Imino-bridged heterocycles. VII. N-aminobenzocycloheptapyridinimines

Condensation of anhydrous hydrazine with a variety of benzocycloheptapyridinones led to N-aminobenzocycloheptapyridinimines. Regiospecific ring closures occurred in all the systems investigated.     

Addition reactions of heterocycles. VII. Pyrrole and C-Acetyl-N-phenylnitrilimine

The addition reaction of C-acetyl-N-phenylnitrilimine to pyrrole has been investigated. The products obtained show that the reaction proceeds via two distinct pathways. The 1,3-addition reaction leads to the non-cyclic-adduct III, whereas the 1,3-cycloaddition reaction gives a mixture of regioisomeric Δ₂-pyrroline IV and V, and Δ₁ -pyrroline VI and VII mono-cycloadducts. These latter compounds cannot be isolated because they undergo a further 1,3-cycloaddition reaction leading to the N-substituted bis-adducts X and XI, and to the bis-adduets XII and XIII. The stereochemical assignment for X, XI, XII and XIII is provided by nmr data which suggest also that in X and XI the rotation around the exocyclic N-C bond is relatively slow on the instrument time scale.     

Fused-s-triazino heterocycles. VII. 1,3,5,7,9b-Pentaazaphenalene and 1,3,4,6,8,9b-hexaazaphenalene

Cyclization of 2,6-diaminopyrazine to two new heterocyclic ring systems, 1,3,5,7,9b-pentaazaphenalene and 1,3,4,6,8,9b-hexaazaphenalene is reported.     

Synthesis of new fundamental heterocycles. Part VII. Synthesis of 2-azaxanthene

2-Azaxanthone ( 5 ) has been conveniently prepared by condensation of the morpholine enamine of 1-benzyl-4-piperidone witli salicylaldehyde followed by chromium trioxide oxidation and subsequent aromatization. Lithium aluminum hydride reduction of 5 afforded the new fundamental heterocycle 2-azaxanlhene.     

Preparation,lithiation and transformation of N-(benzotriazol-1-ylmethyl) heterocycles

Indole, carbazole, pyrrole, imidazole, benzimidazole, 2-methyl- and 2-phenylbenzimidazole, and 1, 2, 4-triazole have each been converted into their N-(benzotriazol-1-ylmethyl) derivatives. The pyrrole, indole, and carbazole adducts undergo smooth lithiation at the inter-ring methylene group and subsequent reaction there with electrophiles. For the imidazole, benzimidazole, and triazole systems, lithiations at other molecular positions competed.     

Efficient Synthesis and Antiproliferative Evaluation of New Bioactive N-, P-, and S-Heterocycles

Russian Journal of General Chemistry - Organophosphorus compounds are attractive and fruitful branch of chemistry that includes many tools and methods for easy research and targeted drugs...     

Totally synthetic steroid heterocycles. Part 7.. A facile approach to 16-oxa-D-homoestrogens

In search of biologically active modified steroids, novel 16-oxa-D-homoestrone and -D-homoestradiol 3-methyl ethers were synthesized from 16-oxa-3-methoxy- D -homoestra-1,3,5(10),8,14-pentaen-17a-one. The straightforward synthesis involved stereoselective two-step reduction of the 8,14-diene system. The B/C stereoisomers were also derived from the estrapentaene. The stereostructures of these heterocyclic estrogens were determined on the basis of their spectral data.     

Mass spectral fragmentation patterns of heterocycles. VII . Reinvestigation of fundamental processes in phenothiazines

Electron impact induced fragmentation patterns of simple phenothiazines have been reinvestigated using metastable ion studies, exact mass measurements and deuterated derivatives. Secondary fragmentation processes involving ions m/e 198, 171, 167, 166, 154, 140 and 139 have been clarified. Mechanisms for the release of sulfur (SH· and CSH·) nitrogen (HCN and H₂CN·) containing fragments from phenothiazine molecular ion are proposed based on the deuterium content of the daughter ions obtained from 1,9-dideutenophenothiazine. A revised mechanism for the expulsion of ketene from 10-acetylphenothiazine is suggested based on the fragmentation pattern of the 1,9-dideuterioderivative. The composition of m/e 140 was determined by high resolution measurement to be C₁₀H₆N and not C₁₁H₇ as previously reported.     

Direct N- and C-alkenylation of nitrogen-containing heterocycles with magnesium alkylidene carbenoids

Treatment of magnesium alkylidene carbenoids, which were generated from 1-chlorovinyl p-tolyl sulfoxides with isopropylmagnesium chloride at −78 °C in toluene, with N-lithio nitrogen-containing heterocycles gave N-alkenylated products in moderate to good yields. Also, the reaction of C-lithio indoles, which were generated from N-protected indoles, with magnesium alkylidene carbenoids gave C-2 or C-3 alkenylated products, corresponding to the protective group. The intermediate of these reactions were found to be the alkenyl anion, which could be trapped with electrophiles to give the heterocycles having fully substituted alkenes.     

Studies on the chemistry of O,N- and S,N-containing heterocycles. 3. Synthesis of 1,5-benzothiazepines with potential CNS activity

The synthesis of a series of novel triazolo[3,4-d][1,5]benzothiazepines 6 and 7, obtained from the activated 1,5-benzothiazepine derivatives 3 and carbohydrazides 4, is described. Under mild reaction conditions some intermediates 5 can be isolated.     

Studies on the chemistry of O,N- and S,N-containing heterocycles. 4 . Investigations on the nucleophilic substitution of activated 1,5-benzothiazepines

The reaction of the activated 1,5-benzothiazepine 1a with various amines is studied. In contrast to the phenylsubstituted derivative 1b no ring contraction but nucleophilic substitution is observed. Two novel ring systems 8 and 9 are obtained by nitrosation of 3g and by reaction of 1a with anthranilic acid, respectively.     

Structure of N-(1-silatranylmethyl) and N-(trimethoxysilyl-methyl) derivatives of nitrogen-containing heterocycles according to data of NMR, IR, and UV spectroscopy

The ¹H, ¹³C, ¹⁵N, and ²⁹Si NMR, IR, and UV spectra of N-(1-silatranylmethyl) and N-(trimethoxysilylmethyl) derivatives of nitrogen heterocycles have been studied. The dependence and interrelation of the chemical shifts of ²⁹Si and ¹⁵N nuclei of the silatranyl group in the spectra of N-(1-silatranylmethyl)-substituted nitrogen heterocycles are determined by the nature of the heterocyclic system. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1857–1865, December, 2006.     

Studies on the chemistry of thienoanellated O,N- and S,N-containing heterocycles. 6. Synthesis of some thienoanellated [1,4]benzoxazepines

Substituted thieno[2,3-b][1,4]benzoxazepine derivatives as well as thieno[3,2-b][1,4]benzoxazepine deriva- tives have been synthesized. They are thienoanalogues of loxapine, a potent antipsychotic drug. Research activities concentrate on the preparation of structurally modified compounds of loxapine to minimize its undesirable extrapyramidal symptoms.     

Chemistry of Phosphorus Ylides. Part 36 Reactions of 2-Hydroxyisoindole-, Isoindoline-, and Indane-1,3-Dione With Stable and Active Phosphonium Ylides

Abstract

The stabilized alkylidenephosphoranes namely, acetyl-, benzoyl-, methoxycarbonyl-, and ethoxycarbonyl-methylenetriphenylphosphorane react with 2-hydroxyisoindole-1,3-(2H)dione to give the corresponding isoindoline-ylidenes, along with triphenylphosphane oxide. On the other hand, the reaction of active phosphacumulenes, (N-phenyliminovinylidene)-, and (2-oxovinylidene)-triphenylphosphorane with hydroxyisoindole-, isoindoline-, and indane-1,3-dione afforded phosphanylidenecyclobutylidenes derivatives, together with triphenylphosphane oxide. Mechanisms accounting for the formation of the new products are discussed. The antimicrobial activities for the new compounds are also reported.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Chemistry of Phosphorus Ylides. Part 37. The Reaction of Phosphonium Ylides with Indoles and Naphthofurans. Synthesis of Phosphanylidenes,Pyrans, Cyclobutenes,and Pyridazine as Antitumor Agents

The reaction of the stabilized phosphonium ylides 2a , 2b with indolinones 1a , 1b and naphthofuranone 13 afforded the corresponding propylidene and ethylidene derivatives 4a , 4b , 4c , 4d and 14a , 14b . On the other hand, the active phosphacumulenes 5a , 5b react with compounds 4a , 4b , 4c , 4d by [4 + 2]‐cycloaddition to give the stable phosphanylidene indole pyranones 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h . Although compounds 14a , 14b afforded the naphthofuropyrans 16a , 16b , 16c , 16d and triphenylphosphane. Moreover, the phosphallene ylide 7 react with compounds 4a , 4b , 4c , 4d and 14a , 14b to give phosphanylidenecyclobuteneindoline 9a , 9b , 9c , 9d and naphthalenones 18a , 18b , respectively. In addition, the naphthofuropyridazine 21 was obtained from the reaction of the hydrazone 19 and the phosphacumulene 5a . The antitumor activity of some of the new compounds was evaluated, in vitro, against colon and hepatocellular carcinoma cell lines. They showed values closed to that recorded by the reference drug Doxorubicin.     

Novel polycyclic heterocycles. VII. Synthesis of tetracyclic ketones and derivatives from tricyclic 5,11-dihydrodibenz[b,e][1,4] oxazepines

Michael addition of 5,11-dihydrodibenz[b,e][1,4]oxazepines to acrylonitrile gave 5,11-di-hydrodibenz[b,e][1,4]oxazepine-5-propionitriles, which were converted to the corresponding methyl 5-propionates. Mild alkaline hydrolysis of these esters furnished the key intermediates, the 5,11-dihydrodibenz[b,e] [1,4]oxazepine-5-propionic acids. In the preferred procedure, these propionic acids were cyclized to the tetracyclic ketones in yields of 60-90%, by the action of one equivalent of trifluoroacetic anhydride in benzene. When ring C was involved in cylcization, 1,2-dihydro-3H,7H-quino[8,1-cd][1,5]benzoxazepin-3-ones were obtained, and when ring A was involved, 1,2-dihydro-3H,8H-quino[1,8-ab] [4,1]benzoxazepin-3-ones were formed. With 1c , both modes of cyclization were observed. In an alternative procedure that gave lower yields, the propionic acids were first converted to the corresponding acid chlorides, and these were cyclized by means of anhydrous stannic chloride; as anticipated, the products by this method were identical with those obtained via the trifluoroacetic anhydride method. Several reactions of these tetra-cylcic ketones, e.g., their ease of oxime formation, and dehydrogenation to the α,β-unsaturated ketones, are described. The α,β-unsaturated ketones do not form oximes. The structures assigned to the ketones are based on interpretations of their pmr, uv, and ir spectra. These assignments were confirmed by an X-ray analysis of a single crystal of one representative ketone, 2b ; the X-ray study was also useful in indicating the thermodynamically preferred conformation of 2b . The structures of all the other compounds followed from similar spectral interpretations. The mass spectra of a few compounds are also discussed.     

Electronic structure of sulphur compounds—VII photoelectron spectra of thiocarbonyl heterocycles

The photoelectron spectra of α-substituted thiocarbonyl heterocycles have been analysed. By observing the effects of methyl substitution on the spectra, it was possible to assign the first five bands. These assignments were confirmed by semi-empirical calculations (CNDO/S).     

Synthesis of Indoles through Highly Efficient Cascade Reactions of Sulfur Ylides and N-(ortho-Chloromethyl)aryl Amides

Batting the ylides: A simple procedure carried out under mild conditions allows the direct and efficient synthesis of structurally diverse indoles. This approach involves a cascade reaction of sulfur ylides and N-(ortho-chloromethyl)aryl amides.