NL8700356A - NEW METHOD. - Google Patents

Description

, «= - · t - New working method -

The invention relates to a process for the preparation of 4- (6'-methoxy-2-naphthyl) butan-2-one.

European patent application 3074 describes a process for the preparation of 4- (6'-methoxy-naphthyl-butan-5.

which process comprises catalytic hydrogenation with hydrogen gas. However, while the process gives a high yield of the desired product, the use of hydrogen gas presents the risk of explosions.

A new process for the preparation of 4- (6'-methoxy-2-naphthyl) -butan-2-one. has now been found, with which high yields can be obtained without the additional danger of explosions.

The invention accordingly provides a process for the preparation of 4- (6'-methoxy-2'-naphthyl) butan-2-one, which process comprises the catalytic transfer hydrogenation in the presence of cyclohexene of a compound of formula 1, wherein X and Y are both a hydrogen atom or together represent a second bond between the carbon atoms to which they are attached, and R. represents a carboxy group or an ester group. .

which can be converted therein by hydrogenation.

Ester groups which can be converted to carboxy groups by hydrogenation are well known to those skilled in the art. Suitable examples of such ester groups are groups of formula 2 wherein R 1 alkenyl has 2 to 5 carbon atoms.

one or a group of formula 3, wherein one of the symbols

Rg, and R is phenyl, optionally substituted by halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 5 carbon atoms or nitro, and the other two symbols may or may not be different and each hydrogen or phenyl, optionally substituted ... .

as defined above.

R2 is preferably allyl or a group of formula 4, 5 or 6, wherein each of the phenyl groups is optionally substituted as defined above.

Generally, the optional substituents are located at the para or meta sites. Preferably 8700356-2 is not more than. one such substituent is present. Of the halogens, bromine and chlorine are preferred.

Particularly suitable groups for them are benzyl, p-methoxybenzyl, p-bromobenzyl, p-methylbenzyl and p-5 chlorobenzyl and 3-allyl.

Most preferably R2 is benzyl.

The hydrogen transfer is carried out in the presence of a catalyst, for example a transition metal catalyst such as palladium. A suitable palladium catalyst • | Q, for example, is palladium on carbon. Other metal catalysts that can be used are, for example, Raney nickel or a soluble catalyst for homogeneous hydrogenation.

Suitable solvents for the reaction are, for example, lower alcohols, esters and aromatic hydrocarbons. Particularly suitable solvents are hydrocarbons such as benzene or toluene.

The reaction is normally carried out at an elevated temperature, for example 60-120 ° C and most efficiently at reflux temperature, usually 70-100 ° C.

When the reaction is complete (eg, judged by tic), the desired compound can be obtained by filtering off the catalyst and removing the solvent, for example, by evaporation under reduced pressure. If desired, the compound thus obtained can be further purified by recrystallization, for example from aqueous ethanol.

The catalytic transfer hydrogenation of a compound of formula 1 is preferably carried out with a compound in which X and Y represent a second bond between the carbon atoms to which they are bonded, in view of the efficient preparation of such compounds by reaction of 6-methoxy- 2-naphthaldehyde with an ester of acetoacetic acid (European patent application 3074).

The following examples illustrate the invention: 8700356 * * - - 3 -

Example I

Set-up 3-neck flask, equipped with a stirrer, a gas inlet, a gas outlet, a heating mantle, a back * 5 cooler with a Dean and -Stark receiver and a thermometer.

Method 3-Benzyloxycarbonyl-4- (6'-methoxy-2'-naphthyl) -but-3-en-2-one (110 g) and 10% palladium on carbon (10 g) were placed in the reaction vessel. The vessel was well purged with nitrogen and toluene and cyclohexene were added in a single amount. No change in temperature was taken. The mixture was stirred well and heated to reflux temperature of 77 ° C in 0.5 hour. Any water present in the reaction mixture was removed with the Dean-and-Stark apparatus. After heating under reflux for 2 hours, the heating was turned off and the mixture cooled. Water (20 ml) was added, the reaction vessel was well purged with nitrogen, and the mixture was filtered through a Celite bed which was washed with ethyl acetate (2 x 100 ml). The combined solvents were removed under water pump vacuum at 50 ° C to give a light brown-yellow solid (70.3 g). The crude compound was dissolved in hot ethanol (280 ml) at 70 ° C and filtered and the solution allowed to cool. The product was filtered off under suction, washed with cold ethanol (50 ml) and sucked dry.

The solid was dried in a vacuum oven at 60 ° C and 15 mm for 2 hours to obtain 56.4 g (81%) of the product, mp. 81 ° C.

30

Example II

Using the same general procedure of Example I, 3-allyloxycarbonyl-4- (6'-methoxy-2'-naphthyl) -but-3-en-2-one (3.1 g) in ethanol (50 ml) was added 2 \ refluxed with 35 cyclohexene (10ml) and 10% palladium on carbon (430mg) to give the title compound (1.2g) which, after recrystallization from 80% aqueous ethanol, has a 8700356 * -4-4 melting point 78.5 ° C.

Example III

Using the same general procedure of Example I, 3-p-methoxybenzyloxycarbonyl-4- (6'-methoxy-2'-naphthyl) -but-3-en-2-one (1 g) was cyclohexene (20 g) for 2 hours. ml) and ethanol (50 ml) under reflux with 10% palladium on carbon (200 mg). The solution was filtered and the solvent was evaporated to give the title compound (310 mg) which, after recrystallization from 80% aqueous ethanol, had a melting point of 80.5 ° C.

/ 8700356

Claims (8)

Process for the preparation of 4- (6-methoxy-2'-naphthyl) butan-2-one, characterized in that it comprises the catalytic transfer hydrogenation, in the presence of cyclohexene, of a compound of formula 1, wherein X * and Y are each a hydrogen atom or together represent a second bond between the carbon atoms to which they are attached, and Rj is a carboxy group or an ester group which can be converted therein by hydrogenation. 2. Process according to claim 1, characterized in that R ^ is an ester group of formula 2, wherein alkenyl is with 2 to 5 carbon atoms or a group of formula 3, wherein one of the symbols R ^> R ^ and R Phenyl is optionally substituted by halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 5 carbon atoms or nitro, and the other two symbols are different or not and each is hydrogen or phenyl optionally substituted as defined above. 3. Process according to claim 2, characterized in that R2 in formula 2 is 3-allyl and X and Y together represent a second bond between the carbon atoms to which they are attached. Process according to claim 2, characterized in that R2 in formula 2 is a group of formula 4, 5 or 6, wherein each of the phenyl groups is optionally substituted in the para or meta position by halogen, alkyl with 1 to 5 carbon atoms, alkoxy of 1 to 5 carbon atoms or nxtro, and X and Y together represent a second bond between the carbon atoms to which they are attached. Process according to claim 4, characterized in that Ro is benzyl or p-methoxybenzyl. 30 Z Process according to any one of claims 1 to 5, characterized in that the hydrogenation catalyst comprises palladium or Raney nickel or a soluble catalyst for homogeneous hydrogenation. Process according to any one of claims 35 to 6, characterized in that the hydrogenation is carried out in an inert organic solvent 8700356-6. Process according to any one of claims 1 to 7, characterized in that the hydrogenation is carried out at 60-120 ° C. 9. 9-Allyloxycarbonyl-4- (6'-methoxy-2'-naphthyl) but-3-en-2-one. -o-o-o-o- 870 03 5 6, ί ^. * Λ · * COCHj ^^ - v / CHX — CY -COORj \ ch3o 1 1 2 f -c — R, -CH, _ ^ 0) l 3 "- CH _C- © è. 8700356 '. Beecha "> Group p.l.c., BRENTFORD, Great Britain