Claudio Saitz

New synthesis of naphtho- and benzoxazoles: Decomposition of naphtho- and benzoxazinones with KOH

A method that allows the synthesis of 4 different heterocyclic systems of fused aryl oxazoles, i.e., naphtho[1,2-d], naphtho[2,1-d], naphtho[2,3-d], and benzo[d]oxazoles in reasonable yield is described. This method consists of the decomposition of naphtho- and benzoxazinones with KOH.

Photoreduction of oxoisoaporphines by amines: laser flash and steady-state photolysis, pulse radiolysis, and TD-DFT studies.

Photoreduction of oxoisoaporphine (OIA) (1-aza-benzo-[de]anthracen-7-one) and its 5-methoxy (5-MeO-OIA) derivative by selected amines (two non-alpha-hydrogen-donating amines (1,4-diaza[2.2.2]-bicyclooctane (DABCO) and 2,2,6,6-tetramethylpiperidine (TMP)) and three alpha-hydrogen-donating amines (triethylamine (TEA), diethylmethylamine (DEMA), and dimethylethylamine (DMEA))) has been studied in deaerated neat acetonitrile solutions using laser flash and steady-state photolysis. The triplet excited states of OIA and 5-MeO-OIA are characterized by intense absorption maxima located at lambda(max) = 450 nm and lifetimes of 34.7 +/- 0.5 and 44.6 +/- 0.4 micros, respectively. In the presence of tertiary amines, both triplets are quenched with a rate constant that varies from the near diffusion limit (>10(9) M(-1) s(-1)) to a rather low value (approximately 10(7) M(-1) s(-1)) and shows the expected dependence on the reduction potential for one-electron-transfer reactions. The transient absorption spectra observed after quenching of the respective triplet states are characterized by distinct absorption maxima located at lambda(max) = 480 and 490 nm (for OIA and 5-MeO-OIA, respectively) and accompanied by broad shoulders in the range of 510-560 nm. They were assigned to either solvent-separated radical ion pairs and/or isolated radical anions. In the presence of alpha-hydrogen-donating amines these species undergo protonation that leads to the formation of neutral hydrogenated radicals A1H(*)/A2H(*) with two possible sites of protonation, N and O atoms. Pulse radiolysis and molecular modeling together with TD-DFT calculations were used to support the conclusions about the origin of transients.

Photoreduction of oxoisoaporphines. Another example of a formal hydride-transfer mechanism

Photoreduction of 5,6-dimethoxy-, 5-methoxy- and 2,3-dihydro-7H-dibenzo[de,h]quinolin-7-one (A) by tertiary amines in oxygen-free solutions generates long-lived semi-reduced metastable photoproducts, A-NH(-), via a stepwise electron-proton-electron transfer mechanism with a limit quantum yield of about 0.1 at high TEA concentrations. These metastable photoproducts revert thermally to the initial oxoisoaporphine nearly quantitatively in the presence or absence of oxygen. We present spectrophotometric, NMR and UV-vis data for the metastable photoproducts. The spectrophotometric results and PM3 and ZINDO/S calculations support the proposed mechanism for the photoreduction of the oxoisoaporphines.

Unexpected Imidazoquinoxalinone Annulation Products in the Photoinitiated Reaction of Substituted‐3‐Methyl‐Quinoxalin‐2‐Ones with N‐Phenylglycine

Photoinduced electron transfer between N‐phenylglycine (NPG) and electronically excited triplets of 7‐substituted‐3‐methyl‐quinoxalin‐2‐ones in acetonitrile generate the respective ion radical pair, where by decarboxylation the phenyl‐amino‐alkyl radical, PhNHCH2•, is generated. This radical reacts with the 3‐methyl‐quinoxalin‐2‐ones ground states, leading to the product 2. Other, unexpected, 7‐substituted‐1,2,3,3a‐tetrahydro‐3a‐methyl‐2‐phenylimidazo[1,5‐a]quinoxalin‐4(5H)‐ones, annulation products, 3a–f, were generated; likely by the addition of two PhNHCH2• radicals, to positions 3 and 4 of the quinoxalin‐2‐ones. The reaction mechanism includes a photoinduced one electron transfer initiation step, propagation steps involving radical intermediates and NPG with radical chain termination steps that lead to the respective products 2a–f and 3a–f and NPG by‐products. The proposed mechanism accounts for the strong dependency found for the initial photoconsumption quantum yields on the electron‐withdrawing power of the substituent. Therefore, photolysis of common reactants widely used such as NPG and substituted quinoxalin‐2‐ones may provide a simple synthetic way to the unusual, unreported tetrahydro‐imidazoquinoxalinones 3a–f.

NEW HETEROCYCLIC SKELETONS DERIVED FROM THE APORPHINE ALKALOID BOLDINE

ABSTRACT The abundant aporphine alkaloid (S)-(+)-boldine (1) was selectively nitrosated with sodium nitrite in acetic acid affording 8-nitrosoboldine (2) which was hydrogenated catalytically to give 8-aminoboldine (3). The latter was used as the starting material for annulations with ethyl ortho-formate to afford the corresponding oxazole (“boldine-9,8-oxazole”, 4), and with methyl benzoylformate giving the phenyl-oxazinone (“boldine-9,8-phenyloxazinone”, 5). This later product was treated with KOH/EtOH at room temperature and converted quickly into the ring-contracted phenyloxazole (“boldine-9,8-phenyloxazole”, 6) in moderate yield.

SYNTHESIS OF AMINONAPHTHALENE DERIVATIVES USING THE BUCHERER REACTION UNDER MICROWAVE IRRADIATION

A very simple and efficient method to prepare aminonaphthalene derivatives in good yield using the Bucherer reaction under microwave irradiation in a closed vessel is described. A reaction time of 30min at 150 Watts of microwave power was established as the optimum irradiation conditions when approximately 2 g of the initial hydroxynaphthalene was used in the synthesis.

Synthesis of Benzo[b]thiophene Carboxamides Connected to 4‐Arylpiperazines through a Benzylic Spacer: Potential Ligands with 5‐HT1A Binding Affinity

Abstract New benzothiophene arylpiperazine derivatives 8 (a–f) were synthesized as potential serotoninergic agents with 5‐HT1A receptor affinity. Preparation of the derivatives was performed by treating N‐[2‐(chloromethyl)phenyl]‐4,7‐dimethoxybenzo[b]thiophene‐2‐carboxamide (7) with a series of substituted 4‐arylpiperazines.

Spectral and Kinetic Study of 3-Methylquinoxalin-2-ones Photoreduced by Amino Acids: N-Phenylglycine Radical Chain Reactions and N-Acetyltryptophan Decarboxylation

Transient intermediates were identified in the photoreduction of 3-methylquinoxalin-2-one derivatives by N-phenylglycine, NPG, and N-acetyltryptophan, NAT. For both reductants it can be postulated a sequence of reaction comprising first a photoinduced single electron transfer followed by a proton transfer from the radical cation of the electron donor to the radical anion of the 3-methylquinoxalin-2-one giving rise to the reported products. The effect of the concentrations of NPG and the quinoxalin-2-one on the rate of photoconsumption of this last were quantified, and the lifetimes of the possible intermediates estimated. In the photoreduction by NAT, processes leading to the decarboxylation of NAT and radical adduct product compete with the expected SET from the indoyl N to the excited triplet of quinoxalin-2-ones as revealed by the detection of the deprotonated N-acetyltryptophan radical [NAT-H](•). This radical is formed almost instantly after the laser pulse and has a secondary delayed growth via a delayed proton transfer from the indoyl radical cation NAT(•+) to the quinoxalin-2-one radical anions. The decarboxylation of NAT that mimics C-terminus tryptophan in proteins is biologically relevant because might cause damages at cellular and the whole organism level. As far as we know this is the first report of a radical decarboxylation of N-acetyltryptophan leading to photoproducts.

Complete assignment of the 1H and 13C NMR spectra of 2‐phenyl‐3H‐naphtho[2,1‐b][1,4]oxazin‐3‐one, 2‐p‐methoxyphenylnaphtho[1,2‐d]oxazole and 2‐phenylnaphtho[1,2‐d]oxazole. Concerted use of one‐ and two‐dimensional NMR techniques

The 1H and 13C NMR spectra of 2‐phenyl‐3H‐naphtho[2,1‐b][1,4]oxazin‐3‐one, 2‐p‐methoxyphenylnaphtho[1,2‐d]oxazole and 2‐phenylnaphtho[1,2‐d]oxazole were totally assigned using a combination of one‐ and two‐dimensional NMR techniques. In addition to correlation of the proton signals by a COSY spectrum and one‐bond heteronuclear correlation, complete assignment of the 1H and 13C NMR spectra of these heterocyclic compounds required the application of long‐range CH coupling information, particularly for quaternary resonance assignments and for orientations of individual spin systems relative to one another.

Synthesis of calix[4]arenes bearing benzothiazolyl, benzoxazolyl and benzoimidazolyl heterocycles

A novel series of calix[4]arenes bearing benzothiazole, benzoxazole, and benzoimidazole groups were obtained by the reaction of the corresponding 2-mercaptoheterocycle with 5,11,17,23-tetra-tert-butyl-25,27-bis[2-(chloroacetamido) ethoxy]-26,28-di-hydroxycalix[4]arene and structurally characterised by IR, 1H NMR, 13C NMR, Mass spectra and elemental analyses. From their analytical data, it was found these compounds had cone conformations.