DE3348463C2 - 5-Membered hetero:aromatic chloro:acetamide derivs. - Google Patents

Abstract

(A)A5-membered heteroaromatic chloroacetamide deriv. of formula (I) is new. (where Ar is a 5-membered heteroaromatic gp.contg. 1 or 2 ring heteroatoms chosen from O, S and N, and bonded via a ring C atom to the N atom of the N(Y)COCH2Cl gp., and where if Ar is pyrazolyl, N(Y)COCH2Cl is in the 4-position; Y is allene, CH2CH=C=CH2, 1-8C alkyl, 3-8C alkenyl, 3-8C alkinyl, 3-8C cycloalkyl, 5-8C cycloalkenyl, 3-8C cycloalkyl, 1-5C alkyl, these hydrocarbyl gps.being opt. substd. by F, Cl, or Br; or Y is CGR1COY1, R2A3, A-OR3, CHR5CHR5=NOR4 or CHR6NMeCOMe; R1 is H or 1-5C alkyl; Y1 together with the CO gp. to which it is attached forms an ester or amide gp.; R2 is CH2 or CH2CH2 each opt. substd. by 1-5C alkyl (Editor - not in spec.have assumed alkyl) A3 is a heteroaromatic ring chosen from a di- or tri-azole bonded via a ring N to R2, a5-membered heteroring contg.1-3, O, S and/or N heteroatoms, and bonded via a ring C to R2, pyrimidine, 2-oxo-1-pyrrolidinyl in which a CH2 gp. is opt. replaced by O, S or NMe, and 5-oxo and/or bicyclic benz(c) bonded derivs. such as 2-oxo-1-pyrrolidinyl gps.; R3 is H, 1-8C alkyl, 3-8C alkenyl, 3-8C alkinyl, 3-8C cycloalkyl, 5-8C cycloalkenyl, 3-8C cycloalkyl 1-5C alkyl (these hydrocarbyl gps. being opt. substd.) or N=CR4R4' R4 is 1-5C alkyl, 3-5C alkenyl, 3-5C alkinyl, 3-8C cycloalkyl, 3-8C cycloalkenyl, 3-8C cycloalkyl, 1-5C alkyl (these hydrocarbyl gps.being opt. substd. by F, Cl, or Br) or allene; R4' is H or as R4; A is hydrocarbyl gp. bonded with R3 to form heteroring contg. 1 or 2 O heteroatoms so that the N and O atoms are joined by A and are sepd. by up to 3C atoms; R5 and R5' are each H or Me or together form (CH2)3 or (CH2)4; R6 is H or 1-3C alkyl). (B) The intermediate heterocyclic cpds. (II) and (III) are also new (where R7 is COCH2OH or H).(I) are selective herbicides used in e.g. soya, cotton, etc

Description

The present invention relates to new thiophene compounds in the 3-position Wear amino group. These connections are used as intermediate connections for new ones Thiophene herbicides, which in the 3-position represent an N-substituted chloroacetamido group wear, provided. The thiophene herbicides are described in DE-OS 33 03 388 and correspond to formula I.

wherein R₁ and R₂ are independently methyl or methoxy,
A represents the CH₂ or CH₂-CH₂ group or monomethylated derivatives thereof, and
RC _1-3 alkyl means.

The thiophene compounds according to the invention correspond to the formula (A)

wherein
R₁ and R₂ are independently CH₃ or OCH₃;
Z₁ represents H or the group AOR in which
A represents the CH₂ or CH₂CH₂ group or monomethylated derivatives thereof;
and RC represents _1-3 alkyl; and
Z₂ is H, COOCH₂OH or COCH₂Cl, where Z₁ is hydrogen if Z₂ is COCH₂Cl.

The thiophene compounds of the formula (A) are new. GB Patent 1,548,398 describes very generally N-acylated heteroarylamine derivatives of a general formula in which the acyl group can be a halogenated C _2-7 alkanoyl group and the hetero ring can be a thiophene ring which is optionally substituted by a C _1-6 alkyl group. Associated intermediates are also described. However, the thiophene compounds of the formula (A) according to the invention are neither specifically described in GB Pat. No. 1,548,398, nor is their structure suggested by this patent. Furthermore, GB Patent 1,548,398 relates to pharmaceuticals and their intermediates, while the thiophene compounds according to the invention are valuable intermediates for herbicidal thiophene derivatives of the chloroacetamide class.

A suitable meaning of A is e.g. B. CH₂, CH (CH₃), CH₂CH₂, CH (CH₃) CH₂; R is for example CH₃, C₂H₅ and nC₃H₇.

The compounds of the formula (A) according to the invention were specifically provided for Process for the preparation of compounds of formula I by in itself known way

• a) in a compound of formula II wherein R₁, R₂, A and R have the above meaning,
  the HO group of the N-hydroxyacetyl group is substituted by Cl, or
• b) a compound of formula III wherein R₁ and R₂ have the above meaning, with a compound of formula IVL-AOR IVworin A and R have the above meaning
  and L represents a group which can be split off under the conditions of an N-alkylation reaction, or
• c) a compound of formula VII wherein R₁, R₂, A and R are as defined above, with chloroacetyl chloride or a reactive functional derivative thereof, N-chloroacetylated.

The compounds of the formula II, III and VII correspond to sub-formulas of the formula (A). These connections are new.

The compounds of formula II can be obtained by ammonolysis of the esters of the compounds of the formula VIII

wherein R₁ and R₂ have the above meaning, with a carboxylic acid, and subsequent Introduction of a group Y (as defined above) in compounds of the formula VIII N-alkylation can be obtained.

Such esters are obtained e.g. B. by N-acylation of the corresponding compounds Formula IX

wherein R₁ and R₂ are as defined above, with a suitable ester of HOCH₂COCl, e.g. B. with CH₃CO-OCH₂COCl.

The compounds of formula III are by N-acylation of a compound of Formula IX obtained with chloroacetyl chloride.

Compounds of the formula VII can be obtained by N-alkylation of compounds of the formula IX can be obtained. Such alkylation can by known methods, with the help of suitable alkylating agents (e.g. of halides), or, where appropriate, reductively over a Schiff base or over an amide.

The compounds of formula IX also correspond to a sub-formula of formula (A). These connections are new.

The compounds of formula IX can be obtained by reducing the corresponding NO₂ compounds are obtained, for. B. by catalytic hydrogenation under  Hydrogen pressure in the presence of palladium. Compounds of formula IX the one CH₃ group in the 2- or 4-position, can be reduced by reducing the corresponding Thiophene carboxylates with the help of complex hydrides such as Na bis (methoxyethoxy) aluminum hydride can be obtained. If desired, the Compounds of the formula IX also by hydrolysis of the corresponding carbamate esters, e.g. B. the corresponding benzyl carbamate can be obtained. The thereby as Starting compounds required carbamate esters can e.g. B. from the corresponding Acids through which azides are obtained, followed by a Curtius rearrangement.

The preparation of the compounds according to the invention is described in the following Examples explained; Temperatures are given in ° C. Pressure specifications in torr and Rf values on silica gel, unless otherwise stated.

EXAMPLES Example 1: 2,4-Dimethyl-3-aminothiophene

To a mixture of 890 ml (3 mol) sodium bis (2-methoxyethoxy) aluminum hydride (70% solution in toluene) and 600 ml of dry toluene, with vigorous stirring, one Solution of 100 g (0.58 mol) of 3-amino-4-methylthiophene-2-carboxylic acid methyl ester in 700 ml of dry toluene was added dropwise in such a way that the reaction temperature did not exceed 55 °.

After the addition has ended, the mixture is stirred for a further 30 minutes and then the reaction mixture carefully, in small portions, at 0 ° to 1200 ml of a 20% KOH solution.

The toluene phase is then separated, dried over MgSO₄ and concentrated in vacuo. The remaining brown liquid is distilled under reduced pressure to give thus the analytically pure title compound of bp 49-52 ° / 0.01 Torr.

Example 2: 4-methoxy-2-methyl-3-aminothiophene

A well-stirred mixture of 55.4 g (0.2 mol) of benzyl-N- (4-methoxy-2-methyl thien-3-yl) carbamate, 40 g (0.7 mol) KOH, 600 ml ethanol and 120 ml water become 2 Heated under reflux for hours. The resulting solution is then concentrated in vacuo and the residue diluted with 500 ml of water. It separates a slightly yellow oily phase, which is taken up in 400 ml of diethyl ether. The aqueous phase is also extracted with 400 ml ether.  

The combined ether solutions are dried (Na₂SO₄) and filtered. Through the filtrate dry HCl gas is then passed for 30 minutes, with ice bath cooling care is taken that the temperature does not exceed 10 °.

The precipitated hydrochloride of the title compound has an mp of 230 ° (the free Base melts at 61-63 °).

Example 3: N- (2,4-Dimethylthien-3-yl) acetoxyacetamide

To 12.7 g (0.1 mol) of 2,4-dimethyl-3-aminothiophene, 13.8 g (0.1 mol) of K₂CO₃, 20 ml Water and 150 ml of CH₂Cl₂ are 15 g (0.11 mol) at room temperature Acetoxyacetyl chloride added dropwise.

After the exothermic reaction has ended, the mixture is stirred for a further 1 hour. The organic phase is evaporated, washed with water, dried (MgSO₄) and concentrated in vacuo. The solid residue is treated with hexane and provides the analytically pure one Title compound of mp 110-112 °.

Example 4: N- (2,4-Dimethylthien-3-yl) hydroxyacetamide

Through a stirred solution of 15.9 g (0.07 mol) of N- (2,4-dimethylthien-3-yl) acetoxyacetamide in 300 ml CH₃OH NH₃ gas is passed for 30 minutes.

After the exothermic (40 °) reaction (steamed by cooling with ice water) Stirred for a further 30 minutes and then the reaction solution was evaporated to dryness. The remaining residue is recrystallized from ethyl acetate, the analytically pure Title compound in the form of colorless crystals of mp. 85-87 ° is obtained.

Example 5: N- (2-Ethoxyethyl) -4-methoxy-2-methylthiophene-3-amine

To 70 ml (0.245 mol) of sodium bis (2-methoxyethoxy) aluminum hydride (70% solution in Toluene) and 30 ml of dry toluene, while stirring, a solution of 9.4 g (0.041 Mol) of N- (4-methoxy-2-methylthien-3-yl) ethoxyacetamide in 125 ml of dry toluene dripped. After the exothermic reaction has ended, stirring is continued for 90 minutes and then the reaction solution carefully, in small portions, at -10 ° to 100 ml of one Given 20% KOH solution.

The toluene phase is separated off and the aqueous phase twice with 100 ml of toluene extracted. The combined toluene solutions are dried (over Na₂SO₄) and in  Vacuum concentrated. The remaining light brown liquid is analytically pure, Rf = 0.32 (hexane / diethyl ether 1: 2).

Example 6: N - [(Methoxymethyl) ethyl-2,4-dimethyl-thiophene-3-amine

The solution of 6.4 (0.05 mol) 2,4-dimethyl-3-aminothiophene and 5.3 g (0.06 mol) Methoxyacetone in 100 ml dry toluene is heated to boiling under reflux until it boils has separated the theoretical amount of water at the water separator (2½ hours). Man leaves the toluene phase until it has reached room temperature and then narrows it in Vacuum on. The remaining Schiff base is clean enough for the next stage.

9.2 g (0.048 mol) of this residue are dissolved in 100 ml of dry toluene and without Cool to a well-stirred solution of 28 ml (0.098 mol) sodium bis- (2- methoxyethoxy) aluminum hydride (70% solution in toluene) in 15 ml dry toluene given.

After the exothermic reaction (44 °), stirring is continued for a further 90 minutes the brown reaction solution then carefully, in small portions, at -10 ° to 40 ml one Given 20% KOH solution.

The toluene phase is separated off, dried (Na₂SO₄) and concentrated in vacuo. The remaining oil is after column chromatography on silica gel (eluent Hexane / diethyl ether 3: 1) distilled under reduced pressure (Kugelrohr) and has one Bp 94-95 ° at 0.01 Torr.

Example 7

The following compounds of formula VII are analogous to one or more of the Obtain Examples 3 to 6 above:

Example 8: N- (2,4-Dimethylthien-3-yl-N-methoxyethyl-hydroxyacetamide

Dry 18.4 g (0.1 mol) of N- (2,4-dimethylthien-3-yl) hydroxyacetamide in 50 ml Dimethylformamide (DMF) become a well-stirred suspension of 3.0 g (0.1 mol) NaOH (80% dispersion in mineral oil) dropped in 50 ml dry DMF.

After the exothermic reaction (50 °), the solution of the Na salt is left on Cool to room temperature and then treat it with a solution of 10.4 g (0.11 mol) 2-chloroethyl methyl ether in 20 ml dry DMF. When the addition is complete, it will The reaction mixture was heated to 100 ° for 4 hours and then evaporated to dryness (40 ° / 0.1 Torr).

The residue is taken up in 200 ml of diethyl ether, washed with 250 ml of water, dried over MgSO₄ and filtered. The oily residue after evaporation of the Filtrates remaining is chromatographed on a silica column. You elute with Diethyl ether and receives the desired compound as a viscous liquid (Rf = 0.25 / diethyl ether).

Example 9: N- (2,4-Dimethylthien-3-yl) -N-methoxyethylchloroacetamide (Method a)

0.93 g (0.008 mol) of mesyl chloride in 20 ml of dry CH₂Cl₂ become one without cooling stirred mixture of 2.0 g (0.008 mol) of N-2,4- (dimethylthien-3-yl) -N-methoxyethyl hydroxyacetamide and 0.92 g (0.008 mol) of 4-dimethylaminopyridine (DMAP) in 80 ml dry CH₂Cl₂ added.

The mixture thus obtained, the DMAP hydrochloride and the methanesulfonate Contains starting compound, is heated for 25 hours and then under vacuum evaporated.

The remaining oil solidifies after chromatography on silica gel (eluted with diethyl ether) and cooling at -20 °; Mp 54-55 °.

Example 10: N- (1H-Pyrazol-1-ylmethyl) -N- (2,4-dimethylthien-3-yl) chloroacetamide (Method b)

To a well-stirred mixture of 19.35 g (0.095 mol) of N- (2,4-dimethylthien-3- yl) chloroacetamide, 4.15 g (0.01 mol) benzyldimethylhexadecylammonium chloride, 40 g (1st  Mol) NaOH, 200 ml CH₂Cl₂ and 40 ml H₂O become 17 g (0.11 mol) solid Given 1-chloromethyl-pyrazole hydrochloride such that the temperature does not exceed 25 ° exceeds.

After the addition has ended, the reaction mixture is stirred for 2½ hours Room temperature stirred. Then 100 ml of H₂O are added. The organic phase will separated, washed with 3,200 ml portions of water, dried over Na₂SO₄ and Evaporated to dryness. The residue is chromatographed on silica gel. Elution with Hexane-diethyl ether 1: 1 provides the analytically pure title compound in the form of a syrup, after cooling overnight at -20 °, mp. 88-89 ° (crystallization in Diethyl ether).

Example 11: N- (4-methoxy-2-methylthien-3-yl) -N- (ethoxyethyl) chloroacetamide (Method c)

To a well-stirred mixture of 6.05 g (0.03 mol) of N- (2-ethoxyethyl) 4-methoxy-2- methylthiophene-3-amine, 4.15 g (0.03 mol) K₂CO₃, 10 ml H₂O and 100 ml CH₂Cl₂, 3.4 g (0.03 mol) of chloroacetyl chloride in 10 ml of CH₂Cl₂ were added dropwise without cooling the solution. After the end of the exothermic reaction (27 °) is 1 hour at room temperature continued stirring.

The CH₂Cl₂ phase is separated, washed twice with 100 ml H₂O, dried (Na₂SO₄) and evaporated in vacuo. The remaining crude title compound is analytically pure; Rf = 0.23 (hexane / diethyl ether 1: 2). A small portion of this material becomes one Kugelrohr distillation subjected: bp 168-170 ° / 0.05 Torr.

The following compounds of formula I are one or more of the Process according to Examples 9 to 11 obtained: (Me is CH₃; Et is C₂H₅).  

Table A

Claims (1)

Thiophene compounds of the formula (A) wherein R₁ and R₂ are independently CH₃ or OCH₃;
Z₁ represents H or the group AOR in which
A represents the CH₂ or CH₂CH₂ group or monomethylated derivatives thereof; and
RC represents _1-3 alkyl; and
Z₂ is H, COCH₂OH or COCH₂Cl, where Z₁ is hydrogen if Z₂ is COCH₂Cl.