Low-temperature 15N NMR spectra of reduced 1,3-heterocyclic systems

The ¹⁵N NMR spectra of the O-inside cis-fused conformer of perhydropyrido[1,2-c][1,3]thiazine shows a shielding of the nitrogen of 23.0 ppm relative to the trans-fused conformer. In contrast, ¹⁵N shifts for the cis-and trans-fused conformers of perhydro-oxazolo[3,4-a]pyridine and perhydrothiazolo[3,4-a]pyridine show corresponding shieldings of only 0.6 and 2.5 ppm, respectively.     

Compounds with bridgehead nitrogen. 42—1H NMR and stereochemistry of isomeric 6a-methylperhydroindolo[3,2,1-i,j]benzoxazines and the position of conformational equilibrium in perhydropyrrolo[1,2-c][1,3]oxazine

The ¹H NMR parameters of the NCH₂O protons in the spectrum of perhydropyrrolo[1,2-c][1,3]oxazine show its existence in solution at room temperature in the O-inside cis-fused conformation. rel-(3aS,6aS,6bR,10aS,11aS)-6a-Methylperhydroindolo[3,2,1-i,j]benzoxazine and rel-(3aS,6aS,6bS,10aR,11aS)-6a-methylperhydroindolo[3,2,1-i,j]benzoxazine are shown to adopt cis- and trans-fused conformations, respectively, for the corresponding bicyclic moiety.     

Compounds with bridgehead nitrogen: 46—The 1H NMR spectra and stereochemistry of derivatives of 1,3,3a,4,5,6,6a,11a-octahydroindolo[3,2,1-ij][3, 1]benzoxazine

The ¹H NMR parameters of the NCH₂O protons of the reduced pyrrolo[1,2-c][1,3]oxazine moiety in rel-(3aS,6aS,11aS)-1,3,3a,4,5,6,6a,11a-octahydro-6a-methylindolo[3,2,ij][3, 1]benzoxazine and in the alkaloid rosibiline indicate a trans ring fusion for the grouping. The O-inside cis-fused moiety is present in the related rel-(3aR,6aS,11aS)-octahydro-6a-methylindolo[3,2,1-ij][3, 1]benzoxazine and in Wieland–Gumlich glycol formal.     

Proton magnetic resonance studies of compounds with bridgehead nitrogen: XXVIII—Stereochemical studies with perhydropyrido[1,2-c] [1,6,3]dioxazocines and 2-alkylperhydropyrido[1,2-c] [1,3,6]oxdiazocines

A series of perhydropyrido[1,2-c][1,6,3]dioxazocines and 2-alkylperhydropyrido[1,2-c][1,3,6]oxdiazocines have been prepared. 6-p-Nitrophenyl-3,4-dimethylperhydropyrido[1,2-c][1,6,3]-dioxazodioxazocine is shown to adopt the cis fused ring conformation in solution with the nitrogen lone pair axial with respect to the piperidine ring. The 2-alkylperhydropyrido[1,2-c][1,3,6]oxdiazocines adopt a similar cis fused ring conformation and with increasing steric requirement of the 2-alkyl substituent the 8-membered ring increasingly favours the chair-chair conformation, rather than the chair–boat conformation favoured by the 2-methyl substituted compound.     

Unexpected Direction of Iodocyclization of 3-Allylthio-5-phenyl-4H-1,2,4-triazole

The reaction of 3-allylthio-5-phenyl-4H-1,2,4-triazole with iodine to give a mixture of 5,6-dihydro-5-iodomethyl-3-phenyl[1,3]thiazolo[2,3-c][1,2,4]triazole, 6,7-dihydro-6-iodo-3-phenyl-5H-[1,2,4]triazolo[3,4-b][1,3]thiazine, 5,6-dihydro-6-iodomethyl-2-phenyl[1,3]thiazolo[3,2-b][1,2,4]triazole, and 6,7-dihydro-6-iodo-2-phenyl-5H-[1,2,4]triazolo[5,1-b][1,3]thiazine has been studied. The structure of the products obtained was established using ¹H NMR spectroscopy of their dehydriodination products.     

The stereochemistry of 1,6,7,12b-Tetrahydro-2H,4H-[1,2] oxazino[3′,4′:1,2]-pyrido[3,4-b]indole and of 1,2,3,6,7,12b-Hexahydro-3-methyl-4H-pyrimido[3′,4′:1,2]pyrido[3,4-6] indole

From an analysis of nmr spectral data, 1,6,7,12b-tetrahydro-2H,4H-[1,3 ]oxazino[3′, 4′ :1,2]-pyrido[ 3,4-b ]indole is shown to exist in solution at room temperature almost entirely in the cis-fused ring conformation with the nitrogen lone pair bisecting the C4 methylene group whereas under the same conditions 1,2,3,6,7,12b-hexahydro-3-methyl-4H-pyrimido[3′,4′:1,2] pyrido-[3,4-b ]indole exists as an approximately 50:50 equilibrium mixture of the cis and trans-fused ring conformations.     

Proton magnetic resonance studies of compounds with bridgehead nitrogen atoms: XXXII—The 1H n.m.r. spectra and stereochemistry of 4-aryl-1,6,7,11b-tetrahydro-2H,4H-[1,3]oxazino[4,3-a]isoquinoline, 4-aryl-1,2,6,7,12,12b-hexahydro-4H-[1,3]oxazino[3′,4′:1,2]pyrido[3,4-b]indole and of related systems

cis(4-H,11b-H)-4-Aryl-1,6,7,11b-tetrahydro-2H,4H-[1,3]oxazino [4,3-a]isoquinoline and the related thiazino compound preferentially adopt in solution the O (or S) inside cis-conformation in contrast to cis(1-H,4a-H)-1-arylperhydropyrido[1,2-c][1,3]oxazine which adopts the trans fused conformation. 1-(β-Hydroxy-ethyl)-1,2,3,4-tetrahydro-β-carboline condenses with benzaldehyde to give the 1,3-oxazine derivative rather than the dimeric structure reported in the literature.     

Compounds with bridgehead nitrogen: 45—the 1H NMR spectra and stereochemistry of some dimethylperhydro-oxazolo[3,4-a]pyridines

The positions of conformational equilibria in 1,5-, 1-6- and 1,8-dimethylperhydro-oxazolo[3,4-a]pyridines were determined by ¹H NMR spectroscopy. The cis-(H-5, H-8a)-1,6-dimethyl-perhydro-oxazolo[3,4-a]pyridine. In contrast, r-1,t-6,t-8a-1,6-dimethylperhydro-oxazolo[3,4- a]pyridine preferred the cis-fused conformation. Three of the 1,8-dimethylperhydro-oxazolo[3,4-a]pyridines adopted the trans-fused conformations (with distortion of the system in the case of the r-1,c-8,c-8a derivative) and the r-1,c-8,t-8a-1,8-dimethyl derivative adopted the cis-fused conformation.     

Complete assignment of the 1h- and 13c-nmr spectra of [1]benzothieno[2,3-c]naphtho[1,2-h]quinoline and [1]benzothieno[2,3-c]naphtho[1,2-h][1,2,4]triazolo[4,3-a]quinoline. Concerted use of two-dimensional nmr techniques

The ¹H- and ¹³C-nmr spectra of [1]benzothieno[2,3-c]naphtho[1,2-h]quinoline and [1]benzothieno[2,3-c]-naphtho[1,2-h][1,2,4]triazolo[4,3-a]quinoline were totally assigned using a combination of two-dimensional nmr techniques. After correlation of the proton signals by a COSY spectrum and one-bond heteronuclear correlation, complete assignment of the ¹H- and ¹³C-nmr spectra of the novel heterocyclic compounds required the application of long-range CH coupling information particularly for quarternary resonance assignments and the orientations of individual spin systems relative to one another.     

Compounds with bridgehead nitrogen. 40—Stereochemistry of perhydronaphthaleno[3,4-e]pyrido[1,2c]-[1,3]oxazines

Seven of the possible diastereoisomeric perhydronaphthaleno[3,4-e]pyrido[1,2-c][1,3]oxazines have been synthesized and the configurations and preferred conformations of these assigned on the basis of IR and ¹H NMR spectroscopy and the application of conformational principles.     

Ring distortion effect on δ13C values of bicyclo[4.n.0] alkanes

The ¹³C NMR spectra of trans- and cis-fused bicyclo[4.n.0]alkanes, where n=4, 3 and 2, were determined. The distortion of the six membered ring, which is due to the strain arising from the 1,2 fusion of cyclohexane with a smaller ring, is apparent mainly for the chemical shifts of the ring junction carbons. Both for the trans-and for the cis-fused hydrocarbons the results support a cyclohexane in a chair conformation, distorted to a different degree according to the size of the other ring. The geometries of the different compounds in the series were calculated.     

Proton magnetic resonance studies of compounds with bridgehead nitrogen atoms—XXIV: The stereochemistry of octahydroimidazo [1,5-a] pyridine and of some N-acetyloctahydroimidazo [1,5-a] pyridines

Octahydroimidazo[1,5-a]pyridine is shown to preferentially adopt the trans-fused ring conformation in solution at room temperature. The NMR spectra of the rotational isomers of some N-acetyloctahydroimidazo[1,5-a]pyridines and N-acetyloctahydro-1H-pyrido[1,2-c]pyrimidine are described, and the stereochemistry about the N-acetyl bonds and the cis or trans nature of the ring fusion defined.     

Synthesis and Transformations of 2-R-5-Aryl-5,6-dihydro-7H-[1,2,4]-triazolo[5,1-b][1,3]thiazin-7-ones

A new procedure for preparation of 2-R-5-aryl-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by condensation of 5-R-1,2,4-triazole-3-thiones with 3-arylacryloyl chlorides was developed. The thiazine ring of the [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones is easily cleaved by treating with ammonia and hydrazine affording amides and hydrazides of 3-aryl-3-(1H-1,2,4-triazol-5-ylsulfanyl)propanoic acids. The latter react with isothiocyanates furnishing carbamoyl thiohydrazides of 3-aryl-3-(1H-1,2,4-triazol-5-ylsulfanyl)propanoic acids that in alkaline media undergo cyclization into 4-aryl-5-[2-(4H-1,2,4-triazol-5-ylsulfanyl)-2-phenylethyl]-2,4-dihydro-3H-1,2,4-triazole-5-thiones.     

(8,9-Dihydro-7H-imidazo[1,2-c][1,3]diazepin-5-yl)-cyanamide und homologe imidazo-bizyklen

The reaction of the 2-(ω-aminoalkyl)imidazoles 4a-f with N-cyanodi-phenylimidocarbonate ( 7 ) leads to appropriately hydrogenated imidazo-[1,5-a]imidazoles, imidazo[1,2-c][1,3]diazepines and imidazo[1,2-c][1,3]diazocines ( 9a-f ), which are similar to (7,8-dihydroimidazo)[1,2-c]pyrimidin-5-yl)cyanamides ( 3 )[1] in respect to their chemical and spectroscopic properties.     

Proton magnetic resonance studies of compounds with bridgehead nitrogen atoms—XIX Configurational and conformational studies with derivatives of hexahydropyrido [2,1-c][1,4]oxazin-4(3H)-ones

A series of substituted hexahydropyrido [2,1-c][1,4]oxazin-4(3H)-ones has been prepared by reaction of the sodio derivative of the appropriate piperidyl carbinol with ethyl chloroacetate. From a study of their NMR spectra the configurations of these compounds have been assigned and the conformation of the perhydro-1, 4-oxazinone moiety shown to be that with the ring oxygen atom and the angular hydrogen on the same side of the plane defined by C3? C(O)? N. The synthesis and NMR spectra of hexahydro-2H-pyrido [1,2-d][1,4]oxazepin-5(4H)-one, 1,6,11,11a-tetrahydro [1,4]-oxazino [4,3-b]isoquinolin-4(3H)-one and of hexahydropyrido [2,1-c][1,4]thiazin-4(3H)-one are also discussed. cis-6,9a-H-6-Methyl-hexahydropyrido[2,1-c][1,4]oxazin-4(3H)-one is shown to exist in a conformation containing a deformed perhydropyridine ring.     

Tricyclic heteroaromatic systems. 1,2,3,4-tetrahydropyrazolo[4,3-c][l]benzazepin-1-ones as potential antitumor agents

The synthesis of 1,2,3,4-tetrahydropyrazolo[4,3-c][1]benzazepin-1-ones 1 and that of its 10-methyl derivative 2 is reported. The preparation of the latter from 3-(2-aminobenzyl)3-pyrazolin-5-one and triethyl ortho-formate gave as the main product a derivative of the new tricyclic ring system, pyrazolo[1,5-c][1,3]benzo-diazepine. The structures of the new compounds synthesized were assigned by means of a ¹³C nmr study.     

Synthesis of derivatives of pyrazolo[1,5-a]pyrrolo[1,2-c][1,3,6]-benzotriazocine,a new class of compounds with potential CNS activity

The synthesis of derivatives of pyrazolo[1,5-a]pyrrolo[1,2-c][1,3,6]benzotriazocine was obtained by the reaction of arylaldehydes with some 1-(2-aminophenyl)-5-(pyrrol-1-yl)pyrazoles, as hydrochlorides. Characterization of this new class of compounds was effected with ir, pmr and ¹³C nmr spectral data.     

A Facile Synthesis of Oxoindenothiazine and Dioxospiro(indene‐2,4′‐thiazine) Derivatives from (Substituted ethylidene)hydrazinecarbothioamides

(E)‐2‐[2‐(1‐Substituted ethylidene)hydrazinyl]‐5‐oxo‐9b‐hydroxy‐5,9b‐dihydroindeno[1,2‐d][1,3]‐thiazine‐4‐carbonitriles and (E)‐5‐oxo‐[(E)‐(1‐substituted ethylidene)hydrazinyl]‐2,5‐dihydroindeno[1,2‐d][1,3]thiazine‐4‐carbonitriles have been obtained from the reaction of 2‐(substituted ethylidene)hydrazinecarbothioamides with 2‐(1,3‐dioxo‐2,3‐dihydro‐1H‐inden‐2‐ylidene)propanedinitrile ( 1 ) in ethyl acetate solution. However, (Z)‐6′‐amino‐1,3‐dioxo‐3′‐substituted‐2′‐[(E)‐(1‐phenylethylidene)hydrazono]‐1,2′,3,3′‐tetrahydrospiro(indene‐2,4′‐[1,3]thiazine)‐5′‐carbonitriles were observed during the reaction of N‐substituted‐2‐(1‐phenylethylidene)hydrazinecarbothioamides with ( 1 ). The structure assignment of products has been confirmed on the basis of ¹H‐, ¹³C‐NMR, and mass spectrometry, as well as theoretical calculations.     

Synthesis and 13C-NMR study of pyrazolo[4,5-c] and pyrazolo[4,3-c benzazepines. III

The synthesis of pyrazolo[4,5-c][1]benzazepin-10-ones 10 and 13 and pyrazolo[4,3-c][1]benzazepin-10-ones 11 and 12 is reported. The structure of compounds 10-13 and that of their parent compounds 2-5 ensues from a ¹³C nmr study.     

Quino[1,2-c]quinazolines. I. Synthesis of quino[1,2-c]quinazolinium derivatives and the related indazolo[2,3-a]quinoline derivatives as analogs of the antitumor benzo[c]phenanthridine alkaloids

9,10-Dimethoxy-1,2,3,4,12,13-hexahydro-1-oxoquino[1,2-c]quinazolinium perchlorate, 1,2,3,4,13,24-hexahydro-1-oxo[1,3]dioxolo[4,5-g]quino[1,2-c]quinazolinium perchlorate, 6-methyl-2,3,9,10-tetramethoxyquino-[1,2-c]quinazolinium perchlorate and 2,3-dimethoxy-13-methyl[1,3]dioxolo[4′,5′:6,7]quino[1,2-c]quinazolinium perchlorate were synthesized as analogs of the potent antitumor benzo[c]phenanthridine alkaloids nitidine and fagaronine. The related 2,3,8,9-tetramethoxyindazolo[2,3-a]quinoline and 2,3-dimethoxy[1,3]dioxolo-[4,5-g]indazolo[2,3-a]quinoline were also synthesized. Further, the novel formation of 6,7-dimethoxy-2-(2-ethylamino-4,5-dimethoxyphenyl)quinoline via reductive alkylation with Raney nickel in refluxing ethanol is also reported.