Indoles, dihydro

Indole, 3-(dialkylaminomethyl-) alkylation, 4, 275 Indole, 2,3-dibromo-synthesis, 4, 215 Indole, 2,6-dibromo-3-methyl-synthesis, 4, 215 Indole, 1,3-dichloro-synthesis, 4, 214 Indole, dihydrodehydrogenation, 4, 283, 311 in non-silver photography, 1, 383 Indole, 2,3-dihydro-synthesis, 4, 327, 352 Indole, 2,3-dihydroxy-tautomerism, 4, 37, 199 Indole, 4,6-dimethoxy-... 

Indoline l//-Indole, 2,3-dihydro- Methyl sulfoxide Methane, sulfinylbis-... 

Table XVII.E-7 summarizes the variation in the structures of the aza-arene compounds identified in tobacco and/ or tobacco smoke. Of particular interest with regard to the 294 aza-arenes cataloged in Table XVII.E-6 is that only twenty-three of the 294 have been identified as tobacco components. Of the twenty-three, just fifteen have been identified in both tobacco and smoke. The number of aza-arenes identified in smoke is 286. Those isolated from or identified in tobacco in greater than trace amounts include l//-indole, 2,3-dihydro-l//-indole, 9//-pyrido[3,4-/ ]indole (norharman), l-methyl-9//-pyrido[3,4-/ ]indole (harman), l//-purine, and quinoline.

IH-Indole, 2,3-dihydro-2-methyI-IH-Indole, 2,3-dihydro-3-(3-pyridinyl)- 1587, 4249 2917a ... 

This methodology can be used in an intramolecular fashion to synthesize different nitrogen heterocycles. Ruthenium-catalyzed cycloisomerizations of aromatic homo- and bis-homopropargylic amines/amides to indoles, dihydro-isoquinolines, and dihydroquinolines have been developed. 

Pyrano[3,4-b]indol-3-ones are the most useful equivalents of the indol-2,3-quinodimethane synthon which are currently available for synthetic application. These compounds can be synthesized readily from indole-3-acetic acids and carboxylic anhydrides[5,6]. On heating with electrophilic alkenes or alkynes, adducts are formed which undergo decarboxylation to 1,2-dihydro-carbazoles or carbazoles, respectively. 

In the case of vinylfurans and vinylpyrroles there is the possibility of cycloaddition involving either the cyclic diene system or the diene system including the double bond. 2-Vinylfuran reacts in high yield with maleic anhydride in ether at room temperature to form the adduct involving the exocyclic double bond. Similarly, 2- and 3-vinylpyrroles react with 7T-electron-deficient alkenes and alkynes under relatively mild conditions to give the corresponding tetrahydro- and dihydro-indoles (Scheme 51) (80JOC4515). 

Indigocarmine (2[l,3-dihydro-3-oxo-5-sulfo-2ff-indol-2-ylidene]-2,3-dihydro-3-oxo-lff-indole-5-sulfonic acid di-Na salt) [860-22-0] M 466.4, pK 2.8, pK2 12.3. Its... 

The formation of l-methyl-5-aminonaphthalene when dihydro-lysergic acid is fused with potassium hydroxide requires rings (A) and (Cb The presence of an indole nueleus (rings (A) and (B) ) is established by the formation of 3 4-dimethylindole, m.p. 115-7°, pierate, m.p. 185-7°, by decarboxylation of an indole acid obtained when dihydrolysergic acid is fused with potassium hydroxide. ... 

The key step in syntheses of if/-quebrachamine (122-127) and if/-dihydro-cleavamine (12S) is the oxidation of tertiary amines with mercuric acetate to cyclic imonium salts, which give rise to an intramolecular electrophilic attack on an indole. 

A second direct route to an extended 3,4-dihydro-j8-carbolinium system (120) using the Bischler-Napieralski ring closure is based on the cyclization of intermediates of general structure 118. Three approaches to intermediates of this type have been developed in connection with stereospecific syntheses in the indole alkaloid field. The first approach, introduced independently by Stork and Hill and by van Tamelen and co-workers and often used... 

Two other approaches to the same type of end-product have been recorded. In the first a 2-(2-pyridyl)- or 2-(l-isoquinolyl)-indole is converted, by way of the corresponding gramine, in conventional steps into the 3-(j8-bromoethyl) derivative (e.g. 125), which cyclizes to the 3,4-dihydro-j8-carbolinium salt 124. The other is based on a condensation of 3-(j8-bromoethyl)indole (126) with a 2-halopyridine,... 

Another approach to the l-oxo-l,2-dihydro-j8-carboline system is that due to King and Stiller. When 2-ethoxy carbonyl-3-formyl-indole is condensed with hippuric acid the azlactone 162 is formed, which, with 10% methanolic potassium hydroxide, gives a mixture of the orthoester 163 and the potassium salt 164. 

Most of the substitution reactions of di-, tetra, and hexa-hydro-carbolines and of their oxo derivatives are similar to those of the parent indole or indolenine derivatives. Nitration and bromination of harma-line (l-methyl-3,4-dihydro-j8-carbolme) are referred to in Section IV, A, 1. Sulfonation and azO COupling ° proceed as expected for indole derivatives. The preparation of chlorinated and iodinated derivatives of 6-nitroharmaline has been reported,but their structures have not been established. 

Formation of a quinonoid carboline-type anhydro-base requires loss of resonance stabilization of the indole moiety. In the carboline anhydro-bases this is counterbalanced by the preservation of a 677 system in the hetero ring. No such balancing factor is present in the case of 3,4-dihydro-j3-carboline derivatives. Formation of the exocyclic anhydro-base in the latter case preserves benzenoid resonance. It is noteworthy that in the two cases where formation of a carboUne-type anhydro-base was reported in dihydro derivatives additional aromatic conjugation is present. 

The third structural possibility, the formulation of the compounds as pseudo-bases (445) was eliminated in the case of the anhydro-bases derived from p /r-iV -alkyl-l-methyl-3,4-dihydro-j8-carbolinium salts on the basis of their ultraviolet absorption spectra. A structure such as 445 demands indole-type absorption (A jax 280 mp) which was not encountered in the spectra of the anhydro-bases under discussion. This is in accord with general experience. Pseudo-bases are generally found only when dehydration to anhydro-bases is structurally impossible Indole-type absorption was indeed found in the case of the product obtained by treatment of 3,4-dihydro-)3-carboline methiodide (452 R = H) with alkali.In acid solution this compound gave the expected absorption (A jax 355 mp). In alkaline solution, however, an indole-type absorption (A jax 285 mp) was observed. On this basis formulation of the product as a derivative of 2-formylindole (454) ( max 315 mp) was rejected. Although the indole-type absorption is in accord with the pseudo-base structure 453 (R = H), the elemental analysis and molecular weight were not compatible with this formulation and the product was regarded as a dimeric anhydro-base (455). 

At the time of the previous review (76AHCS1), 3//-indole was unknown. Reeently it was found that this eompound is formed when an etheral solution of 2,3-dihydro-A-indolylaeetophenone is irradiated at 308 or 313 nm... 

Alternatively, the desethylcatharanthine can be obtained from the adduct 21 in the reaction of 2-(indol-2-yl)acrylate 20 and A-alkoxycarbonyl-1,2-dihydro-pyridine 8f(81CC37). 

The reaction of Ab-acetyl-1 -hydroxytryptamine (39) with mesyl chloride (MsCl) in THF in the presence of EtsN provides 1-acetyl-1,2,3,8-tetrahydropyrrolo[2,3-(j] indole (49a, 35%) (70JA343), Ab-acetyl-6-mesyloxytryptamine (50a, 4%), Ab-acetyl-2,3-dihydro-2-oxotryptamine (51a, 5%), l-acetyl-3a-(4-chlorobutoxy)-l,2,3,3a,8,8a-hexahydropyrrolo[2,3-(j]indole (52a, 7%), and Ab-acetyltryptamine (53a, 2%) as shown in Scheme 6 (2000H483). In the same reaction with MsCl, l-hydroxy-Ab-methoxycarbonyltryptamine (34) produces 50b (7%), 51b (34%), and 52b (9%), while the formation of 49b is not observed at all. In the case of Ab-trifluoroacetyl-l-hydroxytryptamine (48), 49c (45%), 50c (8%), 51c (4%), and 52c (6%) are produced. These data suggest that the yield of 49 increases, whereas the yield of 51 decreases in the order of electron-withdrawing ability of Ab substituents (COOMe < COMe < COCF3). Stability of 49 seems to govern the quantity of 51, which is probably formed by hydrolysis of 49. 

For a structure-activity relationship study on 5//-pyrido[4,3-(j]indoles (y-carbolines), we needed both 1-unsubstituted 271 and 1-substituted methyl 2,3-dihydro-3-oxo-5//-pyrido[4,3-(j]indole-4-carboxylates 272 (Scheme 42). 

Thus, novel 2-substituted methyl 2,3-dihydro-l-methyl-3-oxo-5//-pyrido[4,3-/j] indole-4-carboxylates are available. Since the methyl group at the 1 position is expected to react with various reagents, many 1-substituted derivatives could be produced. 

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