CA1091255A - Process for the preparation of 2,3-dichloroanisole - Google Patents
Process for the preparation of 2,3-dichloroanisoleInfo
- Publication number
- CA1091255A CA1091255A CA285,808A CA285808A CA1091255A CA 1091255 A CA1091255 A CA 1091255A CA 285808 A CA285808 A CA 285808A CA 1091255 A CA1091255 A CA 1091255A
- Authority
- CA
- Canada
- Prior art keywords
- solvent
- mixture
- preparation
- dichloro
- dichloroanisole
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
Sodium methylate is reacted in an aprotic polar solvent or in a mixture of such solvents with 1,2,3-trichloro-benzene in the presence of a cuprous catalyst and at temperatures ranging between 70°C and the boiling temperature of the solvent to produce 2,3-dichloroanisole which is useful in particular for the preparation of 2,3-dichloro-4-(2-thenoyl) phenoxyacetic acid - valuable diuretic and uricosuric agent.
Sodium methylate is reacted in an aprotic polar solvent or in a mixture of such solvents with 1,2,3-trichloro-benzene in the presence of a cuprous catalyst and at temperatures ranging between 70°C and the boiling temperature of the solvent to produce 2,3-dichloroanisole which is useful in particular for the preparation of 2,3-dichloro-4-(2-thenoyl) phenoxyacetic acid - valuable diuretic and uricosuric agent.
Description
1091'~55 The present invention is concerned with a new process for the preparation of 2,3-dichloro anisole.
2,3-dichloro anisole is a compound known for a number of years and used especially in the preparation of 2,3-dichloro-4-(2-thenoyl) phenoxyacetic acid - diuretic and uricosuric agent.
It has been prepared, in particular, by the reaction of a methyl-ation agent with 2,3-dichlorophenol (Holleman, Recueil des Travaux Chimiques des Pays-Bas 37,104) or by the reaction of sodium methylate with 1,2,3-trichlorobenzene in solution in meth-anol at 180C ~Holleman, Recueil des Travaux Chimiques des Pays-Bas 37,200). In the latter case, numerous products are formed and the overall yield of the reaction is limited.
This invention is concerned with a new process for the preparation of 2,3-dichloro anisole from 1,2,3-trichloro-benzene a rather inexpensive commercial product. The process makes it possible to obtain anisole with high yields and without the formation of by-products. This process is much easier to apply than the previously described process which also uses sodium methylate as it is carried out at ordinary pressure and at only slightly elevated temperatures. The use of such a process makes it possible to obtain dichloroanisole and conse-quently 2,3-dichloro-4-(2-thenoyl) phenoxyacetic acid, more economically.
The process according to the invention consists of reacting sodium methylate with 1,2,3-trichlorobenzene in solu-tion in a polar aprotic solvent, or in a mixture of such solvents, as for example dimethylformamide, the dimethyl ether of ethylene-glycol, the dimethyl ether of diethyleneglycol, in the presence of catalytic quantities of copper in the form of iodide, bromide, or cuprous oxide, at temperatures ranging between 70C and the boiling temperature of the solvent used. ~nder these conditions, no rearrangement is observed of the benzene ~ing substituents -- 1- ~
lV~ S
known rearrangements - which in general indicates the formation of a benzyne, nor is any substitution of two or three of the halogen atoms of the benzene ring o~served, even in the presence of an excess of sodium methylate.
The following examples illustrate the in~ention with-out consequently limiting it.
12.2 g of sodium is dissolved in 250 ml of anhydrous methanol and the solvent eliminated to isolate the product MeONa from MeOH. The product is placed in suspension in 60 ml of dimethyl ether and ethyleneglycol and the suspension is poured into 200 ml of anhydrous dimethylformamide. 80 g of trichloro-benzene and 2 g of cuprous iodide is added to the medium and maintained at about 75C for a least 8 hours. During this period, it is possible to add additional sodium methylate to the medium in order that the reaction may take place more quickly.
After cooling, the solution is filtered and poured into 4 volumes of water saturated with sodium chloride; dichloroanisole and dichlorobenzene is then extracted from this mixture, in dichlor-ethane. After desiccation of the solution and evaporation ofthe solvents, 16 g of dichloroanisole is obtained in the form of an oil, which contains a small amount of trichlorobenzene.
To isolate the final product, rather than pouring the reacting medium into the water after filtration, it is possible to eliminate the solven~s under reduced pressure. In order to ; separate the dichloro anisole from the remaining traces of trichlorobenzene, the crude oil obtained is distilled under ordinary pressure (E = 230~C) or under reduced pressure (E15 = 114C) or the mixture is steam-distilled, trichlorobenzene being distilled first. In this way pure crystallized 2,3-dichloroanisole is obtained (F = 33C~ with a yield of more than 85%.
1091;~.~5 In this reaction, it is also possible to use sodium methylate from which any solvent has been remoYed by heating to a temperature greater than 200C. There is also the possibility of adding less than the stoichiometric quantity of methylate to the medium at the beginning of the reaction, but effecting several additions during heating.
; 0.1 mole of sodium methylate is prepared by dissolving 2.3 g of sodium in 50 ml of methanol. 100 ml of anhydrous dimethylformamide is then poured into the solution and the methanol is rapidly evaporated under reduced pressure. Then 5.45 g of trichlorobenzene and 1 g of CuI is added to the medium, : which is brought to 120C in 2 hours. The medium is then cooled, filtered, and poured into 3 volumes of water. The solution is saturated, e.g., by adding sodium chloride, after which it is placed in contact with a solvent not miscible with water, such -; as ethyl ether or dichlorethane. The organic phase is decanted and dried, after which the solvent is evaporated. 5 g of oily residue is obtained, which contains a mixture of dichloro-2Q anisole ~80~ and of starting product. This mixture is purified as described in Example 1.
.
It has been prepared, in particular, by the reaction of a methyl-ation agent with 2,3-dichlorophenol (Holleman, Recueil des Travaux Chimiques des Pays-Bas 37,104) or by the reaction of sodium methylate with 1,2,3-trichlorobenzene in solution in meth-anol at 180C ~Holleman, Recueil des Travaux Chimiques des Pays-Bas 37,200). In the latter case, numerous products are formed and the overall yield of the reaction is limited.
This invention is concerned with a new process for the preparation of 2,3-dichloro anisole from 1,2,3-trichloro-benzene a rather inexpensive commercial product. The process makes it possible to obtain anisole with high yields and without the formation of by-products. This process is much easier to apply than the previously described process which also uses sodium methylate as it is carried out at ordinary pressure and at only slightly elevated temperatures. The use of such a process makes it possible to obtain dichloroanisole and conse-quently 2,3-dichloro-4-(2-thenoyl) phenoxyacetic acid, more economically.
The process according to the invention consists of reacting sodium methylate with 1,2,3-trichlorobenzene in solu-tion in a polar aprotic solvent, or in a mixture of such solvents, as for example dimethylformamide, the dimethyl ether of ethylene-glycol, the dimethyl ether of diethyleneglycol, in the presence of catalytic quantities of copper in the form of iodide, bromide, or cuprous oxide, at temperatures ranging between 70C and the boiling temperature of the solvent used. ~nder these conditions, no rearrangement is observed of the benzene ~ing substituents -- 1- ~
lV~ S
known rearrangements - which in general indicates the formation of a benzyne, nor is any substitution of two or three of the halogen atoms of the benzene ring o~served, even in the presence of an excess of sodium methylate.
The following examples illustrate the in~ention with-out consequently limiting it.
12.2 g of sodium is dissolved in 250 ml of anhydrous methanol and the solvent eliminated to isolate the product MeONa from MeOH. The product is placed in suspension in 60 ml of dimethyl ether and ethyleneglycol and the suspension is poured into 200 ml of anhydrous dimethylformamide. 80 g of trichloro-benzene and 2 g of cuprous iodide is added to the medium and maintained at about 75C for a least 8 hours. During this period, it is possible to add additional sodium methylate to the medium in order that the reaction may take place more quickly.
After cooling, the solution is filtered and poured into 4 volumes of water saturated with sodium chloride; dichloroanisole and dichlorobenzene is then extracted from this mixture, in dichlor-ethane. After desiccation of the solution and evaporation ofthe solvents, 16 g of dichloroanisole is obtained in the form of an oil, which contains a small amount of trichlorobenzene.
To isolate the final product, rather than pouring the reacting medium into the water after filtration, it is possible to eliminate the solven~s under reduced pressure. In order to ; separate the dichloro anisole from the remaining traces of trichlorobenzene, the crude oil obtained is distilled under ordinary pressure (E = 230~C) or under reduced pressure (E15 = 114C) or the mixture is steam-distilled, trichlorobenzene being distilled first. In this way pure crystallized 2,3-dichloroanisole is obtained (F = 33C~ with a yield of more than 85%.
1091;~.~5 In this reaction, it is also possible to use sodium methylate from which any solvent has been remoYed by heating to a temperature greater than 200C. There is also the possibility of adding less than the stoichiometric quantity of methylate to the medium at the beginning of the reaction, but effecting several additions during heating.
; 0.1 mole of sodium methylate is prepared by dissolving 2.3 g of sodium in 50 ml of methanol. 100 ml of anhydrous dimethylformamide is then poured into the solution and the methanol is rapidly evaporated under reduced pressure. Then 5.45 g of trichlorobenzene and 1 g of CuI is added to the medium, : which is brought to 120C in 2 hours. The medium is then cooled, filtered, and poured into 3 volumes of water. The solution is saturated, e.g., by adding sodium chloride, after which it is placed in contact with a solvent not miscible with water, such -; as ethyl ether or dichlorethane. The organic phase is decanted and dried, after which the solvent is evaporated. 5 g of oily residue is obtained, which contains a mixture of dichloro-2Q anisole ~80~ and of starting product. This mixture is purified as described in Example 1.
.
Claims (3)
1. A process for the preparation of 2,3-dichloro-anisole, which comprises reacting sodium methylate in an aprotic polar solvent or in a mixture of such solvents with 1,2,3-tri-chlorobenzene, in the presence of cuprous bromide, iodide or oxide and at temperatures ranging between 70°C and the boiling tempera-ture of the solvent.
2. Process according to Claim 1, wherein the solvent is selected from the group consisting of dimethylformamide, the dimethyl ether of ethyleneglycol, the dimethyl ether of diethyl-eneglycol, and mixtures thereof to form an aprotic polar solvent.
3. Process according to Claim 2, wherein a mixture of dimethyl ether of ethyleneglycol and of dimethylformamide is used as a solvent.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7626214A FR2363539A1 (en) | 1976-08-31 | 1976-08-31 | 2,2-Di:chloro anisole, intermediate for diuretic - prepd. from 1,2,3-tri:chlorobenzene by reaction with sodium methylate |
| FR76/26214 | 1976-08-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1091255A true CA1091255A (en) | 1980-12-09 |
Family
ID=9177257
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA285,808A Expired CA1091255A (en) | 1976-08-31 | 1977-08-30 | Process for the preparation of 2,3-dichloroanisole |
Country Status (2)
| Country | Link |
|---|---|
| CA (1) | CA1091255A (en) |
| FR (1) | FR2363539A1 (en) |
-
1976
- 1976-08-31 FR FR7626214A patent/FR2363539A1/en active Granted
-
1977
- 1977-08-30 CA CA285,808A patent/CA1091255A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| FR2363539A1 (en) | 1978-03-31 |
| FR2363539B1 (en) | 1980-03-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |