Ethanol, - 1-arylated

Early work by Papa et al. indicated that reduction of carbonyl compounds with Raney nickel in alkaline solution gave the corresponding hydrocarbon or alcohol products, and formation of the hydrocarbon was only feasible in the case of aromatic carbonyl compounds at 80-90 C. Mitchell et al. reported an improved method under neutral conditions using W-7 Raney nickel in 50% aqueous ethanol, aryl aldehydes, alkyl aryl and diaryl ketones can be reduced to the methylene products in high yields. Aromatic substituents such as nitro, cyano and halogen also suffer reduction under these conditions. 

The reactant corresponding to retrosynthetic path b in Scheme 2.2 can be obtained by Meerwein arylation of vinyl acetate with o-nitrophcnyldiazonium ions[9], Retrosynthetic path c involves oxidation of a 2-(o-nitrophenyl)ethanol. This transformation has also been realized for 2-(o-aminophenyl)ethanols. For the latter reaction the best catalyst is Ru(PPhj)2Cl2. The reaction proceeds with evolution of hydrogen and has been shown to be applicable to a variety of ring-substituted 2-(o-aminophenyl)ethanols[10]. 

PMMA is not affected by most inorganic solutions, mineral oils, animal oils, low concentrations of alcohols paraffins, olefins, amines, alkyl monohahdes and ahphatic hydrocarbons and higher esters, ie, >10 carbon atoms. However, PMMA is attacked by lower esters, eg, ethyl acetate, isopropyl acetate aromatic hydrocarbons, eg, benzene, toluene, xylene phenols, eg, cresol, carboHc acid aryl hahdes, eg, chlorobenzene, bromobenzene ahphatic acids, eg, butyric acid, acetic acid alkyl polyhaHdes, eg, ethylene dichloride, methylene chloride high concentrations of alcohols, eg, methanol, ethanol 2-propanol and high concentrations of alkahes and oxidizing agents. 

In some instances, ring contraction is accompanied by cyclization to indole derivatives. For example, l-aryl-6-oxo-l,4,5,6-tetrahydropyridazines with a carboxyl or methyl group at position 3 give indoles when treated with an ethanolic solution saturated with hydrogen chloride or in the presence of BF3 etherate. 

The reaction of appropriate 1,3-diketones (302) with hydroxylamine hydrochloride in pyridine (79MI41601) has been reported to result in a regiospecific synthesis of 3-alkyl-5-arylisoxazoles, as has the reaction of an a -bromoenone (307) with hydroxylamine hydrochloride in ethanol in the presence of potassium carbonate (81H(16)145). Regiospecific syntheses of 5-alkyl-3-phenylisoxazoles also result from the reaction of an a-bromoenone (307) with hydroxylamine in the presence of sodium ethoxide (81H(16)145). 3-Aryl-5-methylisoxazoles were prepared from phosphonium salts (304) and hydroxylamine (80CB2852). 

Diaryloxaziridines are even less stable. With oxaziridines (66 Ar = Ph or 4-Me2NC6H4) acid amide formation at 25 °C proceeded in the course of 66 and 10 h respectively in the latter case there were equal amounts of H and aryl migration. Ethanol as solvent again accelerated the reaction, in the latter case by a factor of lO. ... 

In 1883, Bottinger described the reaction of aniline and pyruvic acid to yield a methylquinolinecarboxylic acid. He found that the compound decarboxylated and resulted in a methylquinoline, but made no effort to determine the position of either the carboxylic acid or methyl group. Four years later, Doebner established the first product as 2-methylquinoline-4-carboxylic acid (8) and the second product as 2- methylquinoline (9). Under the reaction conditions (refluxing ethanol), pyruvic acid partially decarboxylates to provide the required acetaldehyde in situ. By adding other aldehydes at the beginning of the reaction, Doebner found he was able to synthesize a variety of 2-substituted quinolines. While the Doebner reaction is most commonly associated with the preparation of 2-aryl quinolines, in this primary communication Doebner reported the successful use of several alkyl aldehydes in the quinoline synthesis. 

In 1893 Pietro Biginelli reported the first synthesis of 4-aryl-3,4-dihydropyrimidin-2(l//)-ones (DHPMs) via an one-pot process using three components. Thus, DHPM 7 was synthesized by mixing benzaldehyde (5), ethyl acetoacetate (6), and urea (3a) in ethanol at reflux in the presence of a catalytic amount of HCl. 

Reactivity in this ring system is sufficient for facile hydrolysis (20°, 2 hr or 100°, 1 min) of the 2-, 4-, 6-, and 7-methoxypteridines in high yield and for easy substitution (75-90% yields) of the 7-methylthio group with methanolic hydrazine hydrate (65°, 15 min), dimethylamine (65°, 30 min), and ethanolic ammonia (125°, 6 hr). The 7-acyloxy intermediate in thionation of 7-oxopteridine with phosphorus pentasulfide is readily substituted (80°) to form pteridine-7-thione. The chloro group in 6-aryl-2,4-diamino-7-chloro-pteridine still reacts readily with hydrazine (100°, several minutes) in spite of the two deactivating amino substituents. 

Bromoquinolines behave in the Suzuki reaction similarly to simple carbocyclic aryl bromides and the reaction is straightforward. Examples include 3-(3-pyridyl)quinoline (72) from 3-bromoquinoline (70) and 3-pyridylboronic acid (71) (91JOC6787) and 3-phenyl-quinoline 75 from substituted 3,7-dibromoquinoline 73 and (2-pivaloylaminophenyl)boronic acid 74 (95SC4011). Notice that the combination of potassium carbonate and ethanol resulted in debromination at the C(7) position (but the... 

Subsequently it was found140 that ethyl 2-alkyl-1//-azepine-1-carboxylates can be isolated from a mixture of isomeric 1//-azepines by stirring the mixture with potassium hydroxide in ethanol at room temperature. Apparently, this method, which is limited to 2-alkylated azepines, depends on the slower rate of hydrolysis (and subsequent decomposition of the resulting 1H-azepine-l-carboxylic acid) of the sterically hindered 1-(ethoxycarbonyl) group. Although the yields of l//-azepines are poor (4-7%, vide supra), the method provides access to otherwise difficult to obtain, isomerically pure 2-alkyl-1//-azepines. Under the basic hydrolysis conditions aryl 2-alkyl-l//-azepine-1-carboxylates undergo transesterification to the l-(ethoxycarbonyl) derivatives. 

Aryl-substituted biguanides (c.g. 1) can be condensed with 1-benzoylacetone to provide 1,3,5-triazocine derivatives,13 Two isomers of product 2 can be isolated upon recrystallization from ethanol. The isomers, probably tautomers 2A and 2B, exhibit the same melting point and rapidly interconvert in solution, thereby giving identical NMR spectra in deuteriochloroform at room temperature. 

The addition of a-(acylamino) esters to 3-aryl-2-propenoates, with sodium ethoxide in ethanol or sodium hydride in benzene as base, is a frequently ultilized procedure9-" A The initial Michael adducts cyclize to 3-aryl-5-oxo-2-pyrrolidinecarboxylic acids with modest to high trans diastereoselectivities 10°. 

It is essential that reagent grade CHC13 is used in the synthesis as the trace of ethanol stabilizer removes the aryl isocyanate byproduct and prevents it... 

As discussed in Section 8.10, dediazoniation in methanol or ethanol yields mixtures of the corresponding aryl ethers and arenes, except with alcohols of very low nucleo-philicity such as trifluoroethanol, in which the aryl ether is the main product. Therefore aryl ethers are, in general, synthesized by alkylation of the respective phenol. Olah and Wu (1991) demonstrated, however, that phenylalkyl and aryl ethers can be obtained in 46-88% yield from benzenediazonium tetrafluoroborate using alkoxy- and phenoxytrimethylsilanes in solution in Freon 113 (l,l,2-trichloro-l,2,2-tri-fluoroethane) at 55-60 °C with ultrasonic irradiation. As seen from the stoichiometric... 

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