WO2010070659A2 - A novel heterogeneous catalyst for the preparation of arylacetaldehydes - Google Patents

Abstract

The present invention relates to a novel, simple and heterogeneous catalyst for the aryl ethylene oxide isomarization reactions. The present invention also provide an environmentally benign and economically superior process for the preparation of arylacetaldehydes from aryl ethyleneoxides by isomerization using glass wool as the catalyst, under vapor phase conditions. The preparation of 4-isobutyl-a-methyl phenyl acetaldehyde, a precursor to the API Ibuprofen is described.

Description

A NOVEL HETEROGENEOUS CATALYST FOR THE PREPARATION OF

ARYLACETALDEHYDES

TECHNICAL FIELD

The present invention relates to a process for the preparation of arylacetaldehydes using a novel, inexpensive heterogeneous catalyst. More particularly, the invention relates to the preparation of arylacetaldehydes and derivatives using glass wool as the catalyst. This application claims the benefit of Indian Provisional application No. 2721/CHE/2008 dated November 6, 2008.

BACKGROUND OF THE INVENTION Arylacetaldehydes are known to be used directly or indirectly as valuable intermediates in the production of fragrance compositions and flavourings. In addition such compounds can also be used as synthons in the manufacture of pharmaceuticals, insecticides, fungicides and herbicides These compounds, more preferably phenylacetaldehydes are usually prepared such that the reaction is carried out in a fixed bed reactor under gas phase conditions.

Known procedures for the preparation of phenyl acetaldehydes which can also be earned out in an industrial scale are (a) dehydrogenation of phenyl ethanols- wherein only partial conversion is possible and separation of starting material from the end product involves huge losses since phenyl acetaldehydes are thermally unstable. Formation of auto condensation products during fractionation is another draw back in these procedures. Moreover, halogen containing phenyl acetaldehydes cannot be prepared by this route, since undesired side reaction can occur under the above reaction conditions, (b) Rearrangement of epoxides using homogeneous or heterogeneous catalysts.

Homogeneous catalysts like Lewis acids including zinc chloride, borontrifluoride etherate are generally used for the isomerization of epoxides to carbonyl compounds. These acid catalysts are generally used in stoicheometric quantities. These catalysts are however corrosive thus leading to corrosion of equipments and the procedure thereby involves aqueous work up and difficult isolation techniques. In addition, large amounts of salts are produced during neutralization which can lead to large effluents, containing heavy salt matter. Chemo and regioselective conversion of epoxides to carbonyl compounds in 5M lithium perchlorate in diethyl ether medium is described by Sankararaman and coworkers (J. Org. Chem. 1996, 61, 1877-1879). Trost et al. reported that lithium perchlorate in refluxing benzene to be a very useful reagent for the rearrangement of several epoxides as it shows higher selectivity compared to strong Lewis acids (J. Am. Chem. Soc, 1973, 95, 5321). The perchlorate salts however are not eco friendly, explosive in nature and not suitable for large scale preparation. The process also involves difficult separation techniques.

Aldehydes are obtained from carbonyl chlorides by a Rosenmund reduction. Such reaction proceeds smoothly in the liquid phase with acyl chlorides. Other acyl chlorides for example arylalkylcarbonyl chlorides generally give lower yields coupled with catalyst poisoning.

These drawbacks are not associated with heterogeneous catalysts (zeolites in H form, titanium containing zeolites with well defined pores system). Different styrene oxides can be rearranged in a fixed bed reactor under gas phase conditions. Holderich et.al. (US 4929765 -1988; US 498051 1 - 1987) found that MFI type materials are superior to other oxides. (eg.TiO2, P₂O₅/SiO₂, gamma alumina, E^CVSiC^, bentonite).The possible reason for high region selectivity over MFI material might be related to the stabilization of the alpha carbo cation intermediate formed during the rearrangement. When conventional oxides are used, one of the major side product is 1, 3, 5-triphenyl benzene, formed via the aldol condensation involving three molecules of phenyl acetaldehyde. Conventional catalysts are, furthermore, deactivated because of the formation of 1 , 3, 5-triphenyl benzene and coke.

The side reactions can be suppressed by the use of zeolites, such as ZSM-5 (Si/Al=18.8).which hinder the formation of aldol condensation and consecutive products because of the steric constraints of the frame work of the catalyst. Lower temperature lead to larger amounts of triphenyl benzene (7.6% at 200⁰C, compared to 1.5% at 300⁰C- Holderich et.al Pat 0228675- 1990). This can be explained by a slower desorption of the product at lower temperature.However, 2-methyl styrene oxide is rearranged to a mixture of 2-methyl propanal and phenyl acetone with selectivity of approximately 20%aldehyde and 60% ketone over ZSM-5 (Si/Al=18.8). Some of the problems associated with these catalysts are difficult preparative methods, poor selectivity and difficulty in separating the by-products formed due to auto cyclization and poor lives of the catalyst caused because of coating of the surface.

European patent 100177 describes the reaction of styrene oxides over a titanium containing zeolite at 30-1200⁰C, in liquid phase to give phenyl acetaldehydes. The catalyst used for this purpose has to be made by a complicated process from expensive very pure materials such as tetra alkyl orthosilicates, tetra alkyl orthotitanates and tetra propylammonium hydroxide. There are also other prior art. methods for rearranging epoxides to carbonyl compounds, for instance, cyclododecanone is obtained over Pd- or Rd doped Al₂C^ from epoxy cyclododecane. (Neftekhimiya 16, (1976) 250-254). It is expressly pointed out that zeolites are not suitable for this reaction. These catalysts are system specific and involve issues relating to the preparation and regeneration/recycling of the catalyst.

Similarly the use of A-zeolites for the rearrangement of butylene oxide to butyraldehyde has been disclosed. (Hokkaido Daigaku Kogakubu, Hokuku 67, (1973), 171-178). The selectivity (52-72%) leaves something to be desired. A-zeolites are very difficult to regenerate following deactivation by coking, owing to a very high temperature that is required for the regeneration during which the crystal structure of these zeolites is destroyed.

EP-A228, 675 discloses a system where zeolites of the pentasil, mordenites, erionites, chabazite or L-type are used and the reaction is carried out at from 200⁰C to 500⁰C, preferably at 200⁰C to 400⁰C, under atmospheric pressure. These catalyst systems are not useful for halogenated starting materials.

Hence there is a need to develop novel, simple and inexpensive heterogeneous catalysts for the preparation of aryl acetaldehydes. Surprisingly the inventors found that glass wool could act as a heterogeneous catalyst under vapor phase conditions towards successful transformation of aryl ethylene oxides in to the corresponding aldehydes. OBJECTIVE OF THE INVENTION

Accordingly, the primary object of the present invention is to provide environmentally benign, economically superior, simple heterogeneous catalyst for epoxide isomerization.

Another object of the present invention is to provide a process for preparing arylacetaldehydes of formula 1

Ar-CHR-CHO

Wherein

Ar is a substituted or unsubstituted aryl group

R is H or lower alkyl groups comprising of Ci-Cio carbon atoms

by catalytic rearrangement in the presence of glass wool as heterogeneous catalyst

Another object of the present invention is to provide a simple, convenient process that can be utilized for industrial scale manufacture of phenyl acetaldehydes, which are useful intermediates for API's such as Ibuprofen, under vapor phase isomerization of aryl ethylene oxides using glass wool as heterogeneous catalyst.

This invention has several advantages over prior art methods such that the catalyst provides greater selectivity and catalyst lifetime, in addition to availability/cost, in particular if halogenated ethylene oxides are used. Moreover, the present process facilitates complete conversion with selectivities >90%, without any separating problems. This method also provides very good yields with halogen-containing starting materials. Once the end products are isolated, they can in general be used without additional purifications. An additional advantage is the use for long time on stream, easy regenerability of the catalyst in the event of coking or the catalyst may also be refreshed as it is very cheap and readily available.

DETAILED DESCRIPTION OF THE INVENTION

FIGURE-I shows a time controlled desorption profile of a glass wool sample treated with ammonia FIGURE-2 shows a temperature programmed desorption profile recorded at 20cc He flow for a glass wool sample treated with ammonia. FIGURE-3 shows SEM pictures of glass wool FIGURE-4 Tubular reactor. FIGURE-5 shows powder XRD of glass wool. FIGURE-6 shows Al ²⁹ NMR of glass wool. FIGURE-7 SEM morphology of glass wool.

The present invention relates to the preparation of arylacetaldehydes by isomerization of the corresponding aryl ethyleneoxides using glass wool as the catalyst. In one of the preferred modes of the invention, the aryl ethylene oxide is heated to vaporize the same and the vapors are passed through a bed of glass wool as catalyst, at reaction temperatures in the order from 100-700⁰C, more preferably from 200⁰C to 500⁰C. The reaction is carried out at atmospheric pressure or thereabout and with or without the addition of gaseous diluents in the mixture. The reaction may also be carried out at sub atmospheric or pressures somewhat above atmospheric and in the presence or absence of inert diluents such as steam or nitrogen. Vacuum may also be advantageously used to aid in vapourizing the starting material without heating them to high temperatures.

A tubular catalyst chamber of desired width and length is loaded with the catalyst glass wool of desired volume. The aryl ethylene oxide is vapourized and the vapors are passed through the externally heated tubular reactor loaded with the catalyst, at a desired flow rate. The vapours flow through the hot catalyst and the resultant product vapours are cooled and collected. The product thus obtained is pure enough to be used as such for their applications.

The advantage of the green chemistry in this transformation, coupled with continuous batch process, make this method more suitable for industrial applications. The reaction without glass wool did not prove useful, as the resultant product showed incomplete conversion coupled with lot of impurities by Gas Chromatography analysis, though some product was obtained by simple thermolysis during the reaction. This clearly indicates the catalytic activity of glass wool in the rearrangement reaction. The 4-isobutyl-a-methylstyrene oxide is thermally unstable but in the presence of the heterogeneous catalyst namely glass wool, the rearrangement takes place resulting in the formation of the corresponding phenyl acetaldehyde which is a key intermediate in one of the commonly employed manufacturing processes for Ibuprofen.

Glass wool is an inorganic synthetic vitreous fiber, largely composed of aluminum and calcium silicates that are derived from rock, clay, slag or glass. These synthetic inorganic fibers are amorphous in nature. After the fusion of a mixture of natural sand and recycled glass at 1450⁰C, the glass that is produced is converted in to fibers. The cohesion and mechanical strength of the product is obtained by the presence of a binder that cements the fiber together. Ideally a drop of binder is placed at each fiber intersection. This fiber mat is then heated to around 200⁰C (to polymerize the resin) and is calendared to give strength and stability. The powder XRD of dry glass wool showed no discrete crystalline structure and confirmed its amorphous nature, unlike zeolites. The BET surface area measurement for glass wool indicated very poor surface area 1.08 m² and no porosity. The glass wool treated with ammonia was checked for time controlled desorption measurement (Figure 1) and temperature programmed desorption - NH₃ measurement (Figure 2) which revealed strong and weak acidic sites in the glass wool molecule These acidic sites are believed to aid in the isomerization reaction of aryl ethylene oxides to corresponding aryl aldehydes. Under aqueous alkaline and acidic conditions, the silicate network of synthetic vitreous fibers can be attacked, resulting in the bleaching of individual ions and the eventual disruption of the entire fiber network. Glass wool is used widely as an insulating material. Here the inventors surprisingly found and established its property of weakly acidic heterogeneous catalyst system under vapor phase condition more suitable for isomerization of epoxides, particularly styrene oxides to the corresponding phenyl acetaldehydes which are very difficult to prepare by other methods.

In one of the embodiment of our invention, the reactor system is a fixed bed, vertical downward flow reactor (Figure 4) made up of quartz tube of 40 cm length and 2 cm internal diameter. This quartz reactor is heated to the requisite temperature with the help of a tubular furnace controlled by a digital temperature controller cum indicator. The bottom of the reactor is provided with a thermo well in which the chromel-alumel thermo couple is kept to measure the temperature at the middle of the catalyst bed. About 1 g of the catalyst is taken in the reactor. The top portion of the reactor is connected to a glass bulb having two inlets. Reactant is fed in to the reactor through one inlet by a syringe infusion pump that can be operated at different flow rates. The bottom of the reactor is connected to a chilled condenser and a receiver in which the products are collected. The catalyst is preheated to 500⁰C for 6 h with in flow of air through the catalyst (generated from an aerator). This activated glass wool is cooled to the required reaction temperature under nitrogen flow, before the epoxide is fed in to the reactor for rearrangement, at the desired temperature/flow rate. The product is collected in the receiver and can be used as such for further applications. Styrene oxide (density- 1.053 g/ml ) isomerization to phenyl acetaldehyde was studied, with a reaction time of 30 minutes. (Table l).In the absence of the catalyst, the isomerization did not proceed to the expected extent. The conversion was low.

The phenyl acetaldehyde obtained was confirmed by NMR spectral data and mass analysis. Halogen substituted styrene oxides like.3-chloro styrene oxide; 4-chloro styrene oxide underwent rearrangement smoothly to the corresponding phenyl acetaldehydes under vapor phase conditions using glass wool as catalyst. We have also observed that silica gel (desiccant form as well as silica gel for column chromatography) and aluminum oxide (neutral as well as basic forms) did not catalyze the reaction to the same extent similar to glass wool under the set conditions. In addition to incomplete conversion, we have also observed impurities in these cases, by spectral data.

The isomerization is believed to occur via the benzylic carbo cation formation, which is formed after the coordination of the catalyst at its acidic centers with the epoxide oxygen. This carbocation is stabilized by the aromatic ring system. Subsequent hydride shift, lead to the formation of the corresponding phenyl acetaldehyde.

The catalytic activity of glass wool is specific to aryl ethylene oxides, towards rearrangement to the corresponding phenyl acetaldehydes. Epoxides which are not attached to aromatic system did not undergo isomerization under these conditions. For example epichlorohydrin, phenyl glycidyl ether (prepared and characterized) did not undergo the rearrangement to the corresponding aldehydes under these conditions. This might be because of the unfavorable conditions that exist for stabilization of the carbocation or hydride shift for subsequent formation of the product. The highly selective nature of the catalyst is demonstrated from our findings that phenyl glycidic esters did not undergo isomerization in presence of glass wool under vapor phase conditions. This selective property of glass wool as heterogeneous catalyst, due to the presence of weak and strong acidic sites in the molecule can be extended to other organic transformations by one skilled in the art.

The details of the invention, its object and advantages are explained hereunder in greater details by way of example and it is to be understood that the invention, as fully described herein is not intended to be limited by the examples mentioned herein.

EXAMPLES

Example- 1

Isomerization of Styrene oxide.

Styrene oxide vapors are fed in to the activated glass wool, placed inside the tubular reactor at a flow rate of 6 ml/h. The temperature for the rearrangement reaction is maintained at 300°C.The product vapors are cooled and collected at the receiver. 91% recovery of phenyl acetaldehyde, with a GC purity of 91.3%.The proton NMR is neat. Example-2

Isomerization of m-chloro styrene oxide. m-chloro styrene oxide vapors are fed in to the activated glass wool, placed inside the tubular reactor at a flow rate of 3 ml/h. The temperature for the rearrangement reaction is maintained at

300°C.The product vapors are cooled and collected at the receiver. 70% recovery of m-chloro phenyl acetaldehyde, with a GC purity of 94.3%. The proton NMR is neat. The m/z value is 154.

Example-3

Isomerization of 4-isobutyl-a-methylstyrene oxide to Ibuprofen aldehyde. (Scheme- 1.) 4-isobutyl-a-methylstyrene oxide is prepared following the procedure indicated in J.Org.Chem V 64, No 14, 1999, page 5034. This epoxide is fed into the reactor over the activated glass wool at 300⁰C, at a flow rate of 3 ml/h. 61% yield of 4-isobutyl-a -methyl phenyl acetaldehyde is obtained; with a GC purity of 90%.The IR spectrum is superimposible with that of a reference material.

C₁₃H₁₈O 2-(4-Isobutyl phenyl)-2-methyl oxirane 2-(4-Isobutyl-phenyI)-propionaldehyde

MoI. Wt.: 190.28 C₁₃H₁₈O

MoI. Wt.: 190.28

Precurser to Ibuprofen

Scheme 1- Isomerization of 2-(4-isobutyl phenyl)-2-methyl oxirane

Claims

We claim

1) A method of use of glass wool as a heterogeneous catalyst for organic transformations.

2) A method of use as claimed in claim 1 where said organic transformations are carried out under vapor phase conditions.

3) A process for the preparation of aryl acetaldehydes of general formula (I), where Ri - R₅ are individually hydrogen, lower alkyl, alkoxy, halogen, halo alkyl and / or lower alkylthio and R₆ is hydrogen, alkyl or substituted alkyl groups, comprising the use of the corresponding epoxide of the structural formula II, where Ri - R₅ are individually hydrogen, lower alkyl, alkoxy, halogen, halo alkyl and / or lower alkylthio and R₆ is hydrogen, alkyl or substituted alkyl groups using glass wool as the catalyst ..

Formula (I).

4) A process of claim 3, where the said process is carried out under vapor phase conditions.

5) A process of claim 3, where the said preparation is carried out in the temperature range 100⁰C to 700⁰C. 6) A process of claim 5,where the said temperature is preferably in the range 200⁰C to 500⁰C.

7) A process of Claim 3,where the said epoxide of the structural formula (II) is subjected to a catalytical rearrangement reaction at a temperature from 200⁰C to 500⁰C and a weight hourly space velocity of 0.1 - 20 h^"1 over the glass wool catalyst.

8) The process of claim 3 where said aryl acetaldehyde is 4-isobutyl-a-methyl phenyl acetaldehyde and said epoxide is structural formula (II) where Ri, R₂, R₄, R₅ represent hydrogen, R₆ is methyl and R₃ is isobutyl group.