CA1041554A - Process for preparing a s-trialkoxy benzene - Google Patents
Process for preparing a s-trialkoxy benzeneInfo
- Publication number
- CA1041554A CA1041554A CA215,573A CA215573A CA1041554A CA 1041554 A CA1041554 A CA 1041554A CA 215573 A CA215573 A CA 215573A CA 1041554 A CA1041554 A CA 1041554A
- Authority
- CA
- Canada
- Prior art keywords
- benzene
- process according
- tribromo
- trialkoxy
- mole
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/16—Preparation of ethers by reaction of esters of mineral or organic acids with hydroxy or O-metal groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
ABSTRACT
A 1,3,5-trialkoxy benzene having 1-3 carbon atoms in each of the alkoxy-groups is prepared at high overall yields, with minimal formation of hazardous or polluting by-products by reacting a 1,3,5-trihalo benzene, for example 1,3,5-tribromo benzene with an alkalimetal alcoholate having 1-3 carbon atoms in the molecule in the presence of a copper salt, e.g. cuprous iodide or cupric chloride, and an aprotic solvent such as e.g. dimethylformamide. The product is readily recovered from the reaction mixture in an overall yield as high as 90%.
A 1,3,5-trialkoxy benzene having 1-3 carbon atoms in each of the alkoxy-groups is prepared at high overall yields, with minimal formation of hazardous or polluting by-products by reacting a 1,3,5-trihalo benzene, for example 1,3,5-tribromo benzene with an alkalimetal alcoholate having 1-3 carbon atoms in the molecule in the presence of a copper salt, e.g. cuprous iodide or cupric chloride, and an aprotic solvent such as e.g. dimethylformamide. The product is readily recovered from the reaction mixture in an overall yield as high as 90%.
Description
This invention relates to a process for preparing a 1,3,5-trialkoxy benzene (a s-trialkoxy benzene). More particularly this invention relates to a process for preparing a s-trialkoxy benzene of which each of the alkoxy groups contains 1 to 3 carbon atoms.
s-Trialkoxy benzenes with Cl 3 alkoxy groups are well known and t~.
versatile compounds. They are used e.g. as starting material in the pro-duction of other organic compounds. Some of them find application in the textile and pharmaceutical industry.
Hitherto s-trialkoxy benzenes have been prepared mainly by -alkylation processes which involve at least two reaction steps. An example 7~ ' of such a process is the acid catalysed alkylation of phloroglucinol with ;~
an alcohol, yielding mainly a dialkoxy phenol, followed by alkylation of the last hydroxyl group e.g. with a dialkylsulphate, in alkaline medium.
The known processes suffer from several disadvantages such as moderate overall yields, the many rèaction steps involved and the rigorous reaction conditions required. :
Another drawback is that not all the required starting materials are readily and/or economically available.
This invention provides a process for preparing a s-trialkoxy benzene in one single reaction step and at high overall yields from a start-ing material which is readily available.
- Accordingly the present invention provides a process for pre-paring a s-trialkoxy benzene having 1 or 2 carbon atoms in each of the alkoxy groups which comprises reacting 1,3,5-tribromo benzene with an alkalimetal ,' alcoholate having 1 or 2 carbon atoms in the molecule in an aprotic solvent , and in the presence of a copper salt catalyst, and recovering the formed s-trialkoxy benzene.
: .
;~ 1,3,5-Tribromo benzene is used as the starting material of the ~` process of the invention. When compared with other s-trihalo benzenes it .: ~ ` .
.. .
~'; - 1 - ~,"
,, .
appeared to be less prone to reduction, which may be a competitive side reaction. Moreover 1,3,5-tribromo benzene is the most readily available of the trihalo benzenes.
The alkalimetal alcoholate to be used in the process of the invention can either be added as such to the reaction mixture or it can be formed in situ, e.g. by adding freshly cut sodium or potassium metal to the alcohol.
The use of an excess of alkalimetal alcoholate in respect of the 1,3,5-tribromo benzene was found to be beneficial.
Examples of suitable aprotic solvents are heterocyclic bases such as pyridine, 2-substituted pyridines, ~-picoline and collidine. Prefer-ably, however, tertiary amides such as e.g. N-formyl-morpholine, dimethyl-acetamide and in particular dimethylformamide are used in the process of the invention. It was found that they act as a kind of co-catalyst in this way substantially reducing the reaction time required. By using dimethylformamide for example the required reaction time was reduced by about 80% as compared with the reaction times generally required with the pyridine type compounds.
Copper ~I) salts which find application in the process of the invention are e.g. cuprous cyanide and cuprous thiocyanate. Very good results were obtained with a cuprous halogenide, especially cuprous iodide. Copper (II) salts, in particular cupric chloride and cupric bromide, were found to be even more effective in that they further reduced the required reaction time at the same level of concentration.
- Although the copper salts used in the process of the invention act as a catalyst, more than trace was found to be necessary for effective catalysis. In general up to 0.3 mole of the copper catalyst per mole of 1,3,5-tribromo benzene are recommended.
However, when using a copper halide such as cuprous iodide, cupric chloride or cupric bromide as the catalyst, not more than Q05-0.15 :
~ ;o - 2 -mole copper-catalyst per mole of s-tribromo benzene were found to be required for obtaining substantially quantitive yields of the s-trialkoxy benzene.
The reaction is carried out at elevated temperatures. Depending ~ -on the compositions of the mixture the required temperatures will range from some 80 to 200C. Advantageously the mixture is heated under reflux. After completion of the reaction, which in most cases is achieved in 10 to 15 hours, the s-trialkoxy benzene can be separated from the reaction mixture and purified by any method known per se, e.g. by low temperature crystalliza-tion. Preferably the s-trialkoxy benzene is separated directly from the reaction mixture by distillation. In this way the compound can be obtained in a very pure form in yields well in excess of 90%.
; The following non-limitative examples will serve to illustrate the invention.
Example I.
Preparation of 1,3,5-trimethoxy benzene Sodium (4.6 g, 0.2 mole) was dissolved in methanol (40 ml) and to the resulting solution dimethylformamide (40 ml) was added. Cuprous ; iodide (1.0 g, 0.0056 mole) and 1,3,5-tribromo benzene (10 g, 0.03 mole) were added and the whole mixture was heated under reflux for 2 hours. The ~ -hot mixture was filtered to remove inorganic products, cooled, and diluted with water (lO0 ml), whereupon the bulk of the product precipitated from solution. This was collected by filtration and the remainder of the pro- -~
duct was obtained from the aqueous layer by extraction with ether (4 x 30 ml.). The combined ether extracts were washed with water, dried (Na2S04) and evaporated to give a pale yellow oil. The combined product was then recrystallized from petroleum ether (bp 40-60C) at -78C to give ;
'' '" .' ~,.c-'.,' ., '.-.
3 ~
10415~4 4.1 g (75%) of the 1,3,5-trimethoxy benzene as colourless crystals, mp 51-2C. Direct distillation of the crude reaction mixture yielded 5.2 g of 1,3,5-trimethoxy benzene (95%).
The solubility of the product in petroleum ether was responsible for the lower yields obtained in the first case.
1,3,5-Trimethoxy benzene is known as a useful compound in the pharmaceutical industry. It can also serve as starting material for the preparation of phloroglucinol.
Example II-Pre~aration of 1,3,5-triethoxy benzene To To a mixture of 81.6 g sodium ethanolate (1.2 mole) and 400 ml dimethylformamide were added 4 g cupric chloride and 63 g s-tribromo benzene (0.2 mole).
The resulting mixture was heated on a water bath during five hours with continuously stirring. When the reaction was completed the excess dimethylformamide was distilled off in vacuum. The residue was ~ -treated with water and extracted three times with toluene. The extracts were combined and distilled. In this way 17.6 g 1,3,5-triethoxy benzene were obtained, having a boiling point of 175C (24 mm Hg) and a melting point of 42-43C.
Having now particularly described and ascertained the nature of our said invention and in what manner the same is to be performed, we -declare that what we claim is: ;
x '. ' .;
~, ..
~; : ,.
..
; = , - ., .... ~
s-Trialkoxy benzenes with Cl 3 alkoxy groups are well known and t~.
versatile compounds. They are used e.g. as starting material in the pro-duction of other organic compounds. Some of them find application in the textile and pharmaceutical industry.
Hitherto s-trialkoxy benzenes have been prepared mainly by -alkylation processes which involve at least two reaction steps. An example 7~ ' of such a process is the acid catalysed alkylation of phloroglucinol with ;~
an alcohol, yielding mainly a dialkoxy phenol, followed by alkylation of the last hydroxyl group e.g. with a dialkylsulphate, in alkaline medium.
The known processes suffer from several disadvantages such as moderate overall yields, the many rèaction steps involved and the rigorous reaction conditions required. :
Another drawback is that not all the required starting materials are readily and/or economically available.
This invention provides a process for preparing a s-trialkoxy benzene in one single reaction step and at high overall yields from a start-ing material which is readily available.
- Accordingly the present invention provides a process for pre-paring a s-trialkoxy benzene having 1 or 2 carbon atoms in each of the alkoxy groups which comprises reacting 1,3,5-tribromo benzene with an alkalimetal ,' alcoholate having 1 or 2 carbon atoms in the molecule in an aprotic solvent , and in the presence of a copper salt catalyst, and recovering the formed s-trialkoxy benzene.
: .
;~ 1,3,5-Tribromo benzene is used as the starting material of the ~` process of the invention. When compared with other s-trihalo benzenes it .: ~ ` .
.. .
~'; - 1 - ~,"
,, .
appeared to be less prone to reduction, which may be a competitive side reaction. Moreover 1,3,5-tribromo benzene is the most readily available of the trihalo benzenes.
The alkalimetal alcoholate to be used in the process of the invention can either be added as such to the reaction mixture or it can be formed in situ, e.g. by adding freshly cut sodium or potassium metal to the alcohol.
The use of an excess of alkalimetal alcoholate in respect of the 1,3,5-tribromo benzene was found to be beneficial.
Examples of suitable aprotic solvents are heterocyclic bases such as pyridine, 2-substituted pyridines, ~-picoline and collidine. Prefer-ably, however, tertiary amides such as e.g. N-formyl-morpholine, dimethyl-acetamide and in particular dimethylformamide are used in the process of the invention. It was found that they act as a kind of co-catalyst in this way substantially reducing the reaction time required. By using dimethylformamide for example the required reaction time was reduced by about 80% as compared with the reaction times generally required with the pyridine type compounds.
Copper ~I) salts which find application in the process of the invention are e.g. cuprous cyanide and cuprous thiocyanate. Very good results were obtained with a cuprous halogenide, especially cuprous iodide. Copper (II) salts, in particular cupric chloride and cupric bromide, were found to be even more effective in that they further reduced the required reaction time at the same level of concentration.
- Although the copper salts used in the process of the invention act as a catalyst, more than trace was found to be necessary for effective catalysis. In general up to 0.3 mole of the copper catalyst per mole of 1,3,5-tribromo benzene are recommended.
However, when using a copper halide such as cuprous iodide, cupric chloride or cupric bromide as the catalyst, not more than Q05-0.15 :
~ ;o - 2 -mole copper-catalyst per mole of s-tribromo benzene were found to be required for obtaining substantially quantitive yields of the s-trialkoxy benzene.
The reaction is carried out at elevated temperatures. Depending ~ -on the compositions of the mixture the required temperatures will range from some 80 to 200C. Advantageously the mixture is heated under reflux. After completion of the reaction, which in most cases is achieved in 10 to 15 hours, the s-trialkoxy benzene can be separated from the reaction mixture and purified by any method known per se, e.g. by low temperature crystalliza-tion. Preferably the s-trialkoxy benzene is separated directly from the reaction mixture by distillation. In this way the compound can be obtained in a very pure form in yields well in excess of 90%.
; The following non-limitative examples will serve to illustrate the invention.
Example I.
Preparation of 1,3,5-trimethoxy benzene Sodium (4.6 g, 0.2 mole) was dissolved in methanol (40 ml) and to the resulting solution dimethylformamide (40 ml) was added. Cuprous ; iodide (1.0 g, 0.0056 mole) and 1,3,5-tribromo benzene (10 g, 0.03 mole) were added and the whole mixture was heated under reflux for 2 hours. The ~ -hot mixture was filtered to remove inorganic products, cooled, and diluted with water (lO0 ml), whereupon the bulk of the product precipitated from solution. This was collected by filtration and the remainder of the pro- -~
duct was obtained from the aqueous layer by extraction with ether (4 x 30 ml.). The combined ether extracts were washed with water, dried (Na2S04) and evaporated to give a pale yellow oil. The combined product was then recrystallized from petroleum ether (bp 40-60C) at -78C to give ;
'' '" .' ~,.c-'.,' ., '.-.
3 ~
10415~4 4.1 g (75%) of the 1,3,5-trimethoxy benzene as colourless crystals, mp 51-2C. Direct distillation of the crude reaction mixture yielded 5.2 g of 1,3,5-trimethoxy benzene (95%).
The solubility of the product in petroleum ether was responsible for the lower yields obtained in the first case.
1,3,5-Trimethoxy benzene is known as a useful compound in the pharmaceutical industry. It can also serve as starting material for the preparation of phloroglucinol.
Example II-Pre~aration of 1,3,5-triethoxy benzene To To a mixture of 81.6 g sodium ethanolate (1.2 mole) and 400 ml dimethylformamide were added 4 g cupric chloride and 63 g s-tribromo benzene (0.2 mole).
The resulting mixture was heated on a water bath during five hours with continuously stirring. When the reaction was completed the excess dimethylformamide was distilled off in vacuum. The residue was ~ -treated with water and extracted three times with toluene. The extracts were combined and distilled. In this way 17.6 g 1,3,5-triethoxy benzene were obtained, having a boiling point of 175C (24 mm Hg) and a melting point of 42-43C.
Having now particularly described and ascertained the nature of our said invention and in what manner the same is to be performed, we -declare that what we claim is: ;
x '. ' .;
~, ..
~; : ,.
..
; = , - ., .... ~
Claims (14)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for preparing a s-trialkoxy benzene having one or two carbon atoms in each of the alkoxy groups, which comprises reacting 1,3,5-tribromo benzene with an alkali metal alcoholate having one or two carbon atoms in the molecule in an aprotic solvent and in the presence of a copper salt catalyst and recovering the formed s-trialkoxy benzene.
2. A process according to claim 1 wherein the alkali metal alcoholate is a sodium or potassium alcoholate.
3. A process according to claim 2 wherein the copper salt is a copper halide.
4. A process according to claim 3 wherein the copper halide is cuprous iodide, cupric chloride or cupric bromide.
5. A process according to claim 1, 2 or 3 wherein the aprotic solvent is a tertiary amide.
6. A process according to claim 1, 2 or 4 wherein the aprotic solvent is dimethylformamide.
7. A process according to claim 2, 3 or 4 wherein about 0.05-0.15 mole of copper salt is used per mole of 1,3,5-tribromo benzene.
8. A process according to claim 1, 2 or 3 wherein the s-trialkoxy benzene is separated from the reaction mixture by direct distillation.
9. A process according to claim 1 in which s-trimethoxy benzene is prepared by reacting sodium methoxide with 1,3,5-tribromo benzene in the presence of cuprous iodide as catalyst.
10. A process according to claim 9 in which the reaction is effected by heating in dimethylformamide as solvent.
11. A process according to claim 9 or 10 wherein about 0.05-0.15 mole of cuprous iodide is used per mole of 1,3,5-tribromo benzene.
12. A process according to claim 1 in which s-triethoxy benzene is prepared by reacting sodium ethoxide with 1,3,5-tribromo benzene in the presence of cupric chloride as catalyst.
13. A process according to claim 12 in which the reaction is effected by heating in dimethylformamide as solvent.
14. A process according to claim 12 or 13 wherein about 0.05-0.15 mole of cupric chloride is used per mole of 1,3,5-tribromo benzene.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB5742873 | 1973-12-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1041554A true CA1041554A (en) | 1978-10-31 |
Family
ID=10479169
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA215,573A Expired CA1041554A (en) | 1973-12-11 | 1974-12-10 | Process for preparing a s-trialkoxy benzene |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPS5749526B2 (en) |
| CA (1) | CA1041554A (en) |
| DE (1) | DE2458191C3 (en) |
| FR (1) | FR2253729A1 (en) |
| NL (1) | NL179047C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL49803A (en) * | 1975-06-28 | 1979-11-30 | Fisons Ltd | Preparation of pyrogallol |
| JPS5553229A (en) * | 1978-10-13 | 1980-04-18 | Otsuka Chem Co Ltd | Preparation of alkoxyphenol compound |
-
1974
- 1974-12-02 NL NLAANVRAGE7415674,A patent/NL179047C/en not_active IP Right Cessation
- 1974-12-06 JP JP49141066A patent/JPS5749526B2/ja not_active Expired
- 1974-12-09 DE DE2458191A patent/DE2458191C3/en not_active Expired
- 1974-12-09 FR FR7440244A patent/FR2253729A1/en active Granted
- 1974-12-10 CA CA215,573A patent/CA1041554A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| FR2253729B1 (en) | 1978-05-05 |
| FR2253729A1 (en) | 1975-07-04 |
| NL179047B (en) | 1986-02-03 |
| DE2458191A1 (en) | 1975-06-19 |
| DE2458191B2 (en) | 1977-10-06 |
| JPS5749526B2 (en) | 1982-10-22 |
| JPS50100032A (en) | 1975-08-08 |
| DE2458191C3 (en) | 1978-06-01 |
| NL179047C (en) | 1986-07-01 |
| NL7415674A (en) | 1975-06-13 |
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