Quinazolines and 1,4-benzodiazepines. XLVI. Photochemistry of nitrones and oxaziridines

The cyclic nitrones 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5a ) and 1,3-dihydro-7-methylthio-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5b ) are photoisomerized to readily isolable oxaziridines, 7-chloro-4,5-epoxy-5-phenyl-1,3,4–5-tetrahydro-2H-1,4-benzodiazepin-2-one ( 6a ) and 4,5-epoxy-5-phenyl-1,3,4,5-tetrahydro-7-methylthio-2H-1,4-benzo-diazepin-2-one ( 6b ). Oxaziridine 6b upon further irradiation gave ring expansion and ring contraction products, 4,6-dihydro-2-phenyl-9-methylthio-5H-1,3,6-benzoxadiazocin-5-one ( 7b ) and 4-benzoyl-3,4-dihydro-6-methylthioquinoxalin-2(1H)-one ( 8b ) respectively. The ring contraction product, 4-benzoyl-6-chloro-3,4-dihydroquinoxalin-2(1H)-one ( 8a ), was obtained from irradiation of oxaziridine 6a .     

Homo-1,4-addition to cyclo-octa-1,4-diene and cyclohepta-1,4-diene

Cyclo-octa-1,4-diene and cyclohepta-1,4-diene give the bicyclic derivatives IIa–b and IVa–b on reaction with Br₂-CCl₄ or I₂-AgClO₄-MeOH respectively. Cyclo-octa-1,4-diene also undergoes homo-1,4-addition in the Prevost reaction with I₂-AgOAc or I₂-AgOCOPh in benzene.     

Saturated heterocycles. Part 216 . Synthesis,structure and ring opening of trans-perhydro-1,4-benzoxazepin-3-one derivatives

trans-Perhydro-1,4-benzoxazepin-3-ones 2a-c were synthesized and transformed to condensed-skeleton perhydro-trans-1,4-benzoxazepines 3a,b , the thiones 4a,b , the urea derivatives 5a,b , and N-acylated compounds 6a-e . Compounds 6b,d were ring-opened by hydrochloric acid in ethanol to yield trans-2-(1-carbethoxyethoxy)-1-acylaminomethylcyclohexane derivatives 7b,d . The ¹H- and ¹³C-nmr investigation and X-ray analysis of 5b and 6c,d proved that the expected N-acylated derivatives were formed and that both rings of the trans anellated compounds have a chair conformation.     

The non-aqueous reactions of some 1,4-benzodiazepines.

The data presented for the behavior of 3-hydroxy-1,4-benzodiazepines during non-aqueous titrations indicate that: (a) the First stage protonation during titration as a base with perchloric acid occurs at the N—4 position and is relatively unaffected by substitution at the 3-position, except when the substituent is electron-withdrawing; (b) deprotonation during titration as an acid with tetrabutylammonium hydroxide occurs at the N-1 position rather than at the 3-OH substituent; (c) the similarity of the u.v. spectra of neutral and basic solutions of lorazepam indicate that a tautomerism in basic solution postulated previously does not occur to any great extent; and (d) titration with tetrabutylammonium hydroxide should be acceptable as an assay method tor lorazepam.     

Polycondensed nitrogen heterocycles. VII. 5,6-Dihydro-7-h-pyrrolo[1,2-D]-[1,4] benzodiazepin-6-ones. A novel series of annelatcd 1,4-benzodiazepines

The synthesis of a novel class of annelated 1,4-benzodiazepinen, the 2-R-3 methyl-5,6-dihydro-7H-pyrrolo[1,2-d][1,4]benzodiazepin-6-ones (Ve-e), is described. The reaction of 2-(o-aminophenyl)-3-R-5-methylpyrroles(IIIa,b) with bromoacetyl bromide in the presence of triethylamine produced the title compounds. An alternative synthetic route was achieved by means of the reactions of 1a,b with the appropriated α-aminoacids. The catalytic reduction of IVe-e over 10% palladium on charcoal led in good to excellent yields directly to the formation of pyrrolo[1,2-d]-[1,4]benzodiazepines (Ve-e).     

Electronic excitations of 1,4-disilyl-substituted 1,4-disilabicycloalkanes: a MS-CASPT2 study of the influence of cage size

We present a multistate complete active space second-order perturbation theory computational study aimed to predict the low-lying electronic excitations of four compounds that can be viewed as two disilane units connected through alkane bridges in a bicyclic cage. The analysis has focused on 1,4-disilyl-1,4-disilabicyclo[2.2.1]heptane (1a), 1,4-bis(trimethylsilyl)-1,4-disilabicyclo[2.2.1]heptane (1b), 1,4-disilyl-1,4-disilabicyclo[2.1.1]hexane (2a), and 1,4-bis(trimethylsilyl)-1,4-disilabicyclo[2.1.1]hexane (2b). The aim has been to find out the nature of the lowest excitations with significant oscillator strengths and to investigate how the cage size affects the excitation energies and the strengths of the transitions. Two different substituents on the terminal silicon atoms (H and CH3) were used in order to investigate the end group effects. The calculations show that the lowest allowed excitations are of the same character as that found in disilanes but now red-shifted. As the cage size is reduced from a 1,4-disilabicyclo[2.2.1]heptane to a 1,4-disilabicyclo[2.1.1]hexane, the Si...Si through-space distance decreases from approximately 2.70 to 2.50 A and the lowest allowed transitions are red-shifted by up to 0.9 eV, indicating increased interaction between the two Si-Si bonds. The first ionization potential, which corresponds to ionization from the Si-Si sigma orbitals, is lower in 1b and 2b than in Si2Me6 by approximately 0.9 and 1.2 eV, respectively. Moreover, 1b and 2b, which have methyl substituents at the terminal Si atoms, have slightly lower excitation energies than the analogous species 1a and 2a.     

Stereoselective syntheses of 1,4-dideoxy-1,4-imino-octitols and novel tetrahydroxyindolizidines

A new route for the preparation of four new indolizidines, (1R,2S,6S,7S,8aS)- and (1R,2S,6R,7R,8aS)-1,2,6,7-tetrahydroxyindolizidine (30 and 32) and (1S,2R,7S,8S,8aR)- and (1S,2R,7R,8R,8aR)-1,2,7,8-tetrahydroxyindolizidine (44 and 46), is reported. The synthesis is based on Knoevenagel homologation of the readily available enantiomerically pure pyrrolidin-carbaldehydes 13 and 37followed by asymmetric dihydroxylation of the subsequent alkenyl pyrrolidines and cyclization of the corresponding imino-octitols. The new indolizidines and their precursors (imino-octitols 20, 25, 26) and indolizidinones 28a and 28b have been tested for inhibitory activities toward 26 glycosidases. The enzymatic inhibition of trans-7-hydroxy-d-(-)-swainsonine (44) toward alpha-mannosidases is similar to that described for trans-7-hydroxy-l-(+)-swainsonine (11b) toward naringinase (alpha-l-rhamnosidase from Penicillium decumbens).     

Quinazolincs and 1,4-benzodiazepines. LXXXVI. The synthesis of imidazothienodiazepines and imidazopyrazolodiazepines

The thieno[3,2-e][1,4]diazepin-2-one ( 1a ), the thieno[2,3-e] [ 1,4] diazepin-2-one ( 1b ), the pyrazolo[3,4-e][1,4]diazepin-2-one ( 1c ) and a chloro analog of 1b , compound 1d , were each converted to derivatives of the novel tricyclic ring systems 4H-imidazo[1,5-a]thieno[2,3-f] [1,4]-diazepine, 4Himidazo[1,5a]thieno[2,3f][1,4]diazepine and 4H-imidazo[ 1,5-a]pyrazolo[4,3-f]-[1,4]diazepine. Depending on the substituents desired on the imidazo ring, two different synthetic pathways were employed.     

Novel photoisomerization of 5-chloro-1,4-dihydro-9-methyl-naphthalen-1,4-imine

Direct photolysis of 5-chloro-1,4-dihydro-9-methyl-naphthalen-1,4-imine in cyclohexane gave a mixture of 1-chloronaphthalene and isomeric dihydrocyclobut[b]indoles $\text{5}$ and $\text{6}$. Dihydrocyclobut[b]indoles $\text{5}$ and $\text{6}$ thermally rearranged to give 1-benzazepines $\text{7}$ and $\text{8}$, respectively.     

Some nitro derivatives of 1,4-benzodioxino[2,3-b]pyridine. Crystal and molecular structure of 2,7,8-trinitro-1,4-benzodioxino[2,3-b]pyridine

The electrophilic nitration of 1,4-benzodioxino[2,3-b]pyridine 1 with nitric acid in sulfuric acid has been studied. Some of the products of nitration including 7 - and 8 -nitro derivatives 2a and 2b , respectively, 7,9-, 7,8- and 6,8-dinitro derivatives 3a , 3b and 3c , respectively, and 2,7,8-trinitro derivative 4 have been isolated and characterized. The structure of isomers have been assigned for derivatives 3b and 4 while tentative structures have been proposed for the other products. The cyclopentadienyliron complex of 1 gives the same reaction products under similar conditions while for some other milder nitrating reagents no reaction was observed. 2,7,8-Trinitro-1,4-benzodioxino[2,3-b]pyridine 4 crystallizes in the monoclinic system, space group P2₁/c; the dihedral angle between the planes of outer rings was found to be 174.65(8) degrees. The planes of the nitro groups have been found to be rotated with respect to the appropriate pyri-dine and benzene ring planes by 11.13(11) degrees for the 2-nitro group and 47.56(9) and 29.80(9) degrees for the 7-nitro and 8-nitro groups, respectively.     

Diels-Alder Reactions of 5,8-Ethano-5,8-dihydro-1,4-naphthoquinone with Cyclic Dienes

Diels-Alder cycloadditions of 1,3-cyclohexadiene and cyclopentadiene to π -facially dissymmetric 5,8-ethano-5,8-dihydro-1,4-naphtboquinone (1) were examined. The stereochemical outcome of the reactions, determined by a combination of chemical and spectral methods, indicates that addition of cyclic dienes to 1 occurs preferentially at the face syn to the etheno-bridge of 1. Cycloadducts 7a/7b and 8a/8b obtained from Diels-Alder reactions of 1 with cyclopentadiene and 1,3-cyclohexadiene undergo [2+2]-photocyclization to give caged compounds 9a/9b and 10a/10b , respectively. Stereoselective reduction of the enedione double bond in 7a/7b and 8a/8b with aqueous TiCl₃ in acetone affords cis-bis-bicyclic ring-fused 1,4-cyclo-hexadiones 11a/11b , and 12a/12b , respectively.     

Trimethylsilylcyanid als Umpolungsreagens,VI. Anionische 1,4- O→C-Silylgruppen-Umlagerung

Trimethylsilyl Cyanide — A Reagent for Umpolung, VI. Anionic 1,4-O→C-Silyl Group Rearrangement The adducts 6 from substituted acroleins 5a – f and trimethylsilyl cyanide form the anions 6 _A on deprotonation at −78°C, which are silylated by trimethylsilyl chloride to 7 or (and) 8 in positions 3 or (and) 1. On warming up to room temperature, 6a _A and 6b _A undergo smoothly 1,4-O→C-silyl group rearrangements to form 13a _A and 13b _A which can be trapped by silylation. 6c – d _A decompose on warming up. Triethylsilyl instead of trimethylsilyl groups decelerate the rearrangement appreciably. Structure and configuration of the different products are determined.     

Novel 1,4-dihydropyridine calcium antagonists. I. Synthesis and hypotensive activity of 4-(substituted pyridyl)-1,4-dihydropyridine derivatives

A series of 4-(substituted pyridyl)-1,4-dihydropyridine derivatives were synthesized and their hypotensive effects examined. Several compounds, 2-(N-benzyl-N-methylamino)ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitro-2-pyridyl)-3,5-pyridinedicarboxylate (2b), its 4-(4-nitro-2-pyridyl) analogue (2g), 4-(3-trifluoromethyl-2-pyridyl) analogue (2c), 4-(2-trifluoromethyl-3-pyridyl) analogue (3e), 4-(4-cyano-2-pyridyl) analogue (2e), 4-(2-cyano-3-pyridyl) analogue (3d), and 4-(6-bromo-2-pyridyl) analogue (2i), were found to have a hypotensive activity parallel to that of nicardipine; 2c and 3e, in particular, had approximately twice the duration of nicardipine, and 2e had the most potent hypotensive activity of all the derivatives synthesized.     

Design and synthesis of novel tricycles based on 4H-benzo[1,4]thiazin-3-one and 1,1-dioxo-1,4-dihydro-2H-1lambda6-benzo[1,4]thiazin-3-one

This paper reports our recent efforts to develop novel tricycles based on 4H-benzo[1,4]thiazin-3-one ( 2) and 1,1-dioxo-1,4-dihydro-2H-1lambda(6)-benzo[1,4]thiazin-3-one (3) using 1,5-difluoro-2,4-dinitrobenzene (1). All of these tricycles integrate two privileged structures into one skeleton, including 3,8-dihydro-5-thia-1,3,8-triaza-cyclopenta[b]naphthalene-7-one (4, 10, 12), 5,5-dioxo-3,5,6,8-tetrahydro-5lambda(6)-thia-1,3,8-triaza-cyclopenta[b]naphthalene-7-one (5, 11), 3,8-dihydro-5-thia-1,2,3,8-tetraaza-cyclopenta[b]naphthalene-7-one (6), 5,5-dioxo-3,5,6,8-tetrahydro-5lambda(6)-thia-1,2,3,8-tetraaza-cyclopenta[b]naphthalene-7-one (7), 3,8-dihydro-1H-5-thia-1,3,8-triaza-cyclopenta[b]naphthalene-2,7-dione (8), and 5,5-dioxo-3,5,6,8-tetrahydro-1H-5lambda(6)-thia-1,3,8-triaza-cyclopenta[b]naphthalene-2,7-dione (9). A typical library of scaffold 5 was synthesized in a parallel solution-phase manner and analyzed by HPLC-UV-MS or HPLC-UV-ELSD method.     

Polyesters derived from 1,4-oxathian-2-ones

1,4-Oxathian-2-one ( 1a ) was prepared in high yield by oligomerization of methyl(2-hydroxyethyl)mercaptoacetate ( 3 ) followed by catalytic depolymerization in vacuo. A similar sequence starting with methyl(2-hydroxyethyl)sulfonylacetate ( 5 ) afforded the corresponding sulfone, 1,4-oxathian-2-one-4,4-dioxide ( 1c ), however, 1,4-oxathian-2-one-4-oxide ( 1b ) could not be obtained by this procedure. Ring opening melt polymerization of 1a and 1c afforded low molecular weight crystalline polyesters 2a and 2c . Oxidation of 2a with m-chloroperoxybenzoic acid produced the corresponding polyester 2b containing sulfoxide groups. Thermogravimetric analyses and visual observations indicated 2b to be thermally unstable relative to 2a and 2c .     

Dilute-solution properties of trans-1,4-polyisoprene

Trans-1,4-polyisoprene was fractionated by both fractional precipitation and preparative gel permeation chromatography to obtain possibly sharp fractions of narrow molecular weight distribution. Selected fractions were characterized by light scattering, viscosity, and gel permeation chromatography. Necessary corrections for molecular heterogeneity were applied. Some of the characteristic relations between [η] and M _w are [η] = 1.81 × 10^?4 M in benzene at 30°C, [η] = 1.38 × 10^?4 M in n-hexane at 30°C, which are found to be in good agreement with literature data when corrected for molecular heterogeneity.     

Linchpin construction of unsymmetrical 1,4-alkynediols

A one-pot preparation of unsymmetrical 1,4-alkynediols such as 2a by the coupling of trimethylsilylacetylene and two different aldehydes or ketones is reported. The dilithiated species 5 is generated by the sequential addition of the first aldehyde or ketone 1b to a solution of lithium trimethylsilylacetylide, followed by the addition of methyllithium, which removes the trimethylsilyl protecting group. Addition of the second aldehyde or ketone then leads to the unsymmetrical 1,4-alkynediol 2a.     

Zur synthese von 3,4-dihydro-2H-1,4-benzoxazin-2- und 3-carbonitrilen. II. Mitteilung über studien zur chemie der 1,4-oxazine

Reaction ofo-aminophenols la, lb and lc with alkeyl dibromopropionates selecrively leads to 2-substitured dihydro-1,4-benzoxazines. This high regioselectivity is explained by initial elimination of hydrogen bromide from the dibromopropionate to from a reactive Michael acceptor, which cyclized to the benzoxazines 3a, 3b and 3c after Michael addition to the amines 1. This mechanism is proven by reaction of the amines la-ld with the Michael acceptor 15 to yield the 2-carbonitriles 16a-l6d. Substitution of the methoxyl group in 18 by cyanide leads to the 3-carbonitrile 19.     

Photolysis of 2-amino- and 2-methylamino-1,4-naphthoquinone

Pyrex-filtered sunlight irradiation of solutions of 2-amino-1,4-naphthoquinone unexpectedly failed to produce cyclobutane dimers. Irradiation in acetic anhydride led to the formation of the trimeric 6-[3'-amino-2'-(1,4-naphthoquinonyl)]-dibenzo[b,h]carbazole-5,13:7,12-diquinone as well as 3,3'-diaraino-2,2'-bi-1,4-naphthoquinonyl and diben=zo[b,h]carbazole-5,13;7,12-diquinone. Similar treatment of 2-methyl=amino-1,4-naphthoquinone afforded 6-[3'-methylamino-2'-(1,4-naphthoqui=nonyl)]-dibenzo[b,h]carbazole-5,13:7,12-diquinone and 6-methyl-dibenzo=[b,h]carbazole-5,13:7,12-diquinone.     

Synthesis of Dibutadienyl Piperazines, 1,1-Dithio and 1,4-Dithio Substituted Dienes from Nitrodienes

Nitrodiene 1a , 1b reacted with 1,4-dithiolbutan and gave the heterocyclic compounds 3a , 3b . 1b gave with 1,3-acetonedithiol the compound 5b . The nitrodiene compound 1b reacted with o-dithiolbenzene ( 6 ) and yielded the ketene dithioacetal ( 7b ). Heterocyclic compounds 11a , 11b , 12a , and 12b were prepared from the reactions of 9a with 2,2'-oxydiethanethiol. The compounds 9a , 9b were prepared from 2-nitropentachloro-1,3-butadiene and alkylthiols ( 8a , 8b ). Mono(thio) substituted diene compound 9b gave dibutadienyl piperazine 14b with piperazine in diethylether.