Total assignment of the 1H and 13C NMR spectra of pyrrolizino-[3,4,5-a,b]isoquinoline,benzo[1,2]pyrrolizino[3,4,5-a,b]isoquinoline and 2-methylthiopyrrolizino[3,4,5-a,b]isoquinoline

The total ¹H and ¹³C nmr spectral assignments of pyrrolizino[3,4,5-a,b]isoquinoline, benzo-[1,2]pyrrolizino[3,4,5-a,b]isoquinoline and 2-methylthiopyrrolizino[3,4,5-a,b]isoquinoline are reported. The concerted use of the COSY, HMQC, HMBC and nOe-difference experiments is used to generate total assignments of the ¹H and ¹³C nmr spectra.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 5. [1]Benzothieno[2,3-c]naphtho[2,1-f]-quinoline and [1]benzothieno[2,3-c]naphtho[1,2-g]quinoline

Two previously unknown heterocyclic ring systems, namely, [1]benzothieno[2,3-c]naphtho[2,1-f]quinoline ( 4 ) and [1]benzothieno[2,3-c]naphtho[1,2-g]quinoline ( 5 ) were synthesized via photocyclization of 3-chloro-N-(2-phenanthryl)benzo[b]thiophene-2-carboxamide ( 8 ) followed by chlorination and dechlorination. The total assignment of their ¹H- and ¹³C-nmr spectra was determined by utilizing inverse-detected HMQC and HMBC two-dimensional nmr spectroscopic methods.     

Proton,carbon-13 and fluorine-19 NMR studies of 9,10,11,12-tetra-fluoro-5,6-dihydrobenzo[b]naphth[2,1-f]oxepin: ‘Through-space’ carbon-fluorine coupling was revealed

The ¹H, ¹³C and ¹⁹F nmr spectra of 9,10,11,12-tetrafluoro-5,6-dihydrobenzo[b]naphth[2,1-f]oxepin ( 1 ) were totally assigned using a combination of two-dimensional nmr techniques. Unequivocal interpretation of the spectral data allowed the complete assignments of the resonances. In addition, the spectra of compound 1 revealed an unusual through-space carbon-fluorine coupling which was further supported by NOE and modeling experiments.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 19. Thieno[3′,2′:4,5]thieno[2,3-c]-naphtho[1,2-f]quinoline,thieno[3′,2′:4,5]thieno[2,3-c]naphtho-[1,2-f][1,2,4]triazolo[4,3-a]quinoline and thieno[3′,2′:4,5]-thieno[2,3-c]naphtho[1,2-f]tetrazolo[1,5-a]quinoline

Photocyclization of 3-chloro-N-(3-phenanthryl)thieno[2,3-b]thiophene-2-carboxamide ( 5 ) yielded only one of the two possible structural isomers, thieno[3′,2′:4,5]thieno[2,3-c]naphtho[1,2-f]quinolin-6(5H)-one ( 6 ), which was further elaborated to afford the unsubstituted ring system 10 , its triazole 11 and tetrazole 12 . The structural confirmation of 10 was achieved by the total assignment of its ¹H and ¹³C nmr spectra by the concerted utilization of two-dimensional nmr spectroscopic methods.     

Synthesis of 6-cyanopyrido[2,3-d]pyrimidinones in the reaction of 6-amino-4-pyrimidinones with arylidene derivatives of malonodinitrile

This paper describes the synthesis of a new series of 7-amino-5-aryl-6-cyano-5,8-dihydropyrido-[2,3-d]pyrimidin-4(3H)-ones 3 from the reaction of 6-amino-4-pyrimidinones 1 with arylidene derivatives of malonodinitrile 2 . The structure of the final compounds was determined on the basis of nmr measurements, especially by ¹H, ¹H-, ¹H, ¹³C COSY, DEPT, HMBC and HMQC experiments.     

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.     

Unusual schmidt rearrangement of 7,7a,8,9,10,12-hexahydro benzo[h]pyrrolo[1,2-b]-isoquinoline-7,10-dione

The reaction of 7,7a,8,9,10,12-hexahydrobenzo[h]pyrrolo [1,2-b]isoquinoline-7,10-dione 2 with sodium azide in sulfuric acid afforded the unexpected cyano derivative 5 . The proposed structure for 5 is supported by ¹³C nmr, ¹H nmr and HMBC spectra.     

Synthesis of spiro[2H-indole-2,1′-1H-isoindole]-3,3′-diones,spiro[1H-isobenzofuran-1,2′-2H-indole]-3,3′-diones and spiro[benzofuran-2,1′-isobenzofuran]-3,3′-diones via transannular reactions of eight membered ring intermediates

An auto oxidation-rearrangement product 4 was isolated from a high dilution reaction of ninhydrin with 3,4,5-trimethoxyaniline in water. A general synthesis of this compound and its derivatives 4–6 was devised by oxidation of tetrahydroindeno[1,2-b]indol-10-ones 1–3 with sodium periodate to give isoindolo[2,1-a]-indole-6,11-diones 4–6 in good yield. Compounds 4–6 can be easily transformed into spiro[1H-isobenzofuran-1,2′-2H-indole]-3,3′-diones 8–10 , spiro[2H-indole-2,1′-1H-isoindole]-3,3′-diones 11–13 and isoindole[1,2-a:2′,1′-b]pyrimidine-5,15-diones 15, 16 in high yields. Analogous reactions were performed on 3-amino-5a, 10a-dihydroxybenzo[b]indeno[2,1-d]furan-10-one ( 17 ) to give a dibenzoxocintrione 18 , spiro-[benzofuran-2,1′-isobenzofuran]-3,3′-dione 19 and an isoindol-1-one 20 .     

The synthesis of benzo[b]phenanthro[d]thiophenes and anthra[b]benzo[d]thiophenes

The synthesis of benzo[b]phenanthro[2, 3-d]thiophene ( 5 ), benzo[b]phenanthro[4, 3-d]thiophene ( 6 ), benzo-[b]phenanthro[2, 1-d]thiophene ( 9 ), benzo[b]phenanthro[3, 2-d]thiophene ( 14a ), anthra[1, 2-b]benzo[d]thiophene ( 24 ), anthra[2, 3-b]benzo[d]thiophene ( 29 ) and anthra[2, 1-b]benzo[d]thiophene ( 30 ) is described as well as the preparation of 13-methylbenzo[b]phenanthro[3, 2-d]thiophene ( 14b ).     

Heterocyclizations in the pyrido[2,3-b]pyrazine series

In this paper, we report the results of heterocyclizations in the pyrido[2,3-b]pyrazine series to give the pyrido[2,3-e] or [3,2-e]pyrrolo[1,2-a]pyrazine. The Clauson-Kaas reaction on 2,3-diaminopyridine is investigated; regioselectivity on the 3-amino group is shown by ¹H- and ¹³C-nmr. Synthesis and reactivity of the original pyrazino[2,3-g]indolizine series is also reported.     

Chemistry of thienopyridines. XXXVI. Further studies on nitration in the thieno[2,3-b]- and thieno[3,2-b]pyridine systems

Three compounds, thieno[3,2-b]pyridine 4-oxide, 7-nitrothieno[3,2-b]pyridine 4-oxide ( 1 c), and 6-cyano-thieno[2,3-b]pyridine, undergo nitration by means of a mixture of nitric and sulfuric acids to yield 3,7-dinitro-thieno[3,2-b]pyridine (3%), 3,7-dinitrothieno[3,2-b]pyridine 4-oxide ( 1d ) (26%), and 6-carbamoyl-5-nitrothieno[2,3-b]pyridine ( 6b ) (11%), respectively. Structures of the products were ascertained by spectral means, notably infrared, ¹H nmr, and ¹³C nmr. It is proposed that 1d exists (at least in part) as a tricyclic structure and that 6b may result from an intramolecular mechanism of nitration. An attempt to de-N-oxygenate 1c with excess triphenylphosphine removes more than one oxygen atom per molecule (as triphenylphosphine oxide) without producing an identified thienopyridine product.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 11. Synthesis and total assignment of the 1H and 13C NMR spectra of isomeric benzothienonaphthoquinolines using multiple inverse detected two-dimensional NMR methods

Two novel heterocyclic ring systems, namely, [1]benzothieno[2,3-c]naphtho[1,2-f]quinoline and [1]benzothieno[2,3-c]naphtho[2,1-g]quinoline have been synthesized and characterized by inverse detected two-dimensional nmr methods. Unequivocal total assignments of the proton and carbon nmr spectra were made through the concerted utilization of HMQC (Heteronuclear Multiple Quantum Correlation) and a combination of HMBC (Heteronuclear Multiple Bond Correlation) and HMQC-TOCSY (HMQC with proton TOtal Correlation Spectroscopy).     

The synthesis of novel polycyclic heterocyclic ring system via photocyclization. 18. Benzo[h]naphtho-[1′,2′:4,5]thieno[2,3-c]quinoline and benzo[h]naphtho-[1′,2′:4,5]thieno[2,3-c] [1,2,4]triazolo[4,3-a]quinoline

The synthesis of two previously unknown polycyclic ring systems, benzo[h]naphtho[1′2′:4,5]-thieno[2,3-c]quinoline ( 1 ) and benzo[h]naphtho[1′,2′:4,5]thieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline ( 2 ), was achieved via oxidative photocyclization of 1-chloro-N-(1-naphthyl)naphtho[2,1-b]thiophene-2-carboxamide ( 5 ). The total assignment of their ¹H and ¹³C nmr spectra was determined by the concerted use of two-dimensional nmr methods.     

Synthesis of anthra[b]thiophenes and benzo[b]naphtho[d]thiophenes

All isomers of the parent anthra[b]thiophenes and benzo[b]naphtho[d]thiophenes, namely anthra[2,3-b]thio-phene, anthra[2,1-b]thiophene, anthra[1,2-b]thiophene, benzo[b]naphtho[2,3-d]thiophene, benzo[b]naphtho[2,1-d]thiophene and benzo[b]naphtho[1,2-d]thiophene were synthesized using a new procedure.     

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.     

Synthesis of 3-aryl-6H-isoxazolo[3,4-d]pyrazolo[3,4-b]pyridines and 3-aryl-6H-isoxazolo[5,4-d]pyrazolo[3,4-b]pyridines

The synthesis and characterization of a number of 3-aryl-6H-isoxazolo[3,4-d]pyrazolo[3,4-b]pyridines and 3-aryl-6H-isoxazolo[5,4-d]pyrazolo[3,4–6]pyridines from common precursors, 5-benzoyl-4-chloro-1H-pyrazolo-[3,4-b]pyridines, has been described. The structures were determined by unambiguous chemical synthesis and by isolation and ¹³C nmr analysis of some key, isolated, intermediates. The ability of these compounds to displace [3H]flunitrazepam from CNS binding sites was also observed.     

Synthesis of substituted dihydrobenzo[f]pyrimido[4,5-b]-quinolines as tetracyclic 5-deaza nonclassical folates

Cyclocondensation of 2,4,6-triaminopyrimidine ( 10 ) with chlorovinyl aldehyde 7 afforded the linear regioisomer 9,1 1-diamino-5,6-dihydrobenzo[f]pyrimido[4,5-c]quinoline ( 1 ) while the cyclocondensation of 2,6-diamino-4-hydroxypyrimidine ( 11 ) or 6-amino-2,4-dihydroxypyrimidine ( 12 ) with chlorovinyl aldehyde 7 was regiospecific affording the linear regioisomers 9-amino-11-oxo-5,6-dihydrobenzo[f]pyrimido[4,5-c]quinoline ( 2 ) and 9,11-dioxo-5,6-dihydrobenzo[f]pyrimido[4,5-c]quinoline ( 3 ) respectively. The linear structures of these compounds were established by ¹H nmr and ¹³C nmr spectral data.     

Nitration of dithieno[3,4-b:3′,2′-d]pyridine and dithieno[2,3-b:3′,2′-d]pyridine

The nitration of dithieno[3,4-b:3′,2′-d]pyridine ( 2 ) and dithieno[2,3-b:3′,2′-d]pyridine ( 3 ) has been studied. Nitration of 2 occurred in both positions of the c-fused thiophene ring, while 3 was predominantly substituted in the 2-position. The structures of the nitro derivatives were proven by extensive use of ¹H and ¹³C nmr spectroscopy.     

Nitration of dithieno[3,2-b:3′,2′-d]pyridine and dithieno[3,2-b:3′,4′-d]pyridine

Nitration of dithieno[3,2-b:3′,2′-d]pyridine ( 4 ) and dithieno[3,2-b:3′,4′-d]pyridine ( 5 ) has been studied. Nitration of 4 occurred in both positions of the C ring, while 5 was predominantly substituted on the 3,4-fused ring. The structures of the nitro derivatives were proven by extensive use of ¹H and ¹³C nmr spectroscopy.     

Study of Friedel-Crafts acetylation of indolobenzo[b]furans,indolobenzo[b]thiophenes,pyrrolocarbazole, and pyrrolophenothazine dioxide by1H NMR spectroscopy

The reactivity towards Friedel-Crafts acetylation of the new heterocyclic systems indolo[5,6-d]- and indolo[5,4-d]benzo-[d]furans, 3H pyrrolo[2,3-c]carbazole, indolo[7,6-d]-, indolo[4,5-d]- and indolo[5,4-d]benzo-[b]thiophenes and 3H-pyrrolo[2,3-c]phenothiazine-11,11-dioxide have been studied. Under acid conditions these heterocycles behave like indole to give dimerization products, but anomalies were observed in a number of cases. These principles have been established by detailed analysis of the ¹ H NMR spectra of the reaction products. Georgian Technical University, Tbilisi 380075. D. I. Mendeleev Russian Chemical Technological University, Moscow 125047. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1078–1091, August, 1995. Original article submitted June 12, 1995.