Indian Patents. 272843:"PROCESS FOR PREPARING ALKYL ALKOXYBENZOATES IN ONE STEP"

Title of Invention	"PROCESS FOR PREPARING ALKYL ALKOXYBENZOATES IN ONE STEP"
Abstract	Process for preparing a compound of the formula by contacting, in an organic solvent in the presence of an aqueous solution of a base, hydroxy benzoic acid with a compound of the formula RnX, wherein R is an alkyl group having 1 to 6 C-atoms and X is an acid rest group having a valence n, weherein the organic solvent is an alkyl substituted aromatic hydrocarbon.

Full Text	PROCESS FOR PREPARING ALKYL ALKOXYBENZOATES IN ONE STEP The present invention relates to a process for preparing a compound of the formula: (Figure Removed)by contacting hydroxy benzoic acid with a compound of the formula RnX, wherein R is an alkyl group having 1 to 6 carbon atoms and X is an acid rest group having a valency n. The acid esters are useful as selective inhibitor in stereospecific polymerization. They are also used as starting raw materials in many drugs. Processes for the preparation of said esters are known in the art. In RO 88669 A, Ar(OR)n is alkylated with RX (X= Br, iodo, sulfate) at 20-30 °C in a polar aprotic solvent like dimethylsulfoxide, dimethylformamide or dimethylacetamide in the presence of 1 0- 1 5% NaOH or KOH. JP 60214753A discloses a one step process for preparing the esters from hydroxyl benzoic acid with several inert solvents but the yields reported are poor and all below 60%. Other processes start from potassium salts of aromatic hydroxycarboxylic acids using a phase transfer catalyst. Preparation of the potassium salts requires evaporation of water or mechanical grinding which is not viable on industrial scale. Some of the methods employ dry reaction at very high temperature which is also industrially not feasible. The methods described above have several disadvantages like either usage of large excess of polar aprotic solvents or ammonium salts as phase transfer catalyst which are difficult to break or neutralize hence enters in waste water to pollute it. Preparation of potassium salt requires evaporation of water or mechanical grinding which is not viable on industrial scale. Some of the methods employ dry reaction at very high temperature which is also industrially not feasible. The main object of the invention is a process for preparing alkyl benzoic acid alkyl ester in one step with a high yield using a solvent that can be easily recovered. This aim is achieved according to the invention in that the organic solvent is an alkyl substituted aromatic hydrocarbon. Preferably a xylene or toluene or a mixture is used as solvent. The process according to the invention allows preparing alkyl alkoxy benzoates in one step, starting from one single raw material, viz. aromatic hydroxyl carboxylic acid, with high yield of over 95% and without having to recover any intermediate or added compound. The process comprises the production of a compound having the formula (1) (Figure Removed)wherein R is an alkyl radical having 1 to 6, preferably 1 to 2 carbon atoms by reacting a compound of the formula (2) (Figure Removed)with a compound of the formula RnX, wherein R is an alkyl group having 1 to 6 carbon atoms and X is an acid rest group having a valency n. The OH-group can be in the m-, o- or p- position. Preferably R is an alkylgroup having 1 to 2 carbon atoms. Preferred acid rest groups are sulfates. Preferably RnX is a dialkylsulfate of the formula (RO)2SO2, in which R has the above meaning. The amount of alkyl groups present in the amount of compound RnX is at least equal to the number of alkyl groups to be introduced in the amount of compound (2) and preferably exceeds this last amount by at least 20% and at most 100%. Preferably the excess of alkyl groups is between 25 and 50%. The contacting takes place in the presence of an alkyl substituted aromatic hydrocarbon solvent, toluene or xylene being preferred and in the presence of a base in an aqueous solution. The amount of the base is chosen such that the pH value is in the range from about 6 to 10, preferably 8 to 10 and preferably the process is carried out at a temperature above 70°C, preferably in the range of 80-95°C. The benzene ring can be (mono or di) substituted with halogen atoms, alkyl groups having 1 to 4 C-atoms and alkoxy groups having 1 to 4 C-atoms. The process according to invention allows converting hydroxyl benzoic acid to corresponding alkoxy benzoic acid alkyl esters in one step with an excellent yield and purity. The reaction can be performed by adding hydroxybenzoic acid to a mixture of the organic solvent and the compound having the formula RnX. A base solution is added to the mixture and the pH of the reaction is set at 6-10 preferably between 8 and 10. The concentration of the base in the aqueous solution can be 10 -50% and is preferably 25-40% and more preferably 30-40%. Sodium and potassium hydroxide are preferred as the base. After completion of the base addition, the mass is stirred further for 15 minutes. Then the aqueous phase and the organic solvent phase are separated. The organic solvent layer is washed with water and distilled to give the pure product directly. The invention is elucidated by the following illustrative examples, without being restricted thereto. Example I 15 g (0.108 mole) of 4-hydroxybenzoic acid and 54.4 g (0.353 mole) of diethylsulfate were introduced into a glass flask containing xylene (75 ml). The mixture was heated to 90 C. The pH of mass was checked by a calibrated pH electrode immersed in the mass. The pH was maintained between 8-10 by drop wise addition under stirring of a 35% aqueous NaOH solution [13.6 g (0.326 mole) NaOH flakes in 25 ml water] in 90 minutes. The mass is further stirred for 15 minutes after addition of NaOH, Then the mass was cooled to ambient temperature and 75 ml water was added. The upper organic phase containing the formed product was separated from the lower aqueous phase, washed with 2% NaOH aqueous solution (75 ml) and finally with water. Evaporation of solvent gave 20.5 gm (97.6%) of p-ethoxy ethylbenzoate having purity 98.6% by HPLC. Example 2 30 g (0.217 mole) of 4-hydroxybenzoic acid and 87.6 g (0.695 mole) of dimethylsulfate were introduced into a glass flask containing xylene (150 ml). The mixture was heated to 85°C. The pH of mass was checked by a calibrated pH electrode immersed in the mass. The pH was maintained between 8-10 by drop wise addition under stirring of a 76 gm (0.665 mole) 35% aqueous NaOH solution in 60 minutes. The mass is further stirred for 15 minutes after addition of NaOH. Then the mass was cooled to ambient temperature and 150 ml water was added. The upper organic phase containing the formed product was separated from the lower aqueous phase, washed with 2% NaOH aqueous solution (75 ml) and finally with water. Evaporation of solvent gave 35.3 gm (98.05%) of p-methoxy methylbenzoate having purity 98.42% by HPLC. Claims I. Process for preparing a compound of the formula (Figure Removed)by contacting, in an organic solvent in the presence of an aqueous solution of a base, hydroxy benzoic acid with a compound of the formula RnX, wherein R is an alkyl group having 1 to 6 C-atoms and X is an acid rest group having a valence n, characterized in that the organic solvent is an alkyl substituted aromatic hydrocarbon. 2. Process according to claim 1, wherein the organic solvent is chosen from the group consisting of toluene and xylene. 3. Process according to claim 1, wherein X is sulfate. 4. Process according to claim 1, wherein R is methyl or ethyl. 5. Process according to any of claims 1 to 4, wherein the number of alkyl groups present in the amount of compound RnX is between 25 and 50% in excess to the number of hydroxy 1 and acid groups to be substituted. 6. Process according to claim 1, wherein the reaction is carried out at 80-95°C. 7. Process according to claim 1, wherein the reaction is carried out at a pH of 8-10. 8. Process for preparing a compound substantially as herein described with reference to the foregoing examples.

Full Text

PROCESS FOR PREPARING ALKYL ALKOXYBENZOATES IN ONE STEP
The present invention relates to a process for preparing a compound of the formula:
(Figure Removed)by contacting hydroxy benzoic acid with a compound of the formula RnX, wherein R is an alkyl group having 1 to 6 carbon atoms and X is an acid rest group having a valency n.
The acid esters are useful as selective inhibitor in stereospecific polymerization. They are also used as starting raw materials in many drugs.
Processes for the preparation of said esters are known in the art.
In RO 88669 A, Ar(OR)n is alkylated with RX (X= Br, iodo, sulfate) at 20-30 °C in a polar aprotic solvent like dimethylsulfoxide, dimethylformamide or dimethylacetamide in the presence of 1 0- 1 5% NaOH or KOH.
JP 60214753A discloses a one step process for preparing the esters from hydroxyl benzoic acid with several inert solvents but the yields reported are poor and all below 60%.
Other processes start from potassium salts of aromatic hydroxycarboxylic acids using a phase transfer catalyst. Preparation of the potassium salts requires evaporation of water or mechanical grinding which is not viable on industrial scale. Some of the methods employ dry reaction at very high temperature which is also industrially not feasible.
The methods described above have several disadvantages like either usage of large excess of polar aprotic solvents or ammonium salts as phase transfer catalyst which are difficult to break or neutralize hence enters in waste water to pollute it. Preparation of potassium salt requires evaporation of water or mechanical grinding which is not viable on industrial scale. Some of the methods employ dry reaction at very high temperature which is also industrially not feasible.
The main object of the invention is a process for preparing alkyl benzoic acid alkyl ester in one step with a high yield using a solvent that can be easily recovered.
This aim is achieved according to the invention in that the organic solvent is an alkyl substituted aromatic hydrocarbon.
Preferably a xylene or toluene or a mixture is used as solvent.
The process according to the invention allows preparing alkyl alkoxy benzoates in one step, starting from one single raw material, viz. aromatic hydroxyl carboxylic acid, with high yield of over 95% and without having to recover any intermediate or added compound.

The process comprises the production of a compound having the formula (1)

(Figure Removed)wherein R is an alkyl radical having 1 to 6, preferably 1 to 2 carbon atoms by reacting a compound of the formula (2)
(Figure Removed)with a compound of the formula RnX, wherein R is an alkyl group having 1 to 6 carbon atoms and X is an acid rest group having a valency n. The OH-group can be in the m-, o- or p- position.
Preferably R is an alkylgroup having 1 to 2 carbon atoms.
Preferred acid rest groups are sulfates. Preferably RnX is a dialkylsulfate of the formula (RO)2SO2, in which R has the above meaning.
The amount of alkyl groups present in the amount of compound RnX is at least equal to the number of alkyl groups to be introduced in the amount of compound (2) and preferably exceeds this last amount by at least 20% and at most 100%. Preferably the excess of alkyl groups is between 25 and 50%.
The contacting takes place in the presence of an alkyl substituted aromatic hydrocarbon solvent, toluene or xylene being preferred and in the presence of a base in an aqueous solution. The amount of the base is chosen such that the pH value is in the range from about 6 to 10, preferably 8 to 10 and preferably the process is carried out at a temperature above 70°C, preferably in the range of 80-95°C.
The benzene ring can be (mono or di) substituted with halogen atoms, alkyl groups having 1 to 4 C-atoms and alkoxy groups having 1 to 4 C-atoms.
The process according to invention allows converting hydroxyl benzoic acid to corresponding alkoxy benzoic acid alkyl esters in one step with an excellent yield and purity. The reaction can be performed by adding hydroxybenzoic acid to a mixture of the organic solvent and the compound having the formula RnX. A base solution is added to the mixture and the pH of the reaction is set at 6-10 preferably between 8 and 10. The concentration of the

base in the aqueous solution can be 10 -50% and is preferably 25-40% and more preferably 30-40%. Sodium and potassium hydroxide are preferred as the base.
After completion of the base addition, the mass is stirred further for 15 minutes. Then the aqueous phase and the organic solvent phase are separated. The organic solvent layer is washed with water and distilled to give the pure product directly.
The invention is elucidated by the following illustrative examples, without being restricted thereto.
Example I
15 g (0.108 mole) of 4-hydroxybenzoic acid and 54.4 g (0.353 mole) of diethylsulfate were introduced into a glass flask containing xylene (75 ml). The mixture was heated to 90 C. The pH of mass was checked by a calibrated pH electrode immersed in the mass. The pH was maintained between 8-10 by drop wise addition under stirring of a 35% aqueous NaOH solution [13.6 g (0.326 mole) NaOH flakes in 25 ml water] in 90 minutes. The mass is further stirred for 15 minutes after addition of NaOH, Then the mass was cooled to ambient temperature and 75 ml water was added. The upper organic phase containing the formed product was separated from the lower aqueous phase, washed with 2% NaOH aqueous solution (75 ml) and finally with water. Evaporation of solvent gave 20.5 gm (97.6%) of p-ethoxy ethylbenzoate having purity 98.6% by HPLC.
Example 2
30 g (0.217 mole) of 4-hydroxybenzoic acid and 87.6 g (0.695 mole) of dimethylsulfate were introduced into a glass flask containing xylene (150 ml). The mixture was heated to 85°C. The pH of mass was checked by a calibrated pH electrode immersed in the mass. The pH was maintained between 8-10 by drop wise addition under stirring of a 76 gm (0.665 mole) 35% aqueous NaOH solution in 60 minutes. The mass is further stirred for 15 minutes after addition of NaOH. Then the mass was cooled to ambient temperature and 150 ml water was added. The upper organic phase containing the formed product was separated from the lower aqueous phase, washed with 2% NaOH aqueous solution (75 ml) and finally with water. Evaporation of solvent gave 35.3 gm (98.05%) of p-methoxy methylbenzoate having purity 98.42% by HPLC.

Claims

I. Process for preparing a compound of the formula

(Figure Removed)by contacting, in an organic solvent in the presence of an aqueous solution of a base, hydroxy benzoic acid with a compound of the formula RnX, wherein R is an alkyl group having 1 to 6 C-atoms and X is an acid rest group having a valence n, characterized in that the organic solvent is an alkyl substituted aromatic hydrocarbon.
2. Process according to claim 1, wherein the organic solvent is chosen from the group
consisting of toluene and xylene.
3. Process according to claim 1, wherein X is sulfate.
4. Process according to claim 1, wherein R is methyl or ethyl.
5. Process according to any of claims 1 to 4, wherein the number of alkyl groups present
in the amount of compound RnX is between 25 and 50% in excess to the number of
hydroxy 1 and acid groups to be substituted.
6. Process according to claim 1, wherein the reaction is carried out at 80-95°C.
7. Process according to claim 1, wherein the reaction is carried out at a pH of 8-10.
8. Process for preparing a compound substantially as herein described
with reference to the foregoing examples.

Documents:

http://ipindiaonline.gov.in/patentsearch/GrantedSearch/viewdoc.aspx?id=fbaz6xEY88B8mvpk0In4RQ==&loc=+mN2fYxnTC4l0fUd8W4CAA==

« Previous Patent

Next Patent »

Patent Number

272843

Indian Patent Application Number

1015/DEL/2007

PG Journal Number

19/2016

Publication Date

06-May-2016

Grant Date

28-Apr-2016

Date of Filing

10-May-2007

Name of Patentee

SAUDI BASIC INDUSTRIES CORPORATION

Applicant Address

P.O.BOX 5101, 11422 RIYADH, SAUDI ARABIA,SAUDI ARABIA.

Inventors:

#	Inventor's Name	Inventor's Address
1	SAINANI, J.	SABIC RESEARCH & TECHNOLOGY PVT. LTD., PLOT # 5&6, SAVLI GIDC, SAVLI-BARODA, HIGHWAY, MAJUSAR-3917775, GUJARAT,INDIA

PCT International Classification Number

C09K

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA