Crotonate compounds esters

Primary fatty amines also add (Michael addition) to esters of acryUc acid, H2C=CHCOOH, methacrylic acid, H2C=C(CH2)COOH, or crotonic acid, CH2CH=CHC00H. Hydrolysis of the Michael ester forms an amphoteric surfactant. Crotonic acid can be used to form the amphoteric compound... 

Poly(vinyl alcohol) has the structure 10.67. Poly(vinyl acetate) is the fully esterified derivative of polyfvinyl alcohol), in which the -OH groups are replaced by -OCOCH3 groups. As indicated in Table 10.5, commercial polyvinyl sizes are effectively copolymers of polyfvinyl acetate) and polyfvinyl alcohol) that vary in the degree of saponification of the ester groups. These products may comprise 100% of either polymer, or combinations of the two monomers in any proportions. Crotonic acid (2-butenoic acid), widely used in the preparation of resins, may also be a component. This compound exhibits cis-trans isomerism (Scheme 10.17). The solid trans form is produced readily by catalysed rearrangement of the liquid cis isomer. 

Palladium(II) acetate was found to be a good catalyst for such cyclopropanations with ethyl diazoacetate (Scheme 19) by analogy with the same transformation using diazomethane (see Sect. 2.1). The best yields were obtained with monosubstituted alkenes such as acrylic esters and methyl vinyl ketone (64-85 %), whereas they dropped to 10-30% for a,p-unsaturated carbonyl compounds bearing alkyl groups in a- or p-position such as ethyl crotonate, isophorone and methyl methacrylate 141). In none of these reactions was formation of carbene dimers observed. 7>ms-benzalaceto-phenone was cyclopropanated stereospecifically in about 50% yield PdCl2 and palladium(II) acetylacetonate were less efficient catalysts 34 >. Diazoketones may be used instead of diazoesters, as the cyclopropanation of acrylonitrile by diazoacenaph-thenone/Pd(OAc)2 (75 % yield) shows142). 

The Michael-type reaction of an anion (generated from compound 77) with ethyl crotonate yielded the corresponding ester 78 in 82% yield (Scheme 19). Alkylation of compound 77 with benzyl bromide afforded derivative 79 in 85% yield. The attempted reactions of the anion with oxiranes and trimethylsilyl chloride did not lead to the expected substitution products and the starting oxadiazoles were recovered in 70-80% yields <2001ARK101>. 

Mironov et al. (26) also tried to cyclize acyloxysilanes with some success in making a series of silalactones. They used the series HMe2SiOOC(CH2) CH=CH2 (n = 0, 1, 2, 8). When n = 0, vinylpoly-merization of the acrylate occurred. This was also true for crotonic, cinnamic, and methacrylic esters to complicate and confuse the experiments, but with n = 1, 2, or 8, the compounds reacted readily. 

The formal total synthesis of the novel /3-lactam antibiotic thienamycin has been accomplished from an isoxazoline derivative generated by [3 + 2] dipolar cycloaddition <79H(l2)l 183). Reaction of the nitrile oxide derived from 3-nitropropanal dimethyl acetal with methyl crotonate gave the isoxazoline (477) regio- and stereo-selectively. The isoxazoline was converted to amino ester (478) by hydrogenation and then to /3-lactam (479) by ester saponification and ring closure with DCC. Treatment of (479) with p-nitrobenzyl chloroformate and reaction of the derived acetal (480) with excess N-p-nitrobenzyloxycar-bonylcysteamine gave thioacetal (481), a compound which has previously been converted into ( )-(8S )-thienamycin (Scheme 106). 

When crotonate esters were employed the regioisomers 501 were mainly formed, accompanied by a significant amount of non-cyclic compounds 502 formally arising from insertion of the Si=C group in an ally lie C—H bond (equation 167). The reaction of silenes 149 and 150 with crotonate esters are the only examples known so far where the product distribution is different when the reaction is conducted under photolytic conditions or in the absence of light. Thus, in the dark reaction of 150 with methyl crotonate the relative ratio 501 (R1 = 1-Ad, R2 = Me) 502 (R1 = 1-Ad, R2 = Me) = 3.75 1 was obtained, while under photolytic conditions only minor amounts of 501 were detected245. The nominal insertion product 503 is also the major product in the reaction of methacrylate esters with 149 and 150 (equation 168). The minor product in this reaction is the l-sila-3-oxacyclohex-4-ene 504 (relative ratio 503 504 = 5.7 l)245. 

A synthesis of this compound was devised by Ohmizu, Iwasaki and co-workers and featured a three-component tandem conjugate addition/enolate trapping as key step (Scheme 12.24) [82]. In this synthesis, the acyl anion equivalent cyanohydrin 165 was first treated with LDA and allowed to react with methyl crotonate 166. The resulting enolate was trapped with 2,3,5-trimethoxy benzylbromide 168 to afford crude intermediate 169, which was immediately deprotected in situ to afford ketone product 170. Both the ester and the ketone functionalities were then reduced at low temperature to afford the corresponding diol 171. Upon treatment with trifluoroacetic acid, the desired Friedel-Craft cyclization adduct 172 was obtained. The latter tricyclic compound was then further elaborated to the final target 164 through a short sequence of standard transformations. 

Anti-inflammatory potencies were measured in mice by a 5-day modification of the Tonelli croton oil ear assay. The most potent topical anti-inflammatory compounds were 17a-heterocyclic esters in the 16a-methyl series where the 21-substit-uent was either chloro or fluoro. Thus, [21-chloro-17-(2 -furoate)] was eight-fold more potent than betamethasone valerate, while [21-fluoro-17-(2 -furoate)], [21-chloro-17-(2 -thenoate)] and 6a-fluoro-21-chloro-17-(2 -furoate)] were three-fold as potent as betamethasone valerate. 

This chapter has emphasized the role of DNA mutations in the pathways leading to cancer. However, a number of chemicals are cancopromoting purely because of their ability to activate certain enzymes, where there exists no direct or indirect influence on DNA mutations. This functional class of compounds promotes or prevents cancer orJy when present on a chronic basis, i.e, at elevated levels every day for many years. The notion that bile salt metabolites may result in chronic stimulation of protein kinase C was discussed earlier. The related event of fiber decreasing exposure of the colon to bile salts was also outlined. The chronic exposure theory applies to the phorbol esters that are present in certain plants. People who drink tea made from the plant Croton flaveti tend to acquire esophageal cancer. This cancer results from chronic exposure to phorbol esters, which occurs in the leaf extract or in an oil prepared from the plant (croton oil). The phorbol esters enter the cell, bind to protein kinase C, and activate this enzyme. Activated protein kinase C, in turn, activates the MAP kinase cascade (Ueda et aL, 1996). The continual activation of protein kinase C, when combined with mutations in specific proto-oncogenes, may lead to cancer and sustain the cells in the cancerous state. 

Phorbol esters were first detected in oil prepared from seeds of Croton tiglium, and are the most widely studied skin tumor promoters however, many other chemical compounds have been shown to possess skin tumor-promoting properties, for example, phenobarbitol, DDT, and the peroxisomal prolifera-tors. Within a few hours after application of a single effective dose of phorbol 12-myristate 13-acetate (also known as TPA and 12-O-tetradecanoyTphor-boTl3-acetate, CAS 16561-29-8) to mouse skin, localized edema and erythema characteristic of inflammation and irritation are evident, and within 24 h there is leukocytic infiltration of the dermis. Within 1 or 2 days after a single promoter treatment, stimulation of mitotic activity in the basal cell layer of the epidermis is evident and continues for several days. This results in an increased number of... 

Michael addition of l-(alkoxycarbonyl)methylphosphonate anions to unsaturated compounds provides a methodology for the elaboration of new reagents and also for the preparation of phosphonylated heterocycles. Thus, in the presence of basic catalysts, diethyl l-(ethoxycarbonyl)alkyl- and l-(ethoxycarbonyl)methylphosphonates add to a.p-nnsaturatcd esters and nitriles.Addition of diethyl l-(ethoxycarbonyl)methylphosphonates under basic conditions to methyl or ethyl acrylates, acrylonitrile, and benzalacetophenone occurs readily and gives rise to products of addition to one and two molecules of the unsaturated compound (Scheme 8.14). ° - ° Reaction of a-substituted phosphonoacetates with acrylates is less vigorous, and attempts at addition to crotonic and methacrylic esters fail. mi-zos-zos... 

Pudovik, A.N., Addition of dialkyl phosphites to unsaturated compounds. Part 6. Addition of dialkyl phosphites to ethyl esters of cinnamic and crotonic acids. Zh. Obshch. Khim.. 22. 1143. 1952 Chem. Abstr, 47, 4836h, 1953. 

Hydrogen-bonding solvents may also act as Lems adds and modify the conformation of a,P-unsaturated esters. This effect has been proposed by d An-gelo and cowoikers [91] to account for the stereoselectivity of the 1,4-addition of an amine to crotonate 10 (Ar = 2-Np). While this compound exhibits the s-cis-syn conformation in the crystal, the facial diastereodifferentiation observed is in agreement with the reaction through the s-trans conformer, possibly due to the protic nature of the solvent. 

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