Halogenated cinnamic acids

Halogenated Cinnamic Acids and Esters Thereof, Processes for the Preparation Thereof and Halogenated Aryldiazonium Salts M. Beller etal, US Patent 5,516,932 (May 14, 1996)... 

The chloride is readily available as a by-product of benzyl chloride [100-44-7] production (see Chlorocarbon and chlorohydrocarbons-BENZYL chloride, BENZAL CHLORIDE, AND benzotrichloride). The yield is comparable to the Perkin-based process, but the difficulty associated with removal of trace halogenated impurities makes the resultant cinnamic acid less desirable for many appHcations. 

Esters can be obtained from halogenated olefins using a metal carbonyl catalyst (87), eg, /n j -l-bromo-2-phenylethylene is treated with nickel carbonyl in the presence of methanol to afford the corresponding methyl cinnamate (see Cinnamic acid). 

This procedure has been used to prepare a variety of substituted a-bromohydrocinnamic acids 2 p-acetyl-a-bromohydro-cinnamic acid was prepared for the first time by this method. The method illustrates a typical application of the Meerwein reaction for the arylation of unsaturated substrates.3 In this reaction a catalytic amount of a copper(I) salt is used to reduce an aryl diazonium salt forming an aryl radical and a copper(II) halide. Addition of the aryl radical to an unsaturated substrate forms an alkyl radical that is reoxidized by the copper(II) halide present forming an alkyl halide and regenerating the copper(I) salt catalyst. In this preparation, the product, an a-bromo acid, is formed in an acidic reaction mixture and dehydro-halogenation does not occur. However, dehydrohalogenation... 

Keywords cinnamic acid, stilbene, halogenation, addition, gas-solid reaction... 

Shikimic acid (64) is the biosynthetic precursor to an array of aromatic compounds, including benzoic and cinnamic acids/ This pathway is utilized by microorganisms and plants, but not by animals, which obtain essential shikimate building blocks like phenylalanine from their diets/ Red algae are known to be a prolific source of halogenated phenolic metabolites derived from shikimic acid, comprising approximately 5% of known algal metabolites/ ... 

Haloalkynes and 1-haloalkenes The Hunsdiecker reaction occurs when the conjugated acids are treated with these positive halogen salts. There is a stricter limitation for such a reaction with alkenoic acids as they must be a-unsubstituted, and the P-carbon supports a positive charge well (e.g., cinnamic acid and analogues). 

Cinnamic acid, like other unsaturated compounds, forms addition-products with the halogen hydrides, hypochlorous acid, bromine, and so forth. It yields esters, an acid chloride, and an amide. The hydrogen atoms in the benzene ring may be replaced by the halogens, nitro groups, amino groups, and the sulphonic acid group. 

In this problem, the halogen used for a good leaving group will be bromine. Bzz adds across the doxable bond of cinnamic acid. At this point, base is introduced to abstract the acidic proton so that the carboxylate ion is created. 

The high instability of bromine monochloride (the heat of formation of which has been estimated as 0.3 kcal.mole ) provides some difficulty in studying its reactions. Nonetheless, the rate of addition of mixtures of chlorine and bromine (with the total concentration of halogen constant) to c/s-cinnamic acid in carbon tetrachloride-acetic acid mixtures was greatest when [Br2]/[Cl-i] was unity . The kinetic form of the reaction was the same as that for the other interhalogens and for bromine, but not for chlorine. The possible intervention of bromine monochloride in the reaction of allyl trimethylammonium perchlorate with hypobromous acid in aqueous acid has also been reported here, the kinetics were . 

Both approaches represent a useful guide for the basic design, prediction and understanding of solid state reactions. In addition, Schmidt demonstrated the feasibility of a possible engineering route for the preparation of photoreactive assemblies based on modified cinnamic acids with halogen substituents in order to obtain stereocontrolled hh cyclobutane derivatives. ... 

ASYMMETRIC HALOGENATION AND HYDROHALOGENATION OF tranS-CINNAMIC ACID IN CRYSTALLINE CYCLODEXTRIN COMPLEXES... 

As one of the enzymic reactions, asymmetric synthesis catalyzed by cyclodextrins has been studied in the past, but gave all the products in a low optical yield. We have already found a strong chiral induction for the chlorination of methacrylic acid in the crystalline cyclodextrin complexes. 100 % enantiomeric excess (e.e.) of (-)-2,3-dichloro-2-methyl-propionic acid and 88 % e.e. of its enantiomer were isolated in a- and 3-cyclodextrins, respectively. This paper describes asymmetric addition of gaseous halogens and hydrogen halides in the crystalline complexes comprising trans-cinnamic acid as a reactant and a- or 3-cyclodextrin as chiral matrix. Asymmetric bromination of menthyl cinnamate and of salts from the acid and several chiral amines have been reported, but gave low chiral inductions up to 2 16 % e.e.. 

Table I. Gas-Solid Halogenation and Hydro-halogenation of trans-Cinnamic Acid in the Cavity of Cyclodextrin Complexes or without...

Table III. Asymmetric Halogenation and Hydrohalogenation of trans-Cinnamic Acid in Crystalline Cyclodextrin Complexes...

The second stage (Experiment [D2]) involves the addition of bromine to the intermediate formed in the first step, frans-cinnamic acid. The product of this halogenation is e T/fizro-2,3-dibromo-3-phenylpropanoic acid. The stereochemistry involved in the formation of this second intermediate is a result of the nature of the anti addition of molecular bromine to a trans alkene. The details are given in the discussion in Experiment [D2]. 

The result of the halogenation of frans-cinnamic acid, as in the case of (E)-stilbene in Experiment [A2b], is an anti addition of molecular bromine. The enantiomeric products are shown here ... 

Trichloro- and tribromo-isocyanuric acids have been reported to react with cinnamic acids ArCH=CHC02H in Na0H/H20/Et20 at room temperature to produce ( )-2-halostyrenes ArCH=CHX (X = C1 or Br) regioselectively in 25-95% yield. Electrophilic addition of the halogen atom has been identified as the rate-limiting step by using Hammett correlations and DFT calculations. " ... 

One of the more operationally simple approaches to the preparation of vinyl hahdes is the Hunsdiecker decarboxylative halogenation of alkenyl carboxylic acids. While a number of modifications to this reaction have been reported, one of the most practical versions used tiiethylamine and NXS to promote the reaction (Scheme 7.107) [172, 173]. The reaction was remarkably fast and high yielding. Given the ability to generate vinyl chlorides, bromides, and iodides from readily available alkenyl carboxylic acids, this is a very attractive approach, hi related work, the combination of Selectfluor and KBr converted a series of cinnamic acid derivatives into vinyl bromides. The reaction time was longer (5h), and the reaction was selective for the formation of the p-( )-isomer [174]. 

Cognate preparations. Phenylpropynoic acid. Place a solution of 88 g (84 ml, 0.5 mol) of ethyl cinnamate (Expt 6.137) in 50 ml of carbon tetrachloride in a 500-ml round-bottomed flask. Immerse the flask in ice and add 80 g (25.5 ml, 0.5 mol) of bromine from a separatory funnel slowly with frequent shaking. The halogen will disappear rapidly at first, but more slowly towards the end of the reaction no hydrogen bromide is evolved and the time of the addition is about 20-25 minutes. Allow the mixture to stand for 1 hour, pour the solution into a large evaporating dish and permit the excess of bromine and the carbon tetrachloride to evaporate spontaneously in the fume cupboard. The crude ethyl 2,3-dibromo-3-phenylpropanoate will remain as a solid cake this... 

Bimetallic Pd/Ni [121] andPd/Co [122] systems have exhibited considerable catalytic activity in the Heck reaction of nonactivated chloroarenes with ethyl acrylate, acrylonitrile, and acrylic acid. For instance, ethyl acrylate and acrylonitrile reacted smoothly with chlorobenzene in the presence of Nal and catalytic amounts of NiBr2, Pd2(dba)3, and o-Tol3P in DMF to give E-isomers of ethyl cinnamate and cinnamonitrile, respectively [121]. The reaction occurred via the nickel-catalyzed halogen exchange between ArCl and Nal, followed by the conventional palladium-catalyzed olefination of the iodoarene generated in situ. 

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