Benzylic halides carbonylation

Very recently another reaction, which involves a palladium-catalyzed benzyl halide carbonylation step, has been commercialized by Clariant AG. Here, the carbonylation of 1,2-xylyl dichloride in the presence of a palladium-phosphine catalyst yields isochromanone (eq. (10)) [54]. 

Benzoic acid, mercapto-lithographic printing plates, 101 Benzonitrile hydrolysis metal catalysis, 449 Benzoquinone dioximates metal complexes non-integral oxidation states, 144 Benzylamine oxidase, 700 Benzyl halides carbonylation... 

The development of the Grignard-type addition to carbonyl compounds mediated by transition metals would be of interest as the compatibility with a variety of functionality would be expected under the reaction conditions employed. One example has been reported on the addition of allyl halides to aldehydes in the presence of cobalt or nickel metal however, yields were low (up to 22%). Benzylic nickel halides prepared in situ by the oxidative addition of benzyl halides to metallic nickel were found to add to benzil and give the corresponding 3-hydroxyketones in high yields(46). The reaction appears to be quite general and will tolerate a wide range of functionality. 

Not unexpectedly, alkylation of the double carbonylated complex proceeds via a base-catalysed interfacial enolization step, but it is significant that the initial double carbonylation step also involves an interfacial reaction, as it has been shown that no pyruvic acid derivatives are obtained at low stirring rates. Further evidence comes from observations of the cobalt-catalysed carbonylation of secondary benzyl halides [8], where the overall reaction is more complex than that indicated by Scheme 8.3. In addition to the expected formation of the phenylacetic and phenylpyruvic acids, the reaction with 1-bromo-l-phenylethane also produces 3-phenylpropionic acid, 2,3-diphenylbutane, ethylbenzene and styrene (Scheme 8.4). The absence of secondary carbonylation of the phenylpropionylcobalt tetracarbonyl complex is consistent with the less favourable enolization of the phenylpropionyl group, compared with the phenylacetyl group. 

Analogous carbonylation reactions using nickel and iron carbonyl based systems also produce alkanecarboxylic acids [11, 13, 14]. The mechanism of the conversion of benzyl halides into arylacetic acids using iron pentacarbonyl is not as well defined as it is for reactions promoted by nickel or molybdenum carbonyl complexes. Iron... 

When sodium ethoxide is used in place of sodium hydroxide in the carbonylation reaction of benzyl halides with dicobalt octacarbonyl, ethyl esters are produced instead of the acids [15], Esters are also produced directly from iodoalkanes through their reaction with molybdenum hexacarbonyl in the presence of tetra-/i-butylammo-nium fluoride [16]. Di-iodoalkanes produce lactones [16]. The reaction can be made catalytic in the hexacarbonyl by the addition of methyl formate [16]. t-Butyl arylacetic esters are produced in moderate yield (40-60%) under phase-transfer catalytic conditions in the palladium promoted carbonylation reaction with benzyl chlorides [17]. 

Selected examples of the conversion of benzyl halides into arylacetic acids using iron carbonyl complexes... 

Complexes of other metals are also capable of catalyzing useful carbonylation reactions under phase transfer conditions. For example, certain palladium(o) catalysts, like Co2(C0)g, can catalyze the carbonylation of benzylic halides to carboxylic acids. When applied to vinylic dibromides, unsaturated diacids or diynes were obtained, using Pd(diphos)2[diphos l,2-bis(diphenylphosphino)ethane] as the metal catalyst, benzyltriethylammonium chloride as the phase transfer agent, and t-amyl alcohol or benzene as the organic phase(18),... 

Carbonvlation of Benzyl Halides. Several organometallic reactions involving anionic species in an aqueous-organic two-phase reaction system have been effectively promoted by phase transfer catalysts(34). These include reactions of cobalt and iron complexes. A favorite model reaction is the carbonylation of benzyl halides using the cobalt tetracarbonyl anion catalyst. Numerous examples have appeared in the literature(35) on the preparation of phenylacetic acid using aqueous sodium hydroxide as the base and trialkylammonium salts (Equation 1). These reactions occur at low pressures of carbon monoxide and mild reaction temperatures. Early work on the carbonylation of alkyl halides required the use of sodium amalgam to generate the cobalt tetracarbonyl anion from the cobalt dimer(36). 

As the supported glycol catalysts worked better in promoting reactions in a single solvent system, we explored the direct carbonylation of benzyl halides using an alcohol solvent, base, and cobalt carbonyl. Our initial experiments concentrated on the reaction of benzyl bromide at room temperature and one atmosphere carbon monoxide. We chose sodium hydroxide as the base, methanol as the solvent, and looked at the product distribution. We were interested in the selectivity to ester and the reactivity of this system. The results are given in Table III. 

A recent report( ) on the use of iron carbonyl and potassium carbonate in a similar carboxyalkylation scheme to prepare methyl phenylacetate prompted us to examine the use of carbonate on alumina in a similar manner. It was suggested that if the amount of free base was less than the amount of iron carbonyl than ether formation would not occur being that iron carbonyl was a better electrophile than benzyl halide. Under our conditions, the metal carbonyl anion... 

Before addition of the benzyl halide, the only carbonyl adsorption peak is found at 1900 cm, indicative of the cobalt tetracarbonyl anion. After addition, this band immediately disappears and peaks at 2000 cm l are observed. These most likely represent the corresponding acyl complex. Reaction with methoxide yields the product and regenerates the cobalt anion. In the absence of sufficient methoxide, the reaction requires attack by the much... 

The results from our work on the reaction of propylene oxide with cobalt carbonyl and base in methanol are given in Table VIII. Several base/metal oxide combinations were evaluated under mild reaction conditions. The difference in activity between the bases was not as pronounced as that observed in the reaction with benzyl halides with the exception of potassium methoxide which, when used alone, gave exclusively the hydroxy ether resulting from methoxide addition to the epoxide ring. However, the activity of sodium... 

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. 

The transition metal-complex-catalyzed carbonylation of benzyl halides to yield phenylacetic acids is an extensively studied reaction [Eq. (7)]. 

Substrates suitable for oxidative conversion into carbonyl compounds are alkenes, primary or secondary alcohols, and benzyl halides. Polystyrene-bound alkenes have been converted into aldehydes (with the loss of one carbon atom) by ozonolysis followed by reductive cleavage of the intermediate ozonide (Entry 1, Table 12.3). 

Many of the common laboratory methods for the preparation of alcohols have been discussed in previous chapters or will be considered later thus to avoid undue repetition we shall not consider them in detail at this time. Included among these methods are hydration (Section 10-3E) and hydroboration (Section 11-6D), addition of hypohalous acids to alkenes (Section 10-4B), SN1 and Sn2 hydrolysis of alkyl halides (Sections 8-4 to 8-7) and of allylic and benzylic halides (Sections 14-3B and 14-3C), addition of Grignard reagents to carbonyl compounds (Section 14-12), and the reduction of carbonyl compounds (Sections 16-4E and 16-5). These methods are summarized in Table 15-2. 

In other variations ketones are produced. The acyliron monoanion may be alkylated again with another alkyl halide to form a transient acyl-alkyl iron intermediate, which rapidly decomposes into ketone and the polynuclear iron carbonyl complex. This reaction is limited, however, because only very reactive alkylating agents such as methyl, allyl, and benzyl halides will react with the weakly nucleophilic acyliron monoanions ... 

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