Pd-Mediated synthesis of 7H-benzo[3,4]azepino[1,2-a]indole-6-carboxylic acid derivatives from indole-containing Baylis-Hillman adducts

We synthesized novel tetracyclic fused indole derivatives via the intramolecular Heck reaction of indole-containing Baylis-Hillman adducts in good to moderate yields.     

Highly Selective One-Pot Coupling Reaction of Indole,Aromatic Aldehydes,and 4-hydroxycoumarin Using Copper Octoate as a Homogeneous Catalyst

A facile protocol for the one-pot, multicomponent reaction of indole, 4-hydroxycoumarin, and aromatic aldehydes was developed using copper octoate as an inexpensive, commercially available, and efficient catalyst. This highly selective reaction eliminates the formation of homodimeric by-products (bisindoles and biscoumarins) and selectively results in the formation of heterodimeric adducts containing both indole and coumarin heterocycles.     

Ytterbium triflate catalyzed synthesis of β-functionalized indole derivatives

Ytterbium triflate was shown to be effective in promoting the synthesis of substituted indole derivatives starting from indole, aldehydes, and dimethyl malonate by a Yonemitsu-type three component reaction. The whole process was carried out in solvent-free conditions and furnished the desired adducts in 42-67% yield.     

A multicomponent synthesis of gem-(β-dicarbonyl)arylmethanes

The reaction of aldehydes with β-dicarbonyls and electron-rich aromatics was investigated to generate in a multicomponent fashion crossed adducts of biological relevance. 4-Hydroxycoumarin, triacetic acid lactone, indole, and a selection of aliphatic and aromatic aldehydes representative of various electronic and steric conditions were employed. The reaction showed a surprising dependence on the solvent, with 1:1 chloroform–water giving the best yield of heterodimeric adducts. The mechanistic rationale for the formation of hetero- rather than homodimeric adducts is discussed.     

Identification of oxidation products and free radicals of tryptophan by mass spectrometry

New oxidation products and free radicals derived from tryptophan (Trp) oxidation under Fenton reaction conditions were identified using mass spectrometry. After the oxidation of tryptophan using hydrogen peroxide and iron (II) system (Fenton reaction), mono- and dihydoxy tryptophans and N-formylkynurenine were identified using electrospray mass spectrometry (ES-MS) and ES-MS/MS. Besides these products, new products resulting from the reaction of tryptophan and oxidized tryptophan and 3-methyl indole derivatives were also identified. The 3-methyl indole derivatives resulted, most probably, from the oxidation process and not from in-source processes. A dimer formed by cross-linking between two Trp radicals (Trp-Trp), similar to the previously described tyrosine dimer was observed, as well as the corresponding monohydroxy-dimer (Trp-Trp-OH). Tandem mass spectrometry was used to identify the structures of these new oxidation products. Free radicals derived from tryptophan oxidation under Fenton reaction were detected using as spin trap the DMPO. The free radical species originated during the oxidation reaction formed stable adducts with the spin trap, and these adducts were identified by ES-MS. New adducts of oxidized tryptophan radicals, namely monohydroxy-tryptophan and dihydroxy-Trp dimer radicals, with one and two DMPO spin trap molecules where identified. Tandem mass spectrometry was used to confirm the proposed structure of the observed adducts.     

Cu(I)-phosphine complex: An efficient catalyst for synthesis of 3-indole derivatives through one-pot MCR under mild conditions

An efficient copper (I) halotriphenylphosphine catalyzed one-pot multicomponent reaction (MCR) of 3-substituted indole derivatives has been developed using a variety of aldehydes (aromatic, aliphatic, and heteroaromatic), indole, and active methylene substrates such as malononitrile and ethyl 2-cyano acetate. This reaction proceeds smoothly and obtained good to excellent yields (68–93%) using water as green solvent under ambient conditions. The obtained products were confirmed by ¹H, ¹³C NMR, and mass spectroscopy techniques. The one-pot MCR occurs through formation of Knoevenagel adducts then followed by Michael addition of indole.     

New procedure to mask the 2,3-pi bond of the indole nucleus and its application to the preparation of potent opioid receptor agonists with a Corynanthe skeleton

Treatment of indole alkaloids with hypervalent iodine in the presence of ethylene glycol provides 2,3-ethylene glycol bridged adducts that could be converted into the original indoles under mild reductive conditions. This procedure, which involves masking of the reactivity of the indole nucleus at the beta-position, was utilized for the modification of the benzene ring of the indoline derivative and was applied to the preparation of potent opioid receptor agonists with the Corynanthe skeleton. [reaction: see text]     

Facile and Efficient Michael Addition of Indole to Nitroolefins Catalyzed by Zn(OAc)2 · 2H2O

The Zn(OAc)₂2H₂O-catalyed Michael addition reaction of indole to electron-deficient nitroolefins to afford the corresponding adducts in good to excellent yields with high selectivity is reported.     

Direct amination of olefins through sequential triazolinedione ene reaction and carbanion-assisted cleavage of the N-N urazole bond

[formula: see text] Allylic amines 5 are obtained in 30-55% overall yields by the base-catalyzed hydrolysis of trialkylated allylic urazoles 3; the latter are prepared by the TAD ene reaction of the appropriate olefin and further N-alkylation with alpha-bromoacetophenone. The proposed mechanism for this novel urazole rupture is based on the generation of a carbanion adjacent to the hydrazide functionality, which induces urazole ring-opening by cleavage of the N-N bond.     

Samarium triiodide-catalyzed conjugate addition of indoles with electron-deficient olefins

The SmI₃-catalyzed reaction of indoles with electron-deficient olefins generated the corresponding Michael adducts in high yields. The substitution on the indole nucleus occurred exclusively at the 3-position and N-alkylation products have not been observed.     

Synthesis of aromatic aldehydes via 2-aryl-n,n'-diacyl-4-imidazolines

Diacylimidazolium ions yield adducts with aromatic compounds. Thus the N,N'-diacetylimidazolium ion and indole gives 1,3-diacetyl-2-(3-indolyl)-4-imidazoline. Less reactive substrates such as thiophene, anisole and 1,3-dimethylbenzene fail to react with this reagent but do form adducts (e.g. 1,3-bis-(trifluoroacetyl)-2-(2-thienyl)-4-imidazoline) with an imidazole/trifluoroacetic anhydride reagent. All of the adducts could be converted to the corresponding aldehyde under mild conditions. The synthetic scope of the new synthesis is similar to that of the Vilsmeier-Haack reaction.     

Solid-phase syntheses of 1,2,4-trisubstituted urazole and thiourazole derivatives

Solid-phase syntheses of 1,2,4-trisubstituted urazole and thiourazole derivatives have been accomplished. The synthesis began with the coupling of carbonylimidazole-Wang resin with a disubstituted hydrazine. The resultant carbazate was coupled with an isocyanate or isothiocyanate. Subsequent heating of the resin in the presence of triethylamine or potassium t-butoxide induced cyclization and released the desired (thio)urazole into solution. Most of the products were obtained in high yields and purities. Structural diversity can be further expanded at the R(2) substituent by performing the palladium-mediated Suzuki coupling reaction.     

An efficient synthesis of novel chromeno[3’, 4’：5, 6]pyrano[2, 3-b]indole derivatives

An efficient two-step method was described for the synthesis of chromeno[3',4':5,6]pyrano[2,3-b]indole derivatives. The three-component reaction of 4-hydroxycoumarin, variously substituted benzaldehydes and indolin-2-one was promoted by P2O5 in refluxing ethanol to give trimolecular adducts, which were then cyclized in 1,2-dichloroethane under reflux using POCl3.     

A combination of water and microwave irradiation promotes the catalyst-free addition of pyrroles and indoles to nitroalkenes

A combination of water and microwave irradiation was used for the first time to perform a catalyst-free nitro-Michael addition of pyrroles and indoles. Under superheated conditions, the water trends to ionize by changing its chemical and physical properties. Therefore, we performed a new green-protocol using the water either as environmentally no harm solvent or as catalyst. The reaction success is independent from the kind of pyrrole, indole or nitroalkenes rapidly affording the corresponding adducts and giving excellent yields.     

Vibrational frequencies and structural determinations of urazole

The vibrational frequencies and corresponding normal mode assignments of urazole are examined theoretically using the Gaussian98 set of quantum chemistry codes. All normal modes were successfully assigned to one of eight types of motion (N--H stretch, C=O stretch, C--N stretch, N--N stretch, N--H bend, C=O bend, N--C--N bend, ring torsion) utilizing the C2 symmetry of the molecule. The molecular orbitals of urazole are examined. The simultaneous double inversion of the amine groups in urazole is also examined.     

A new approach for the synthesis of 2-substituted indole derivatives via Michael type adducts

4,7-Dihydroindole undergoes regioselective alkylation at the 2-position of the indole nucleus through conjugate addition with α,β-unsaturated carbonyl compounds. The oxidation of the Michael adducts affords the corresponding 2-substituted indole derivatives which were characterized by spectroscopic methods.     

Preparation,lithiation and transformation of N-(benzotriazol-1-ylmethyl) heterocycles

Indole, carbazole, pyrrole, imidazole, benzimidazole, 2-methyl- and 2-phenylbenzimidazole, and 1, 2, 4-triazole have each been converted into their N-(benzotriazol-1-ylmethyl) derivatives. The pyrrole, indole, and carbazole adducts undergo smooth lithiation at the inter-ring methylene group and subsequent reaction there with electrophiles. For the imidazole, benzimidazole, and triazole systems, lithiations at other molecular positions competed.     

Concise assembly of the polycyclic frameworks associated with the hapalindole and fischerindole alkaloids

[reaction: see text] Reaction of N-methylindole (4) with 6,6-dibromobicyclo[3.1.0]hexane (5) in the presence of silver tetrafluoroborate affords conjugate 7 in 67% yield. This product can be readily elaborated to compounds 12b and 13b which embody the polycyclic frameworks associated with members of the hapalindole and fischerindole classes of alkaloids. The chiral-auxiliary-substituted 6,6-dibromobicyclo[3.1.0]hexanes 21 and 22 react with indole to give adducts likely to be useful in the enantioselective total synthesis of the title alkaloids.     

Determination of amitrole and urazole in water samples by capillary zone electrophoresis using simultaneous UV and amperometrical detection

In this paper, capillary zone electrophoresis with amperometric detection (CZE-AD) was first applied to the simultaneous separation and determination of amitrole and urazole in water samples. A simple end-column electrochemical detector was used in combination with a commercially available capillary electrophoresis instrument with UV detection. The effects of several important factors were investigated to find optimum conditions. A carbon disk electrode was used as working electrode. Separation and determination of these compounds in water samples were performed in 0.030 mol l(-1) acetate buffers at pH 4.5, 25 kV as separation voltage and the samples were introduced by hydrodynamic mode for 1.5 s. Most of the studies realized showed that the direct electrochemical detection is more sensitive and selective than UV detection. Under the optimum conditions, excellent linearity was observed between peak amperometric signal and analyte concentrations in the range of 0.19-1.35 mg l(-1) for amitrole and 0.20-1.62 mg l(-1) for urazole. The detection limits were 63 and 68 microg l(-1) for amitrole and urazole, respectively. The utility of this method was demonstrated by monitoring water samples, and the assay results were satisfactory. The detection limits using a previous preconcentration step for amitrole and urazole in spiked mineral water samples were 0.6 and 1.0 microg l(-1) for amitrole and urazole, respectively.     

Role of phosphorus adducts in the indolization reaction between arylhydrazones and phosphorus trichloride

The reaction between arylhydrazones and PCl₃ can give both diazaphospholes and indoles, via a common hypothetical diazaphospholine intermediate. The product ratio depends on the reaction conditions. In particular when a solvent which dissolves the phosphorus adducts is employed, indole is the almost exclusive reaction product. A mechanism is suggested for the whole indolization reaction. It Involves an acid promoted cleavage of the P-N bond of the diazaphospholine to give intermediates similar to those of the accepted Fischer indolization mechanism, where the dichlorophosphino group, substituting a hydrogen atom should have an important role in promoting of the loss of the amino group in the last stage of the reaction, via a “Wittig-like” elimination of Cl₂PNH₂.