4-Bromocinnamic acid

In our own preliminary studies [86] on parallel procedures under microwave-enhanced conditions, we have used the Radley s RDT 24 place PTFE carousel reaction station on the turntable of the Matsui M 169BT microwave oven. In this way, we have studied the catalytic activity of RhCl3 and Pd(OAc)2 towards the reduction or dehalo-genation of 4-bromocinnamic acid and structurally similar compounds. A nine-reaction matrix was used under microwave-enhanced conditions as illustrated in Scheme 13.9 - greatly reduced reaction times and easy optimization of reaction conditions are immediate benefits. As robotics come to play an increasingly important role in chemistry, one can immediately see more sophisticated labeling experiments being undertaken. 

Ethyl benzoylacetate has been prepared by the condensation (by means of sodium ethylate) of ethyl acetate with ethyl benzoate,1 acetophenone with ethyl carbonate,2 and acetophenone with ethyl oxalate, with subsequent heating 3 by treatment of ethyl phenylpropiolate4 or a-bromocinnamic acid 5 with concentrated sulfuric acid, and of ethyl diazoacetate with benzalde-hyde 6 by the condensation of benzene with the monoethyl ester of malonyl monoacid chloride and aluminum chloride,7 of benzoyl chloride with the product of the reaction of magnesium and ethyl chloroacetate in ether,8 of alcohol on benzoylacetimino ethyl... 

This procedure has been used by the submitters and others to prepare the following cinnamic acids from substituted benzal-dehydes o-nitrocinnamic acid (70%),2 -nitrocinnamic acid (77%),2 w-cyanocinnamic acid (71%),3 o-chlorocinnamic acid (82%),4 m-chlorocinnamic acid (53%),4 -chlorocinnamic acid (73%),4 2,4-dichlorocinnamic acid (70%),4 3,4-dichlorocinnamic acid (81%),4 w-bromocinnamic acid (31%),4 -methoxycinnamic acid (60%),4 and 3,4-dimethoxycinnamic acid (77%).4... 

Refluxing with zinc in ethanol reduced a-bromocinnamic acid to cinnamic acid in 80% yield [997]. Allylic chlorines in y,y,y-trichlorocrotonic acid were partly or completely hydrogenolyzed by zinc and sodium amalgam [5/9]. Hydrogenolysis of allylic bromine in oc, -unsaturated esters with zinc in acetic acid gave predominantly, y-unsaturated esters in 65-97% yields [998]. 

The procedure described is essentially that of Perkin.1 Phenylpropiolic acid can also be prepared from ether solutions of /3-bromostyrene 2 and /3-chlorostyrene 3 with sodium and carbon dioxide by the action of alcoholic alkali with a-bromocinnamic acid,2 /3-bromocinnamic acid 4 or ethyl a-bromocinnamate 5 and by the action of carbon dioxide on sodium phenylacetylide.6... 

II). trans-m-Bromocinnamic acid (14.8 g), ethanol (173 ml) and concentrated sulfuric acid (0.4 ml) were combined and heated at reflux for 15 hours. About 150 ml of the ethanol was distilled off, and the remaining solution was poured into ice/water (140 ml). The cold mixture was made strongly alkaline with 40% sodium hydroxide and extracted with methylene chloride (4x60 ml). The combined methylene chloride extract was dried over anhydrous potassium carbonate. The potassium carbonate was removed by filtration and the solvent stripped off under reduced pressure. trans-ethyl-3-Bromocinnamate, was obtained as a partially solidified oil. (IR spectrum was consistent with this compound). 

Mixtures of isomers were obtained from the reaction of cis- and trans-a-bromocinnamic acid with arylthiolate ions (Angeletti and Montanari, 1958). The corresponding m- and p-nitro acids reacted faster but gave complete retention. The slower reaction of the unsubstituted acids was probably followed by isomerization of the product, since j9-thioacrylic acids isomerize in similar media (Montanari, 1960). 

The structurally related a-bromocinnamic acid (257) gave only dehydrobromination with alkali (Owen and Sultanbawa, 1949a). 

Reaction with vinylic bromides. The reaction of a vinylic bromine atom with dimethylcopperlithium proceeds with retention of configuration. Thus Irans-a-bromocinnamic acid (I) reacts with the reagent to give, after treatment with acidified water, trans-a-methylcinnamic acid (2). This behavior contrasts with the reaction of... 

Some cinnamic acids have been efficiently prepared by coupling halogeno-benzenes with acrylic acid using catalytic quantities of Pd(OAc)2. 2-Bromo-iodobenzene reacts specifically to give 2-bromocinnamic acid addition of a triarylphosphine is necessary to effect displacement of bromide. 

Configurational retention is observed in the reaction of lithium dimethyl-cuprate with /ra j-a-bromocinnamic acid to yield (592) and (593). The corresponding esters were more prone to isomerization during the same reaction... 

The synthesis of 4-vinylindan (430) has been effected in the following way [1067, 1068] (Scheme 119). o-Bromotoluene (426) was oxidized to the corresponding benzaldehyde which was then converted by the Perkin method into o-bromocinnamic acid (427). Reduction of the double bond, intramolecular cyclization of the dihydro derivative obtained, in the form of the acid chloride, and hydrogenolysis of the oxo group led to 4-bromoindan (428). The reaction of the lithium derivative of the latter with ethylene oxide formed the -hydroxyethyl derivative, dehydration of which gave the CD fragment (430). 

---