CS195279B2 - Method of preparing cycloalkano/b/thienyl ureas - Google Patents

Description

The invention relates to a process for the preparation of cycloalkano (b) thienylureas of the formula I

wherein Z is hydrogen or (C 1 -C 4) alkyl, Y is hydrogen, halogen, cyano, U is> C = O,> CHOH, n is 1 or 2, X is oxygen or sulfur, R 1 is hydrogen or alkyl 1-4 carbon atoms and Ra denotes as below:

hydrogen alkyl C 1 -C 12 cycloalkyl C 3 -C 6 allyl methallyl

2-butenyl

2-propynyl hydroxy alkoxy C 1 -C 6 allyloxy methallyloxy

2-butenyloxy methoxymethyl phenoxy -CH2-CH2-OH, -CH2-CH2-O-CH3 -CH2-CH2-S-0H3 -CH2-CH (OR) 2, -CH ₂ -CF 3, -CH 2 CN -CH2-CO2R1 '- NH — CO2R1

5 2 7 8

199279

wherein m is 0, 1 or 2 and Q is selected from the group consisting of when n = Q is hydrogen

4-chloro

3,4-methylenedioxy 2 (3 or 4) -methoxy 4-ethoxy 4-butoxy 4-methylthio

2,4-idimethyl

2,4- dimethoxy

2,4-Chloro-4-nitro a

2-methyl-4-bromoan-1-one hydrogen

4-chloro-4-methoxy and 3,4-methylenedioxy when n = 2 hydrogen

R 5 denotes hydrogen, C 1 -C 4 alkyl. C 3 -C 6 cycloalkyl, allyl, 2-propynyl and wherein m is as defined above, or wherein R a and R 3 together with the nitrogen to which they are attached denote morpholino, piperidino, pyrrolidino, 4-phenylpiperazino, 4-carbetoxypiperazino, 4- ( 4-methoxyphenyl) -piperazino, 1,2,3,4-tetrahydroquinolino or a radical of formula

lflS2tá

The compounds of formula I are prepared. by reacting one mole equivalent of the compound of formula II

wherein Z, ¥, U and n are as defined above with 1 to 1.5 mol equivalents of the compound of formula III / * 2

H -NC (Rfh

Where R 2 < R 3 have the above-mentioned advantage in an organic solvent inert to the reactants at a temperature of 0 to 100 ° C.

Preferably, the amine is used in the form of an acid addition salt and the reaction is carried out in the presence of an acid acceptor.

Preferred compound of formula

wherein R 2 is hydrogen, C 1 -C 8 alkyl, allyl, C 1 -C 12 -propynyl, methoxymethyl or hydroxyla alkoxy R 3 is hydrogen or C 1 -C 4 alkyl is prepared by reacting a

the 4,5,6,7-tetrahydro-7-oxobenzo (b) thien-7-yl isocyanate formed in an aromatic solvent selected from the group consisting of benzene, toluene, xylene and a mixture of xylene isomers with phosgene at reflux, A C 1 -C 3 alkanol solvent with an excess of an amine of the formula wherein R 2 and R 3 are as defined above and the product is isolated.

The aforementioned cycloalkano (b) thienylureas may be in the form of cis- or trans-isomers and in the form of racemic mixtures or in the form of optically active isomers.

The reaction can be carried out using approximately equimolar amounts of isocyanate or isothiocyanate and amine or amine salt and acid, although it is generally preferred to use an excess of isocyanate or isothiocyanate of 5% to 50% wherein the cycloalkane ring does not contain a hydroxyl group. The reaction may be carried out at atmospheric pressure or overpressure at a temperature in the range 0 to 100 degrees Celsius, but is preferably carried out at atmospheric pressure at 0 to 70 degrees Celsius in the presence of an organic solvent.

Suitable solvents are aprotic aromatic solvents such as benzene, toluene and xylene; chlorinated hydrocarbons such as methyl chloride, chloroform and dichloroethane; an ether such as tetrahydrofuran, diethyl ether, dimethoxyethane, dimethylene glycol, dimethyl ether or dloxane; C 1 -C 4 lower alkyl ketones such as acetone, methyl ethyl ketone, methylbutyl ketone and methyl isobutyl ketone, or a mixture of these solvents.

When the cycloalkano- (b-thiophenamine) salt is used in the above reaction, it is desirable to add an acid acceptor to the reaction mixture. alkaline earth metals such as calcium carbonate and strongly basic ion exchange resins, and suitable alkalis in a two-phase system using a immiscible hydrocarbon solvent such as benzene or toluene, or a chlorinated hydrocarbon such as chloroform or dichloroethane.

The preparation of the isocyanates required as starting products in the above reaction is readily accomplished by reacting the appropriate cycloalkano (b) thiophenamines, or acid addition salts thereof, with phosgene, preferably under anhydrous conditions, i.e. under an inert gas such as nitrogen. The reaction is carried out at a temperature of about 0 to 40 ° C, preferably 10 to 20 ° C, and then heated to a temperature of about 50 to 100 ° C, preferably 60 to 80 ° C. The reaction is usually also carried out in the presence of an organic solvent such as benzene, toluene or xylene.

Isothiocyanates may be prepared by reacting suitable cycloalkano (bthiophenamines) with an equimolar amount of carbon disulfide, thiethylamine and carbodiimide represented by the formula:

Where G is cyclohexyl, cycloheptyl, C 4 -C 6 alkyl and the like. The reaction is conveniently carried out in the presence of a solvent such as tetrahydrofuran or an ether such as diethyl ether , at a temperature of -10 to +25 ° C. The product can be isolated by distillation or chromatography.

Alternatively, isothiocyanates of the formulas may be prepared by reacting ϊ, Γ-thiocarbonyldiimidazole with cycloalkano (f) thiophenamines of the formula in the presence of chloroform at ambient temperature. . '

The compounds of the invention are useful as growth stimulating agents for animals such as poultry, fur animals and agricultural animals, and the use of said compounds for this purpose has the advantage of improving feed conversion for said animals. The term 'feed conversion' refers to the ratio of feed unit weight per unit of increment and by improvement in feed conversion is meant an increase in weight gain from that unit of feed consumed;

In practice, the cycloalkano (b) thienyl urea of formula (I) or an optically active growth-stimulating isomer is administered to the animals usually with or in the feed. However, said compounds may be administered as a subcutaneous implant under the skin of said animal or as a parenteral injection. When administered in the feed to poultry, turkeys, sheep, cattle, goats and the like, an effective amount of 0.0001 to 0.08% by weight, preferably 0.001 to 0.04% by weight, is usual. urea of formula I to increase and improve feed conversion.

when administered to said animals, the active compounds as parenteral injections or subcutaneous implants are administered in an amount of about 0.001 to 0.2 mg, preferably 0.005 to 0.10 mg per kg of body weight per day, achieving the desired improvement in weight gain and increase feed conversion.

Tests with 1 day old chickens revealed 1 to 9 ppm

4,5,6,7-tetrahydrobenzo (b) thien-4-ylurea when fed to chickens causes

3.3 to 6.6% improvement in weight gain and also brings 2.7 to 4.7% improvement in feed conversion.

The compounds of the invention are also useful as herbicidal compositions. They are effective for controlling undesirable broadleaf and grass weeds when applied to soil containing the seeds of said undesired weed or when applied to the foliage of such plants. Usually, 5.60 to 16.8 kg / ha, preferably 9 to 11.2 kg / ha are suitable for such control of undesirable plants.

In the following, the invention is illustrated in more detail by means of exemplary embodiments.

Example 1

Preparation of 1-methoxy-3- [4,5,6,7-tetrahydro- ^11- benzo (b) -thten-4-yl] -urea

A mixture of 5 g of methoxy-amine hydrochloride in 60 ml of methylene chloride is cooled to about 15 DEG C. and 6 g of triethylamine in 15 ml of methylene chloride are added. After 20 minutes, 5.38 g of 4,5,6,7-tetrahydrobenzo (b) thien-4-yl-isocyanate in 20 ml of methylene chloride is added over 20 minutes at 15-20 ° C. After stirring for 1 hour, the mixture was filtered and the filtrate washed with water and then with aqueous sodium bicarbonate solution. The solution was dried and evaporated to give a solid. The solid was recrystallized from acetone-heptane to yield

5.1 g of 1-methoxy-3- (4,5,6,7-tetrahydro-benzo [b] thien-4-yl) -urea, m.p. 138.5-141 ° C.

Similarly prepared is 1-ethoxy-3- (4,5,6,7-tetrahydrobenzo (b) thien-4-yl) urea and 1-butoxy-3- (4,5,6,7-tetrahydrobenzo (b) thien) -4-yl) urea using ethoxyamine hydrochloride and optionally n-butoxyamine hydrochloride instead of methoxyamine hydrochloride.

Example 2

Preparation of 1- (benzyloxy) -3- [4,5,6,7-tetrahydro-benzo (b) -thien-4-yl] urea

O-benzylhydroxyamine hydrochloride and 4,5,6,7-tetrahydrobenzo [b] thien-4-yl-isocyanate were reacted as described in Example 6 to give 1- (benzyloxy) -3- (4,5,6, 7-J-tetrahydrobenzo (b) thien-4-yl) urea, which is recrystallized from 95% ethyl alcohol-methylisobutyl ketone, melting at 96.5 to 99 ° C.

Example 3. .

Preparation of 1-hydroxy-1-methyl-3- [4,5,6,7-tetrahydro-benzenes (b) thien-4-yl] -urea

The method described in Example-6 is reacted with N-methylhydroxylamine hydrochloride and _4> 5,6,7-tetrahydrpbenzo (4-bJthíen yllsokyanatanu give 1-hydroxy-l-methyl-3- [4,5,6,7 -tetrahydrobénzp (b Jthien-4-yl] -urea, which is recrystallized from acetone-hexane-ether to give crystals melting at 98 to 102 ⁱⁿ C.

Example 4

Preparation of 1-methoxy-1-methyl-3- [4,5,8,7-tetrahydrobenzo (b) thien-4-yl] urea

According to the method described in Example 1, N, O-dimethylhydroxylamine hydrochloride and 4,5,6,7-tetrahydrobenzo (b) thien-4-yl isocyanate were reacted to give 1-methoxy-1-methyl-3- [4,5] 6,7-tributylbenzp (bthien-4-yl) urea, which is crystallized from acetone-hexane-ether to give the product m.p. 60-62.5 ° C.

195273 9

Example á '^; * ·· * · '\; · £ · -

Preparation of 1-phenethyl-3- [4,5,6,7-tetrahydrobenzo (b] thien-4-yl] urea '

A mixture of 3.82 g of phenylethylamine in 100 ml of diethyl ether under a nitrogen atmosphere is treated with 5.38 g of 4,5,6,7-tetrahydro-benzo (b) thien-4-yl-isocyanate, in 25 ml of diethyl ether, after the addition of a second solution after drops. After stirring at room temperature for 1 hour, the mixture was filtered and washed with ether to give 7.9 g of 1-phenethyl-3- [4,5,6,7-tetrahydro-benzo (b) thien-4-yl] -urea, m.p. 163-166 ° C. C.

In the same manner, methylamine, ethylamine, isopropylamine, n-hexylamine and cyclohexylamine are reacted with the aforementioned isocyanates to give 1-methyl-1-ethyl-, 1-isopropyl-, 1-hexyl and 1-cyclohexyl-3- [4, 5,6,7-tetrahydrobenzo (b) thien-4-yl] urea.

Example

Preparation of 1,1-dimethyl-3- [4,5,6,7-tetrahydrobenzo (bthien-4-yl) urea

A solution of 6,27 g of 4,5,6,7-tetrahydrobenzo (bthien-4-ylisocyanate) in 200 ml of diethyl ether is saturated with gaseous dimethylamine through the capillary tube with stirring. This was crystallized from acetone-hexane ether to give 1,1-dimethyl-3- [4,5,6,7-tetrahydrobenzo (b) thien-4-yl] urea melting at 117-120 ° C. .

An identical product is obtained when 4,5,6,7-tetrahydrobenzo (b) thiophen-4-amine is reacted with an equivalent amount (or excess) of dimethylcarbamoyl chloride and triethylamine in dimethylformamide. The reaction mixture was stirred for several hours and then filtered. The filtrate was evaporated to dryness and the residue was purified by crystallization from acetone-hexane; to give the title compound.

Example 7

Preparation of 1-benzyl-3- [4,5,6,7-tetrahydrobenzo (b) thien-4-yl] urea

Using the procedure described in Example 6, except that diethyl ether was used instead of methylene chloride, 1-benzyl-3- [4,5,6,7-tetr ahydrobenzo (b) thien-4-yl] urea was obtained by reaction of benzylamine and 4,5, 6,7-tetrahydrobenzo (b) thien-4-yl isocyanate. The product melts at 211-214 ° C.

The title compound is also obtained by reacting benzyl isocyanate with 4,5,6,7-tetrahydrobenzo (b) thiophen-4-amine in ether. Example

Preparation of 1-hydroxy-3- [4,5,6,7-tetrahydrobenzo (b) thien-4-yl] urea The above compound was prepared as described in Example 6 by the reaction of 4,5,6,7'-tetrahydrobenzo (b) thien-4-ylisocyanate with hydroxylamine hydrochloride in the presence of triethylamine. The product melts at 158.5-160 ° C. '

Example 1 9

Preparation of N- [4,5,6,7-tetrahydrobenzo (b) thien-4-yl] -4-morpholinecarboxamide Using the procedure described in Example 6, except that diethyl ether was used in place of methylene chloride, 4 was reacted. 5,6,7-tetrahydrobenzo (b) thien-4-ylisocyanate with morpholine to give N- [4,5,6,7-tetrahydro-benzo (b) thien-4-yl] -4-morpholinecarboxamide which melts at 152-154 ° C. He did

Preparation of 4,5,6,7-tetrahydrobenzo (b) thien-4-yl isocyanate

A sample of 47.6 g of 4,5,6,7-tetrahydrobenzo (b) thiophen-4-amine hydrochloride was stirred in 150 ml of water and 350 ml of 10% sodium hydroxide was added. The mixture was shaken and extracted twice with benzene. The extract was dried and evaporated to dryness to give an amine which accumulated under nitrogen. The amine is then added dropwise to 866 ml of a 12.5% (benzene) phosgene solution under a nitrogen atmosphere at 20 degrees Celsius. After stirring at room temperature for 1 hour, the mixture was gradually heated to 60 ° C and maintained at this temperature for 7 hours. The mixture was cooled to room temperature and evaporated to dryness to give a residue which was distilled; 22.4 g of 4,5,6,7-tetrahydrobenzo (bthien-4-ylisocyanate) is obtained, m.p. 98-101 ° C / 0.6 torr.

Example 11

Preparation of 4,5,6,7-tetrahydrobenzo (b) thien-4-yl-isocyanate

A sample (47.5) of 4,5,6,7-tetrahydrobezo (b) thiophen-4-amine hydrochloride is stirred in methylene chloride-water and 5% sodium hydroxide solution is gradually added until the pH is about 10. The methylene chloride layer is removed and the aqueous layer was extracted with methylene chloride. The organic layers were combined, dried over magnesium sulfate and evaporated to dryness to give an oily amine. The amine is stirred in 500 ml of ethyl acetate under a nitrogen atmosphere and 25.4 g of triethylamine are added. After about 15 minutes, 20.9 g of carbon disulfide was added to give a precipitate. An additional 200 mL of ethyl acetate was added and the solid was powdered with a spatula. After stirring for one hour, add

51.5 g of dicyclohexylcarbodiimide and stirring was continued overnight. Then the mixture was heated at 50 ° C for 2 hours and cooled. The solid was removed by filtration and washed with ethyl acetate. The filtrate was evaporated to give a mixture of a solid and most of the oil. The solid was removed by filtration and ether was added. The ether filtrate was evaporated to dryness to give crude isothiocyanate, which was purified by chromatography on silica gel using 65/35 (v / v) petroleum ether 2-methyl chloride.

Preparation of N- [4,5,6,7-tetrahydrobenzophenylthien-4-yl] -4-piperidinecarbocarboxamide

5.85 g of 4- ₍ 5,6,7-tetrahydrobenzo [b] thien-4-yl-1-isothiocyanate) was stirred in 50 ml of tetrahydrofuran and 2.81 g of plperldine was added. The temperature rises to 40 to 50 ° C. After 2.5 hours the mixture was heated at reflux for 3.5 hours. After stirring overnight, the mixture was evaporated to dryness.

185278 to give a sticky tan solid.

Ether was added to this material and the white insoluble product was separated. The crude product, 5.25 g, melts at 102-104 ° C. Example 13

The following compounds of Table I below were prepared using the methods described in the previous examples.

Y_'L_Ri X R2_ Rs__Solvent Melting point (° C)

Η H — CHO O H n-hexyl ether 70.5 to 74.5

Η H — CH 3 S H ethyl ether 104 to 107

CH 3 ΗH ŠH ethyl THF 118-121

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185279

Example Ϊ4

Preparation of 4,5,6,7-tetrahydro-7-oxobenzo (b) thien-4-ylisocyanate and urea. Conversion of 4,5,6,7-tetrahydro-7-oxobenzo (b) thiophen-4-amine hydrochloride to 4,5,6,7-tetrahydro-7-oxobenzo (b) thien-4-yl. It is cooled by heating the toluene mixture of hydrochloride at reflux temperature while phosgene is introduced, cooled and filtered when the mixture becomes less cloudy, and the filtrate is evaporated to give crude 4,5,6,7-tetrahydro-7-oxobenzo (b). ) thien-4-yl isocyanate, i, peak no. = 2250 cm ^-1 .

Addition of NH 3 / MeOH solution to this isocyanate affords 4,5,6,7-tetrahydro-7-oxobenzo (bthen-4-ylurea).

Example _15: · ^The following compounds were prepared! reactions

4,5,6,7-tetrahydro-7-oxobenzo [b] thien. 4-yl isocyanate with suitable amines in inert solvents as described in Example 13.

Product

Amines R1 R2

NH 2 - OCH 3 H

NH2 — OH ........................ H

CH3NH — OH — CHS

CH 3 NH - OCH 3 - CH 3

CH 2 = CH-CHa-NH 2 H

CH3C-CH2-NH2 H (CH3) 2NH-GHs

C6H5CH2NH2 H

C2H5NH2 H

CH 2 Cl 2 NH 2 H

H h

^> ch-nh ₁ η

Example 16

The following tests were performed to evaluate the ability of 4,5,6,7-tetrahydro-benzo (b) thien-4-ylurea to promote growth of chickens.

In these experiments, one day old chickens are placed in heated cages and fed and water is given to them at will. There are 5 males and 5 females per cage in each experiment and three cages are used for treatment. Treatment consists of a basal diet plus 1.3 or 9 ppm of the test compound. Chickens are weighed at the beginning and end of the fermentation. Food consumption is determined for an experimental period that is 13 days from the start when the chicks are one day old. The basal diet used and the results are shown below.

· —OCH3 —OH, —OH —OGH3 —CH2 — CH = GH2. —CH2 — C = OH — CH2 —CH2 — CeH5.

—N — C4H9

O

-CH (CH 5) 2

Basic chicken feed

ground yellow grain 53,45: soya meal (49%) 28.0 .% manhanden — fish flour (60%) 5.0 4/0 cereal gluten meal (60%) : · 5.0 % dehydrated alpha alpha and flour (17/0/0 j 2,0 -4/0 Stabilized fat 4.0 % Middle orthophosphate Calcium 1,2 7% ground limestone _; 0.5 % sodium chloride 0.3 % -Ittram No. 3 0.05 % ++ vitamin premix 0.5 7% - 7 100,00%

52 79

16

Vitamin mixture per tonne and Ca pantothenate AO g Vitamin K (mehadiohj 1.0 g DL methionine 453.6 g parvo (10%) folic acid 13,0 g BHT 113.6 g choline chloride (50%) 906.0 g Vitamin A (30,000 j / g) 100,00 g proferm (44 mg / kg), B1a 227.0 g Vitamin Ds (200,000 j / g) 5.0 g corn oil • 50,0g Vitamin E (44,093 j / kg) 45,4 g fine ground corn 2582,4 g riboflavin 4.0 g - niacinamide 25,0 g 4536,0 g + Tra-min No. 3 * 0.454 kg / t

Manganese iron zinc copper iodine cobalt calcium

12.50% 62.5 ppm

6,00 30,0

5.00 25.0

0.65 3.25

0.35 1.75

0,25 1,25

15,30 mih.

18,35 max ..................

Experiments with chickens

Average 13-day increment per chicken (g)

Surface (Ppm) 1928 Experiment Diameter Percent improvement 1929 1930 1931 1. Inspection _—, · 189 175 180 188 163 2. 4,5,6,7-tetrahydro- and 181 193 182 200 189 3.3 3. Benzo (b) thien-4- 3 199 186 197 198 195, 6.6 4. -ylurea 9 190 198 191 191  193 5.5 Average 13denní feed / increment ratio in kg / kg Hládlná Experiment Diameter Percent (ppm) 1928 1929 1930 1931 improvement 1. Inspection 1.54 1.52 1.48 1.48 1.50 2. 4,5,6,7-tetrahydro- 1 1.48 1.45 1.49 1.44 1,46 ' 2.7 3. Benzo (b) thien-4- 3 1.47 1.40 1.44 1.40 1.43 4.7 4. -ylurea ' 9 1.45 1.45 1.48 1.40 1.44 4.0

Example 17

Evaluation of improved growth and feed in sheep given an implant containing the test compound

To determine the effect of 4,5,6,7-tetrahydro-benzo (b) -thien-4-ylurea on sheep, lambs are randomly selected in groups of six. Sheep are weighed and feed and water allowed at will. Feeding is weighed daily and unused feed from the previous day is collected and weighed. The test animals receive the same feed as the control animals, but the test animals receive one or more subcutaneous implants containing the test compound at the bottom of the ear. The composition of the implant used is shown below. At the end of the six-day period the lambs are weighed again and the total feed consumed is counted.

In these experiments, six replicates were used for six lambs per treatment and each animal received from about 11 mg to 1 x 35 mg of the test compound.

The average of the six-week increment is given in Table II and the in kg / kg feed is given in Table III. From these data it can be seen that lambs implanted with 11 mg or 99 mg of the test compound show approximately 10% by weight. addition to untreated controls Six weeks after implantation. Feed utilization was also improved at the same time by about 5% over untreated controls.

Lamb feed% ground corn on the cob 15.0 ground yellow corn '48.0 soybean meal (49%) 10.0 ground dried alfalfa 15.0 molasses 10.0 iodinated salt 0.5 middle calcium orthophosphate 1.0 premix · 0 , 5

100.0

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Premix per tun ton zinc 5.00 copper 0.65 tra-min No. 3 (1)> 454 iodine 0.35 Vitamin A (30,000 j / g) 133 cobalt 0.25 Vitamin Ds (200,000 j / g) 5 corn oil 100 ALIGN! Implant - pellet mg ground grain 3848 4,5,6,7-tetr ahy dr obenzo (b) - (1) Tra-min No: 3: % -thien-4-ylurea 11.0 i'-. .  · ' glyceryl-12-hydroxystearate 10.50 calcium ·· 21,00 magnesium stearate 0.50 manganese 12.50 . .?. . iron '' ·. 6.00 ‘22,00

Table II

Average 6-week weight increment (kg / lamb)

Implants with active substance

and) 1 2 3 4 5 6 Diameter Control 0 8.50 8.70 9.93 6.50 7.03 6.75 7.90 4,5,6,7-tetrahydro-benzo (b) -thien-4- 1 11.25 9.32 9,30 8.63 8.05 6.68 8.86 -ylmo- 9 10.83 9.80 8.75 7.20 8.53 7.20 8.69

čovina

(a) Approximate weight: 22 mg each

Composition: 50% active ingredient + 50% carrier

Table III

Average weight gain. in kg / kg of fodder

Number of implants with active substance

kou a) 1 2 3 4 5 6 Diameter Control 0 7.88 6.77 7.41 8.82 9.18 8.16 8.04 4,5,6,7-te- trahydro- benzo (b) -thien-4- 1 6.63 6.58 7.41 8.21 8.05 8.49 7.57 -ylmočo- 9 6.51 6.75 7.80 8.38 7.56 7.97 7.49

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a) Average weight 22 mg each Composition: 50% active ingredient + 50% carrier Example 18

Mouse growth control assays.

CFI female mice from the Carworth Farm six weeks old were admitted. They were put in a cage in a tempered room (72 ° F to 76 ° F) with automatic light control, 14 hours on, 10 hours off. The basal diet used in these studies is “Purina Laboratory Choro” (see description below) Water is also allowed at will.

Thirteen days after the start, the mice weighed in groups of ten and were randomly assigned to different treatments. The concentration of the different compounds in the diet is shown in the following tables. Twelve days later, the mice were weighed again and the experiment discontinued. At least three cages (30 mice) of control mice not treated with diet were included in each experiment, data are shown in Table IV as percent weight gain relative to control, followed by a description of the diet to which increment enhancing compounds were added.

The feed to which growth-promoting compounds have been added is described below.

Feed

Analysis of crude protein, not less than 23.0% crude fat, not less than 4.5,% crude fiber, not less than 0.0% ash, less than 9.0%

Folders:

meat meal, bone meal, skimmed milk powder, wheat meal, fish meal, animal liver meal, dried fried beet pulp, ground pressed corn, oatmeal, soybean meal, raw sugar molasses, with butylhydroxyanisol, canned animal fat, addition, vitamin B12 calcium pantothenate, choline chloride, folic acid, addition of riboflavin, dried malt, thiamine, niacin, addition of vitamin A, D-activated plant sterol, addition of vitamin E, calcium carbonate, calcium phosphate, iodized salt, iron-ammonium citrate, iron oxide, magnesium oxide, cobalt carbonate, copper and zinc oxide.

Table IV

Effect of 4,5,6,7-tetrahydrobenzo (b) thien-4-yl-ureas as an animal growth promoting agent given as a percentage of the weight gain relative to controls using mice as test animals

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TABLE V

Effect of cycloalkano (b) thienylureas as an animal growth promoting agent given as · percent weight gain relative to controls using mice as test animals

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Claims (3)

OBJECT OF THE INVENTION A process for the preparation of cycloalkanophthienylureas of the formula I hydrogen alkyl C 1 -C 12 cycloalkyl C 3 -C 6 allyl methallyl 2. The process of claim 1 wherein the amine is in the form of an acid addition salt and the reaction is carried out in the presence of an acid acceptor. 2-methyl-4-bromo hydrogen hydrogen 4-chloro 4-methoxy a 3,4-methylenedioxy R 3 denotes hydrogen, C 1 -C 1 alkyl, C 3 -C 6 cycloalkyl, allyl, 2-propynyl and wherein m is as defined above, or wherein R 2 and R 5 together with the nitrogen to which they are attached denote morpholino, piperidino, pyrrolidino; -phenylpiperazino, 4-carbethoxypiperazino, 4- (4-methoxyphenyl) -piperazino, 1,2,3,4-tetrahydroquinolino or a radical of formula (I); reacting one mole equivalent of a compound of formula II wherein Z, Y, U and n are as defined above with 1 to 1.5 mole equivalent of a compound of formula III wherein R 2 and R a are as defined above, in an organic solvent inert to the reactants at a temperature 0 ° C to 100 ° C. 2,4-dichloro-4-nitro a 2,4- dimethoxy 2.4- β-dimethyl 2-butenyloxy methoxymethyl phenoxy —CH2 —CHa — OH —CH2 —CH2 —O —CH2 —CH2 —CH2 —CH — —CH3 —CH2 —CH (OR1) 2 —CH2 — CF3 —CH2 — CN —CH2 — CO2R1 — NH— CO 2 R 1 wherein Z is hydrogen or C 1 -C 4 alkyl, Y is hydrogen, halogen, cyano, U is> C = O,> CHOH, n is 1 or 2, X is oxygen or sulfur, R 1 is hydrogen or alkyl having 1 to 4 carbon atoms and R2 is as follows: OJ • s · where m is 0,1 or 2 and Q is selected from the group consisting of when η = Ό when η = 1 when η - 2 -hydrogen 4-chloro 3,4-methylenedioxy 2 (3 or 4) -methoxy 4-ethoxy 4-butoxy 4-methylthio 2-propynyl hydroxy alkoxy C1-C6 allyloxy methallyloxy 2-butenyl 3. The process of item 1, for preparing a compound of the formula wherein R2 is hydrogen, C1-C18 alkyl, allyl, alkoxy C1-C12-propynyl, methoxymethyl or hydroxyl and R8 is hydrogen or C1-C18 alkyl, wherein: reacting the compound of the formula in an aromatic solvent selected from the group consisting of benzene, toluene, xylene and a mixture of xylene isomers with phosgene at reflux to form 4,5,6,7-tetrahydro-7-oxobenzo (b) thien-7-yl isocyanate isolated and reacting in a C 1 -C 8 alkanol solvent with an excess amount of an amine of the formula Η -N ««> / R 3 * 3 wherein R 2 and R 8 are as defined above, and the product is isolated.