Ethyl cinnamate reduction

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]. 

Curious observation were made on attempted condensation of certain phenyl -substituted ethylene oxides with thiourea and related reagents, among them acetamide, benzamide, and thiobarbituric acid. Ktilbene oxide and ethyl epoxy tin nam a te, for example, underwent remarkably ready reduction on treatment with thiourea (Eq, 686), giving itilbene and ethyl cinnamate respectively, together with urea and free sulfur. 

Scheme 2 shows Rapoport s synthesis [15]. The cinnamic acid derivative 3 prepared from m-methoxy benzaldehyde [20] was ethylated by diethyl sulfate to give ethyl cinnamate derivative 4, followed by Michael addition with ethyl cyanoacetate to afford compound 5. Compound 5 was converted to lactam 6 by the reduction of the cyano group and subsequent cyclization. Selective reduction of the lactam moiety of 6 was achieved by treatment with trimethy-loxonium fluorob orate followed by sodium borohydride reduction. Amine 8 was obtained by the reductive methylation of amine 7. Amine 8 was converted to compound 9 by methylene lactam rearrangement [21], followed by selenium dioxide oxidation to provide compound 10. Allylic rearrangement of compound 10 and subsequent hydrolysis gave compound 12. The construction of the decahydroisoquinoline structure began with compound 12,... 

High catalytic activities, with turnovers of up to 9(X) cycles min , is displayed in the transfer hydrogenation of a,p-unsaturated ketones, such as benzylideneacetone and chalcone, using 2-propanol and catalytic amounts of [Ir(3,4,7,8-Me4-phen)COD]Cl (phen = 1,10-phenanthroline COD = 1,5-cyclo-octadiene) in a weakly alkaline medium. Other Ir-chelated complexes are also active catalysts in this reaction, with over 95% selectivity for the 1,4-reduction mode. Divalent lanthanide derivatives, such as Sml2 or Ybh in stoichiometric quantities, in THF and t-butyl alcohol or methanol reduce ethyl cinnamate and cinnamic acid to give the saturated derivatives. " Similarly, 3-methylcyclohexenone is reduced to 3-methylcyclohexen-l-ol in 67% yield, but a,p-unsaturated aldehydes are nonselectively reduced with these systems. 

Double potential-step chronocoulometry [1,2,221] may be used similarly to DPSCA. The working curves now include the charge ratio —Qb/Qf, which takes the value 0.414 for a simple electron transfer reaction. The reductive cyclization of ethyl cinnamate (see Chapter 21) illustrates the use of the technique [226,227]. 

The Sn2 mechanism is ruled out for reaction between the tertiary halide, r-BuBr, and radical anions derived from the more easialy reduced compounds cinnamonitrile (9) ethyl cinnamate (12a), methyl styryl ketone (23a), and phenyl styryl ketone (20a). Reduction of the activated alkenes in the presence of an excess of r-BuBr leads to mixtures of products where a r-Bu group has been introduced in a- or j0-position or in the phenyl ring. For 9 and 12a small amounts of butylated hydrodimers were obtained in addition, and for the enone 23a formation of the unsaturated alcohol with introduction of the /-Bu group at C-1 was a major product [192]. In this case the mechanism is unambiguously reduction of the activated alkene followed by electron transfer to r-BuBr concerted with halide cleavage, in... 

The starting materials, frans-3,4-methylenedioxycinnamyl alcohol (61a) and frans-2-methoxy-3,4-methylenedioxycinnamyl alcohol (61b) were prepared from the corresponding benzaldehyde via substituted ethyl cinnamate by means of the Horner-Emmons reaction and lithium aluminium hydride reduction. Condensation of compound (61 a) or (61 b) with compound (47) gave compound (62a) or (62b), respectively, followed by ring closure to afford compound (63a) or (63b). Intramolecular Diels-Alder reaction of compound (6 2) led to the formation of the aromatized compounds as by-product in both cases. Moreover, in the reaction of... 

A rate acceleration in the reaction of iodobenzene (39a) and ethyl acrylate (40) has been observed qualitatively [13] while at room temperature under atmospheric pressure no reaction occurs, ethyl cinnamate (41) is obtained in high yield if a pressure of 10 kbar is applied (Scheme 7.10). Surprisingly, diarylated acrylate 42, which arises by a second Heck reaction onto 41, is not formed at normal pressure, while at 10 kbar 42 can be obtained as the sole product. Interestingly, if bromo-benzene (39b) is used instead of iodobenzene (39a), the adduct 43 was also formed, which is explained by the addition of 45 to a second molecule of ethyl acrylate and subsequent reductive elimination and double bond isomerization. In this case, high pressure seems to slow down the reductive elimination leading to 41 suf-... 

In the case of aromatic esters, a few groups such as nitro and bromo survived at the reduction conditions, whereas hydroxy and amino groups completely suppressed the reaction. Considering the case of ethyl cinnamate, the fully saturated alcohol was the sole product of the reduction. In all the examined cases a molar ratio of NaBH /ester of 3 1 was always used in order to achieve the best yields. 

Scheme 10.8 Reduction of ethyl cinnamate to propanoic acid ester.

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 —... 

Isomerization has been observed with many a,j3-unsaturated carboxylic acids such as w-cinnamic 10), angelic, maleic, and itaconic acids (94). The possibility of catalyzing the interconversion of, for example, 2-ethyl-butadiene and 3-methylpenta-l,3-diene has not apparently been explored. The cobalt cyanide hydride will also catalyze the isomerization of epoxides to ketones (even terminal epoxides give ketones, not aldehydes) as well as their reduction to alcohols. Since the yield of ketone increases with pH, it was suggested that reduction involved reaction with the hydride [Co" (CN)jH] and isomerization reaction with [Co (CN)j] 103). A related reaction is the decomposition of 2-bromoethanol to acetaldehyde... 

The procedure described is essentially that of Ballard and Dehn.1 Stilbene has also been prepared by reduction of desoxy-benzoin,20 benzaldehyde,23 and benzil 2o-2c by dehydrogenation of ethyl benzene,30 toluene,30- 33- 3, and bibenzyl 33-3alkaline reduction of phenylnitromethane,40 phenylnitroacetonitrile,40 and desoxybenzoin 43 by distillation of benzyl sulfone,50 benzyl sulfide,60-63 calcium cinnamate,5 cinnamic acid,5d phenyl cinna-mate,6e-6/ and diphenyl fumarate ie by dehydrohalogenation of a,a -dichlorobibenzyl60 and benzyl chloride 63 by dehalogenation of a,a,c/,a -tetrachlorobibenzyl70 and benzal chloride 73 by the coupling of cinnamic acid and phenyldiazonium chloride 8 by de-... 

Ethyl phenols are a result of enzymatic activities linked to the decarboxylation of cinnamic acids and the subsequent reduction in vinyl phenols caused by the Brettanomyces/Dekkera yeast genus (Chatonnet et al., 1992), apart from very small quantities produced in peculiar... 

L-Phenylalanine,which is derived via the shikimic acid pathway,is an important precursor for aromatic aroma components. This amino acid can be transformed into phe-nylpyruvate by transamination and by subsequent decarboxylation to 2-phenylacetyl-CoA in an analogous reaction as discussed for leucine and valine. 2-Phenylacetyl-CoA is converted into esters of a variety of alcohols or reduced to 2-phenylethanol and transformed into 2-phenyl-ethyl esters. The end products of phenylalanine catabolism are fumaric acid and acetoacetate which are further metabolized by the TCA-cycle. Phenylalanine ammonia lyase converts the amino acid into cinnamic acid, the key intermediate of phenylpropanoid metabolism. By a series of enzymes (cinnamate-4-hydroxylase, p-coumarate 3-hydroxylase, catechol O-methyltransferase and ferulate 5-hydroxylase) cinnamic acid is transformed into p-couma-ric-, caffeic-, ferulic-, 5-hydroxyferulic- and sinapic acids,which act as precursors for flavor components and are important intermediates in the biosynthesis of fla-vonoides, lignins, etc. Reduction of cinnamic acids to aldehydes and alcohols by cinnamoyl-CoA NADPH-oxido-reductase and cinnamoyl-alcohol-dehydrogenase form important flavor compounds such as cinnamic aldehyde, cin-namyl alcohol and esters. Further reduction of cinnamyl alcohols lead to propenyl- and allylphenols such as... 

Selective reductions of substituted alkynes are equally successful with tris(dimethyl-phenylphosphine)norbomadienerhodium(I) hexafluorophosphate. This cationic complex of Rh is superior to other catalysts, including deactivated Pd-on-CaC03. Thus, 1 is hydrogenated in acetone to ethyl ci -cinnamate in quantitative yield with no trace of the rranj-isomer or of the completely reduced acid. Use of deactivated Pd-on-CaC03 catalyst results in complete reduction ... 

It is believed that these compounds, characteristic of Brettanomyces and Dekkera, result from decarboxylation of hydroxycinnamic acids, yielding vinyl phenol intermediates and subsequent reduction to produce the ethyl analog (Steinke and Paulson, 1964). As seen in Fig. 3-3 initial decarboxylation is mediated by cinnamate decarboxylase, whereas the reduction step utilizes a vinyl phenol reductase. 

Biochemically, 4-ethyl guaiacol and 4-ethyl phenol originate from ferufic acid and /vcoumaric acid, respectively. The reaction is a two-step process with an initial decarboxylation of the hydroxycinnamic acids catalyzed by cinnamate decarboxylase and the reduction of the vinyl phenol intermediates by vinyl phenol reductase (Fig. 11.1). Although the specific coenzyme involved remains unknown, one possible metabolic benefit of the second reaction to Brettanomyces could be reoxidation of NADH. Under low oxygen conditions such as those found in wines, the availability of NAD can be limited so that carbohydrate metabolism is inhibited (Section 1.5.1). Reduction of the vinyl phenols to the ethyl phenols would allow the cell to increase the availability of NAD and thus maintain metabolic functions. 

Finally, in the context of a recent total synthesis of smyrindiol 69 starting from 2,4-dihydroxybenzaldehyde, the pyrone ring was generated by reduction of the ethyl (2-hydroxyphenyl)-propiolate 67 with the Lindlar catalyst (Scheme 29) [122]. The resulting orf/zo-hydroxy-(Z)-cinnamate ring-closed immediately to the corresponding coumarin 68. 

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