4-bromocrotonic acid

The indium-mediated reaction of 2-(bromomethyl)acrylic acid with carbonyl compounds gives the corresponding 7-hydroxy-a-methylene carboxylic acids, and a-methylene-7-lactones are obtained after acidic workup (Scheme 28).80,144-146 The indium-mediated addition of 4-bromocrotonic acid to a variety of aldehydes and ketones proceeds exclusively at the ct-carbon of the carboxylic acid. The effect of solvent, including an ionic liquid, is minimal allowing a wide choice of conditions (Scheme 29).61... 

Bromocrotonic acid Cleavage 0.1 eq (Ph,P)4Pd + nucleophile (HOBt, morpholine,...) in DMF Product after cleavage Carboxylic acid... 

Retronamine and monocrotaline antibodies were used to detect retronecine and monocrotaline. In an attenqit to inqnove on the relatively high I50 value of our anti-retronecine (1.68 put), we conjugated retronamine, a synthetic derivative of retronecine, to BS A by acylation of the retronamine primary anaine with hexanedioic anhydride giving a hapten intermediate which was then coupled to BSA by water-soluble l-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAC). The tertiary nitrogen of monocrotaline was alkylated with the N-hydroxysuedninoide ester of 4-bromocrotonic acid giving a hapten intermediate which was then coupled to BSA via N-acylation of the lysine primary amines. 

The biochemical reduction of a, -unsaturated -haloaliphatic acids by means of Clostridium kluyveri yielded halogen-free satmated acids. The same products were obtained from saturated -halo acids. However, the same microorganism converted ix, -unsaturated a-halo acids to saturated a-halo acids with R configuration. Yields of reduction of a-fluoro-, a-chloro- and a-bromocrotonic acid ranged from 30% to 100% [330]. 

A common goal of library synthesis is to maximize diversity around a core, so the synthetic route described above was extended to accommodate a variety of substituted aryl groups. The modified route is shown in Scheme 11. The solid-phase starting material was Rink amide resin,36 which had been loaded with y-bromocrotonic acid (attempts to load with other suitable fragments, such as fumaraldehydic acid, or the pentafluorophenol-activated ester, failed). Substituted ort o-iodoanilines could then be used to alkylate... 

Reformatsky reaction.5 The Reformatsky reaction of y-bromocrotonic acid with aldehydes or ketones in THF gives rise to a mixture of branched and linear unsaturated hydroxy acids. The former are the kinetic products and, on equilibration, rearrange to the latter products. 

Methyl derivatives of 2-oxo-2//-pyrido[l,2-a]pyrimidines were prepared by Kato et al.19 and Potts et al.2 by using 2-bromocrotonic acid and ethyl tetrolate, respectively. 

Fig. 4. 27. anti-Selectivity of an E2 elimination of HBr as a reason for the exclusive formation of f-configured a-bromocrotonic acid ethyl ester, syn-selectivity of an E2 elimination of HBr as a reason for the preferential formation of a Z-configured a-bromocrotonic acid ethyl ester. 

When diethyl malonate is the diketone component, the ester (135) is first formed, which then cyclizes to the expected (136). Reaction of (131) with diketene gives a mixture of (137) and (138), the latter on acid cyclization also yields (134). This rearrangement is by a 1,3-shift of the acetoacetyl group to give the transient imine followed by cyclization. Similar rearrangements are known. Compound (139), the 7-one isomer of (134), is obtained from the reaction of (131) with a-bromocrotonic acid (76JHC291). 

The reactions of carbon disulfide with malononitrile in the presence of sodium methoxide in methanol followed by treatment of the resulting dicyanodithioacetate 118 with y-bromocrotonic acid derivatives can also be assigned to this reaction type (90LA115). These reactions give diamino-substituted thienothiophenes 119 as the final products. 

Bromocrotonic Acid l -Bromoerotonic acid. Cf. 1-Bromoisocrotonic Acid)... 

Needles from HgO. M.p. 92°. Sol. EtOH, EtgO, CSg. Mod. sol. hot IlgO. NaHg in EtOH—-> crotonio acid. Py —> 1-bromo-crotonic acid. EtOH 4- H2SO4 —> Et ester of 1-bromocrotonic acid. ... 

Thiazolo[3,2-a]pyridines (CaNS-CjN).— The established synthesis of thia-zolo[3,2-a]pyridines from pyridine-2-thiones and a-bromo-a -unsaturated carbonyl compounds (these Reports, Vol. 1, p. 432 Vol. 2, p. 698) has been further studied. The use of the isomeric a-bromocrotonic acids yields the expected bicyclic products (202), exclusively of the 2,3-trans-configuration, owing to the concurrent isomerization of the cis- to the trans-acid. Activated acetylenes undergo a comparable Michael-addition-cyclization process. Thus, acetylenedicarboxylic acid affords trans-2,3-dicarboxydi-hydrothiazolo[3,2-a]pyridinium salts (204). The intermediate vinyl... 

The 3,4-dihydrodiol of BcP was synthesized from 4-oxo-l,2,3,4-tetrahydro-BcP (15) by Method I (66). The ketone L was itself prepared from 4-oxo-l,2,3,4-tetrahydrophenanthrene via a multistep sequence entailing Reformatsky reaction with methyl bromocrotonate, dehydration of the resulting alcohol, isomerization to the aryl-butyric acid, and cyclization of its acid chloride with SnCl - Full... 

DL-Threonic acid (10) seemed to be a promising source of DL-threose. Therefore, other routes to 10 were elaborated. By a procedure consisting of five steps" 2-propenal (acrolein) — vinylglycoloni-trile — ethyl vinylglycolate — ethyl 4-bromocrotonate — 3-hydroxy-crotonic acid — 10, DL-threonic acid was obtained in an overall yield of 4.1%. Another synthesis of 10 was achieved17 in six steps starting... 

The influence of a Lewis acid in favouring the ring closure was confirmed by the use of a catalytic amount of CpiTiCL in imino-Reformatsky reactions with a-bromoesters, -bromocrotonates and a-bromomethylacrylates the corresponding cis /9-lactams were obtained in excellent yields in THF at rt129. 

Methyl n-amyl carbinol. 247, 254 Methyl n-amyl ketone, 482 Methylaniline (mono), pure, from commercial methylaniline, 562, 570 P-Methylanthraquinone, 728, 740 Methyl benzoate, 780, 781 p-Methyl benzyl alcohol, 811,812 Methyl benzyl ketone, 727, 735 Methyl y-bromocrotonate, 926, 927 2-Methyl-2-butene, 239 Methyl n-butyl carbinol, 247,255 Methyl n-butyl ether, 314 Methyl n-butyl ketone, 475, 481 4-Methylcarbostyril, 855 p-Methylcinnamic acid, 719 4-Methylcoumarin, 853, 854 Methyl crotonate, 926, 927 Methylethylacetic acid, 354, 358 Methylethylethynyl carbinol, 468 Methyl ethyl ketone, 335, 336 purification of, 172 Methyl n-hexyl ether, 314 Methyl n-hexyl ketone, 335, 336 Methyl n-hexyl ketoxime, 348 Methyl hydrogen adipate, 938 Methyl hydrogen sebacate, 938,939 4-Methyl-7-hydroxycoumarin, 834 Methyl iodide, 287 Methyl isopropyl carbinol, 247,255 Methyl 4-keto-octanoate, 936... 

Fig. 1.31. The Wohl-Ziegler bromination of crotonic acid methyl ester D exclusively supplies the bromocrotonic ester G. However, vinyl acetic acid ester C and NBS exclusively yield the dibromo addition product B under Wohl-Ziegler conditions. Here, NBS acts as a Br2 source for addition rather than substitution. The fact that vinyl acetic acid ester and NBS do not react likewise to yield the bromocrotonic ester G is due to an electronic effect discussed in the text.

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