Abstract



In organic reactions, difficulties are often encountered if the organic compound is soluble in an organic solvent and the reagent in water, then the two will react very slowly only at the interface, where these two solutions are in contact, resulting in a negligible reaction. Apart from the synthesis of the desired product, many waste materials are often generated in the course of the synthesis. These wastes should be regenerated, destroyed and disposed consuming much energy and creating heavy burdens on the environment. It is therefore of great importance to develop and use the synthetic methodology that minimize these problems. Perhaps one of the most general and efficient methodology that fulfill this requirement is phase transfer catalyst (PTC).

A phase transfer catalyst is a type of chemical compound, often a quaternary ammonium salt, which facilitates the migration of a particular chemical component in one phase in to another phase in a heterogeneous system.

Advantages of the Phase Transfer Catalyst:

Phase transfer catalysts used are quaternary ‘onium’ salts such as ammonium, phosphonium, antimonium and tertiary sulphonium salts. It is now well established that the PTC reactions have considerable advantages over the conventional procedure. The PTC reactions,

1.Do not have vigorous conditions and the reactions are fast.

2.Do not require expensive aprotic solvents.

3.Do not require high temperatures; the reactions usually occur at low temperatures.

4.There is no need for anhydrous conditions since water is used as one of the phases.

5.With the help of PTC, the anion is available inorganic solvent and so its nucleophilicity increases.

6.In many cases the work up procedure is easier.

7.Many reactions which require strong base like alkoxide, sodamide, sodium hydroxide etc. can proceed even with OH- as it becomes strongly nucleophile in the presence of PTC.

8.Almost all reactions can be carried out by PTC except those which are sensitive to water.

9.Some special advantages in the use of PTC are: the reactions that do not otherwise proceed can be made to proceed in good yields. Modifications of selectivity and modification of product ratio, e.g. O vs C alkylations are also possible. Higher yields through the suppression of side reactions are possible by the use of PTC.

Applications of Phase Transfer Catalysis in organic Synthesis:

It has already been mentioned that phase transfer catalysis can be used in numerous types of reactions due to its advantages over other conventional procedures. Some important applications are given below.

It has already been shown that 1-chlorooctane does not react with sodium cyanide under a variety of conditions, viz stirring and heating for a long time. However if small quantity PTC is used, the reaction goes to a completion in about 2 hrs. Similarly different nitriles and benzoyl cyanides are prepared from alkyl halides and benzoyl chlorides using PTC in good yield.

PTC is useful in technique used in the exchange of halide. The procedure is far superior to conventional methods. A convenient method for conversion of chlorides or bromides to the corresponding fluorides is by the use of quaternary ammonium salts supported on insoluble resin. These resins used can be recoverable.

The displacement of halogen by hydroxyl group under PTC conditions is difficult due to several factors. It is reported that the displacement of halogen by hydroxyl group is best accomplished by the use of ‘betanine’ quaternary salt as PTC. It has been found that phase transfer catalysts have also been used for the conversion of alkyl halides in to the azides and sodium alkyl sulphonates. Similarly the alkyl bromides on reaction with sodium thiocyanate, sodium cyanate and sodium p-toluene sulphonate in presence of quaternary ammonium nitrates gives the corresponding thiocyanates, cyanates and p-toluene sulphonates respectively.

The PTC method is of special interest in the methylation of nitrophenols with methyl iodide, since these phenols are alkylated only by special techniques. Also compounds containing o-dihydroxy group can be methylenated with methylene bromide in 70-80% yield. Heteroanalogs of biphenyl ethers and thioethers have been prepared using PTC.

Carboxylic acids can be esterified with alkyl halides in the presence of triethylamine. In this case, the PTC is obtained in situ by the reaction of triethylamine and alkyl halide. Alternatively, the quaternary ammonium or phosphonium salt can be directly used in the esterifiction of carboxylic acid with alkyl halides.

Dihalocarbenes are synthetically useful intermediates, and are normally generated by the action of a base on chloroform. These reactions usually require anhydrous conditions, since in aqueous solution the dichlorocarbene may undergo hydrolysis. Thus it usually gives yield less than 5%. It is now found that the use of phase transfer catalyst, the addition product obtained is in 60-70% yield. The dichlorocarbene, thus generated in situ by the PTC method has been used for a number of synthetic purposes.

Use of phase transfer catalysis permits experimental simplification for a veriety of alkylation methods. Use of quaternary ammonium hydroxides in the form of ion exchange resins catalyses the alkylation of ethyl malonate, ethyl cyanoacetate and cyanoacetamide with a variety of alkyl halides in good yield. Aziridines cannot be easily alkylated under conventional conditions due to rapid decompositions to open chain compounds. It has been shown that the alkylation of aziridine can be carried out quantitatively under PTC conditions. In similar methodology heterocyclic compounds such as imidazole, carbazole, pyridine, oxyindole derivatives can be alkylated conveniently using PTC. Such compounds can be selectively alkylated. Phase transfer glycosidation of pyrimidine derivatives have also been accomplished in the synthesis of potential interferon inductor intermediate. N-alkylation of ? –lactams has also been reported, a step in the synthesis of nocardicin.

It is found that benzoin condensations of aldehydes are strongly catalyzed by quaternary ammonium cyanide in a two phase system. In a similar way, acyloin condensations are easily effected by stirring aliphatic or aromatic aldehydes with quaternary catalysts. The use of phase transfer catalyst has made Darzen’s reaction very simple and the yields are 70-80%. The Michael reaction for active nitriles to acetylenes can be catalysed by addition of a quaternary ammonium chloride. The phase transfer catalyst provides a simple and convenient method for conducting Williamson ether synthesis.

The PTC catalysed Wittig reaction is limited to only aldehydes. No olefin is obtained from ketones. In spite of this limitation the method is very convenient and useful for the preparation of a variety of olefins of the type RCH=CHR.

The phase transfer catalysed Wittig-Horner reaction using aqueous sodium hydroxide and either tetraalkylammonium salts or crown ethers as a catalyst has been explored for the synthesis of olefins.

Using PTC, heterocyclic compounds such as coumarins flavones oxazines, furans, thiazoles, pyrroles have been prepared conveniently with good yield.

A novel method for the synthesis of ?-lactams using PTC procedure starting from ?-amino acids has been reported.

Many of the oxidation processes using permagnate, chromate, osmium tetroxide, peroxides as oxidizing agents as well as reduction processes with borohydrides, diborane have shown to be successful using PTC.

Conclusion:

PTC offers extremely convenient conditions for a variety of reactions and usually increases the yields and purity of the products and provides a much simpler procedures for the isolation of the products. There are also many reactions that do not proceed satisfactorily unless conducted under PTC conditions. Though PTC is not a universal methodology, nevertheless it is very versatile, the scope of applications is tremendous and when used it offers many advantages.