JPS61268678A - Production enhancer - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] The present invention is used as a production enhancer for animals.

Some concern the use of known chenyl ureas and monoisoureas.

Chenyl ureas have been previously disclosed.

They are used as herbicides and plant growth regulators (German Open Application 2, 040, 579.2,
122,636.2,627,935 and 3,305
, 866 and European Publication Specification 4,931)
.

However, their use as production enhancers in animals is not disclosed.

1. Ceremony! [During the ceremony.

A represents the groups Ia and lb and R1 is hydrogen, halogen, nitro, CN, alkoxy, alkylthio, halogenoalkoxy, halogenoalkylthio, alkoxyalkyl, or optionally substituted from the group consisting of alkyl, acyl, aroyl and aryl. Represents a group that may be used.

R2 represents hydrogen, halogen, nitro, CN, alkoxy, alkylthio, halogenalkoxy, halogenoalkylthio, alkoxyalkyl, or an optionally substituted group from the group consisting of acyl, aroyl, alkyl and aryl, or R1 and R2 together with adjacent CJI atoms represent an optionally substituted saturated or unsaturated carbocyclic or heterocyclic ring, which optionally carries a carbonyl function. Often, R3 is a group CN, C0OR, C0NR'' R9 or C
0RI O, R4 represents hydrogen or alkyl, R5 represents hydrogen, optionally substituted alkyl, cycloalkyl, alkenyl, optionally substituted aryl or heteroaryl, R6 represents hydrogen , optionally substituted alkyl, cycloalkyl, alkenyl, optionally substituted aryl or heteroaryl, R7 is hydrogen, optionally substituted alkyl, cycloalkyl, alkenyl or represents optionally substituted aryl, R8 represents hydrogen, alkyl or cycloalkyl, R9 represents hydrogen, optionally substituted alkyl or optionally substituted aryl, and RIO represents an optionally substituted alkyl or an optionally substituted aryl] It has been found that chenyl ureas or monoisoureas have a remarkable production-enhancing activity in animals. Some of the chenyl ureas and -isoureas of formula 1 are known.

Formula ■ [wherein A represents the group Ia -N C-N R5R' Ia, R1 is hydrogen, halogen, nitro, CN, alkoxy, alkylthio, halogenoalkoxy, halogenoalkylthio, alkoxyalkyl, or acyl, aroyl and represents an optionally substituted group from the group consisting of aryl, R2 is hydrogen, halogen, nitro, CN, alkoxy, alkylthio, halogenoalkoxy, halogenoalkylthio, alkoxyalkyl, or acyl, aroyl, alkyl and aryl; or R1 and R2 together with the adjacent C atoms represent an optionally substituted saturated or unsaturated carbocyclic group; , which may optionally carry a carbonyl function, R3 represents a group CN, COOR7, C0NRI R9 or C0RI O.

R4 represents hydrogen or alkyl; R5 represents hydrogen, optionally substituted alkyl, cycloalkyl, alkenyl, or optionally substituted aryl.

R6 represents hydrogen, optionally substituted alkyl, optionally substituted aryl or heteroaryl, R7 represents hydrogen, optionally substituted alkyl, cycloalkyl, alkenyl, optionally substituted represents optionally substituted aryl or heteroaryl; R8 represents hydrogen, alkyl or cycloalkyl;

R9 represents hydrogen, optionally substituted alkyl, cycloalkyl, alkenyl or optionally substituted aryl, and RIO represents optionally substituted alkyl or optionally substituted For example, the chenyl ureas of the formula [wherein 11i1, R2 and R3 have the above-mentioned meanings] can be used as the chenyl ureas of the formula [H-NR5R6ffr], where R5 and R6 are It can be produced by a method of reacting with amines having the above meaning.

2. Other than 3-methoxycarbonyl-chenyi 2-lysocyanate, , aroyl and aryl, and R2 is hydrogen, halogen, nitro, CN, alkoxy, alkylthio, halogenoalkoxy, halogenoalkylthio, alkoxyalkyl, or acyl, aroyl, alkyl and aryl, or R1 and R2 together with adjacent C atoms represent an optionally substituted saturated or unsaturated carbocyclic ring. represents the formula, which may optionally have a carbonyl function, R3 is a group COOR', CONR'' R9 or C
0RI Represents O.

R7 represents hydrogen, optionally substituted methyl, cycloalkyl, C24-alkenyl or optionally substituted aryl, R8 represents hydrogen or alkyl or cycloalkyl, R9 represents hydrogen, optionally represents optionally substituted alkyl or optionally substituted aryl, and RIO represents optionally substituted alkyl or optionally substituted aryl] Discovered isocyanates.

3. 1 more type V [During the ceremony.

R1, ) i2 and R3 have the meanings indicated in 2 (above)] Novel thenyl isocyanates of the formula (2) according to 2 (above), characterized in that thhenylamines of the following are reacted with phosgene. We also discovered a method for producing similar products.

4.Furthermore, the formula■ [During the ceremony.

n represents 3.4, 5 or 6.

A represents the groups Ia and 1b -N-C-NR5R6I a and R3 represents the group CN, C0 if n represents 3.5 or 6;
OR', C0NR'' R9 or C0RI O, or when n represents 4, the group COOCH3, Co
o (C24-alkenyl), represents C0NRI R9 or CORI', and R4 represents hydrogen or alkyl.

R5 represents hydrogen, optionally substituted alkyl, cycloalkyl2alkenyl, optionally substituted aryl or heteroaryl.

R6 represents hydrogen, optionally substituted alkyl, cycloalkyl, alkenyl, optionally substituted aryl or heteroaryl, R7 represents hydrogen, optionally substituted alkyl, cycloalkyl , alkenyl or optionally substituted aryl, R8 represents hydrogen, alkyl or cycloalkyl.

R9 represents hydrogen, optionally substituted alkyl or optionally substituted aryl, and RIO represents optionally substituted alkyl or optionally substituted aryl. We have also discovered new chenyl ureas or -isoureas.

5. Formula■ [During the ceremony.

n represents 3.4.5 or 6.

A represents the groups Ia and 1b -N-C=N-R6l b , R3 represents the group CN, C0 if n represents 3%5 or 6;
OR”, C0NR” Rθ or C0RI O, or when n represents 4, the group COOCH3, C
oo (C2-a-alkenyl), representing C0NR8R9 or C0RIO.

R4 represents hydrogen or alkyl, R5 represents hydrogen, optionally substituted alkyl, cycloalkyl, alkenyl, optionally substituted aryl or heteroaryl.

R6 represents hydrogen, optionally substituted alkyl, cycloalkyl, alkenyl, optionally substituted aryl or heteroaryl, R1 represents hydrogen, optionally substituted alkyl, cycloalkyl , alkenyl or optionally substituted aryl, R11 represents hydrogen, alkyl or cycloalkyl.

R9 represents hydrogen, optionally substituted alkyl or optionally substituted aryl, and RIO represents optionally substituted alkyl or optionally substituted aryl. ] The chenyl ureas or -isoureas of a) A is a group I
When a represents hydrogen and R5 represents hydrogen, chenylamines of the formula ■ [wherein n, R3 and R4 have the above meanings] can be substituted with the formula ■0CN-R6Vl [wherein R6 has the above meanings]. or b) if A represents a group Ia and R4 represents hydrogen, then the isocyanates of the formula ■ [wherein n and R3 have the above meaning] Chenyl isocyanates are reacted with amines of the formula 1 H-NR5R6IT [in which R5 and R6 have the above meanings, or c) when A represents the group Ib, reacted with amines of the formula 1 [in the formula .

n, R'' and R4 are the chenylamines of 1 having the above-mentioned meanings; It was also found that it can be obtained by reacting with halides.

It is completely surprising that the chenyl ureas of formula 1 have production enhancing properties in animals. This new use of partially known chenyl ureas of formula 1 has never been shown in the prior art.

Suitable chenyl ureas of formula I are such that A represents the group Ia or Ib and R1 is hydrogen, halogen, nitro, CN, C,-a-alkoxy, C1-4-furkylthio, optionally substituted. Cl-6-acyl or optionally substituted aroyl, especially benzoyl, or optionally halogen, C1-4-alkoxy, Cl-4-alkylthio, aryl, especially phenyl, aryloxy, especially phenoxy , arylthio, especially phenylthio,
represents C1-6-alkyl which may be substituted by amino, C1-4-fulkylamino, di-01-4-alkylamine or arylamine, in particular phenylamino, or represents phenyl, where the phenyl group is optional. one or more of the following substituents: halogen, C1-4
-alkyl, CN, C, -a-alkoxy, C1-4-
Furkylthio, phenyl, phenoxy, phenylthio,
Amino, Cl-4-flukylamino, Di01-4-alkylamine, C1-4-flucoxyalkyl, C1-
4-halogenoalkyl, CI-4-halogenoalkoxy, cm-4-halogenoalkylthio, methylenedioxy and ethylenedioxy optionally substituted with halogen 7, and acyl.

R2 represents a group mentioned for R1 or R1 and R2 taken together with two adjacent C atoms,
having 5-8 ring members and optionally OH.

C1-4-alkyl, halogen, nitro, CN.

C1-4-alkoxy, C1-4-alkylthio, phenyl, phenoxy, phenylthio, amine, Cl-4-
alkylamino, Cl-4-dialkylamino, ci-
represents a saturated or unsaturated carbocyclic group optionally substituted by a-halogenoalkyl, C1-4-halogenoalkoxy, cm-a-halogenoalkylthio or Cl-4-flucoxyalkyl, where the thiophene ring is replaced with One of the unbonded ring members is a carbonyl function (C=
If R1 and R2 together with the adjacent atoms form a heterocyclic ring, this has 5-6 ring members and has 0, S or N as the petero atom; 13 groups CN, C0OR', CONRI R9* or COR' O, R4 represents hydrogen or Cl-4-alkyl and R5 represents hydrogen or optionally halogen.

C1-4-alkoxy, C1-4-alkylthio, aryl, especially phenyl, aryloxy.

especially phenoxy, arylthio, especially phenylthio, amino, Cl-4-alkylamine or di-ci-4
-C1-6 optionally substituted by alkylamino
-alkyl, or C3-8-cycloalkyl or C2-6-alkenyl, or further represents phenyl or naphthyl, in which the phenyl group optionally carries one or more of the following substituents: halogen, cm-a- Alkyl, CN%C1-4-alkoxy, cm-a-alkylthio, phenyl, phenoxy, phenylthio, amino,
Cl-4-fulkylamino, di-01-4-alkylamino, C1-4-flukoxyalkyl, Cl-4-halogenoalkyl, C1-4-halogenoalkoxy, Cl-
4-halogenoalkylthio, optionally with halogen-substituted methylenedioxy or ethylenedioxy, or optionally with CI-4-alkyl, CN, halogen or C1-4-alkoxycarbonyl represents chenyl, which may be 7- or poly-substituted, and R6, R7 and R9 represent the groups mentioned for R5.

R8 is hydrogen or cm-4-alkyl or C3-8
- represents cycloalkyl, and RIO represents a group other than hydrogen as listed for R5.

Particularly preferred compounds of formula 1 are those in which A represents a radical Ia or Ib and R1 is hydrogen, C1-6-alkyl optionally substituted by fluorine, chlorine or bromine, or optionally 0
represents phenyl optionally substituted by 1-4-alkyl, halogen, C1-4-halogenoalkyl, especially trifluoromethyl, or C1-4-halogenoalkoxy, especially trifluoromethoxy, or nitro or acyl, in particular acetyl, and R2 represents the group mentioned for R1, or R1 and R2, together with the adjacent C atoms, may be optionally substituted by Cl-4-alkyl and optionally represents a saturated 5-8 carbocyclic group which may also have a carbonyl function on the ring member not bonded to the thiophene ring, or together with the adjacent 0M atoms optionally represents a halogen, especially Chlorine, nitro or Cl-4
-represents a fused benzene ring optionally substituted by alkyl, R3 represents a group CN%COOR', CONRI R9 or CORIG, R4 and R6 represent hydrogen;

R5 is hydrogen, C1-6-alkyl, C1-4-furkylthio-c'5-a-alkyl, cycloalkyl having up to 8 carbon atoms, C2-4-alkenyl, optionally 01-4-alkyl, C1-4 -halogenoalkyl, c, -C4-alkoxy, phenyl optionally substituted by halogen, especially chlorine, or nitro, optionally CN, C1-4
- naphthyl or chenyl optionally substituted by alkyl or C1-4-alkoxycarbonyl, R7 is hydrogen, Cl-4-alkyl, in particular methyl, ethyl or n- or t-butyl, C2-4-alkenyl, In particular, it represents allyl or phenyl, and R8 represents hydrogen or C1-4-alkyl.

R9 represents hydrogen or Cl-4-alkyl, especially methyl or ethyl, and RIO represents 01-4-alkyl, especially methyl, or phenyl.

Compounds of formula I which may be mentioned in particular are: A represents a group Ia.

R1 is hydrogen, C1-5-alkyl, especially methyl, ethyl, isopropyl, t-butyl or n-pentyl,
acetyl, phenyl or nitro, R2 represents a group mentioned for R1, or R1 and R2 together are fused to a thiophene ring and optionally Cl-4-alkyl, especially methyl,
represents a cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclohexanone or benzene ring optionally substituted by halogen, in particular chlorine or nitro, and R3 is a group CN, GOOR7, CONRI R9 or C
0RI O, R4 and R6 are hydrogen, R5 is hydrogen, cis-alkyl, cycloalkyl having up to 6 carbon atoms, or optionally halogen, in particular chlorine, nitro, methyl, methoxy or trifluoromethyl; optionally substituted phenyl; R7 represents hydrogen, Cl-4-alkyl, especially methyl, ethyl or n- or tert-butyl, C2-4-alkenyl, especially alkyl, or phenyl;

R8 represents hydrogen.

R9 represents hydrogen or methyl, and RIO represents methyl or phenyl.

In addition to those mentioned in the examples, the following compounds may be mentioned in particular:
Threshold: A part of the chenyl ureas of formula 1 is known.

They are prepared by known methods (German Published Specification 2,122.6
36 and 2,627,935).

Chenyl compounds of the formula (1) in which the group A in the 2-position of the chenyl ring represents a urea group of the formula Ia are the chenyl compounds of the formula (1) 2-
It can be prepared particularly advantageously by a method in which isocyanates are reacted with amines of the formula (1) (see method 2 above).

When 2-isocyanato-3-cyano-4,5-tetramethylene-thiophene and methylamine are used, one reaction process can be represented by the following reaction formula: Preferably used compounds of formula (1) are represented by the formula In the case of the compounds of I, the substituents Ht, H2 and R3 have the preferred meanings given.

The compounds in 2) are new. They are manufactured by the method described under 4, which is explained in more detail below.

In addition to those mentioned in the examples, the following compounds 2) may be mentioned in particular: 2-isocyanato-3-cyanothiophene, 2-isocyanato-3-carbethoxy-5-isobutyl-thiophene, 2-isocyanato-3-cyano-4,5-trimethylene-thiophene, 2-isocyanato-3-methoxycarbonyl-4,5
-1rimethylene-thiophene, 2-isocyanato-3-
Ethoxycarbonyl-4,5-)rimethylene-thiophene, 2-isocyanato-3-t-butoxycarbonyl-
4,5-)rimethylene-thiophene, 2-isocyanato-3-cyano-4,5-pentamethylene-thiophene,
2-isocyanato-3-methoxycarbonyl-4,5-
Pentamethylene-thiophene, 2-isocyanato-3-
Ethoxycarbonyl-4,5-pentamethylene-thiophene, 2-isocyanato-3-t-butoxycarbonyl-4,5-pentamethylene-thiophene, 2-isocyanato-3-carbetoxy-5-phenyl-thiophene and 2-isocyanato- 3-Carbethoxy-4-methyl-5-phenyl-thiophene. Preferably used compounds of formula (1) have the preferred meanings given in the substituents R5 and R6 in the case of compounds of formula 1. The compounds of formula 0 (2) are known organic chemical compounds.

Particular mention may be made of the compounds of the following formula ■: ammonia,
Methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, di-n-propylamine, isopropylamine, diisopropylamine, n-
Butylamine, i-butylamine, secondary-butylamine, t-butylamine, cyclopentylamine,
Cyclohexylamine, aniline, 2-chloroaniline, 3-chloroaniline, 4-chloroaniline, 2-nitroaniline, 3-nitroaniline, 4-nitroaniline, 2-methylaniline, 3-methylaniline, 4-methylaniline, 2-methoxyaniline, 3-methoxyaniline, 4-methoxyaniline, 2-trifluoromethylaniline, 3-trifluoromethylaniline and 4-
Trifluoromethylaniline.

In order to produce the chenyl ureas of the formula (1), the thenyl isocyanates (2) and the amines of the formula (2) are reacted in approximately equimolar amounts. Excess amounts of either component do not provide any substantial benefit.

The reaction can be carried out with or without diluent. Mentioned as diluents are all inert organic solvents. These include, in particular, aliphatic and aromatic optionally halogenated hydrocarbons;
For example, pentane, hexane, heptane, cyclohexane, petroleum ether, henzine, ligroin, benzene, toluene, methylene chloride, ethylene chloride, chloroform,
Carbon tetrachloride, chlorobenzene and. - dichlorobenzene, and ethers, such as diethyl ether, dibutyl ether, glycol dimethyl ether, diglycol dimethyl ether, tetrahydrofuran and dioxane, and ketones, such as acetone, methyl ethyl ketone, methyl isopropyl ketone and methyl isobutyl ketone, and esters, such as methyl acetate. and ethyl acetate, and nitriles such as acetonitrile, propionitrile, benzonitrile and dinitrile glugurate, and amides such as dimethylformamide, dimethylacetamide and N-methylpyrrolidone, and dimethylsulfoxide, tetramethylenesulfone and hexamethylphosphoric triamide. Included.

Catalysts can also be added to accelerate the reaction process. Suitable catalysts are, for example, tertiary amines, such as pyridine, 4-dimethylaminopyridine, triethylamine, trimethylenediamine and trimethylene-tetrahydropyridimidine, and tin-■ and tin-■ compounds, such as tin-■octoate. The tertiary amines listed as reaction accelerators can also be used as solvents.

The reaction temperature can be varied within a substantial range. Generally one reaction is carried out between 0°C and 120°C, preferably between 20°C and 70°C.
It is carried out between ℃ and ℃.

The reaction is normally carried out under normal pressure, but, for example when low-boiling amines are used, it is advantageous to carry out the reaction in a closed vessel under pressure.

In carrying out the process according to the invention, the starting materials are generally used in stoichiometric amounts, although a slight excess of amine is advantageous. Catalysts are preferably used in amounts of from 0, oi to 0.1 mole per mole of reactant, although larger amounts of eg tertiary amines can also be used.

The reaction products are isolated by directly filtering the precipitated products from the corresponding solvents or by distilling off the solvent.

As mentioned above, the chenyl isocyanates (2) are new. Preferred chenyl isocyanates (2) are the substituents R1-Ha in the case of the substituents R1-R3 of the compounds of formula 1;
has the meaning given as being suitable for use. Particularly suitable compounds of method 2 are those mentioned in method 2.

The chenyl isocyanates of 2m can be prepared by reacting the corresponding chenylamines of formula V with phosgene. When using 2-amino-3-acetyl-4,5-tetramethylenethiophene and phosgene, the reaction process can be represented by the following reaction formula: Preferably used chenylamines of formula V are Compounds of the formula V having the meanings given as preferred in the case of the substituent RI R3 of the compounds are known or can be prepared by methods analogous to known methods (K., Gewal et al. F (Gewald), Other Hemische Φ Berichte (Chem, Ber,), 98 (1
965), p. 3571, Hemische Berichte (Che
M, Ber, ), 99 (1966), p. 94, European Publication Specification 4,931).

Particular mention may be made of the following compounds of formula V: 2-amino-3-cyano-4,5-trimethylene-thiophene, 2-
Amino-3-methoxycarbonyl-4,5-)rimethylene-thiophene, 2-amino-3-ethoxycarbonyl-4,5-trimethylene-thiophene, 2-amino-3
-t-'Toxycarbonyl-4,5-)rimethylene-thiophene, 2-amino-3-cyano-4,5-tetramethylene-thiophene, 2-amino-3-methoxycarbonyl-4,5-tetramethylene -thiophene, 2-amino-3-ethoxycarbonyl-4,5-tetramethylene-thiophene, 2-amino-3-t-butoxy-carbonyl-4,5-tetramethylene-thiophene, 2-amino-3-cyano- 4,5-pentamethylene-thiophene, 2-amino-3-methoxycarbonyl-4,5-pentamethylene-thiophene, 2-amino-3-ethoxycarbonyl-4,5-pentamethylene-thiophene, 2
-amino-3-t-butoxy-carbonyl-4,5-pentamethylene-thiophene, ? -amino-3-carbetoxy-4-methyl-5-phenyl-thiophene, 2-amino-3-carbetoxy-4-methyl-5-ethyl-thiophene, 2-amino-3-carbetoxy-5-n-butyl-thiophene, 2 -Amino-3-carbetoxy-5
-isobutyl-thiophene, 2-amino-3-carbetoxy-4-ethyl-5-methyl-thiophene, 2-amino-3-carbetoxy-5-phenyl-thiophene, 2
-Amino-3-carbethoxy-5-ethylthiophene and 2-amino-3-carbethoxy-5-isopropylthiophene.

The reaction of the amine of formula V with phosgene can be carried out with or without a diluent.

As diluents, mention may be made of inert organic solvents, in particular aliphatic and aromatic optionally halogenated hydrocarbons, such as pentane, hexane, heptane, cyclohexane, petroleum ether, benzine, ligroin, Benzene, toluene, methylene chloride, ethylene chloride, chloroform, carbon tetrachloride, chlorobenzene and 0
-dichlorobenzene.

The reaction is carried out at -20 to +180°C, preferably -1O to +100°C.
The reaction carried out at 0°C can be carried out under normal pressure or under elevated pressure.

The starting materials are used in equimolar amounts, but an excess of 2-3 moles of phosgene per mole of amine of formula V is preferred.

The reaction is carried out in the presence or absence of an acid binder.

Acid binders 1 such as tertiary amines such as pyridine or dimethylaniline are suitable.

The reaction in which the amines of formula V are added to a solution of phosgene and the reaction is carried out optionally with further passage of phosgene can also be carried out without a solvent.

As mentioned above, the chenyl ureas of formula (1) are new.

Preferred chenyl ureas of formula I are those in which the groups R3 and A are of formula I
has the meaning given as preferred in the case of the compounds. Particular mention may be made of the abovementioned chenyl ureas.

The chenyl ureas of the formula (3) in which A represents the group Ia and R4 represents hydrogen can be prepared from the corresponding thenyl isocyanates and the corresponding amines by the method described above.

Details of this method have already been given above.

Chenyl ureas of the formula (2) in which A represents the group Ia and R5 represents hydrogen can be prepared from the corresponding chenylamines of the formula (2) by reaction with isocyanates of the formula (2). 2-
Methyl-amino-3-methoxycarbonyl-4,5-)
When rimethylenethiophene and phenyl isocyanate are used, the reaction process can be represented by the following reaction formula: The chenylamines of formula (2) used as starting materials are known or produced by a method similar to a known method. Possible (K, Gewald) Other Hemische
Berichte (Chem, Ber), 98 (1965)
, p. 3571, Chem, Be
r, ), 99 (1966), p. 94, European Publication Specification 4.931, G. Coppola
) and 6 other The Journal of Heterocyclic
Chemistry (J, Heterocycle, Chem,
), 1982, p. 717).

The chenylamines of the formula (1) which are preferably used are those having the meanings given as preferred in the substituents R3 and R4 in the case of the compounds of the formula 1.

Particular mention may be made of the compounds of formula (1) listed on pages 50-52.

The isocyanates used as starting materials are known. Examples which may be mentioned in particular are methyl isocyanate, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tertiary-butyl and phenyl isocyanate; 3. -chlorophenyl isocyanate, 4-chlorophenyl isocyanate and 2,6-dichlorophenyl isocyanate.

The reaction between chenylamines and incyanates according to the invention is preferably carried out in the presence of a diluent. Suitable diluents are all inert organic solvents. They include, in particular, aliphatic and aromatic optionally halogenated hydrocarbons, such as pentane, hexane,
Heptane, -cyclohexane, petroleum ether, benzine, ligroin, benzene, toluene, methylene chloride,
Ethylene chloride, chloroform, carbon tetrachloride, chlorobenzene and 0-dichlorobenzene, and ethers,
For example, diethyl ether, dibutyl ether, glycol dimethyl ether, diglycol dimethyl ether,
Tetrahydrofuran and dioxane, and ketones such as acetone, methyl ethyl ketone, methyl isopropyl ketone and methyl isobutyl ketone, and esters such as methyl acetate and ethyl acetate, and nitriles such as acetonitrile, propionitrile, benzonitrile and dinitrile glutarate, and amides such as dimethylformamide, dimethylacetamide and N-methylpyrrolidone, as well as dimethylsulfoxide, tetramethylenesulfone and hexamethylphosphoric triamide.

Catalysts can also be added to accelerate the reaction process. Suitable catalysts are, for example, tertiary amines such as pyridine, 4-dimethylaminopyridine, triethylamine, triethylenediamine and trimethylene-tetrahydropyridimidine.

The tertiary amines mentioned as reaction accelerators, which are also tin-1 and tin-2 compounds, such as tin-2 octoate or tin-2 chloride, can also be used as solvents.

The reaction temperature can vary within a substantial range, generally one reaction is between 0°C and 120°C, preferably between 20°C and 70°C.
It is carried out between ℃ and ℃.

The reaction is normally carried out under normal pressure, but for example when low clearing point isocyanates are used it is advantageous to carry out the reaction in a closed vessel under pressure.

In carrying out the process according to the invention, the starting materials are generally used in stoichiometric amounts, although a slight excess of isocyanate is advantageous. Catalysts are preferably used in amounts of 0.01 to 0.1 mole per mole of reactant, although higher amounts, such as tertiary amines, can also be used.

The reaction products are isolated by directly filtering the precipitated products from the corresponding solvents or by distilling off the solvent.

The chenyl ureas of the formula (2) in which A represents the formula Ib can be prepared from the corresponding chenylamines of the formula (1) by reaction with the corresponding imide carbonate halides of the formula X. When using 2-ethylamino-3-benzoyl-4,5-hexamethylenethiophene and N-phenyl-imido carbonic acid ethyl ester-chloride, the reaction process can be represented by the following reaction formula: The chenylamines mentioned are preferably used.

Imide carbonate halides are known.

In formula X, R5 and R6 preferably have the preferred meanings given above.

Halogen particularly stands for chlorine.

The following imidocarbonate ester-halides may be mentioned in particular: N-methylimidocarbonate ethyl ester-chloride, N-ethyl-imidocarbonate ethyl ester-chloride, N-propyl-imidocarbonate methyl ester-chloride and N-phenylimidoethyl carbonate. Ester-chloride.

The reaction is optionally carried out in the presence of acid acceptors, catalysts and diluents.

The compounds of formulas 1 and X are preferably used in equimolar amounts. Excess amounts of either component do not provide any substantial benefit.

Diluents that can be used are all inert organic solvents.

These include, in particular, aliphatic and aromatic optionally halogenated hydrocarbons, such as pentane, hexane, heptane, cyclohexane, petroleum ether, benzine, ligroin, benzene, toluene, methylene chloride, ethylene chloride, Chloroform, carbon tetrachloride, chlorobenzene and 0-dichlorobenzene, and ethers such as diethyl ether, dibutyl ether, glycol dimethyl ether, diglycol dimethyl ether, tetrahydrofuran and dioxane, and ketones such as acetone, methyl ethyl ketone, methyl isopropyl ketone and Methyl isobutyl ketone, and esters such as methyl acetate and ethyl acetate, and nitriles such as acetonitrile, propionitrile, benzonitrile and dinitrile glutarate, and amides such as dimethylformamide, dimethylacetamide and N-methylpyrrolidone, and Included are dimethyl sulfoxide, tetramethylene sulfone and hexamethyl phosphoric triamide.

All common acid binders can be used as acid acceptors. They suitably include alkali metal carbonates, hydroxides or alcoholates, such as sodium or potassium carbonate, sodium and potassium hydroxide, and sodium and potassium methylates or ethylates, as well as aliphatic, aromatic or hetero Cyclic amines such as trimethylamine, triethylamine, tributylamine, dimethylaniline, dimethylbenzylamine,
Included are pyridine and 4-dimethylamino-pyridine.

Catalysts that can be used are compounds commonly used for phase transfer of reactants during reactions in two-phase systems of water and water-immiscible organic solvents (phase transfer catalysts). Preferred compounds of this type are particularly those having from 1 to 10.0 carbon atoms per alkyl group. Especially 1 to 8. and 7 of the aralkyl group
It has phenyl as a lyl component, and the number of carbon atoms in the alkyl part of the aralkyl group is preferably 1 to 4. In particular, tetraalkyl- and trialkylaralkyl-ammonium salts such as 1 or 2. Compounds that can be used here are in particular halides, e.g. chlorides,
Bromides and iodides, preferably chlorides and bromides.

Examples that may be mentioned are tetrabutylammonium prolide, benzyl-triethylammonium chloride and methyltrioctylammonium chloride.

The reaction temperature is between about 0°C and 130°C, preferably between about 20°C and
It is kept between 60°C. The process is preferably carried out under normal pressure. Processing is carried out in a conventional manner.

Active compounds are used in animals to increase and promote growth and milk and wool production and to improve feed utilization and meat quality and to shift the meat/fat ratio towards meat.

The active compounds are used for farm animals, livestock animals, ornamental animals and pets.

Farm and farm animals include mammals 1 such as cattle,
Pigs, horses, sheep, goats, rabbits, hares, small deer, as well as haired animals such as mink and chinchillas, poultry such as chickens,
Included are turkeys, geese, ducks and pigeons, fish such as carp, rainbow trout, salmon, eel, tench and pike, and reptiles such as snakes and crocodiles.

Ornamental animals and pets include mammals such as dogs and cats, birds such as parrots and canaries, and fish such as ornamental and tropical fish such as goldfish.

The active compounds are used during all stages of animal growth and production, irrespective of the sex of the animal. The active compounds are preferably used during the intended growth and production stages. Depending on the type of animal, the intended growth and production stage can range from 1 month to 1 month.
Lasts for up to 0 years.

The amount of active compounds administered to an animal to obtain the desired effect can vary substantially depending on the advantageous properties of the active compounds. It is preferably about 0.00% per day.
001-50mg/)Cg, special 1. :o, 01~5
The body weight is mg/kg. The appropriate amount of active compound and the appropriate duration of administration depend, inter alia, on the species, age, sex, health condition as well as the nature of the housing and the method of breeding of the animal, and they can be easily determined by a specialist.

The active compounds are administered to animals in a conventional manner. The nature of administration depends, inter alia, on the species, nature and state of health of the animal.

The active compounds can also be administered at once. However, the active compounds can also be administered intermittently or continuously during all or part of the growth stage. For continuous administration, they can be used once or several times a day, at regular or irregular intervals.

Administration takes place orally or parenterally, in preparations suitable for this purpose or in pure form. Oral preparations include powders, tablets, granules, pills and boli.
, as well as feed, premixes for feed and preparations for administration with drinking water.

Oral preparations contain active compound from 0.01 ppm to 200%
, preferably at a concentration of 0.01 ppm-1%.

Parenteral preparations are injections in the form of solutions, emulsions and suspensions, as well as implants.

The active compounds can be used alone or in combination with other active compounds, mineral salts, rare elements, vitamins, proteins, etc. in the preparation.
It can be present in a mixture with colorants, fats or flavoring substances.

The concentration of active compound in the feed is generally about 0.001-50
0pp, preferably 0.11-50pp.

It is.

The active compounds can be added to the feed neat or in the form of a premix or feed concentrate.

An example of a poultry feed composition containing the active compound according to the invention: 200 g wheat, 340 g corn, 361 g coarse soybean flour, 60 g beef tallow, 15 g dicalcium phosphate, 10 g calcium carbonate, 4 g of iodized sodium chloride, 7.5 g of vitamin/mineral mixture and 2.5 g of active compound premix are thoroughly mixed to give 1 kg of feed.

1 kg of feed mixture is 6001. U, vitamin A,
1001. U, vitamin yD3.10mg vitamin yE
, 1 mg Vitamin YK3.3 mg Noripoflavin,
2mg pyridoxine, 20mcg vitamin BH2,
5 mg calcium pantothenate, 30 mg nicotinic acid, 200 mg choline chloride, 200 mg M n S
O2X H20.

140mg Z n S 04 X 7 H20, lo
omg FeSO4X7H20 and 20mgc7)C
Contains uSoa X5H20.

A 2.5 g active compound premix contains, for example, 10 mg of active compound, 1 g of DL-methione and the remaining amount of soybean flour.

An example of a pig feed composition containing the active compound according to the invention is 630 g of shredded grain feed (200 g of shredded grain feed).
g corn, 150 g shredded barley, 1
(consisting of 50 g shredded oats and 130 g shredded wheat), 80 g fish hikiwari, 60 g coarse soybean hikiwari, 60 g tapioca hikiwari, 38
g of brewer's yeast, 50 g of vitamin/mineral mixture for pigs, 30 g of linseed oil cake flaxseed, 30 g of corn gluten feed, 10 g of soybean oil, log of sugarcane molasses and 2 g of active compound premix (such as for chicken feed). Group T) was thoroughly mixed and fed with 1 kg of feed.

The feed mixtures mentioned above are preferably for feeding and fertilizing chickens and pigs, but they can also be used with the same or similar composition for feeding other animals.

Mouse breeding test SPF Wistar type (breeder Hegeman) weighs 90-
A 110 g female laboratory rat was prepared and fed ad libitum with standard rat chow supplemented with the desired amount of active compound. Differences in the composition of the food did not impair the comparability of the results, as each test system was performed using food from the same source.

The rats had access to water at all times.

Each test group consisted of 12 rats, which were provided with food supplemented with the desired amount of active compound. The control group received food containing no active compound. Comparisons between test groups are warranted because the mean body weight and body weight dispersion of the rats are the same in each test group.

Weight gain and food consumption were measured during the 13-day study.

The results shown in the table below were obtained.

ao rumors
Example 4 Preparation: 5 g (0,023 mol) of 2-aminothe-drobenzothiophene-3-carboxylic acid (K, Gewald, Hemische Berichte).

94 (1966) and 1.4 g.
(0,024 mol) of methyl l anate in 100 m
The chloroform phase was heated under reflux for 24 h, then the chloroform phase was washed three times with 50 ml of water each, dried over sodium sulfate, and the evaporated crude product was recrystallized from ethanol. Ta.

: 5.5g (95%), melting point 202℃ Solution) Elemental analysis 2 Calculated value: G 52.2 Actual value, C
Preparation of 52,2H8,OH5,9 N 18.8 N 18.8 5.3 g (0.03 mol) of 2-amino-3-cyano-
Tetrahydrobenzothiophene (prepared according to the method of K., Gewald, Hemische Berichte, 99.94 (1966)) and 5.1 g (0,033 mol) of 4
-chlorophenylisocyanate was stirred in lOOml dry pyridine at 70°C for 10 hours. The precipitated crude product was filtered off with suction, washed with dilute hydrochloric acid and water and recrystallized from ethanol.

Yield near, 1g (72%): Melting point>250℃ Elemental analysis:
Calculated value: C57J Actual value: C58,0H4,
3H4,2 N 12.7 N 12.7CI
10.7 C110,750ml
4 g (19,4 mmol) of 2-isocyanato-4-tert-butyl-3-cyano-thiophene dissolved in dry toluene were dissolved in 50 ml of 2.1 g (35,6 mmol) of isopropylamine. Add dropwise to the solution in dry toluene. The mixture was stirred at room temperature for 1 hour. To process the solution, add 1 liter of 2.5N
Stirred in hydrochloric acid, the organic phase was separated and washed with 100 ml of NaHCO3 solution. The residue remaining after evaporation of toluene in vacuo was recrystallized from toluene/petroleum ether.

Yield = 1.88g (36.5% of theory) Melting point: 183
-184°C Example 4 6.4g (35mol) of 2-carbomethoxy-3-
Isocyanato-thiophene (Esso Research and Engineering Company, Belgian Patent No. 767)
．． 244-Q) in toluene at 2.2
g (37 mmol) of isopropylamine in 50 ml of dry toluene was added dropwise at 0°C. The mixture was stirred for a further 2 hours at room temperature, the product was then filtered off with suction and dried in vacuo.

Yield: 6.8 g (80.3% of theory) Melting point: 119°C The following compounds were obtained by the method of Examples 1-4: fQ M tQ (Qfi
ff) l”3-111-4
■4 -～
~ to --- -ha111 -N ~-to
RO SOUTH 1 Go to N
-CQ to to to to to
− to △ cQ (6011 prisoners)
- to
The cry! ! cry
Lee -16se+5 Sentry
- to --to 1 1 'l l
lcQ cQ m m
mψ tao 6a
Ro-! Compounds of the following formulas were also obtained in the same manner as in Example 1-4: - -
Prisoner△
△θ To a5 ■
RoCIOGo Go
■The following were also produced: Preparation of starting materials 78 g of 2-cyanato-3-carboethoxythiophene (
A solution of 2-amino-3-carboethoxythiophene (0.46 mol) in 700 ml of toluene is dissolved in 338 ml of a 20% strength phosgene solution (0.68 mol) in toluene.
Added dropwise at 10°C. When the direct addition was complete, the mixture was allowed to reach room temperature for 1 hour and then slowly warmed to the boiling point over 1 hour. The dark brown solution was boiled under reflux for a further 2 hours and the excess phosgene was then driven off by passing into an atmosphere of dry nitrogen. First, toluene was distilled off in vacuo while distilling the residue using an oil pump.

Boiling point: 95° C. under 6 Pa Yield: 61.8 g, 69% of theory Starting materials IIK. Gewald, Hemische Berichte, 1
3571-3577 (1965) and Gewald, E. Schinke and H. Bottcher, Hemische Berichte,
In addition, 94-100 (192) chenyl isocyanates were obtained in the same manner.

The following compounds were obtained in a similar manner: °C
Xun 1 (.

One. ′
i-&! -hI! Example 11a 2-amino-3-t-butoxycarbonyl-4°5-dimethylthiophene batch: 100 g (0.71 mol) tert-butylcyanoacetate, sl, 2 g (0° 71 mol) butanone, 23.9 g (0.75 mol) of sulfur,
71 ml morpholine and 140 ml analytical grade ethanol.

The ketone was dissolved in ethanol and then morpholine and sulfur were added.

Tert-butyl cyanoacetate was added dropwise to the yellow suspension and the mixture was then warmed to 60°C for 3 hours.

After cooling, pour the mixture into 1 liter of water and add 750 ml
of ether was added, the organic phase was separated, the aqueous phase was
Extracted with 0ml of ether. - 2 extracts combined
x 200 ml NaOH (5% strength), 200 m
1c7) Water, 2 x 200 ml 5% strength H2504
, 200 ml water and 200 ml NaHCO3
and dried using NaSO4. After evaporating the solvent in vacuo, 133.8 g remained.

The crude product was seeded and the contents of the flask solidified.

Yield = 50g = 31% of theoretical value Melting point: 82-85℃ Similarly, the expression of aminothiophenes were obtained.

~ cf5 ri ω - ro -Size■Roheto ＜　　　　　( Song

Claims (1)

[Claims] 1. Formula I as a production enhancer for animals ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ I [In the formula, A is the group I a and 1b ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ I a ▲There are mathematical formulas, chemical formulas, tables, etc.▼1b Represents R^1, hydrogen, halogen, nitro, CN, alkoxy,
Alkylthio, halogenoalkoxy, halogenoalkylthio, alkoxyalkyl, or an optionally substituted group from the group consisting of alkyl, acyl, aroyl and aryl, R^2 is hydrogen, halogen, nitro, CN, alkoxy,
represents alkylthio, halogenoalkoxy, halogenoalkylthio, alkoxyalkyl, or an optionally substituted group from the group consisting of acyl, aroyl, alkyl and aryl, or R^1 and R^2 represent adjacent C atoms. together with represent an optionally substituted saturated or unsaturated carbocyclic or heterocyclic ring, which may optionally carry a carbonyl function, R^3 is a group CN , COOR^7, CONR^3R^9 or COR^1^0, R^4 represents hydrogen or alkyl, R^5 is hydrogen, optionally substituted alkyl,
Represents cycloalkyl, alkenyl, optionally substituted aryl or heteroaryl, R^6 is hydrogen, optionally substituted alkyl,
Represents cycloalkyl, alkenyl, optionally substituted aryl or heteroaryl, R^7 is hydrogen, optionally substituted alkyl,
represents cycloalkyl, alkenyl or optionally substituted aryl, R^8 represents hydrogen or alkyl or cycloalkyl, R^9 represents hydrogen, optionally substituted alkyl or optionally substituted and R^1^0 represents optionally substituted alkyl or optionally substituted aryl]. Formula III other than 2,3-methoxycarbonyl-thieny-2-lysocyanate ▲There are mathematical formulas, chemical formulas, tables, etc.▼III [In the formula, R^1 is hydrogen, halogen, nitro, CN, alkoxy,
Alkylthio, halogenoalkoxy, halogenoalkylthio, alkoxyalkyl, or an optionally substituted group from the group consisting of alkyl, acyl, aroyl and aryl, R^2 is hydrogen, halogen, nitro, CN, alkoxy,
represents alkylthio, halogenoalkoxy, halogenoalkylthio, alkoxyalkyl, or an optionally substituted group from the group consisting of acyl, aroyl, alkyl and aryl, or R^1 and R^2 represent adjacent C atoms. together with represent an optionally substituted saturated or unsaturated carbocyclic ring, which may optionally carry a carbonyl function, R^3 is a group COOR^7, CONR^ 8R^9 or C
OR^1^0, R^7 represents hydrogen, optionally substituted methyl, cycloalkyl, C_2-_4-alkenyl, or optionally substituted aryl, R^8 is hydrogen or represents alkyl or cycloalkyl, R^9 represents hydrogen, optionally substituted alkyl or optionally substituted aryl, and R^1^0 represents optionally substituted thienyl isocyanates representing good alkyl or optionally substituted aryl. 3. Formula V ▲There are mathematical formulas, chemical formulas, tables, etc.▼V [In the formula, R^1, R^2 and R^3 have the meanings stated in claim 2] Thienylamines of phosgene A method for producing thienyl isocyanates of formula III according to claim 2, characterized in that the thienyl isocyanates are reacted with 4.Formula VI ▲There are mathematical formulas, chemical formulas, tables, etc.▼VI [In the formula, n represents 3, 4, 5, or 6, and A is the group I a and 1b ▲There are mathematical formulas, chemical formulas, tables, etc.▼ I a ▲There are mathematical formulas, chemical formulas, tables, etc.▼1b is represented, and R^3 is a group CN, C if n represents 3, 5 or 6.
OOR^7, CONR^8R^9 or COR^1^0
or when n represents 4, the group COOCH
_3, COO (C_2-_4-alkenyl), CONR
^8R^9 or COR^1^0, R^4 represents hydrogen or alkyl, R^5 is hydrogen, optionally substituted alkyl,
Represents cycloalkyl, alkenyl, or optionally substituted aryl, R^6 is hydrogen, optionally substituted alkyl,
Represents cycloalkyl, alkenyl, or optionally substituted aryl, R^7 is hydrogen, optionally substituted alkyl,
represents cycloalkyl, alkenyl or optionally substituted aryl, R^8 represents hydrogen or alkyl or cycloalkyl, R^9 represents hydrogen, optionally substituted alkyl or optionally substituted and R^1^0 represents optionally substituted alkyl or optionally substituted aryl]. 5.Formula VI ▲There are mathematical formulas, chemical formulas, tables, etc.▼VI [In the formula, n represents 3, 4, 5, or 6, and A is the group I a and 1b ▲There are mathematical formulas, chemical formulas, tables, etc.▼ I a ▲There are mathematical formulas, chemical formulas, tables, etc.▼1b is represented, and R^3 is a group CN, C if n represents 3, 5 or 6.
OOR^7, CONR^8R^9 or COR^1^0
or when n represents 4, the group COOCH
_3, COO (C_2-_4-alkenyl), CONR
^8R^9 or COR^1^0, R^4 represents hydrogen or alkyl, R^5 is hydrogen, optionally substituted alkyl,
Represents cycloalkyl, alkenyl, optionally substituted aryl or heteroaryl, R^6 is hydrogen, optionally substituted alkyl,
Represents cycloalkyl, alkenyl, optionally substituted aryl or heteroaryl, R^7 is hydrogen, optionally substituted alkyl,
represents cycloalkyl, alkenyl or optionally substituted aryl, R^8 represents hydrogen or alkyl or cycloalkyl, R^9 represents hydrogen, optionally substituted alkyl or optionally substituted and R^1^0 represents optionally substituted alkyl or optionally substituted aryl] , a) If A represents the group I a and R^5 represents hydrogen, then the formula VII ▲ Numerical formula, chemical formula, table, etc. ▼VII [wherein n, R^3 and R^4 are as above or b) where A is a group.
When I represents a and R^4 represents hydrogen, then
Formula IX ▲There are mathematical formulas, chemical formulas, tables, etc.▼IX [In the formula, n and R^3 have the above meanings] The thienyl isocyanates of the formula IV H-NR^5R^6IV [In the formula, R^5 and R^6 have the meanings given above], or c) when A represents a group Ib, the formula VII ▲ is a mathematical formula, chemical formula, table, etc. ▼VII [wherein, n, R^3 and R^4 have the above meanings] thienylamines with the formula and Hal
represents a halogen] is reacted with an imide carbonate ester-halide. 6. An animal production enhancer containing a thienyl urea or -isourea of the formula I according to claim 1. 7. Animal feed, animal drinking water, and animal feed and animal drinking water characterized by containing a thienyl urea or -isourea of formula I according to claim 1. Additives for. 8. Use of thienyl ureas or isoureas of formula I according to claim 1 for increasing animal production. 9. A method for producing an animal production enhancer, which comprises mixing a thienyl urea or -isourea of formula I according to claim 1 with a filler and/or diluent. 10. Animal feed and drinking water for animals, characterized in that the thienyl ureas or -isoureas of the formula I according to claim 1 are mixed with feed or drinking water and other auxiliaries as appropriate. and methods for producing additives for animal feed and drinking water.