Synthesis of alkylaminoethanethiolsulfuric acids substituted with heterocyclic moieties

Several alkylaminoethanethiolsulfurie acids substituted with heterocyclic moieties have been synthesized to determine their effectiveness as radiation protection agents. These compounds are represented by the structure R(CH₂)₃NH(CH₂)₂S₂O₃H, where R is 8-quinoly-oxy (V), 8-quinaldyloxy (IX), 5-quinolyloxy (XII), 4-pyridyl (XVI), and 4-pyridylmethyl (XXIII). The diheterocyclic-substituted compound, 2-[bis-(2-phenyl-1, 2, 3, 2H-triazol-4-ylmethyl)amino]ethanethiolsulfuric acid (XIV) was also synthesized.     

Synthesis of substituted pyridazino[4,5-c]pyridazines

Several pyridazino[4,5-c]pyridazines substituted in the 5- and 8-positions with hydroxyl, mercapto and amino groups and in the 3-position with a methyl group or a hydrogen atom have been prepared. In the course of this work five previously unreported pyridazine derivatives have also been synthesized.     

The first preparation of beta-lactones by radical cyclization

beta-Lactones have, for the first time, been prepared by 4-exo-trig radical cyclization. Thus, alpha-ethenoyloxy radicals react in the presence of tributylstannane in a photothermal process to give beta-lactones. Highest yields were obtained when groups capable of stabilizing a carbon-centered radical were present at the 3-position of the alkenoate acceptor.     

Long range optimized two-dimensional proton-carbon chemical shift correlation. Application in the total assignment of the 1H- and 13C-NMR spectra of 9-methylphenanthro[4,3-a]dibenzothiophene

The utilization of the long range optimized proton-carbon chemical shift correlation experiment in the total assignment of the proton and carbon nmr spectra of 9-methylphenanthro[4,3-a]dibenzothiophene is described. The experiment was employed in concert with conventional proton-carbon chemical shift correlation, heteronuclear relayed coherence transfer and broad band homonuclearly decoupled proton-carbon chemical shift correlation experiments. The experiments in combination offer a useful alternative to the ¹³C-¹³C double quantum coherence experiments, providing significantly better sensitivity and nearly the same capabilities.     

Combined application of auto-correlated (COSY) and homonuclear J-resolved two-dimensional NMR spectra for the assignment of congested,non-first order spectra of polycyclic aromatic systems. Assignment of the 1H-NMR spectrum of benzo[2,3]phenanthro-[4,5-bcd]thiophene and an investigation of long range 1H-1H spin-coupling constants

Total assignment of the proton nmr spectrum of benzo[2,3]phenanthro[4,5-bcd]thiophene at 200 MHz is reported. Preliminary identification of the resonances comprising the individual spin Systems was accomplished by the use of auto-correlated two-dimensional proton nmr spectroscopy (COSY). Individual assignments were made on the basis of spin-coupling information which was obtained from the “titled” two-dimensional J-resolved (2DJ) proton nmr spectrum of the title compound. Because of the greater resolving power of the latter experiment relative to conventional proton nmr spectroscopy, a number of long range inter-ring spincouplings were observed. The observation of these long range couplings was crucial to the final assignment of several of the resonances in the spectrum. Resonances due to strong coupling in the 2DJ spectrum were also shown to be a useful means of correlating strongly coupled spins which provides an alternative to the COSY spectrum for this purpose.     

Double quantum filtered zero quantum coherence with broadband homonuclear f1 Decoupling

A pulse sequence is described which combines double quantum filtration and broadband homonuclear F₁ decoupling in a two-dimensional zero quantum (ZQCOSY) nmr experiment.     

Long range heteronuclear chemical shift correlation with one bond modulation decoupling: Phenanthro[1,2-b]thiophene

Long range heteronuclear chemical shift correlation has become an extremely useful technique for complex spectral assignment and structure elucidation. The sensitivity is higher than that afforded by ¹³C-¹³C double quantum INADEQUATE experiment. The long range heteronuclear correlation provides the means of establishing connectivities across heteroatoms. Early attempts to use long range heteronuclear chemical shift correlation by simply optimizing the delays for long range couplings met with varied success. Long range coupling responses to protonated carbon resonances can be modulated by the one bond coupling of the protonated carbon. These modulations can lead to precipitous valleys in the response curve and a corresponding loss of connectivity information. A newly reported pulse sequence employing a BIRD pulse midway through the Δ₂ refocusing delay “decouples” one bond modulation effects substantially increasing the likelihood of observing the desired connectivities. The application of this technique is reported for phenanthro[1,2-b]thiophene. Unequivocal assignment of the title compound is reported using heteronuclear chemical shift correlation and long range correlation with modulation decoupling. The assignment took a total of < 15 hours of spectrometer time.     

Synthesis of the monomethyl isomers of naphtho[1′,2′:4,5]thieno[2,3-c]quinoline

The synthesis of naphtho[1′,2′:4,5]thieno[2,3-c]quinoline ( 11 ) and four monomethyl isomers is described.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 9. Phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline,benzo[f]phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline,and benzo[h]-phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline

The synthesis of three novel polycyclic heterocyclic ring systems are reported via photocyclization. The specific final products in these ring systems are: phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 13 ), benzo[h]-phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 14 ), and benzo[f]phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 15 ).     

Condensed pyridazines. Part III. Rearrangement and ring cyclization during the thermolysis of (z)-methyl 3-(6-azido-3-chloro-1-methyl-4-oxo-1,4-dihydropyridazin-5-yl)-2-methylacrylate

The thermolysis of (Z)-methyl 3-(6-azido-3-chloro-1-methyl-4-oxo-1,4-dihydropyridazin-5-yl)-2-methylacrylate ( II ) provides a new synthetic route to pyrrolo[2,3-c-]pyridazines, specifically, methyl 3-chloro-1,6-dimethyl-4-oxo-1,4-dihydro-7H-pyrrolo[2,3-c]pyridazine-5-carboxylate ( III ) in 91% yield. Treatment of III with ozone provides an entry into the novel pyridazino[3,4-d][1,3]oxazine ring system, specifically, 3-chloro-1,7-dimethylpyridazino[3,4-d][1,3]oxazine-4,5-dione ( IV ) in 73% yield. Compound IV is smoothly hydrolyzed into 6-acetylamino-3-chloro-1-methyl-4-oxo-1,4-dihydropyridazine-5-carboxylic acid ( V ) which is readily recyclized into IV by dehydration with acetic anhydride. Furthermore, IV undergoes a facile reductive ring opening reaction with sodium borohydride to give 3-chloro-6-ethylamino-1-methyl-4-oxo-1,4-dihydropyridazine-5-carboxylic acid ( VI ) in 95% yield.