FIELD OF INVENTION
The present invention relates to a simple process for the preparation of methoxy -2-teralone otherwise known as methoxy-3, 4-dihydro-iH-naphthalene-2-one. Methoxy tetralones are interesting class of compound, which are being used as intermediates for the manufacture of analgesics, anti-inflammatory agents, and antidepressants drugs . Some of the interesting tertralone are 5-methoxy-2- tertralone la, 7-methoxy-2-tertralone Ib and 6-methoxy-2- tertralone Ic
BACKGROUND OF THE INVENTION:
Methoxy -2-tetralones are shown in general Formula I, dimethoxy dihydro naphthalene are shown in general Formula II and dimethoxy naphthalene are shown in general formula III (formula I, Formula II and Formula III are shown in figure-i)
5-Methoxy -2-tetralones la is a key intermediate for a number of drugs namely, rotigotine used in the treatment of restless leg syndrome & human parkinsonism, dopamine D2 agonist N-0923 , dopamine D2 agonist N-0923 and Quinagolide.HCl. 7-Methoxy -2-tetralones Ha is used as an intermediate for the preparation of butorphanol.
Tetrahedron Letters (1996), 37(19), 3243-3246 discloses a method to synthesis of 2-tetralones via a novel 1,2-carbonyl transposition of l-tetralones.
Tetrahedron Letters (1993), 34(41), 6631-4 discloses a new carboannulation strategy by intramolcular addition, of silylenol ethersIV to photochemically generated arene radical cation.. Thus, irradiation of a mixture of silylenol ether IV with 1,4-dicyanonaphthalene in MeCN-H20 gave 72% 7-methoxy-2- tertralone (shown in figure 2)
Journal of Organic Chemistry, 66(21), 7166-7177; 2001 disclose a multi step for the preparation of 5-methoxy -2-tetralone starting from 2-methoxy cinnamic acid.

Tetrahedron, 45(5), 1441-6; 1989 discloses a multi step synthesis for same starting from 2-methoxy benzaldehyde. However all these process are not amenable for scale up due large no of steps, complexity in designing photochemical reactor in case , the use of corrosive and unsafe reagents in another case .
Journal of Medicinal Chemistry, 32(5), 961-8; 1989 disclose a process in which dimethoxy naphthalene III is hydrogenated using sodium, ammonia and alcohol. JP 78-67300 discloses a multi step synthesis for 7-Methoxy-2-tetralone by reaction of 3-MeOC6H4CH2COX (X = halide) with H2C:CH2. using corrosive AICI3
Polonaise des Sciences, Serie des Sciences Chimiques (1971), 19(4), 219-25 disclose a method in which Dialkoxy naphthalenes (I) are treated with alkali metals in NH3 to give 5,8-dihydronaphthalenes. However these methods have draw back of the handling of liquid ammonia as solvent. Liebigs Annalen der Chemie, (2), 435-7; 1985 disclose a process in which 5-methoxy 2- tetralone is converted to 4-methoxy 2- tetralone
JP 2005 289981 discloses a process in which tetralones V [R1-R4 = C1-6 alkyl, C1-6 alkoxy, H, OH; (X1X2, Y1Y2) = (O, H2), (H2, 0)] are prepared, by the reduction of naphthalenes VI [R1-R4 = same as I; (X3, Y3) = (H, OH), (OH, H)] with formic acids in solvents in the presence of noble metal catalysts, (shown in figure 3)
CN1438210 discloses a method which comprises, reduction of 2,7-dimethoxynaphthalene Illb using Na/ethanol in org. solvent (THF, ethanol, benzene, etc.) in the presence of org. amine (propylamine, hexylamine, or triethylamine) and solvent one or several of following solvent ( THF, Benzene, Hexane, pet. Ether, anhydrous alcohol at -2O-5°C to 2,7-dimethoxy 5,8-dihydronaphthalene ilb Further it discloses the process in which the 2,7-dimethoxy 5,8-dihydronaphthalene (I) is demethylated to give tetralone Ib in the presence of ketonic solvent by adjusting pH 1-3 with Cone HC1 under nitrogen as shown in the scheme, (shown in figure 4)

However the method suffers from the draw back the amine used in the stage-oi which is corrective and reactive. Hence the process is not amenable for scale up.
W02004027055 discloses enzymatic stereo selective reduction of 2-tetralone derivatives to form 2-tetralol
JP2003206253 discloses a process in which tetralones I are prepared by hydrogenation of alkoxynaphthalenes II in the presence of noble metal and acid catalysts in solvents and purified by using bisulfites. Yields are low, cost of catalyst are high and hence of no commercial value
JP54i6o357disclose a process in which 7-methoxy-2-tetralone (I) was prepared by the reaction of 3-MeOC6H4CH2COX II (X = halide) with H2C:CH2.& AICI3 in MDC with poor yeild
Though so much is disclosed in literature as cited above still need is felt for scaleable simple method
OBJECT OF THE INVENTION
The object of the present invention is to provide a simple cost effective improved process for producing methoxy -2-teralone with high purity and yield. Methoxy-2-teralone selected from a group consist of 2,6-dimethoxy naphthalene, 2,5-dimethoxy naphthalene and 2,7-dimethoxy naphthalene
Accordingly, the present invention provides a process for preparing methoxy -2-
teralone, comprising the steps of
l.Reducing corresponding dimethoxy naphthalene with alkali metal and alcohol in a
solvent/solvent mixture at 25°C to reflux temperature to dimethoxy dihydro
naphthalene(II)
2. Refluxing the dimethoxy dihydronaphthalene with Cone HC1 to methoxy -2-teralone

DETAILED DESCRIPTION OF THE INVENTION
The present invention provides for a simple method for production of methoxy -2-teralone by reduction of dimethoxy naphthalene with alkali metal and alcohol in a solvent/solvent mixture at 25°C to reflux temperature to dimethoxydihydronaphthalene followed by demethylation using cone HC1 to methoxy -2-teralone
The process is described in more detail below:-
Dimethoxynaphthalene III is reduced with alkali metal and alcohol in a ether solvent or hydrocarbon solvent or its mixture to dimethoxy dihydronaphthalene
Where as alkali metal is selected from the group consists of sodium, potassium and lithium
Alcohol is selected from C-1 to C5 alcohol straight or branched chain.
Ether solvent is defined having general structure R-OR’ where R&R’ are similar or dissimilar groups or together form a ring having up to 5-carbon atoms. They represent by alkyl, aryl or alkoxy alkyl group. As used in this specification the term alkyl refers to straight or branched chain having 1 to 4 carbon atoms selected from a group consisting of methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec butyl, t-butyl. The term alkoxy alkyl refers to member selected from the group consisting of substituted or unsubstituted methoxymethyl, methoxyethyl, methoxypropyl
Some of the non-limiting examples of ether solvents that can be used in the process are diisopropyl ether, diglyme, dimethoxy ethane, di-isobutyl ether, methyl-t-butyl ether, tetrahydrofuran, methyl tetrahydrofuran.
Hydrocarbon solvent is selected from a group consisting of heptane, petroleum ether, hexane, toluene, xylene.

The temperature of the reaction of scheme-1 can vary between room temperature to 12O°C. The preferred temperature is 20 - 75°C and the most preferred temperature is 30±5°C The completion of reaction can be monitored by checking absence of one of the starting materials using standard techniques like in-process monitoring by HPLC. The crude product was obtained after washing the solvent with water and then solvent was striped up to give dimethoxydihydro naphthalene II. The crude dimethoxy dihydronaphthalene was then demethylated by refluxing with acid to get methoxy tetralone I at a temperature ranging from room temperature to boiling point temperature of the solvent used in the process.
The acid is selected from the group consist of cone HC1, aq.H2SO4 and aq.PTS. The most preferred acid is cone HC1 and the most preferred temperature (80±5°C). The completion of reaction can be monitored by checking absence of one of the starting materials using standard techniques like in-process monitoring by HPLC. After completion of reaction the pH was solution was adjusted with solid sodium carbonate to 5-6 and the organic layer was separated. Then the organic layer was treated with aq. sodium metabisulfite. And the adduct thus isolated as solid, was treated with aq. sodium carbonate and was extracted with methylene chloride to give methoxy tetralones which was then fractionally distilled to get very high purity.
The invention is illustrated further by following non-limiting examples: Example-i:
Preparation of 5-methoxy-3, 4-dihydro-iH-napthalene-2one bisulfate adduct
To a solution toluene (8sogm) and 1,6-dimethoxy naphthalene (200g) sodium metal in pieces (l00g) was added carefully at 30±5°C. Isopropyl alcohol (63Og) was added drop wise to the above solution over a period of 3 hours. The reaction mixture was stirred further for 9 hours at 30±5°C. Completion of the reaction was monitored by GC. On completion the solvent was distilled out. The resulting mass cooled to 30±5°C and quenched with ice to get i,6-dimethoxy-5,7 -dihydro naphthalene

pH of the water solution of 1,6-dimethoxy-5,7 -dihydro naphthalene was adjusted to 1-2 using cone. HC1. Further the reaction mixture was heated to reflux and refluxed for 2 hours. Completion reaction is monitored by checking content of 1,6-dimethoxy-5,7 -dihydro naphthalene using GC. It should be NMT 2.0% by GC. On completion the pH of the solution was adjusted to pH 5-6 with sodium carbonate. The organic layer by separated and was treated with sodium meta bisulphite (440g) and DM water (800g) over a period of lhour at 30±5°C. The reaction mixture was further stirred for 12 hours. The preceipted solid was then filtered and sucked dry the product to give s-methoxy-3, 4-dihydro-iH-napthalene-2-one bisulfate adduct in 92.3% (yield). HPLC Purity 96.41%
Preparation of 5-methoxy-3, 4-dihydro-iH-naphthalene-2-one (5-methoxy-2- tertralone) la
A mixture of DM water (17OOg) and sodium carbonate (200g) was stirred at 30±5°C for 15mins. The 5- methoxy-3, 4-dihydro-iH-naphthalene-2-one bisulfate adduct (255g) was added. The resulting solution was then extracted with methylene chloride at 30±5°C. On distillation of methylene chloride under vacuum at 6o°C, then gave I32g of crude product. The crude product was fractionally distillated using under high vacuum at 87, 93°C/2mbar to give title compound in 5-Methoxy-3, 4-dihydro-1H-naphthalene-2-one. HPLC Purity 99.69%
Example-2
Preparation of 7-methoxy-3, 4-dihydro-lH-napthalene-2one bisulfate adduct
To a solution toluene (8sog) and 1,6-dimethoxy naphthalene (2oog) sodium metal in pieces (loog) was added carefully at 30±5°C. Isopropyl alcohol (630g) was added drop wise to the above solution over a period of 3 hours. The reaction mixture was stirred further for 9 hours at 30±5°C. Completion of the reaction was monitored by GC. On completion of reaction, the solvent was distilled out. The resulting mass cooled to 30±5°C and quenched with ice to get 2,7-dimethoxy-3,4 -dihydro naphthalene

pH of the water solution of 2,7-dimethoxy-3,4 -dihydro naphthalene was adjusted to l-2 using cone. HC1. Further the reaction mixture was heated to reflux and refluxed for 2 hours. Completion reaction is monitored by checking content of 2,7-dimethoxy-3,4 -dihydro naphthalene using GC. It should be NMT 2.0% by GC. On completion the pH of the solution was adjusted to pH 5-6 with sodium carbonate. The organic layer by separated and was treated with sodium meta bisulphite (440g) and DM water (8oog) over a period of lhour at 30±5°C. The reaction mixture was further stirred for 12 hours. The solid was then filtered and sucked dry the product to give 7-methoxy-3, 4-dihydro-iH-napthalene-2-one bisulfate adduct in 89% (yield).. HPLC Purity 99.78%, with 2-Tetralone 0.07% and 2,7-Dimethoxy naphthalene 0.05%
Preparation of 7-methoxy-3, 4-dihydro-iH-naphthalene-2-one (7-methoxy-2- tertralone) Ib
A mixture of DM water (1350g) and sodium carbonate (18og) was stirred at 3O±5°C for I5mins. The 7- methoxy-3, 4-dihydro-iH-naphthalene-2-one bisulfate adduct (255g) was added. The resulting solution was then extracted with methylene chloride at 30±5°C. On distillation of methylene chloride under vacuum at 6o°C, then gave 13lg of crude product. The crude product was fractionally distillated using under high vacuum at iio-H4°C/imbar to give 78%( yield), in 7-methoxy-3, 4-dihydro-iH-naphthalene-2-one. HPLC Purity 99.3%

WE CLAIM
1 A process to prepare methoxy-3, 4-dihydro-iH-naphthalene-2-one (I), comprising following steps of
a) Reducing corresponding dimethoxy naphthalene with alkali metal and alcohol in a ether solvent or hydrocarbon solvent or its mixture at 25C to reflux temperature to dimethoxy dihydronaphthalene(II)
b) Adjusting pH of the water solution of the dimethoxy dihydronaphthalene(II) to 0.1- 4 with a acid and refluxing same to get methoxy-3, 4-dihydro-iH-naphthalene-2-one
2 A process as claimed in claim 1 wherein the methoxy-3, 4-dihydro-iH- naphthalene-2-one(I) is selected from a group consist s-methoxy-3, 4-dihydro- iH-naphthalene-2-one (la) , 7-methoxy-3, 4-dihydro-iH-naphthalene-2-one(IB) & 6-methoxy-3, 4-dihydro-iH-naphthalene-2-one(Ic)
3. A process as claimed in claim la) wherein the dimethoxy naphthalene (III) is selected from a group consist of 2,6- dimethoxy naphthalene, 2,5-dimethoxy naphthalene and 2,7-dimethoxy naphthalene
4. A process as claimed in claim la) wherein the alkali metal is selected from the group consists of sodium, potassium and lithium
5. A process as claimed in claim la) wherein the hydrocarbon solvent selected from a group consist of is selected from a group consisting of heptane, petroleum ether, hexane, toluene, xylene
6. A process as claimed in claim la) alcohol is selected from group consist of C-i to C5 alcohol straight or branched chain

7- A process as claimed in claim la) wherein the ether solvents shall have a general formula R-OR\ wherein R&R' are similar or dissimilar groups or together form a ring having up to 5-carbon atoms, representing alkyl, aryl or alkoxy alkyl radical
8. A process as claimed in claim la) the preferred temperature is 20 o 75C and the most prepared temperature is 30±5°C
9. A process as claimed in claim ib) the acid is selected from a group consist of cone HC1, aq.H2SO4 and aq.PTS

10. A process as claimed in claim ib) the most preferred pH is 1-2
11. A process as claimed in claim ib) the most preferred temperature (8o±5°C).