Copper chromite-quinoline

A 500-ml. three-necked flask is fitted with a reflux condenser and a thermometer, the bulb of which reaches far enough into the flask to be covered by the liquid. A solution of 46.0 g. (0.205 mole) of a-phenylcinnamic acid (p. 70) (Note 1) in 280 ml. (307 g., 2.38 moles) of quinoline (Note 2) is added to the flask along with 4.0 g. of copper chromite.2 The reaction flask is heated by means of a mantle or an oil bath until the temperature of the reaction mixture reaches 210-220°. The mixture is kept within this temperature range for 1.25 hours. The solution is then cooled immediately and added to 960 ml. of 10% hydrochloric acid in order to dissolve the quinoline (Note 3). The product is extracted from this mixture with two 200-ml. portions of ether followed by a 100-ml. portion. The combined ether extracts are filtered to remove particles of catalyst, washed with 200 ml. of 10% sodium carbonate, and dried over anhydrous sodium sulfate. The dry solution is removed from the drying agent by filtration and heated on a steam bath to distil the ether. The residue is dissolved in a hexane fraction, b.p. 60-72° (Skellysolve B) the solution is cooled to 0° and filtered to remove /raws-stilbene, if any. The hydrocarbon solvent is removed by distillation, and the czs-stilbene is distilled. The yield is 23-24 g. (62-65%), b.p. 133-136°/10 nun., 95-97°/l mm. tig 1.6183-1.6193, 1.6212-... 

Interestingly, the Fischer indole synthesis does not easily proceed from acetaldehyde to afford indole. Usually, indole-2-carboxylic acid is prepared from phenylhydrazine with a pyruvate ester followed by hydrolysis. Traditional methods for decarboxylation of indole-2-carboxylic acid to form indole are not environmentally benign. They include pyrolysis or heating with copper-bronze powder, copper(I) chloride, copper chromite, copper acetate or copper(II) oxide, in for example, heat-transfer oils, glycerol, quinoline or 2-benzylpyridine. Decomposition of the product during lengthy thermolysis or purification affects the yields. 

Oxidation of II to V is similarly effected by periodic acid.8 Aldehyde V can be saponified and further decarboxylated8 by copper chromite in quinoline to give 5-methyl-2-furaldehyde, affording additional confirmation of the assigned formula. 

Catalyst, alumina, 34, 79 35, 73 ammonium acetate, 31, 25, 27 boron trifluoride etherate, 38, 26 copper chromite, 31,32 36, 12 copper powder in quinoline for pyrolytic decarboxylation,... 

The reaction of indolizines with dialkyl acetylenedicarboxylates in the presence of a dehydrogenating catalyst leads to 1,2-dicarbalkoxycycl-[3,2,2]azines.22 23 Methyl phenylpropiolate may be used instead, although attempts to effect reaction between indolizine and certain other dienophiles including diphenylacetylene, diethyl azodicarboxylate, and 1,3-cyclohexadiene were unsuccessful. Hydrolysis of the diesters yielded the corresponding acids. Subsequent decarboxylation proceeded in high yield using copper chromite in quinoline [Eq. (5)]. 

Decarboxylation of tellurophene carboxylic acids occurs readily in quinoline solution under the action of copper chromite. In this way, 2-(3 (4 )-methoxyphenyl)tellurophenes have been obtained from 2-(3 (4 )-methoxyphenyl)-tellurophene-5-carboxylic acids <1980J(P2)971>. 

Carboxytellurophenes were decarboxylated upon heating in quinoline in the presence of copper powder d or copper chromite. ... 

Decarboxylation of -a-phenylcinnamic acid is effected by refluxing the acid in quinoline in the presence of a trace of copper chromite catalyst both the basic properties and boiling point (237°C) of quinoline make it a particularly favorable solvent. Z-Stilbene, a liquid at room temperature, can be characterized by trans addition of bromine to give the crystalline -dibromide. A little meso-dibromide derived from -stilbene in the crude hydrocarbon starting material is easily separated by virtue of its sparing solubility. 

Copper chromite and copper-chromium oxide are effective catalysts for the decarboxylation of acids in quinoline solution. An example is the decarboxylation of cis-a-phenylcinnamic acid in refluxing quinoline to c/r-stilbene the two catalysts cited... 

Greatly improved yields of the lactone (227) were obtained by the unexpected copper chromite oxidation of (225) or, better, (226). The substituted malonic acid (225) afforded either a mixture of lactone (227) (30%) and acid (226) (34%) on heating with copper chromite in quinoline at 200 °C or 72% of the acetic acid (226) at 150—160°C. Subsequent treatment of the acid (226) with more copper chromite afforded the lactone in 59 % yield. 

Difluoropyrrole (58) has been extensively used in the syntheses of octafluor-oporphyrins and other calyx( )pyrroles. This was first accessed by Leroy and Wakselman by barium-promoted copper chromite decarboxylation of 3,4-difluor-opyrrole-2-carboxylic acid in quinoline at 200°C. The acid was prepared in four steps beginning with a cycloaddition reaction of the protected aziridine 59 and chlorotrifluoroethylene (Fig. 3.26). 

Improvement to the decarboxylation of indole-2-carboxylic acids has been made by the use of microwave radiation. Under these conditions the copper chromite can be eliminated from the standard reagent mixture of copper chromite in quinoline and reactions are faster and cleaner <93JOC5558>. The ketene (399) generated from either the acid chloride or enol ester (398) of indole-3-carboxylic acid undergoes cyclic tetramerization to give the macrocyclic product (400) (Scheme 132) <91JHC1569>. 

Conventional decarboxylation of carboxylic acids involve refluxing in quinoline in presence of copper chromite and the yields are low. However, in the presence of microwaves decarboxylation takes place in much shorter time as illustrated in Scheme 14. 

Styiylamides. Benzoylaminocinnamic acids can be decarboxylated to styrylamides by heating with copper chromite in quinoline at 120-... 

Decarboxylation Reactions. Taking advantage of its basic properties, quinoline is generally useful as a solvent for decarboxylation reactions. It is especially suitable because its relatively high boiling point facilitates the decarboxylation. Examples include the decarboxylation of 3-methyl-2-furoic acid (10) to 3-methylfuran (11) (eq 6), /w-nitrocinnamic acid (12) to m-nitrost)frene (13) (eq and a-phenylcinnamic acid (14) to cis-stilbene (15) (eq 8). Copper catalysts such as copper or copper chromite are used to effect the decarboxylations. 

With the preliminary results in hand, it was crucial that the C2 group on the indole could be readily removed. The C2 carboxylic acid derivatives of coupling products were initially employed toward this endeavor (Scheme 4). There are relatively few decarboxylation methods on indole acids reported in the literature, most of which utilize harsh reaction conditions. Nevertheless, Jagan tested several of the reported methods, including the use of copper chromite in quinoline at 215 °C, copper(I)oxide in DMA at 200 °C, and substoichiometric amounts of indole acid copper salts at 200 Much to his dismay, most of these reactions led to decomposition. Moreover, adjusting temperature or switching to microwave heating failed to provide the desired decarboxylation. 

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