Phenylacetic acid, biphasic carbonylation

Similarly, Pd/tppts was used by Hoechst (Kohlpainter and Beller, 1997) as the catalyst in the synthesis of phenylacetic acid by biphasic carbonylation of benzyl chloride (Fig. 2.29). The new process replaces a classical synthesis by reaction of benzyl chloride with sodium cyanide, followed by hydrolysis of the resulting benzyl cyanide. Although the new process produces one equivalent of sodium chloride, this is substantially less salt production than in the original process. Moreover, sodium cyanide is about seven times as expensive per kg as carbon monoxide. 

In the same way, the biphasic carbonylation of benzyl alcohol (Figure 9.7) was achieved.Phenylacetic acid was obtained in 11% yield, 100% selectivity, and 100% atom utilization. 

Benzyl halides are easily carbonylated to phenylacetic acid derivatives which are valuable intermediates for Pharmaceuticals, cosmetics and fragrances [2,3], Several papers report the aqueous/organic biphasic realization of this reaction [1,19-22] (Scheme 5.3). The main characteristics of these processes are summarized in Table 5.1. 

Carbonylation of Alcohols - Pd(tppts)3 catalyses the carbonylation of benzylic alcohols to the corresponding phenylacetic acids, in the presence of a Bronsted acid cocatalyst such as H2S04 or p-CH3C6H4S03H in biphasic aqueous/organic media (no organic solvent).305,451 For example, benzyl alcohol was converted to phenylacetic acid (Equation 6) and l-(4-isobutylphenyl)ethanol (IBPE) to ibuprofen (Figure 9). 

It is reported that the two-phase carbonylation methodology has been used on a pilot plant scale by Montedison [31 ] for the conversion of benzyl chloride to phenylacetic acid for use in perfume constituents and pesticides (eq. (8)). The carbonylation is run in a biphasic medium employing diphenyl ether and aqueous 40 % sodium hydroxide as solvents. The catalyst system consists of a cobalt carbonyl complex and a benzyltrialkylammonium surfactant. The reaction takes place at low temperature and CO pressure, while benzyl chloride is added continuously to the reaction mixture. 

To determine the mode of operation (see below) it is useful to group these homogeneous catalysts into aqueous biphasic systems (see Section 3.1.1.1) and nonaqueous biphasic systems (see Section 3.1.1.2). Gas-liquid-liquid reactions are also involved in organometallic phase transfer catalysis, e. g., in biphasic carbonylation of benzyl chloride to phenylacetic acid by the catalyst system NaCo(CO)4/Bu4NBr/NaOH [21]. Here, the biphasic system consists of an organic solvent and aqueous alkali. 

The tenside phosphines 38 (n = 1, 2, 3) containing amino and phosphonate moieties were used as ligands to impart surfactant properties to Pd catalysts for the carbonylation (cf. Section 6.5) of benzyl chloride to phenylacetic acid under aqueous-biphase conditions [66], The recovery of the Pd/38 catalyst after the carbonylation reaction, however, was only 85-92%. 

Industrial significance has also been acquired by the aqueous biphasic Pd-catalyzed carbonylation of benzyl chloride to phenylacetic acid [Eq. (1)]. Once more, TPPTS is the ligand of choice [4]. 

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