Nitro, acids cinnamic acid

Monohydric alcohols, aldehydes (including chloral hydrate), ketones, cinnamic acid, amines (2-naphthylaminc is odourless), nitrophenols (resemble both phenol and nitro-compound),... 

Radicaloid substitution has not been extensively studied in the thiophene series. Molecular orbital calculations indicate that substitution should occur in the a-position. This has been found to be the case in the Gomberg-Bachmann coupling of diazohydroxides with thiophenes which has been used for the preparation of 2-(o-nitro-phenyl) thiophene, 2-(p-toluyl) thiophene, " " and 2-(p-chloro-phenyl)thiophene. " Coupling in the /8-position has been used for the preparation of 1,3-dimethyl-4,5-benzisothionaphthene (148) from 2-amino-tt-(2,5-dimethyl-3-thienyl)cinnamic acid (149). A recent investigation describes the homolytic phenylation of 2- and 3-phenyl-... 

For the reduction of nitro-compounds containing a group which may be attacked by nascent hydrogen, as, for example, an aldehyde group, an unsaturated side chain, and so on, special methods must he applied. In such cases ferrous hydroxide or iron powder (cf. Chap. VII. 5, arsanilic acid) are often used. The reduction is carried out thus a weighed amount of ferrous sulphate is caused to act, in the presence of alkali (potassium or sodium hydroxide, baryta), on the substance to he reduced. In this way it is possible to reduce, for example, o-nitro-benzaldehyde to aminobenzaldehyde, and o-nitrocinnamic acid to amino-cinnamic acid. 

Palladium-charcoal has also been used in the presence of cinnamic acid as a hydrogen acceptor. Raney nickel alone and in the presence of hydrogen acceptors, the best being cyclohexanone, has also been utilized, although dehydrogenation did not occur with 6-chloro- and 6-nitro-l,2,3,4-tetrahydrocarbazoles." Selenium has also been used. ... 

Since most anilines are derived from nitro intermediates the reduction of the aromatic nitro group followed by cyclization of the aniline in situ has offered a direct approach to the synthesis of quinolines. The ort/io-nitro cinnamic acid derivatives 28 undergo cyclization, where R corresponds to R , respectively, when treated with zinc in near-critical water at 250 °C... 

A concerted elimination-cyclization mechansim, involving a sulfenyl halide in a 1,3-butadiene-1-thio system, is the most probable mechanism for the formation of benzo[6 Jthiophenes from cinnamic acids or 4-aryl-2-butanones by treatment with thionyl chloride. The reactions shown in Scheme 5 have been carefully worked out, and the intermediates isolated (75JOC3037). The unique aspect of this synthesis is the reduction of the sulfinyl chloride (a) by thionyl chloride to form the sulfenyl chloride (b). The intermediate (b) was isolated and converted in pyridine to the 3-chlorobenzo[6]thiophene-2-carbonyl chloride in 36% yield (73TL125). The reaction is probably initiated by a sulfenyl ion attack on the aromatic ring, since it is promoted by electron-releasing groups para to the site of ring closure. For example, when X in (36) was N02, a 23% yield of (37), a mixture of 5-and 7-nitro derivatives, was obtained, but when X in (36) was OMe, a 54% yield of (37) was obtained, contaminated with some 3,4-dichloro-5-methoxybenzo[6]thiophene-2-carboxylic acid. 

A freshly prepared solution of nitroguanidine in concentrated sulfuric acid contains no nitric acid, for none can be distilled out of it, but it is ready to produce nitric acid (by the hydration of the nitroamide) if some material is present which will react with it. Thus, it gives up its nitro group quantitatively in the nitrometer, and it is a reagent for the nitration of such substances as aniline, phenol, acet-p-toluide, and cinnamic acid which are conveniently nitrated in sulfuric acid solution. 

When a large crystal of cyclonite is added to the diphenylamine reagent, a blue color appears slowly on the surface of the crystal. Powdered cyclonite gives within a few seconds a blue color which rapidly becomes more intense. If cinnamic acid is dissolved in concentrated sulfuric acid, and if finely powdered cyclonite is added while the mixture is stirred, gas comes off at a moderate rate, and the mixture, after standing over night and drowning, gives a precipitate which contains a certain amount of p-nitro-cinnamic acid. 

In a 200-cc. round-bottom flask, fitted with a reflux condenser, are placed 50 g. (0.33 mole) of m-nitrobenzaldehyde (Note 1), 40 g. (0.48 mole) of freshly fused sodium acetate, and 70 g. (0.68 mole) of acetic anhydride. The contents of the flask are well mixed and the mixture heated in an oil bath held at 1800 for about thirteen hours. After the reaction product has been allowed to cool slightly, it is poured into 200-300 cc. of water and then filtered by suction (Note 2). After the solid has been washed several times with water, it is dissolved in a solution of 20 cc. of ammonium hydroxide (sp. gr. 0.9) in about 200 cc. of water. The solution of the ammonium salt, after filtering, is poured into a solution of 15 cc. of sulfuric acid (sp. gr. 1.84) in about 200 cc. of water (Note 3). The precipitated m-nitro-cinnamic acid is filtered, redissolved in ammonium hydroxide, and again precipitated by pouring the solution into dilute sulfuric acid (Note 4). 

A number of functional groups, such as nitro, diazo, carbonyl, disulfide sulfoxide, alkene, and pentavalent arsenic, are susceptible to reduction, although in many cases it is difficult to tell whether the reaction proceeds enzymatically or nonenzymatically by the action of such biologic reducing agents as reduced flavins or reduced pyridine nucleotides. In some cases, such as the reduction of the double bound in cinnamic acid (C6H5CH=CHCOOH), the reaction has been attributed to the intestinal microflora. Examples of reduction reactions are shown in Figure 7.12. 

It is necessary to prepare first, o-nitro-phenyl-propiolic acid, which is itself obtained from o-nitro-cinnamic acid. Cinnamic ester (50 gms.) is nitrated by pouring gradually into cooled nitric acid (sp. g. 1-5). 

Sybilska, D., Debowski, J., Jurczak, J., and Zukowski, J., The a- and P-cyclodextrin complexation as a tool for the separation of o-, m- and p-nitro-, cis- and trans-cinnamic acids by reversed-phase high-performance liquid chromatography, J. Chromatgr., 286, 163, 1984. 

As a preparative method the direct decarboxylation of olefinic acids is almost limited to the formation of styrenes and stilbenes from substituted cinnamic acids. Thermal decomposition of cinnamic acid gives styrene (41%). The yield is nearly quantitative if the reaction is carried out in quinoline at 220° in the presence of a copper catalyst. The yields of substituted styrenes where the aryl radical contains halo, methoxyl, aldehyde, cyano, and nitro groups are in the range of 30-76%. cis-Stilbene and cis-p-nitrostilbene are prepared in this way from the corresponding a-phenylcinnamic acids (65%). One aliphatic compound worthy of mention is 2-ethoxypropene, prepared by heating -ethoxycro-tonic acid at 165° (91% yield). The mechanism of acid-catalyzed decarboxylations of this type has been studied. Isomerization of the double bond from the a,/5- to the /5, y-position before decarboxylation very likely occurs in many instances. ... 

A cooled solution of the diazonium salt is treated with sodium acetate and an acetone solution of the cinnamic acid. Then aqueous cupric chloride is added and the mixture is stirred at room temperature. The aryl radical may carry alkyl, halo, ether, ester, or nitro groups. ... 

Substituted benzaldehydes and malonic acid give cinnamic acids in excellent yields. Among the common nuclear substituents are methyl, halo, " hydroxyl, methoxyl, " cyano, nitro, and diethylamino groups. Other /fi-arylacrylic acids have been made by the use of a-naphthaldehyde, phenanthraldehydes, and furfural. Phenyl-substituted aliphatic aldehydes have also been used in this condensation. ... 

A review of the literature of this reaction to 1941 has been made. The condensation is most valuable for the preparation of substituted cinnamic acids, particularly those containing halo, methyl, and nitro groups. Furfural has been condensed in good yields with acetic anhydride, butyric anhydride, and sodium phenylacetate in the... 

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