2-Ethoxycarbonyl-4-phenyl-6-substituted

Isobutoxy-217, 2-butyl-,218 2-phenyl- (eq. 12.113),218 and 2-ethoxycarbonyl-219 substituted 2,3-dihydro-4H-pyrans were hydrogenated over Raney Ni at room temperature and elevated hydrogen pressures, although rather long reaction times were required for the 2-isobutoxy and 2-phenyl derivatives. 

When large groups, such as phenyl, bromo, ethoxycarbonyl or nitro are attached at position 3, the principal products are l-alkylcinnolin-4(l/f)-ones. Cyanoethylation and acetylation of cinnolin-4(l/f)-one takes place exclusively at N-1. Phthalazin-l(2/f)-ones give 2-substituted derivatives on alkylation and acylation. Alkylation of 4-hydroxyphthala2in-l(2/f)-one with an equimolar amount of primary halide in the presence of a base leads to 2-alkyl-4-hydroxyphthalazin-l(2/f)-one and further alkylation results in the formation of 4-alkoxy-2-alkylphthalazinone. Methylation of 4-hydroxy-2-methyl-phthalazinone with dimethyl sulfate in aqueous alkali gives a mixture of 4-methoxy-2-methylphthalazin-l(2/f)-one and 2,3-dimethylphthalazine-l,4(2//,3//)-dione, whereas methylation of 4-methoxyphthalazin-l(2/f)-one under similar conditions affords only 4-methoxy-2-methylphthalazinone. 

Nitrones or aci-nitro esters react with alkenes to give in some cases A/-substituted isoxazolidines and in others 2-isoxazolines. When the intermediate isoxazolidines were observed, a number of procedures transformed them into the 2-isoxazolines. Acrylonitrile and phenyl rzcf-nitrone esters produced an A/-methoxyisoxazolidine. Treatment with acid generated a 2-isoxazole while treatment with base generated an oxazine (Scheme 118) (68ZOR236). When an ethoxycarbonyl nitrone ester was reacted with alkenes, no intermediate isoxazolidine was observed, only A -isoxazolines. Other aci-mtro methyl esters used are shown in Scheme 118 and these generate IV-methoxyisoxazolidines or A -isoxazolines which can be further transformed (72MI41605). 

Indazole, 5,5-dimethyl-3-trifluoromethyl-4,5-dihydro-trichomonacidal activity, 5, 291 Indazole, 2-ethoxycarbonyl-reactions, 5, 269 Indazole, 3-fluoro-synthesis, S, 263 Indazole, 1-germyl-synthesis, 5, 236 Indazole, 1-glycosyl-synthesis, 5, 289 Indazole, 2-glycosyl-synthesis, 5, 289 Indazole, halo-reactions, S, 266 Indazole, 2-hydroxy-methylation, 5, 269 Indazole, 3-hydroxy-reactions, S, 264 Indazole, 6-hydroxy-diazo coupling, 5, 86 Indazole, hydroxyphenyl-synthesis, S, 288 Indazole, 3-iodo-synthesis, S, 241 Indazole, l-isopropyl-3-phenyl-reduction, 5, 243 Indazole, 3-mercapto-1 -substituted tautomerism, 5, 265 Indazole, methoxy-... 

Reaction of 2-aminopyridine with ethyl 2-cyano-3-ethoxy-3-methyl-, -3-ethyl-, -3-phenylacrylates and ethyl 2-ethoxycarbonyl-3-ethoxy-3-methyl-, -3-phenylacrylates in boiling xylene yielded 2-substituted 4/f-pyrido[l,2-u]pyrimidine-3-carbonitriles and -3-carboxylates (99MI7). Similar reactions of 2-aminopyridine with 2-cyano-3-ethoxyacrylonitrile and its 3-methyl, 3-ethyl, -3-phenyl derivatives in boiling MeCN afforded 4-imino-4//-pyrido[l,2-u]-pyrimidine-3-carbonitrile and its 2-substituted derivatives. 

To complete the section on the synthesis of 4,4 -bipyridines, we summarize the methods reported for the preparation of some substituted 4,4 -bi-pyridines and 4,4 -bipyridinones. These methods are closely analogous to syntheses already discussed for some of the isomeric bipyridines. Thus the Hantzsch reaction using pyridine-4-aldehyde, ethyl acetoacetate, and ammonia gives 3,5-di(ethoxycarbonyl)-1,4-dihydro-2,6-dimethyl-4,4 -bipyridine, which after oxidation, followed by hydrolysis and decarboxylation, afforded 2,6-dimethyl-4,4 -bipyridine. Several related condensations have been reported. Similarly, pyridine-4-aldehyde and excess acetophenone gave l,5-diphenyl-3-(4-pyridyl)pentane-l,5-dione, which with ammonium acetate afforded 2,6-diphenyl-4,4 -bipyridine. Alternatively, 1-phenyl-3-(4-pyridyl)prop-2-enone, A-phenacylpyridinium bromide, and ammonium acetate gave the same diphenyl-4,4 -bipyridine, and extensions of this synthesis have been discribed. Condensation of pyridine-4-aldehyde with malononitrile in the presence of an alcohol and alkaline catalyst produced compounds such as whereas condensations of... 

Photolysis of l-ethoxycarbonyl-5,5-dialkoxytriazolines bearing a 4-alkyl substituent has been found to proceed via 1,3-diradicals, whereas a 1,5 pathway prevails in the absence of 4-substitution.268 Photolysis of the 4-phenyl compound (see Scheme 68) leads to an oxazole.404... 

The electrophilic properties of substituted 6//-l,3-thiazine-6-ones (208) in solution also shows reactivity at C-2 in acidic conditions and at C-6 in basic conditions. The regioselective reaction of 4-ethoxycarbonyl-2-phenyl-6//-l,3-thiazine-6-one with dimethylamine leads, after ring opening and reclosure, to two diasteriomeric 5-dimethylcarboxamido-4-ethoxy-carbonyl-2-phenyl-A2-thiazolines 209 and 210, whose structures were confirmed by X-ray diffraction studies on 210 (Scheme 84) (88BSF897). Com-... 

Via an amidoalkylation of bis(trimethylsilyl)ethyne (12) with methyl 2-chloro-N-ethoxycarbonylglycinate (57) under the influence of aluminum chloride the corresponding N-(ethoxycarbonyl)-a,a-TMS-ethynyl-glycinate (55) is isolated which is converted by means of lithium-di-isopropylamide (LDA) into a carbanion that reacts with alkylhalide to the substituted glycinate 59. Finally, after alkaline hydrolysis the unprotected a-acetylenic-a-aminoacid (60) (e. g. R = Benzyl a-ethynyl-a-phenyl-alanine is then obtained (Scheme 7). 

UV spectra of substituted 1,3,4-oxadiazoles are similar to those of similarly substituted benzenes, particularly in the case of 2-phenyl- and 2,5-diphenyl-l,3,4-oxadiazole (Amax (EtOH) 247.5 nm, log e 4.26, and 280 nm, log e 4.44 respectively). However, no absorption above 200 nm is shown by 1,3,4-oxadiazole itself and calculated values (Section 4.23.2.1) for its long wavelength absorption are in the region of 200 nm compared with Amax ca. 260 nm for benzene. 2-Methyl- and 2-ethoxycarbonyl-l,3,4-oxadiazole, and A2-l,3,4-oxadiazoline-5-thione have the following Amax (log e) values respectively 206 nm (2.62) (methanol), 243 nm (3.2) and 260 nm (4.12) (ethanol). 

Sodium benzenetellurolate adds to the double bond of ethenes with an electron-withdrawing ethoxycarbonyl or nitrile group to form (substituted ethyl) phenyl tellurium compounds10. 

Besides the Fmoc (Section 2.1.1.1.1.3) and the substituted sulfonylethyl groups (Section 2.1.1.1.1.4) that are cleaved by (3-elimination under basic conditions, the A -2-(trimethylsi-lyl)ethoxycarbonyl (Teoc, 43)P 1 and 2-phenyl-2-(trimethylsilyl)ethoxycarbonyl (44)P 1 derivatives (Scheme 21) are readily removed by the action of the fluoride anion, the elimination products of the Grob-type reaction being TMSF, ethene or styrene, and a carbamate which releases carbon dioxide upon aqueous workup. The nature of the cleavage byproducts allows for easy isolation of the free amino compound. 

The synthesis of 2-aminopyrazines (108) unambiguously substituted at the 5-and 6-positions from substituted 2-azabutadienes (107) and ammonia has been described by Lang and Fleury (488). In this way 2-amino-3-cyano(or methoxy-carbonyl)-5-methyl(or ethoxycarbonyl)-6 phenyl(or methyl or 5,6-polymethylene)-pyrazines have been obtained. When the Schiffbase [H2NC(CN)=C(CN)N=C(CN)Ph ... 

---