Cinnamyl alcohol reduction

Hydrogenation of cinnamaldehyde has been studied extensively since selectivity has often been an issue. Under mild conditions the carbonyl group is reduced giving cinnamyl alcohol, whereas at elevated temperatures complete reduction to 3-phenylpropanol [122-97 ] results. It is possible to saturate the double bond without concomitant reduction of the carbonyl group through selective hydrogenation with a ferrous chloride-activated palladium catalyst (30), thereby producing 3-phenylpropanol [104-53-0]. 

One of the first practical methods for the manufacture of cinnamyl alcohol involved reduction of cinnamic aldehyde diacetate with iron filings in acetic acid. This approach suffered from low yields and Hberation of a significant amount of the starting aldehyde. 

The commercial production of cinnamyl alcohol is accompHshed exclusively by the reduction of cinnamaldehyde. 

Phenyl-propyl alcohol, CgH. CHj. CH.2. CHj. OH, is the next highest homologue of phenyl-ethyl alcohol, and is also known as hydro-cinnamyl alcohol. Like the last described bodies it has been known for many years, its first preparation being described in the Aivnalen (188, 202). It occurs as a cinnamic acid ester in storax, and as an acetic ester in cassia oil. It is prepared synthetically by the reduction of cinnamyl alcohol with sodium amalgam and water, or by the reduction of cinnamic or benzyl acetic esters with sodium and absolute alcohol. It has the following characters —... 

In the above reduction cinnamyl alcohol is first formed which then changes to the saturated alcohol. 

By means of this reduction process it is possible to obtain, from the corresponding aldehydes, alcohols such as trichloroethyl alcohol or cinnamyl alcohol, which are not otherwise readily accessible or are otherwise inaccessible. Tnbromoethyl alcohol ( avertin ), an important narcotic, is prepared in this way (F. F. Nord). It is given by the rectum. 

A typical probe reaction for estimating catalytic properties in selective hydrogenations is the hydrogenation of cinnamaldehyde. This molecule contains both a C=C and a C=0 double bond, thus the formation of hydrocinnamaldehyde and/or cinnamyl alcohol by reduction of the one or the other, or the formation of phenyl propanol in the case of complete reduction may indicate the potential of the catalyst for other fine chemical transformations. Indeed, this reaction was one of the first to be tested by CNT-supported catalysts [120]. Noble metals show a high activity in this reaction and... 

Vinylogs of benzylic alcohols, e.g. cinnamyl alcohol, undergo easy saturation of the double bond by catalytic hydrogenation over platinum, rhodium-platinum and palladium oxides [39] or by reduction with lithium aluminum hydride [609]. In the presence of acids, catalytic hydrogenolysis of the allylic hydroxyl takes place, especially over platinum oxide in acetic acid and hydrochloric acid [39]. 

Many more examples exist for reduction of the carhonyl only. Over an osmium catalyst [763] or platinum catalyst activated by zinc acetate and ferrous chloride [782] cinnamaldehyde was hydrogenated to cinnamyl alcohol. The same product was obtained by gentle reduction with lithium aluminum hydride at —10° using the inverse technique [609], by reduction with alane (prepared in situ from lithium aluminum hydride and aluminum chloride)... 

Much more conveniently, even a,)S-unsaturated esters can he transformed into a,)S-unsaturated alcohols by very careful treatment with lithium aluminum hydride [1073], sodium bis(2-methoxyethoxy)aluminum hydride [544] or diiso-butylalane [1151] (Procedure 18, p. 208). An excess of the reducing agent must be avoided. Therefore the inverse technique (addition of the hydride to the ester) is used and the reaction is usually carried out at low temperature. In hydrocarbons as solvents the reduction does not proceed further even at elevated temperatures. Methyl cinnamate was converted to cinnamyl alcohol in 73% yield when an equimolar amount of the ester was added to a suspension of lithium aluminum hydride in benzene and the mixture was heated at 59-60° for 14.5 hours [1073]. Ethyl cinnamate gave 75.5% yield of cinnamyl alcohol on inverse treatment with 1.1 mol of sodium bis(2-methoxy-ethoxy)aluminum hydride at 15-20° for 45 minutes [544]. 

Hydride reduction of a 4-arylidene-5(4H)-oxazolone can also be considered as a nucleophilic ring opening. Here, this process, shown in Scheme 7.190, generates a-(benzoylamino)cinnamyl alcohols 597. °... 

Since cinnamyl aldehyde is the main component of cassia oil (approximately 90%) and Sri Lanka cinnamon bark oil (approximately 75%) [49], it is industrially more important to generate cinnamyl alcohol, which is less abundantly available from nature but is important as cinnamon flavour, by biotransformation of natural cinnamyl aldehyde than vice versa. Recently, a whole-cell reduction of cinnamyl aldehyde with a conversion yield of 98% at very high precursor concentrations of up to 166 g L was described [136]. Escherichia coli DSM 14459 expressing a NADPH-dependent R alcohol dehydrogenase from Lactobacillus kefir and a glucose dehydrogenase from Thermoplasma acidophilum for intracellular cofactor regeneration was applied as the biocatalyst (Scheme 23.8). 

Cinnamyl alcohols.1 These alcohols can be prepared by oxidation of 3-arylpropenes with selenium dioxide in dioxane. The yield compares favourably with that oblained by LiAlH4 reduction of esters of cinnamic acids. 

A third approach to the preparation of allyl lluorovinyl ethers is the reaction of an allylic alcohol with trifluoroacetaldehyde, as illustrated by an alternative synthesis of 37a.17 Cinnamyl alcohol (47) forms with trifluoroacetaldehyde a hemiacetal, which is converted into bromide 48 via the mesy late. Reductive elimination affords 37a, which undergoes Claisen rearrangement within one hour in refluxing carbon tetrachloride to give 2,2-difluoro-3-phenylpent-4-enal (38a).17... 

Reductive alkene isomerizations can also be induced by photochemical excitation. Geometric isomerization and rearrangement can be observed upon electron transfer sensitization with molecules with inverse electron demand. Thus, a substituted cinnamyl alcohol in the presence of excited p-dimethoxybenzene gave geometric isomerization and rearrangement characteristic of a free allyl cation, eq. 32 (94) ... 

The reductive sequence from an appropriate cinnamic acid to the corresponding cinnamyl alcohol is not restricted to lignin and lignan biosynthesis, and is utilized for the production of various phenylpropene derivatives. Thus cinnamaldehyde (Figure 4.23) is the principal component in the... 

The relatively inexpensive and safe sodium borohydride (NaBH4) has been extensively used as a reducing agent because of its compatibility with protic solvents. Varma and coworkers reported a method for the expeditious reduction of aldehydes and ketones that used alumina-supported NaBH4 and proceeded in the solid state accelerated by microwave irradiation (Scheme 7) [50]. The chemoselectivity was apparent from the reduction of frarcs-cinnamaldehyde to afford cinnamyl alcohol. 

Ethylenediamine-bisborane is a white crystalline solid which is quite stable on standing and can be stored at room temperature in a desiccator for several months. It evolves hydrogen slowly on warming and decomposes rapidly at about 90°C. The use of this compound for the reduction of acetone, acrolein, cinnamaldehyde, and acetyl chloride to the corresponding alcohols (isopropyl alcohol, allyl alcohol, cinnamyl alcohol, and ethyl alcohol) has been described.1 Its solubility characteristics and its thermal and hydrolytic stability have been reported.1-4... 

Cinnamic acid, starch ester, I, 303 Cinnamaldehyde, phytochemical reduction of, IV, 79, 91 Cinnamyl alcohol, IV, 91 phytochemical reduction of, IV, 92 Citraconic acid, IV, 327 Citral, phytochemical reduction of, IV, 79... 

The second step is the reduction of cinnamaldehyde to cinnamyl alcohol ... 

Heterogeneous catalysis The heterogeneous catalyst, either the finely dispersed metal itself or the metal adsorbed onto a support, remains in a separate phase during the course of reaction. Examples of hydrogenation of alkenes given below include reduction of oleic acid (6.1) with H2 and Pd-C to octadecanoic acid (6.2) and cinnamyl alcohol (6.3) and Raney nickel in ethanol to 3-phenyl-l-propanol (6.4). 

The lithium aluminium hydride reductions often proceed at room temperature or below and are usually rapid and free from side reactions. The compound to be reduced is added slowly to an excess of the reagent suspended or dissolved in ether (normal addition). Selective reduction of polar groups in the presence of other reducible functions can frequently be achieved by an inverse addition method the reagent is added slowly to the substance to be reduced, so that the reagent is never present in excess. Thus, by inverse addition cinnamaldehyde (6.44) is reduced to cinnamyl alcohol (6.3). Normal addition gives dihydrocinnamyl alcohol (6.4). 

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