JPS61178947A - Manufacture of arylalkyl ketone - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for producing arylalkyl ketones by reacting an aryl compound with an aliphatic acid or a functional derivative of an aliphatic acid or a mixture thereof in anhydrous hydrofluoric acid.

More specifically, the method of the present invention is represented by the following formula.

ArH+ Y-Co-CHX-R--Ar'-CO-C
HX-RI II where ArH is 2-methoxynaphthalene, ^r
゛ is 6°-methoxy-2゛-naphthyl, Y is Ol
halogen or 0-Co-CHX-R, X is hydrogen or halogen, and R is hydrogen or methyl.

Compounds of formula
) reaction (JP 50-18448, Chemical Abstracts 83.789545x, 1975) as an intermediate for the production of Naproxen.

It is known that when 2-methoxynaphthalene is acylated with an aliphatic acid derivative, more specifically an aliphatic acyl halide, in the presence of a Lewis acid, various products are obtained depending on the solvent used. ing. [Journal on the Chemical Society (J
.

CheIIl, Soc, (C) 1966181-5)
.

In particular, 2-methoxy-6-acylnaphthalene was synthesized in nitrobenzene [Organic Synthesis (Org.
, 5ynthesis, 53. 5.1973) ),
In nitroalkane (C, A, 6 rainbow, 12620f,
1966) or in polyphosphoric acid (C, A, 58.154
6gh, 1963).

However, these methods have significant drawbacks when implemented on an industrial scale.

That is, when attempting to carry out these methods with nitrobenzene or nitroalkanes, in addition to the well-known problems associated with the toxicity of nitro derivatives, the type of manipulation required, e.g. during the addition of the reactants and with aluminum chloride requires significant labor and energy costs, such as careful temperature control during cooling of the aluminum derivative, filtration and discharge of the aluminum derivative, and recovery of the nitro derivative by distillation.

Ultimately, this process has only been carried out with acid halides because aliphatic acids are less reactive and acid anhydrides require larger amounts of Lewis acid and solvent.

Polyphosphoric acid is difficult to use because it is viscous, requires high temperatures, is impossible to recover, and is difficult to dispose of.

According to the present invention, it has been found that the compound of formula (1) can be easily prepared in anhydrous hydrofluoric acid according to the above reaction formula.

The first advantage of the method of the invention is that, unlike known methods,
The acylating agent of formula I is not only a halide, but also acids or anhydrides or acid/anhydrides, acid/halides, anhydride/halide mixtures or ternary mixtures can be used.

A second advantage of the process of the invention is that it does not require the use of aluminum chloride or other conventional Friedel-Crafts catalysts, and the addition of these catalysts does not affect the yield.

A further advantage of the process of the invention is that hydrofluoric acid can be easily recovered by distillation due to its low boiling point (I9.5° C.).

The presence of aliphatic acids or functional derivatives thereof in the recovered hydrofluoric acid does not impede the recycling of the hydrofluoric acid.

Another advantage of the process of the invention is that even when using an optically active acylating agent of formula I in which X is chlorine and R is methyl, no substantial racemization occurs and the resulting formula The optically active compound is
It is a suitable intermediate for the stereospecific preparation of Na-broxene according to the prior art.

As a result of the simplicity and flexibility of the method of the invention, it is possible to make various modifications without departing from the spirit of the invention.

The following examples illustrate the invention in a non-limiting manner.

Example 1 ■-(6"-methoxy-2"-naphthyl)propane-1
- Preparation of 56.7 g (0.43 mol) of propionic anhydride and 50 g (0.32 mol) of 2-methoxynaphthalene in 20
Added to 0ml of anhydrous hydrofluoric acid.

The reaction mixture was stirred at 19° C. for 28 hours, then poured into water and extracted three times with 200 ml of methylene chloride.

The combined organic extracts were neutralized with 10% aqueous sodium hydroxide solution, then washed with water, dried over Glauber's salt, and concentrated.

The residue (63 g) contained 84% of the desired product (yield 77
%) and less than 1% of the isomer, 1-(2°-methoxy-
1'-naphthyl)propan-1-one was included.

Pure 1-(6'-methoxy-2'-naphthyl)propan-1-one was obtained by recrystallizing the crude product from suitable solvents such as methanol, heptane, toluene, and mixtures thereof.

Similar results were obtained as described below.

Yield 80% by carrying out the reaction at 37° C. for 8 hours.

A yield of 74% was obtained by reducing the amount of propionic anhydride to 47.8 g (0.37 mol), adding 15 g (0.20 mol) of propionic acid and reacting at 37° C. for 8 hours.

Yield 77% by replacing propionic anhydride with a mixture of 41 g (0.44 mol) propionyl chloride and 33 g (0.44 mol) propionic acid.

Yield 34% by replacing propionic anhydride with propionic acid
.

Example 2 l-(6'-methoxy-2'-naphthyl)ethane-1-
Preparation of propionic anhydride and acetic anhydride (43.9 g, 0.4
89% in the same manner as in Example 1 except that 3 mol)
2-(6'-methoxy-2'-naphthyl)ethane-1
52.5 g of a crude product containing -one was obtained in a yield of 86%. Purified by recrystallization.

Example 3 l-(6′-methoxy-2″-naphthyl)propane-1
Preparation of -one To 225 g of anhydrous hydrofluoric acid are added 49.5 g (0.57 mol) of propionyl chloride, then 70 g (0.4
4 mol) of 2-methoxynaphthalene and 90 g of anhydrous hydrofluoric acid were added at 19°C.

The reaction mixture was held at 40° C. for 71 hours, then Example 1
It was processed in the same way.

The yield was 70 g (73%).

Example 4 Preparation of (S) 1-chloroethyl-(6''-methoxy-2°-naphthyl)ketone 38.3 g (0.3 mol) of (S) 2-chloropropionyl was added to 460 g of anhydrous hydrofluoric acid. Chloride (α) =
+1.64° (net, 1=1) (optical purity 31%),
Then 32 g (
0.2 mol) of 2-methoxynaphthalene was added.

The reaction mixture was kept at 20°C for 22 hours and then Example 1
processed in the same way.

The residue was purified on a silica gel column (toluene effluent) and 4 g of (S)-chloroethyl-(6'-methoxy-
2'-naphthyl)ketone was obtained.

[α]′or=31.2° (C·1%, chloroform), and the optical purity was 27%.

Claims (1)

[Claims] An aryl characterized by reacting 1,2-methoxynaphthalene with a compound of the following formula (I) in anhydrous hydrofluoric acid to produce an arylalkyl ketone of the following formula (II). Method for producing alkyl ketones. Y-CO-CHX-R (I) Ar'-CO-CHX-R (II) However, in formula (I), Y is OH, halogen or OCO-CHX-R, and R is hydrogen or methyl. , X is hydrogen or halogen; in formula (II), Ar' is 6'-methoxy-2'-naphthyl;
and R have the same meanings as above. A method for producing an arylalkyl ketone according to claim 1, which uses a mixture of two, two or more types of formula (I).