Cinnamic aldehyde reduction

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 connection of the aromatic mono-, di- and tri-nitro compounds with phytochemical reduction follows from their activating action in alcoholic fermentation, known for a quarter century.The same applies equally to the excellent activating effect of cinnamic aldehyde its behavior during phytochemical eduction is described on pages 79 and 105. 

Vanadium pentoxide becomes markedly photo-sensitive when immersed in glycerol, benzaldehyde, cinnamic aldehyde, cuminol, or aqueous mannitol solution, and exposed to light. It blackens and undergoes reduction, giving rise, initially, to hypovanadic oxide, VOg. With aqueous solutions of citric acid or tartaric acid carbon dioxide is evolved during the change.9... 

Reduction 156 Diacetyi to acetoin (in beer) cinnamic aldehyde to cinnamic alcohol. 

The analogous reaction which accompanies the reduction of cinnam-aldehyde in alkaline solutions is more amenable to experimental study. This reaction follows scheme (39) ... 

Which of the two is the cis form and which the trans form has not been determined. A third cinnamic acid, viz., iso-cinnamic acid, is also known, but the constitution of it has not been established. Cinnamic acid is found in nature in the resin storax both as the free acid and as the cinnamic alcohol ester, styrin. It is also found in Peru and Tolu balsams as the free acid and as the benzyl alcohol ester, the benzoic acid ester of benzyl alcohol being present also. Thus benzyl alcohol, benzoic acid, cinnamic alcohol and cinnamic acid are all constituents of esters present in these plant resins. Allo-cinnamic acid, the geometric isomer, is obtained from coca leaves from which the alkaloid cocaine is also obtained (p. 896). When cinnamic acid is heated with lime it loses carbon dioxide and yields the unsaturated side-chain hydrocarbon st3rrene, or phenyl ethylene, CeHs—CH = CH2. On reduction it yields first cinnamic aldehyde, found in oil of cinnamon (p. 842) and then cinnamic alcohol. Both cinnamic acid and allo-cinnamic acid yield anhydrides. 

Derivation (1) From oil of cassia or oil of cinnamon occurs as an ester. (2) Reduction of cinnamic aldehyde. 

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... 

By the time comprehensive reviews by Wilds (29) in 1944 and Djerassi (30) in 1953 became available, MPV reactions were a standard reductive technique in the organic chemistry community. For example, a 1945 patent (20) describes the utility of using aluminum alkoxides in the presence of an organic nitrogen as a weak base for the reduction of carbonyl groups on oxo compounds such as 7-hydroxy-cholesterol acetate, benzaldehyde, cinnamic aldehyde, and citronellal. 

Cedergren-Zeppezauer E, Samama J-P, Eklund H (1982) Crystal structure determinations of coenzyme analogue and substrate complexes of liver alcohol dehydrogenase Binding of 1,4,5,6-tetrahydronicotin-amide adenine dinucleotide and trans-4-(N,N-dimethylamino)cinnam-aldehyde to the enzyme. Biochemistry 21 4895-4908 Cherest M, Felkin H, Prudent N (1968) Tortional strain involving partial bonds. The stereochemistry of the lithium aluminium hydride reduction of some simple open-chain ketones. Tetrahedron Lett 2199-2204... 

Aminocinnamoyl compounds (accessible by reduction of the corresponding 2-nitro compounds) undergo cyclization to give quinoline derivatives thus, from 2-nitro-cinnamic aldehydes or -ketones quinoHnes 65 are obtained, while from 2-nitrocinnamic adds the products are 2-quinolones 66 ... 

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... 

For the reduction of nitro-compounds containing a group which may be attacked by nascent hydrogen, as, for example, an aldehyde group, an unsaturated side chain, and so on, special methods must he applied. In such cases ferrous hydroxide or iron powder (cf. Chap. VII. 5, arsanilic acid) are often used. The reduction is carried out thus a weighed amount of ferrous sulphate is caused to act, in the presence of alkali (potassium or sodium hydroxide, baryta), on the substance to he reduced. In this way it is possible to reduce, for example, o-nitro-benzaldehyde to aminobenzaldehyde, and o-nitrocinnamic acid to amino-cinnamic acid. 

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. 

This method is highly selective for unsaturated ketones and aldehydes, whereas reduction of a,p-un-saturated carboxylic acid derivatives, such as esters, amides and nitriles, is very sluggish. Thus, benz-ylideneacetone was selectively and cleanly reduced in the presence of methyl cinnamate, cinnamonitrile or cinnamamide. ... 

In the reductive dimerization of methyl cinnamate to a cyclopentanone [Eq. (5)], similar yields are found at the cathode [42] and with metals (sodium, THE, and TBAI, —78°C) [40]. Because of the potential selective conversion at the electrode, halides can be reduced at the cathode to carbanions in the presence of carbonyl compounds, which are reduced at more cathodic potentials. This way labile carbanions can be obtained and reacted under conditions in which the same species generated by a metalorganic route would decompose. Eor example, trichlorobromoalkane can be cathodically converted in the presence of aldehydes to a dichloromethyl anion 0°C [route a, Eq. (6)] and be trapped to form a dichlorotetrahydrofuran, but for the metallorganic route [route b, Eq. (6)] a reaction temperature of — 110°C is necessary [43]. 

Cinnamic (1), p-coumaric (2), and related acids may be activated by conversion to CoA esters by CoA ligases [e.g., 4-coumarate CoA ligase (EC 6.2.1.12)] in much the same way that fatty acids are activated. The reduction of the CoA esters of cinnamic acids to cinnamyl alcohols involves two enz)mies cinnamoyl-CoA oxidoreductase (which forms the aldehydes) and cinnamyl alcohol dehydrogenase (Grisebach, 1981). Phenylpropanoids appear to be synthesized from the CoA esters of this series of acids by conversion to the corresponding aldehydes, then to the alcohols, and finally, by elimination of a phosphate group, to allyl and propenyl compounds. In many plants, mixtures of all t3q>es co-occur (Fig. 8.7) (Gross, 1981 Mann, 1987). Reduction of the side chain to produce dihydrocinnamic acids and related compounds is also known to occur in nature. 

In conjugate reduction of enones with other transition metals such as chromium, the rates of reduction were shown to be dependent on the conformation of the substrate, with faster reactions being observed with the cisoid forms as compared with the transoid onesJ However, with the Pd/Si/Zn system, the rigid transoid enone of cyclohexenone and the flexible enone of acetylcyclohexene are both reduced in comparable rates. This indicates that palladium interacts exclusively with the olefinic part of the enone without significant participation of the carbonyl. Interestingly, this method is highly selective for unsaturated ketones and aldehydes, as the reduction of corresponding o,jS-unsaturated carboxylic acid derivatives, such as esters, amides, and nitriles, is very slow under the conditions used. Thus, ben-zylideneacetone is selectively and cleanly reduced in the presence of methyl cinnamate, dnnamonitrile, or dnnamamide.t" ... 

The direct transformation of alcohols to the corresponding amines is of growing interest because alcohols are easily available or accessible by chemical means. Amination of alcohols is usually catalyzed by transition metals at high temperatures and elevated pressures. Unfortunately, there is no enzyme known today that allows this particular functional group interconversion (FGl) in one step. Consequently, a multi-enzyme cascade was set up for the amination of alcohols as demonstrated for various benzylic and cinnamic alcohols under physiological conditions [24] aerobic alcohol oxidation toward the aldehyde was performed via a galactose oxidase originating from Fusarium (NRRL 2903 [25]) followed by an in situ co-TA-catalyzed reductive amination step (Scheme 4.5). 

Fig. 3.8. Derivation of some classes of natural products from the final metabolites of the shikimate pathway. In the cases of cinnamic acid and aldehyde derivatives X = H or X = OR. In the case of the cinnamyl alcohol derivatives, reduction occurs only if X = OR. The two phenolic units represent triketide precursors...

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