Esters cinnamate

The cinnamate ester prepared as above (23.2 g. 79 mmol) was added as a solid slowly to refluxing xylene (500 ml) over a period of 3 h at a rate that prevented accumulation of unreacted azidocinnamate in the solution (monitored by gas evolution through a gas bubbler). The solution was refluxed for an additional 2 h after gas evolution ceased. The reaction mixture was cooled and the solvent removed in vacuo. The residue was recrystallized from methanol to give pure product (20.7 g, 99% yield). 

Cinnamate ester yields of 70—95% have been realized, but the substrates are expensive when compared with those employed in the standard Claisen approach. 

Economic Aspects. There are no pubhshed production figures for cinnamic acid. Most of the manufactured acid is consumed internally to generate a series of cinnamate esters for flavor and fragrance appHcations. With this in mind, it was possible to estimate a 1990 usage in the range of 175 metric tons. The cinnamic acid that does find its way into the marketplace has been sold for 12—14/kg in dmm quantities. 

The addition of benzonitrile oxide to acrylic acid gave only the 4-carboxylic acid (441) (59MI41601), while addition to cis- and trans-cinnamic esters gave cis and trans diastereomeric pairs of 4-carboxylic acids (442) (Scheme 100) (59MI41600). Arbisono repeated the experiment and, when methyl c/s-cinnamate was used, in addition to the 4-carboxylic acid some 5-carboxylic acid (442) was isolated (66MI41600). The reaction of vinyl bromides with benzonitrile oxide yielded only an isoxazole and not a bromoisoxazoline (Scheme 101) (78JCR(S)192). 

An interesting footnote to the general synthesis of macrocyclic crown ether-type esters is found in the work of Ors and Srinivasan . These workers used cinnamate esters and diesters as precursors to large ring lactones. Depending on orientation, either truxil-... 

The asymmetric epoxidation of electron-poor cinnamate ester derivatives was highlighted by Jacobsen in the synthesis of the Taxol side-chain. Asymmetric epoxidation of ethyl cinnamate provided the desired epoxide in 96% ee and in 56% yield. Epoxide ring opening with ammonia followed by saponification and protection provided the Taxol side-chain 46 (Scheme 1.4.12). 

Ethyl Cinnamate.—The cinnamic ester of ethyl alcohol is a natural constituent of a few essential oils, including camphor oil and storax. It is formed synthetically by condensing cinnamic acid and ethyl alcohol by dry hydrochloric acid gas. It has a soft and sweet odour, and is particularly suitable for blending in soap perfumes. It is an oil at ordinary temperatures, melting at 12°, and boiling at 271°. Its specific gravity is 1 0546, and its refractive index 1 5590. 

Charrette and Lebel [24] developed a catalytic enantioselective cyclopropa-nation of trans-cinnamate esters with diazomethane. Their procedure involves an argon-flow-mediated diazomethane addition, leading to high yields (up to 80%) in products with up to 80% ee, by using the bis(oxazoHne) arising from phenylglycinol (Scheme 10). 

This version of the Wadsworth-Emmons reaction has been used in the scaled-up syntheses of drugs and drug-candidate molecules. For example, it is used to prepare a cinnamate ester that is a starting material for pilot plant synthesis of a potential integrin antagonist.263... 

Recently, Scott et al. have reported that a Cu complex bearing an axially chiral ligand (49) is an excellent catalyst for aziridination of 2,2-dimethylchromene and cinnamate esters (Scheme 36), though it is also less efficient for the reactions of simple olefins.157,158 On the basis of DFT investigation of the nitrenoid intermediate (50), one of the oxygen atoms of the A -sulfonyl group has been proposed to be interacting with the nitrene N-atom.158... 

The first highly enantioselective aziridination was reported in 1993 (76). Evans et al. found that cinnamate esters are excellent substrates for 55d CuOTf catalyzed... 

Optimal selectivities of cinnamate aziridines are provided by the phenyl-substituted bis(oxazoline) (55d). In contrast, /ra .v-p-mcthyl styrene proved to be most selective with ferf-butyl substituted 55c and acetonitrile as solvent, Eq. 56, conditions that afford the cinnamate ester-derived aziridine in only 19% ee. Styrene is a poor substrate for this catalyst and provides the opposite antipode as the major enantiomer from the same ligand, Eq. 57. 

Sulphinylacetic esters are converted in a one-pot reaction into cinnamic esters, when alkylated with benzyl halides [50],... 

One-pot synthesis of cinnamic esters from methyl phenyisulphinyl-acetate (PhS0CH2C02Me)... 

The reactivity of phenylacetic esters with electron-deficient alkenes is generally fairly poor, even under phase-transfer catalytic conditions. The reaction with cinnamic esters is often accompanied by hydrolysis and the yield of the adduct with chalcone is generally <60% [10]. The activity of the methylene group towards alkylation has been enhanced by the initial complexation of the phenyl ring with chromium tricarbonyl (see Section 6.2), but this procedure has not been applied to the Michael reaction. 

The Heck reaction on polymer-bound iodoarenes is assisted by the addition of a catalytic amount of tetra-n-butylammonium bromide and has been employed in the synthesis of 4-carboxycinnamic esters and amides [33], and 4-aminosulphonyl-cinnamic esters [34], It has also been reported that the presence of an equimolar equivalent of benzyltriethylammonium chloride aids the Pd(II)-mediated reaction of A -acyl-2-iodoanilines with vinylidene carbonate, which leads to A -acyl-2-hydroxy-indolines providing a convenient route to the indoles (80-90%) [35], The catalysed reaction of 2-hydroxy- and 2-tosylaminoiodobenzene with 1,2-dienes produces 1,2-dihydrobenzofurans and 1,2-dihydroindoles, respectively [36]. 

Heck reactions of arenediazonium salts can be conveniently carried out with [Pd(OAc)2] in ethanol. This method was extended to the one-pot sequential diazotation and allylation of aniUnes (Scheme 6.7). The latter were converted to the corresponding diazonium salts at 0 °C with NaNOa + 42 % HBF4. Ethyl acrylate and [Pd(OAc)2] were added and the reaction mixture was heated on a water bath for 1 h. The corresponding cinnamate esters were obtained in 65-80 % yield [22],... 

This method of obtaining cinnamate esters directly from anilines has useful features. It is simple and the yields are comparable to those obtained with isolated diazonium salts. However, in this case isolation of the latter is not required, what is most beneficial in case of unstable diazonium salts. 

The first modern day negative photoresists were developed by the Eastman Kodak Company which utilized cyclized rubbers and cinnamic acid derivatives as photosensitive crosslinking agents (42). The first commercially important photoresist based on this chemistry was known as KPR, which was of a cinnamate ester of polyvinyl alcohol. It was introduced by Kodak in 1954. 

The hydrodimerization of cinnamate esters formed with a chiral alcohol leads to asymmetric induction at the carbon-carbon bond formation step. The ester with bomeol gives a chiral cyclopentanone with greater than 95% enantiomeric excess [55]. A second approach towards achieving a chiral carbon-carbon bond formation has been to use the asymmetric oxazolidones 15 as substrates. These are reduced at... 

Cinnamate esters of rupestrinol (292) and /3-chaenocephaloI (293) have been identified as co-metabolites of rupestrol cinnamate (291) in the shrub Verbesina rupestris ° (cf. Vol. 2, p. 146). 

Other amino acid precursors have been used as starting materials in the Erlenmeyer reaction. A classical reaction of oxazolones is ring opening to give dehydroamino acid derivatives but there are a number of examples when the reverse reaction has been exploited including cyclizations of A-benzoyl-a,p-dehydrophen-ylalanine," a-(acetylamino)cinnamic esters," and 2-(acylamino)-2-alkenamides (Scheme 7.118)." ... 

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