from Methylcellosolv).

Example 7

N- (1-naphthyl) -N '- (2-thienyl-mothyl) thiourea 2.26 g (0.02 mol) of 2-thienyl-amine and 3.7 g (0.02 mol) of 1-naphthyl isothiocyanate are implemented in analogy to Example 2. There are obtained 5.85 g of the title compound, yield 98%, F .: 147-148 ⁰ C (from ethanol).

Examples

N- (β-phenyl-ethyl) -N '- (2-thienyl-methyl) -thiourea 15.5 g (0.1 mol) of (2-thienyl-methyl) isothiocyanate and 12.1 g (0.1 mol) of phenylethylamine implemented in analogy to the examples. There are obtained 22.4 g of the title compound, yield 81%, mp .: 88-89 ° C (from ethanol).

Example 9

N-Pivaloyl-N '- (2-thienylmethyl) thiourea 38g (0.5 mol) ammonium rhodanide, 60.3g (0.5 mol) pivaloyl chloride and 58.5g (0.5 mol) 2-thienyl-amine are implemented in analogy to Example 1. There are obtained 91.5 g of the title compound, yield 71.3%, F.: 90-91 ⁰ C (from ethanol).

Example 10

N- (2-pyridyl) -N '- (2-thienylmethyl) -thiourea. To a suspension of 27.0 g (0.29 mol) of 2-amino-pyridine and 300 ml of benzene are added 45 g (0.29 mol) (2 Thienylmethyl) isothiocyanate added dropwise. The reaction mixture is stirred at room temperature for 5 hours, whereby the initially oily Niedersch 'ag crystallized. The next day the product is filtered. There are obtained 66.74 g of the title compound, yield 92.3%, mp .: 115 ° C (from ethanol).

Example 11

N- (4-methyl-1-pyridyl) -N '- (2-thienylmethyl) -thiourea 10.8 g (0.1 mol) of 2-amino-4-methyl-pyridine and 15.5 g (0.1 mol ) (2-thienyl methylHsothiocyanat are reacted in analogy to example 10. There are 17.1 g de. · obtain compound mentioned in the title, yield 65.2%, m.p .: 139-140 ⁰ C.

Example 12

N, N-Dlcyclohexyl-N'-U-thanyl-methyl-thiourea 18.13 g (0.1 mol) of dicyclohexylamine and 15.5 g (0.1 mol) of (2-thienyl-methyl-isothiocyanate are reacted by analogy with, for example , 5g of the titled compound, yield 75.8%, mp. 119-120 ° C.

Example 13

N-Allyl-N '- {2-thienylmethyl) thiourea 17.1 g (0.3 mol) of allylamine and 46.5 g (0.3 mol) of (2-thienylmethyl) isothiocyanate are prepared analogously to Example 10 implemented.

I: s are 47.1 g of the title compound, yield 73.8%, F.: 88 ⁰ C (from benzene).

Example 14

N, 3-Hydroxy-phenyl) -N '- (2-thienyl-methyl) thiourea To a solution of 7.76 g (0.05 mol) of (2-thienylmethyl) isothiocyanate and 50 ml of tetrahydrofuran are added 5.46 g ( 0.05 mol) of m-amino-phenol was added. The reaction mixture is stirred at room temperature for 5 hours. The precipitated beige-colored powdery crystals are filtered. There are 8,83g of the title compound are obtained, yield 66.9%, m.p .: 175-176 ⁰ C.

Example 15

N-Benzoyl-N '- (2-thienyl-methyl) -thiourea. To a suspension of 1.7 g (0.01 mol) of (2-thienyl-methyl) -thiourea and 30 ml of benzene are added 1.4 g (0, 01 mol) of benzoyl chloride added dropwise. The reaction mixture is refluxed for 16 hours with stirring, then clarified and concentrated. The remaining oil is treated with 3 ml of cold isopropanol. There are obtained 1.57 g of the titled crystalline product. Yield 57.7%, F .: 118 ^° C.

Example 16

N- (n-Butyl) -N '- (2-Thienylmethyl) thiourea To a solution of 1.82 g (0.035 mol) n-butylamine and 50 ml ethanol are added 3.88 g (0.025 mol) (2-thienyl-methylD The temperature of the reaction mixture increases during the addition of 25 ⁰ C to 4O ⁰ C. The reaction mixture is stirred for 5 hours at room temperature.The precipitated crystals are filtered to give 4.4 g of the titled compound, yield 77.1%, m.p .: 55-56 ⁰ C (from a mixture of methanol and water).

Example 17

N- (n-Decyl) -N '- (2-thienyl-mothyl) -thiourea 3.88a (0.025 mol) (2-thienyl-methyl-isothiocyanate and 3.93g (0.025 mol) n-decylamine are prepared by analogy, for example

implemented. This gives 7.25 g of the title compound, yield 92.8%, m.p .: 77-78 ° C (from ethanol).

Example 18

N- (2-furfuryl) -N '- (2-thienyl-methyl) thiourea

9.72 g (0.1 mol) of furfurylamine and 15.5 g (0.1 mol) of (2-thienylmethyl) isothiocyanate are reacted in analogy to the example. There are 17,46 g of the title compound, yield 69.2%, F.: 89 ° C.

Example 19

For piglets, a premix of the following composition was prepared:

ingredients amount Vitamin A 3000000 IE Vitamin D ₃ 600000 IE Vitamin E 4 000 IU Vitamin K3 400 mg Vitamin B ₁ 600 mg Vitamin B ₂ 800 mg Vitamin B ₃ 2,000 mg Vitamin B ₈ 800 mg Vitamin B, 2 10 mg Nicotinic acid (niacin) 4,000 mg Cholinchlo-id 60000 mg Compound according to Example 12 10000 mg Butylhydroxytoluene (antioxidant) 30,000 mg flavorings 8000 mg sodium saccharate 30,000 mg trace elements ¹ manganese 8000 mg iron 30,000 mg zinc 20000 mg copper 6000 mg iodine 100 mg 2 times sawed bran to fill up 1 000 mg

This vitamin and trace element premix was blended into the base feed mixture in an amount of 0.5kg per 100kg.

Example 20

For pranks, a premix of the following composition was prepared:

Ingredients Quantity

Vitamin A 1200000 IU

Vitamin D ₃ 300000 IU

Vitamin E 2 000 IU

Vitamin B ₂ 600 mg

Vitamin B ₃ 2000 mg

Vitamin B ₁₂ 5 mg

Nicotinic acid (niacin) 3000 mg

Choline chloride 40000 mg

Compound according to Example 12. 10000 mg

Butylhydroxytoluene (antioxidant) 30000 mg trace elements

Manganese 6000 mg

Iron 10000 mg

Zinc 15000 mg

Copper 30000 mg

Iodine 100 mg

2 times ground to fill up to 1000 mg

This vitamin and trace compound premix was added to the basic feed in an amount of 0.5 kg per 100 kg.

Example 21

0.5 kg of the premix prepared according to dom Example 19 was admixed with 100.0 kg of a basic feed of the following composition:

ingredients Total weight: amount Corn. g was wit follows: 37.6 kg Geriite 25.4 kg wheat 6.0 kg oats 5.0 kg soy 13.0 kg fishmeal 6.0 kg bran 2.4 kg fat powder 1.5 kg 1.0 kg 1.0 kg 0.5 kg 0.1kg 0.5 kg 100.0 kg amount 55.0% by weight Mineral premix (mineral premix) * 40.0% by weight 'r'utterkalk 5.0% by weight sodium chloride Biolysin Premix of Example 19 inversion of mineral premix ingredients You alciumphosphat Monocalcium phosphate calcium carbonate

The active ingredient content of the piglet feed thus obtained was 0.005% by weight.

Example 22

0.5 kg of the premix prepared according to Example 20 was admixed with a base feed oil of the following composition:

ingredients Total weight: amount Corn 25.0 kg wheat 34.0 kg Extracted soy 18.0 kg milk powder 9.9 kg fishmeal 4.0 kg fodder yeast 2.0 kg fat powder 3.4 kg Mineral Premix according to Example 20 1.8 kg feed lime 1.0 kg Sodium chloride of feed quality 0.4 kg Premix of Example 20 0.5kg 100.0 kg

The active ingredient content of the thus obtained fresh-lard-feeding agent was 0.005% by weight.

Example 23

400 kg of premixed soya flour were weighed into a mixer and 3.1 kg of soybean oil were added with stirring, and stirring was continued until the millbase was coated with oil. Thereafter, 9.1 kg of the product of Example was added and stirring was continued until the end of homogenization.

Finally, after the addition of 9.0 kg of soybean oil, the mixture was again homogenized.

Example 24

To 40kg of corn flour with stirring, 0.5kg of product of Example 2 was added, while continuously charging 3.0kg of propylene glycol into the system. Thereafter, 1.4 kg of dicalcium phosphate was added to the mixture and it was homogenized.

Example 25

0.5 kg of product of Example 12 was added to 40 kg of cornmeal with stirring, and 3.0 kg of propylene glycol were continuously atomized into the system. Thereafter, 1.4 kg of dicalcium phosphate was added to the mixture and it was homogenized.

Example 26

10 kg of alfalfa meal and 15 kg of green vegetable feed concentrate (VEPEX *) were stirred for 1 v / hr, then the nebulization of 1 kg of corn oil was begun at a uniform rate and its supply continued throughout the time of addition of the following ingredients: product of Example 12 , 10kg corn starch, 2.5kg product of Example 12, u, 3kg silica, 0.6kg ascorbic acid, 9kg corn starch and 2.5kg product of Example 12. Thereafter, the mixture was stirred for a further 5 minutes.

Example 27

The procedure was as described in Example 23, but with the difference that butylene glycol was used as the wetting agent instead of the soybean oil.

Example 28

A) 3.5kg potato starch was mixed with 2.9kg product of Example 12. 0.05 kg of mineral oil was atomized into the mixture, then 0.2 kg of sorbic acid, 0.4 kg of silica and 0.1 kg of calcium propionate were added and the mixture was stirred for a further 2 minutes.

B) 4.2 kg fish meal and 22 kg rye bran were mixed and atomized on this mixture 0.6 kg minool oil. Then, with stirring, 4 kg of the mixture prepared as described in section A), 10 kg of cornmeal, 4 kg of the mixture prepared as described in section A) and 9 kg of cornmeal were added and finally 0.6 kg of mineral oil was atomized thereon.

Example 29 There were homogenized 100 kg wheat bran, 10 kg product of Example 4, 2.5 kg calcium carbonate, 0.15 kg a-tocopherol and 0.4 kg calcium propionate with 4 kg propylene glycol.

Example 30

There were homogenized 10kg soy flour, 0.6kg product of example 12 and 2.5kg butylsglycol.

Example 31

50kg of soy flour, 6kg of the example 12,0,5kg of silica, 1,3kg of soybean oil and 0,2kg of calcium propionate were hoi'iogenised.

Claims (6)

1. A process for the preparation of 2- (thienylmethyl) thiourea derivatives of general formula I. U- A _{1 is} hydrogen; C _{1 is} alkyl or C ₄ _e cycloalkyl; A ₂ C ₃ _ ₁₀ alkyl, C ^ ₁₀ alkenyl, C ₄ - ^ cycloalkyl, phenyl-C ₁ _ ₄ alkyl, phenyl-C ₂ -4 alkenyl: optionally substituted by one or more C ₁ ^, alkoxy, C ₁ ^ alkyl and / or hydroxy group (s) substituted phenyl; naphthyl; optionally C ₁ ^ alkyl substituted pyridyl oderFurfuryl means; X represents a valence bond or a group CO; with the proviso that if X is a valence bond, A ₂ is other than phenyl, characterized in that a) for the preparation of compounds of the general formula I, wherein X is a valence bond and Αι and A ₂ are as defined above, a, ) an isothiocyanate of the general formula I A ₂ -NCvS (II) with 2-thienyl-amine of the formula III ^L L _s Jl CIl ₂ -NH ₂ ««) reacted; or
a ₂ ) (2-thienylmethyl) isothiocyanate of the formula V with an amine of the general formula VI (Vl) reacted; or b) for the preparation of compounds of general formula I, wherein X represents a group-CO- and Ai is hydrogen; b,) 2-Thienylamine of formula III with an acyl isothiocyanate of general formula IV A ₂ -CO-NCS (IV) reacted; or
b ₂ ) N- (2-thienylmethyl) thiourea of the formula VII ι - ^(vll) with a carboxylic acid of the general formula VIII A ₂ -COOH (VIII) or a reactive derivative thereof (in which formulas Ai, A ₂ and X have the above meaning). 2. The method of claim 1 bi), characterized in that preparing the acyl isothiocyanate of the general formula IV by reacting ammonium thiocyanate and the corresponding acyl halide and reacted with the 2-thienyl-amine of the formula III in situ. 3. The method of claim 1 b ₂ ), characterized in that is used as a reactive derivative of the carboxylic acid of the general formula VIII, an acid halide advantageous acid chloride. 4. The method according to claim 1, characterized in that N, N-dicyclohexyl-N '- (2-thienyl-methyl) -thiourea is produced. 5. The method according to claim 1, characterized in that N-benzo, l-N '- (2-thienyl-methyl) thiourea;
N-benzyl-N '- (2-thienyl-methyl) thiourea;
N- (p-methoxy-benzoyl) - N '- (2-thienyl-methyl) thiourea; N-cyclohexyl-N '- (2-thienyl-methyl) thiourea;
N- (2,6-dimethyl-phenyl) -N '- (2-thienyl-methyl) thiourea; N- (3-phenyl-acryloyl) -N '- (2-thienyl-methyl) thiourea
will be produced. 6. Beif Jttermittel, feed concentrates and feed, characterized by a content of one or more compound (s) according to any one of claims 1 to 3 as an active ingredient, advantageously in admixture with one or more conventional solid or liquid carrier (s), diluent (s) and / or excipient (s).