Assignment of the 1H- and 13C-NMR spectra of congested helicenes using two-dimensional NMR methods: Phenanthro[3′,4′:3,4]phenanthro[2,1-b]thiophene

Phenanthro[3′,4′:3,4]phenanthro[2,1-b]thiophene has been prepared and its highly congested proton and carbon nmr spectra assigned. The nmr assignments required concerted utilization of two-dimensional nmr techniques which included: COSY, direct and long range optimized heteronuclear chemical shift correlation and heteronuclear relayed coherence transfer.     

Benzannelated analogs of phenanthro[1,2-b]- and [2,1-b]thiophene: Synthesis and structural characterization by two-dimensional NMR and X-ray techniques

Syntheses of benzo[3,4]phenanthro[1,2-b]thiophene, benzo[3,4]phenanthro[2,1-b]thiophene and their 1-methyl analogs are reported as potential constituents of solvent refined coal liquids and for mutagenicity testing. The attempted synthesis of the 13-methyl analogs which gave the 11-methyl isomers is also described. Total assignments of the ¹H- and ¹³C-nmr spectra based on long range optimized heteronuclear protoncarbon two-dimensional chemical shift correlation are reported. Carbon assignments obtained for benzo[3,4]-phenanthro[1,2-b]thiophene using this approach were confirmed with a 125 MHz ¹³C–¹³C INADEQUATE spectrum. X-Ray crystal structures were determined for benzo[3,4]phenanthro[1,2-b]thiophene and 1-methyl-benzo[3,4]phenanthro[2,1-b]thiophene. Both molecules were helically distorted from planarity. Close intramolecular contacts between the bay region H1–H13 and ClMe-H13 of 2.03 and 2.28 Å, respectively, were responsible for the distortions. There were no close intermolecular contacts of <3.5Å. both molecules refined to an R value of <0.05.     

Assignment of the 13C-NMR spectrum of phenanthro[4,3-A]dibenzothiophene through the utilization of two-dimensional relayed coherence transfer and double quantum coherence spectroscopy

Total assignment of the ¹³C-nmr spectrum of the helical molecule phenanthro[4,3-a]dibenzothiophene at 125.762 MHz is reported. Assignments were made by the combined application of ¹³C-¹³C autocorrelated double quantum coherence and heteronuclear relayed coherence transfer (RELAY) experiments.     

The synthesis of naphtho[1,2-b]thiophene and all of the eight isomers of monomethylnaphtho[1,2-b]thiophene

The synthesis of naphtho[1,2-b]thiophene and all of the eight monomethylnaphtho[1,2-b]thiophene isomers is described.     

2,3-Dihydronaphtho[1,2-b]thiophene 1-oxides in the synthesis of 2,3-dihydronaphtho- and naphtho[1,2-b]thiophenes

2,3-Dihydronaphtho[1,2-b]thiophene 1-oxides, obtained by thermolysis of alkyl 1-naphthyl sulfoxides, are reduced by lithium aluminum hydride to 2,3-dihydronaphtho [1,2-b]thiophenes, whereas under the influence of acetic and trifluoroacetic anhydrides they form naphtho[1,2-b]thiophenes.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1629–1633, December, 1989.     

Synthesis of fluorantheno[1,2-b]thiophene and fluorantheno[3,2-b]thiophene,isosteres of benzofluoranthenes

The total syntheses of fluorantheno[1,2-b]thiophene and fluorantheno[3,2-b]thiophene are reported. The common cyclobutanone intermediate which was obtained by [2 + 2] addition of fluorenylidene ketene with 2,3-dihydrothiophene underwent regioselectively α or β ring opening to lead to linear or angular PAC skeleton molecules under desired conditions. 2,3-Dichloro-5,6-dicyanobenzoquinone was applied for aromatization to achieve the formation of PAC's. These two isosteres exhibit very similar uv/visible spectra to benzo[a] and [b]fluoranthenes respectively. Spectroscopic data used for their structural assignments is also discussed.     

Studies on polycyclic thiaarenes: Part II. An improved synthesis of phenanthro[1,2-b]thiophene and a synthesis of acenaphtho[1,2-b]naphtho-[2,3-d]thiophene,a novel polynuclear thiaarene

An improved synthesis of phenanthro[1,2-b]thiophene ( 6 ) from 1-chloro-3,4-dihydrophenanthrene-2-aldehyde ( 2 ) by condensation with thioglycolate followed by hydrolysis, decarboxylation and dehydrogenation is described. A new polycyclic thiophene derivative 14 has also been prepared from acenaphthothiophene ( 7 ) by Friedel-Craft's reaction with phthalic anhydride followed by lactonisation of the keto carboxylic acid 9 and then reduction and finally cyclisation of the resultant aldehyde 13 .     

Synthesis of 1H-[1,2]diazepino[4,5-b]indole derivatives

A synthesis of four 1H-[1,2]diazepino[4,5-b]indole derivatives and some preliminary information about their biological activity are presented. The starting materials were 2-ethoxycarbonylindoles and 2-ethoxy-carbonyl-3-formylindoles, la, b and 2a, b, respectively. 2-Ethoxycarbonyls la, b reacted with 1-dimethylamino-2-nitroethylene and -2-ethoxycarbonyl-3-formylindoles 2a, b in the presence of nitroalkanes (nitromethane or nitroethane) giving 3-(2-nitrovinyl)indoles 3a, b. Reduction of 3a, b yielded β-(2-oxoalkyl)indoles 4. On reaction with an excess of hydrazine hydrate, compounds 4 gave satisfactory yields of 5-oxo-1H-[1,2]diazepino[4,5-b]indoles 5.     

13C NMR spectra of some 1,2-disubstitutedN-vinyl-1H-1,2,4-triazoles

¹³C NMR spectra (20 and 75 MHz, in DMSO-d₆) of a series of 1,3-diaryl-3-(1H-1,2,4-triazol-1-yl)- and 1,3-diaryl-2-(1H-1,2,4-triazol-1-yl)prop-2-en-1-ones were registered. It was shown that the chemical shifts of both the carbon atom of the alkene group and C(3) reflect regio- and stereoisomerism of these compounds. Taking this into account the isomeric structures of several 1,3-diaryl-3-(1H-1,2,4-triazol-1-yl)prop-2-en-1-ones were identified and the configurations relative to the double bond of a number of 1,3-diaryl-2-(1H-1,2,4-triazol-1-yl)prop-2-en-1-ones were determined.     

Total assignment of the 1H and 13C NMR spectra of benzo[f][1]benzothieno[2,3-c]quinoline by inverse-detected two-dimensional NMR techniques

The proton and carbon nmr spectra of benzo[f][1]benzothieno[2,3-c]quinoline have been totally assigned using a combination of 2D nmr methods including concerted use of HMQC (heteronuclear multiple quantum correlation) and HMBC (heteronuclear multiple bond correlation) experiments.     

K-region oxides and imines of benzo[b]phenanthro[2,3-d]thiophene and benzo[b]phenanthro[3,2-d]thiophene

The syntheses of the K-oxides and K-imine derivatives of benzo[b]phenanthro[2,3-d]thiophene and benzo-[b]phenanthro[3,2-d]thiophene are described. The parent hydrocarbons 1 and 2 were oxidized with osmium tetroxide and sodium metaperiodate, and the dialdehydes 12 and 18 so formed, cyclized to the corresponding epoxides 1a,12b-dihydrobenz[b]oxireno[9,10]phenanthro[2,3-d]thiophene ( 7 ) and 1a,12b-dihydrobenz-[b]oxireno[9,10]phenanthro[3,2-d]thiophene ( 13 ). Reaction of the oxiranes with sodium azide gave mixtures of azido-alcohols that, in turn, were transformed to the thiaarene imines 1a,12b-dihydro-1H-benz[b]azirino-[9,10]phenanthro[2,3-d]thiophene ( 8 ) and 1a,12b-dihydro-1H-benz[b]azirino[9,10]phenanthro[3,2-d]thiophene ( 14 ), respectively, with the aid of tri-n-butylphosphine.     

Autocorrelated 13c-13c double quantum coherence two-dimensional nmr spectroscopy: Utilization of a modified version of the technique as an adjunct in the total assignment of the 1h- and 13c-nmr spectra of the mutagen phenanthro[3,4-b]thiophene

Development of successively higher field nmr spectrometers has facilitated the study of increasingly more complex molecules, although smaller molecules such as phenanthro[3,4-b]thiophene still offer very substantial assignment problems because of the highly congested nature of their ¹H- and ¹³C-nmr spectra. Assignments of such spectra, if they are to be unequivocal, frequently require the utilization of two-dimensional nmr spectroscopic techniques. Total assignments of the ¹H- and ¹³C-nmr spectra of phenanthro[3,4-b]thiophene are reported. Assignments were based on a conventional high resolution 500 MHz ¹H-nmr spectrum, autocorrelated two-dimensional ¹H-nmr spectra (COSY), two-dimensional ¹H-¹³C chemical shift correlation spectra and a modified version of autocorrelated ¹³C-¹³C double quantum coherence two-dimensional nmr spectroscopy. From NOE measurements, a separation of 1.99 Å between H1 and H11 was computed, suggesting that phenanthro[3,4-b]thiophene has a pronounced helical conformation in solution.     

Synthesis of benzo[3,2]phenanthro[4,5-bcd]thiophene and chryseno[4,5-bcd]thiophene

Benzo[2,3]phenanthro[4,5-bcd]thiophene and chryseno[4,5-bcd]thiophene were synthesized, so that their mutagenic and carcinogenic activity can be determined.     

13C NMR spectra of thieno[2,3-b][1,5]benzodiazepine neuroleptics

The ¹³C NMR spectra of five thieno[2,3-b][1,5]benzodiazepines and two related benzodiazepinones have been recorded at 22.64 MHz using broad band and off-resonance proton decoupling techniques. Spectral interpretation is facilitated by the presence of one (or more) fluorine substituents in the benzo-ring.     

13C NMR spectra of benzo[b]thiophene and 1-(X-benzo[b]thienyl)ethyl acetate derivatives

Carbon-13 chemical shift assignments are reported for benzo[b]thiophene and 1-(X-benzo[b]thienyl)ethyl acetate derivatives, where X=? CH(OAc)CH₃ substituted at positions 2-7. Substituent chemical shift (SCS) effects for the ethyl acetate group are additive at all positions. A substantial upfield shift was observed at C-3, arising from the peri interaction of H-3 and the 4-ethyl acetate substituent. Carbon-13 relaxation times (T₁) and nuclear Overhauser enhancements (η) have been measured for benzo[b]thiophene and its derivatives, and the contributions of dipolar, T^DD₁, and spin rotation, T^SR₁, relaxation have been determined. Intramolecular dipole–dipole interactions are found to provide by far the most important spin-lattice relaxation mechanism whenever protons are bound directly to the carbons under investigation. Nonprotonated ring carbons are relaxed by both DD and SR mechanisms. Anisotropic motion has an easily observable effect on the DD contribution to T₁, and can form the basis for spectral assignments, as in 1-phenylethyl acetate. Long-range ¹³C? ¹H coupling constants were observed both between ring carbons and between ring carbons with ring side-chain hydrogens. These results have been used for the structure determination of the title compounds.     

Complete1H- and13C-NMR spectroscopic assignment of two pentadecapeptides by reverse C,H correlation techniques

Summary Two oligopeptides representing a wild type and a modified version of the polyprotein cleavage region for proteinase2 A of the human rhinovirus type 2 (HRV 22 A) have been investigated using homo- and heterocorrelated 2 D NMR spectroscopy. Proton-detected C,H correlation techniques turned out to be extremely useful for sequential resonance assignment. In one case, the complete amino acid backbone could be analyzed without using NOESY spectra, thus avoiding ambiguities inherent to this method. No defined tertiary structure of the cleavage region could be detected in either molecule. However, one of the oligopeptides is present to a very low extent in a conformation different from therandom-coil arrangement.

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Vollständige¹H- und¹³C-NMR-spektroskopische Zuordnung von zwei Pentadecapeptiden mittels invers detektierter C,H-Korrelationstechniken

Zusammenfassung Zwei Oligopeptide, die die native Spaltregion für die Proteinase2 A des humanen Rhinovirus von Serotyp 2 (HRV 22 A) beziehungsweise eine modifizierte Version repräsentieren, wurden mit Hilfe von homo- und heterokorrelierter 2 D-NMR-Spektroskopie untersucht. Protondetektierte C,H-Korrelationstechniken erwiesen sich als außerordentlich hilfreich bei der sequenziellen Zuordnung. In einem Fall konnte das gesamte Aminosäureskelett ohne Zuhilfenahme von NOESY-Spektren analysiert und damit die dieser Methode inhärenten Unsicherheiten bei der Zuordnung vermieden werden. In keinem der beiden Moleküle konnte eine definierte Tertiärstruktur der Spaltregion ermittelt werden. Eines der beiden Oligopeptide liegt jedoch zu einem sehr geringen Prozentsatz in einer von derrandom-coil Anordnung abweichenden Konformation vor.

     

Low-temperature 1H and 13C NMR spectra of N-substituted 1,2,3,4-tetrahydropyrazino[1,2-a]indoles

The temperature-dependent (1)H and (13)C NMR spectra of 2-(2-butynyl)-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole (4) (as a representative example of 1-9) in CFCl(3) + CD(2)Cl(2) solution are described and discussed. Below 183 K, the hexahydropyrazine ring inversions become slow on the NMR time-scale and 4 exists in principle as two conformational diastereomers. In fact, only one was observed with the N-2 substituent in an equatorial position as shown by a low-temperature NOESY experiment. The energy barrier for conformational interchange was calculated from NMR data to be 8.3 kcal mol(-1) (1 kcal = 4.184 kJ), in agreement with quantum chemical calculations. Unambiguous assignments for all proton and carbon resonances of 1-9 were made using 1D (APT, DEPT, NOE difference) and 2D (COSY, NOESY, gHMQC, gHMBC) NMR techniques.     

Derivatives of benzo[5,6]cyclohepta[1,2-b]thiophene. Synthesis of 2,3,7,8-tetrahydro-3-oxothieno[1,2-b]cyclohepta[5,6,7-de]isoquinoline and 1,2,3,7,8,11b-hexahydro-3-oxothieno[1,2-b]cyclohepta[5,6,7-de]isoquinoline

The synthesis of the title compounds was carried out by cyclization via isocyanate of (E)-4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]-thiophene-10-ylideneacetic acid and 4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]-thiophene-10-ylacetic acid respectively, which were obtained by the Wadsworth-Emmons modification of the Wittig reaction of 4,5-dihydro-10H-10-oxobenzo[5,6]cyclohepta[1,2-b]thiophene and triethyl phosphonacetate. The structures of these new compounds are described.