The way to obtain 1-(alkoxymethyl)pyrrole compounds

 

(57) Abstract:

The safe and effective way (without a separate receive-kaleidotrope esters and without treatment) introduction alkoxymethyl group on the ring nitrogen atom of a wide range of compounds of the pyrrole due to the interaction of the corresponding pyrrole predecessor in series with dialkoxybenzene, the reagent of Vilsmeier and tertiary amine, obtained using the method of the present invention with high output efficiency and with significantly reduced damage to the environment and human wide range of 1-(alkoxymethyl)pyrrole compounds can be used as an insecticide, acaricide, nematocide and mollusciciding agents. 9 C.p. f-crystals,

Carbonitrile the pyrrole, nitropyrrole, allberry, bizarrely, dialkylphenol, alkylsulfonyl, thiocarboxamides and heteroarylboronic compounds and their derivatives are highly effective insecticidal, acaricidal, nematocidal, molluscicide and endectocide agents that can be used in relation to plants and animals. Typically, these derivatives of pyrrole with alkoxymethyl the Deputy Alkoxysilane pyrrole on the nitrogen atom with the formation of N-(alkoxymethyl)pyrrol usually carried out using a condensation of the corresponding pyrrole C - gaelicmedium ether in the presence of a strong base such as sodium hydride [see for example, J. Muchowski, et al., Journal of Organic Chemistry, 49(1), 203 (1984), or tert-piperonyl potassium (for example, U.S. patent 5010098). However, the use - kaleidotrope esters in the scale of production on an industrial pilot plant is undesirable because of the carcinogenic properties of these esters. Further, the use of such good reason, as a metal hydride or tert-butoxide on a large scale is expensive and dangerous.

The use of alkyls and reagent of Vilsmeier, as it is known, gives alkoxymethyl ether phenolic hydroxyl group, for example, by the method of U.S. patent 4500738. However, this process is not so successful in relation to the nitrogen atom of the pyrrole ring, and the reaction does not go.

Therefore, the aim of the present invention is to provide a safe and efficient way to obtain N-(alkoxymethyl)pyrrol without a separate receive - kaleidotrope esters and without treatment.

Another objective of the present invention is to provide a method for alkoxysilane pyrrole without the use of such strong bases, as metal hydrides or tert-butoxide metals.

Another is a broad range of important pesticide compounds pyrrole. Other objectives and features of the invention will become apparent from the following description.

The safe and effective way to obtain 1-(alkoxymethyl)pyrrole compounds, which includes liaising 1-H-pyrrole compounds with di-(alkoxy)-methane, dimethylformamide and phosphorus oxychloride in the presence of aprotic solvent to form the reaction mixture and treating the reaction mixture with tertiary amine, optionally at elevated temperature.

Using the method of the present invention can be obtained with high yield, efficiency and with significantly reduced damage to the environment and human wide range of pesticide compounds 1-(alkoxymethyl)pyrrole, such as carbonitrile of pyrrole, nitropyrrole, allberry, bizarrely, dialkylphenol, alkylsulfonyl, alkylsulfonyl, carboxamide, thiocarboxamide, heteroarylboronic etc.

Compounds of the pyrrole have many beneficial biological properties such as antibacterial, fungicidal, acaricidal, insecticidal, molluscicide and nematocide activities.

Safe and effective for the medical, and for the agricultural use of pyrrole. In particular, alkoxysilane pyrrole, demonstrating agricultural pesticide properties, tends to improve these properties. However, there are still ways to alkoxysilane nitrogen of the pyrrole rings include use and work with - gaelicmedium ether (carcinogen) or with such a strong base as a metal hydride or a metal alkoxide (harm and expensive), or with both.

It was found that the compounds 1-H-pyrrol you can alkoxysilylated on the nitrogen of the pyrrole ring with obtaining 1-(alkoxymethyl)of pyrrole with high yield and without a strong Foundation metals, and without selection or handling of carcinogenic intermediate compounds, with the cooperation of the connection 1-H-pyrrole with di(C1-C6alkoxy) methane and reagent of Vilsmeier in the presence of aprotic solvent to obtain the reaction mixture and then adding to this reaction mixture of the tertiary amine to obtain the desired compound 1-(C1-C6alkoxymethyl)pyrrole.

Unexpectedly, it was found that the sequential addition of the tertiary amine to the mixture soedinenii beautiful conversion of 1-H-pyrrol into the corresponding 1-(C1-C6alkoxymethyl)pyrrole.

According to one variant of the present invention pyrrole compound of the formula I

< / BR>
where W represents CN, NO2, S(O)nCR or

< / BR>
X represents hydrogen, halogen, CN, NO2S(O)mCR3C1-C4haloalkyl, Q, or phenyl, optionally substituted by one or more halogen, NO2CN, C1-C4alkyl, C1-C4haloalkylthio, C1-C4alkoxy or C1-C4haloalkoxy groups, Y represents hydrogen, halogen, C1-C4haloalkyl or phenyl, optionally substituted by one or more halogen, NO2CN C1-C4alkyl, C1-C4haloalkylthio, C1-C4alkoxy or C1-C4haloalkoxy groups

Z represents hydrogen, halogen or C1-C4haloalkyl

m and n each independently represents an integer 0, 1 or 2, R and R3each independently represents C1-C6haloalkyl, R1and R2each independently represents C1-C4alkyl, C1-C4-haloalkyl or phenyl, optionally substituted by one or more halogen, NO2CN, C1-C4alkyl CLASS="ptx2">

Q is

< / BR>
R4, R5and R6each independently represents hydrogen, halogen NO2CHO or R5and R6taken together with the atoms to which they are attached, form a ring in which R5R6has the structure

< / BR>
R7, R8, R9and R10each independently represent hydrogen, halogen, CN or NO2and

A and A1each independently represents O or S

can safely and effectively be converted into 1-(C1-C6alkoxymethyl)pyrrole of formula II

< / BR>
where W, X, Y and Z have the meanings given above for formula I, and R11represents C1-C6alkyl.

In practice, a mixture of approximately stoichiometric amounts of 1-H-pyrrole, di(C1-C6alkoxy)methane, dimethylformamide and phosphorus oxychloride in an aprotic solvent and stirred at 0-150oC, preferably 20-60oC for about 0.25 to 2.0 hours, then the mixture is treated with about 1-2 molar equivalents of tertiary /3o/Amin, stirred at 0-150oC, preferably about 0 to 60oC, until the completion of the reaction, and slaked with water to obtain the desired 1-(C1-C6alkoxymethyl)pyrrole. When used in the SUB> represents C1-C6alkyl.

< / BR>
Although suitable are the stoichiometric quantity of 1-H-pyrrole, di/C1-C6alkoxy/methane, dimethylformamide and phosphorus oxychloride, the preferred excess of reagent Vilsmeier /DMF and POCl3, about 1.0 to 1.5 molar equivalents, and about 1.0 to 2.0 molar equivalents of di/C1-C6alkoxy/methane. Stoichiometric amounts are based on molar equivalents used the original 1-H-pyrrole.

Aprotic solvents suitable for use in the method of the present invention are aromatic hydrocarbons, halogenated aromatic hydrocarbons, aliphatic NITRILES, esters, etc., the Most preferred aprotic solvents represented by toluene, xylenes, halodendron and acetonitrile.

The reaction rate increases with increasing temperature, however, too high temperature unprofitable and lead to side reactions and reduce output. For the method of the present invention, the preferred temperature in the range of about 0-150oand the most preferred temperature of about 20-60oC.

Tertiary amines suitable for ispol as trialkylamine, dialkylacrylamide, triarylamine, etc., preferably, trialkylamine, and preferably triethylamine.

The method of the present invention can be used to produce 1-(alkoxymethyl)-derivative, 1-H-pyrrole. Preferred 1-H-pyrrole compounds are the compounds of formula I, where W, X, Y and Z have the previously indicated meanings. More preferred compounds of formula I are compounds in which W represents CN or NO2.

X represents hydrogen, halogen or C1-C4haloalkyl,

Y represents hydrogen, halogen or C1-C4haloalkyl, and

Z represents halogen, C1-C4haloalkyl or phenyl, optionally substituted by one or more of the C1-C4haloalkyl groups or one or more Halogens.

Preferred compounds of formula II obtained by the method of the present invention, are compounds in which R11represents C1-C6alkyl, W is CN, or 11O2X represents halogen or C1-C4haloalkyl, Y represents hydrogen or C1-C4haloalkyl, and Z is phenyl, optionally substituted by one or more halogen, or C1SUB>11represents C1-C3alkyl (especially C2H5), W is CN, X is hydrogen, Y is CF3and Z is phenyl, optionally substituted by one chlorine atom or bromine.

For a more complete understanding of the invention are the following examples. They are only illustrative and in no way limit the scope and essence of the invention.

Terms HPZC = HPLC and1H NMR indicate high-performance liquid chromatography and proton nuclear magnetic resonance, respectively.

Example 1

Getting 4-bromo-2-(n-chlorophenyl)-1-(ethoxymethyl)-5- (trifluoromethyl)pyrrole-3-carbonitrile

< / BR>
Stir a mixture of 4-bromo-2-(n-chlorophenyl)-5- (trifluoromethyl)pyrrole-3-carbonitrile /17,4 g, 0.05 m/, diethoxymethane /10.4 g, of 0.10 mol/ and dimethylformamide /4.6 g, 0,0625 mol/ toluene in a nitrogen atmosphere is treated in portions with phosphorus oxychloride /9.6 g, 0,0625 mol/ 35 - 45oC for 10 minutes, heated at 45 - 53oC for about 0.5 hours, cooled to 35oC was added dropwise a triethylamine /7,25, 0,0715 mol/ 2 hours at 35 - 45oC. the Reaction mixture is treated with water, filtered and the filter cake is dried in vacuum at 60oC obtaining and replacing the toluene on the following solvents receive specified in the header of the connection with the following outputs:

Solvent - Output %

Acetonitrile - 94,7

Xylenes - 96,4

Chlorobenzene - 93,6

Example 2

Getting 4-bromo-1-(n-butoxymethyl)-2-(n-chlorophenyl)-5- (trifluoromethyl)pyrrole-3-carbonitrile

< / BR>
Stir a mixture of 4-bromo-2-(n-chlorophenyl)-5-(trifluoromethyl)-pyrrole-3-carbonitrile /17,4 g, 0.05 m), di-(n-butoxy)methane /12,0, 0,075 mol/ and dimethylformamide /4.6 g, 0,063 mol/ in xylene in nitrogen atmosphere is treated with phosphorus oxychloride /9.6 g, 0,063 mol/ portions at 30 - 37oC for 10 minutes, heated at 45 - 50oC for 0.75 hour, cooled to 35oC, was added dropwise a triethylamine /8,1 g of 0.08 mol/ 0.25 hour and heated at 45 - 50oC for additional 0.75 hour. Then the reaction mixture is cooled to 25oC, treated with water and additional xylenes and stirred for 0.5 hour. The phases are separated and the organic phase was concentrated in vacuo to obtain specified in the header of the product as a light brown solid product, so melting is 52.0 - 53.5 inoC, 20.6 g, yield of 94.6%, according to the1H NMR and mass spectroscopy

Example 3

Getting 4-bromo-2-(p-chlorophenyl)-1-(methoxymethyl)-5- (trifluoromethyl)pyrrole-3-carbonitrile

< / BR>
according to the method of example 2, and substituting di-(n-butoxy)methane HP>H NMR and mass spectroscopy

Example 4

Obtain 2-(p-chlorophenyl)-1-(ethoxymethyl)-5-(trifluoromethyl)- pyrrole-3-carbonitrile

< / BR>
Stir a mixture of 2-(p-chlorophenyl)-5-trifluoromethyl) pyrrole-3-carbonitrile (13.5 g, 0.05 m), diethoxymethane (7,8 g of 0.075 mol/and dimethylformamide /5,5, 0,075 mol/ acetonitrile under nitrogen atmosphere is treated with phosphorus oxychloride /11.5g, 0,075 mol/ 0,525 hours at 39 - 45oC, heated at 39 - 45oC for 0.75 hour and added dropwise a triethylamine /10,1 g of 0.10 mol/ 45 - 55oC for 0.5 hours. The reaction mixture is diluted with water, stirred for 16 hours at 25oC and concentrated in vacuo to obtain the crude product. This material is stirred at the boil under reflux with a mixture of toluene and dilute aqueous NaOH and cooled to room temperature. The phases are separated, the organic phase is concentrated in vacuo to obtain specified in the header of the product in the form of a solid substance, so melting 83 - 84,5oC, of 13.1 g, yield 80%, identification according to mass spectroscopy.

1. The way to obtain 1-(alkoxymethyl)pyrrole compounds at a temperature of from 0 to 150oC, preferably from 20 to 60oC, by treating 1-H-pyrrole link what lorida phosphorus in the presence of an aprotic solvent and the resulting reaction mixture is treated with tertiary amine.

2. The method according to p. 1, characterized in that 1-H-pyrrole compound is a compound of the formula I

< / BR>
where W represents CN, NO, S(O)nCR or

X represents hydrogen, halogen, CN, NO2, S(O)mCR3C1-C4haloalkyl, Q or phenyl, optionally substituted by one or more halogen, NO2CN, C1-C4alkyl, C1-C4haloalkylthio, C1-C4alkoxy or C1-C4haloalkoxy groups;

Y represents hydrogen, halogen, C1-C4haloalkyl or phenyl, optionally substituted by one or more halogen, NO2CN, C1-C4alkyl, C1-C4haloalkylthio, C1-C4alkoxy or C1-C4haloalkoxy groups;

Z represents hydrogen, halogen or C1-C4haloalkyl;

n and m each independently is an integer of 0,1 or 2;

R and R3each independently represent C1-C6haloalkyl;

R1and R2each independently represent C1-C4alkyl, C1-C4haloalkyl or phenyl, optionally substituted by one or more halogen, NO2CN, C1-C4alkyl,
Q is

< / BR>
where R4, R5and R6each independently represent hydrogen, halogen, NO2CHO or R5and R6may together with the atoms to which they are attached, form a ring in which R5, R6structure

< / BR>
R7, R8, R9and R10each independently represent hydrogen, halogen, CN or NO2;

A and A1each independently represent 0 or s

3. The method according to p. 2, wherein W is CN or NO2; X represents halogen, C1-C4haloalkyl or phenyl, optionally substituted by one or more halogen or C1-C4haloalkylthio groups; Y represents hydrogen, halogen or C1-C4haloalkyl and Z represents hydrogen, halogen or C1-C4haloalkyl.

4. The method according to p. 1, wherein the aprotic solvent is an aromatic hydrocarbon or an aliphatic nitrile.

5. The method according to p. 4, wherein the solvent is toluene, xylene or acetonitrile.

6. The method according to p. 1, wherein the tertiary amine is three(C1-C6alkyl)amine.

7. The way alkoxymethyl)-pyrrole compound is 1-(C1-C6alkoxymethyl)pyrrole, and di-(alkoxy)methane is di(C1-C6alkoxy)methane.

9. The method according to p. 8, characterized in that di(C1-C6alkoxy)methane is di(ethoxy)methane.

10. The method according to p. 9, characterized in that 1-H-pyrrole compound has the structure



 

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