Indoles silver® oxide

EtOH). No methoxyl is present. It forms a series of crystalline double chlorides with cadmium, zinc or copper, does not give the thalleioquin reaction, and solutions of its sulphate are not fluorescent. It is diacidie and forms two series of salts of which the nitrate, B. HNOj, crystallises in minute prisms, m.p. 196°, insoluble in water. Cinchonamine hydrochloride, B. HCl, laminae or B. HCl. HjO, cubical crystals, has been suggested for use in the estimation of nitrates. When warmed with strong nitric acid the alkaloid furnishes dinitrocinchonamine. It gives an amorphous, monoacetyl derivative, and forms a methiodide, m.p. 208 , which with silver oxide yields an amorphous methylcinchonamine. Raymond-Hamet found that cinchonamine ves typical indole colour reactions and is probably an indole alkaloid. This seems to have been... 

Hydrazones of thiochroman-4-ones are converted into thiochromans under Wolff-Kishner-Huang conditions65 and into the azo dimers by silver oxide.66 Fisher indolization of the phenylhydrazones (33) gives 6,ll-dihydrobenz[6]indolo[2,3-d]thiopyrans (34), which by hydride loss form the thiopyrylium salts (35), or on dehydrogenation produce the pseudoazulenes (36) (heterocyclic analogs of the carcinogen, benz[a]-carbazole), as shown in Scheme 6.87-73... 

In contrast with the relatively facile nucleophilic substitution reactions at the 2-position of the indole system, only 3-iodoindole has been reported to react with silver acetate in acetic acid to yield 3-acetoxyindole (59JOC117). This reaction is of added interest as 3-iodo-2-methylindole fails to react with moist silver oxide (72HC(25-2)127). It is also noteworthy that the activated halogen of ethyl 3-bromo-4-ethyl-2-formylpyrrole-5-carboxylate is not displaced during the silver oxide oxidation of the formyl group to the carboxylic acid (57AC(R)167>. 

Applications of this reaction are not limited to advanced materials, but can be applied to natural product synthesis. Indeed, indoles have quite recently (in 2008) been arylated in the presence of palladium acetate and silver oxide (Scheme 10.52).84... 

Azaindoles are more stable to air oxidation than indoles, are stable to mild reagents like silver oxide and selenium dioxide, but are readily attacked by permanganate. In the structure proof of 7-aza-indole, Kruber oxidized the 1-benzenesulfonyl derivative with potassium permanganate in acetone solution to obtain 2-(benzene-sulfonyl)aminonicotinic acid. The 1-acetyl and 1-benzoyl derivatives gave inconsistent results, which Kruber attributed to their ease of hydrolysis. l-Benzoyl-2,5-dimethyl-4-azaindole and its 3-substituted derivatives give 3-benzamido-6-methylpicolinic acid with permanganate oxidation. ... 

Reaction of indoles with glycosyl halides in the presence of silver oxide and molecular sieve as catalysts gave orthoamides of the type shown in (35) and indole nucleosides (see Chapter 19). ... 

The C-2 selective oxidative C-H coupling of unactivated pyridines with heterocycles was achieved in the presence of Pd(OAc)2, phenanthroline as the ligand, a silver oxidant, and pivalic acid (eq 145). Moderate to good yields were obtained when heteroarenes, such as thiophenes, indoles, furans, indazoles, or xanthines, were coupled to p3uidine (or p3razine, quinoline, pyrimidine). Virtually no homo-coupling or other regioselective (C-3 or C-4) products were observed in the reaction. 

Finally, it is appropriate to close this chapter with an example from the roots of fine chemicals the dyestuff, indigo. Manufacture of indigo involves chemistry (see Fig. 2.15) which has hardly changed from the time of the first commercial synthesis more than a hundred years ago (see earlier). Mitsui Toatsu has developed a two-step process in which indole is produced by vapour-phase reaction of ethylene glycol with aniline over a supported silver catalyst (Inoue et al., 1994). Subsequent liquid-phase oxidation of the indole, with an alkyl hydroperoxide in the presence of a soluble molybdenum catalyst, affords indigo. 

Addition of the propargyl Grignard reagent to 3,4-dihydro-p-carboline followed by silver(I)-mediated oxidative cyclization to the dihydroindolizino[8,7-fo]indole and chemoselective hydrogenation provide racemic harmicine (three steps, 46 % overall yield). 

An early example of a natural product synthesis featuring an indole C-H bond alkenylation was report by Trost and co-workers (Scheme 54). Using stoichiometric Pd(II)-salts in combination with silver tetrafluoroborate, they were able to mediate a oxidative Heck process onto the bicyclic amino-alkene. Using a reductive work-up to reduce the Pd-C bond, they were able to complete a synthesis of ibogamine [76]. 

A number of applications of the above-presented approach have been made in the synthesis of bicyclic amines. It has been used in the preparation of pyrrolo[l,2-a]indoles starting from N-trimethylsilylmethyl indoles, which are reacted with silver fluoride in an oxidation-reduction reaction to provide the desired products in good to excellent yields126 (equation 128). This same approach was applied to the preparation of some... 

X0-derivative (730) of this ring system is formed by Fischer indolization of the JV -methyl-iV -phenylhydrazone of the aldehyde 0CHCHMeCH2C02Et. 2-Methylfuran and C-benzoyl-iV-phenylnitrone, PhCOCH=N(Ph)—O, combine to form a mixture of the cyclo-adducts (731) and (732), together with the condensation product (733)." The iV-acyl-nitrone (734 Ad == 1-adamantyl), generated by oxidation of 7V-adamantane-l-carbonyl-A-methylhydroxylamine with silver sulphate, has been trapped as the 1,3-dipolar cyclo-adduct (735) with... 

Synthesis of left-hand segment began with 7-benzyloxyindole 197. A Vilsmeier-Haack formylation followed by condensation afforded nitroalkene 198. Reduction, acylation with succinic anhydride, and subsequent Bischler-Napieralski cyclization provided dihydro-p-carboline 199. Noyori asymmetric reduction of 199, further treatment with A-iodosuccinimide, followed by activation with silver triflate in the presence of dimethoxy-N,N-diallylaniline furnished the desired coupling product 200. Subsequent saponification and cyclization via a ketene intermediate gave the rearrangement precursor 201. Oxidative skeletal rearrangement initiated by m-CPBA followed by removal of the Fmoc group and conversion of the aniline to the hydrazine furnished Fischer indole precursor 202 (Scheme 35). 

Bromide or stoichiometric Silver(I) Oxide, respectively. In many cases, one or both of the aromatic species can be heteroaromatic such as pyridine, furan, thiophene, quinoline, oxazole, thia-zole, or indole. Symmetrical biaryls have been prepared in excellent yields by the Pd(Ph3P)4-catalyzed homocoupling of ArBr/I under phase transfer conditions. ... 

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