The synthesis of naphthothiopyranopyranones and naphthothiopyranopyranthiones

The synthesis of fused tetracyclic naphthothiopyranopyranones from dihydronaphthothiopyranones I or II has been studied. Compounds I or II have been cyclised in good yield to the corresponding dioxaborin difluoride complexes III, IV, XIII and XIV by treatment with acetic or propionic anhydride and boron trifluoride etherate. These complexes and the Vilsmeier reagent reacted to produce fused tetracyclic 3-substituted naphthothiopyranopyranones V, VI, XV or XVI . The reaction of dioxaborin difluoride complexes III or IV with dimethylthioformamide (DMTF) afforded dimethylaminovinyldioxaborin difluoride complexes IX or X . Treatment of IX or X with hydrochloric acid solution gave naphthothiopyranopyranones VII or VIII . The reaction of VII, VIII, XV or XVI with DMTF/acetic anhydride yielded new products, which was identified as naphthothiopyranopyranthions XI, XII, XVII or XVIII .     

Synthesis of new azo compounds based on N-(4-hydroxypheneyl)maleimide and N-(4-methylpheneyl)maleimide

Maleic anhydride was reacted with p-aminophenol and p-toluidine in the presence of di-phosphorus pentoxide (P?O?) as a catalyst to produce two compounds: N-(4-hydroxy-phenyl)maleimide (I) and N-(4-methylphenyl)maleimide (II). The new azo compounds I(a-c) and II(a-c) were prepared by the reaction of I and II with three different aromatic amines, namely aniline, p-aminophenol and p-toluidine. The structures of these compounds were confirmed by CHN, FT-IR, 1H-NMR, 13C-NMR, mass spectrum and UV/Vis spectroscopy.     

Sydnone Compounds XXX. The Syntheses and Reactions of 3-Aryl-4-Cyanosydnones and 3-Aryl-4-Formylsydnone Oximes

In the presence of pyridine, 3-aryl-4-formylsydnone (II) reacts with hydroxyl-amine hydrochloride to produce 3-aryl-4-formylsydnone oxime (III). This reaction was performed in ethanol solution with reflux or at room temperature; the latter procedure gave an excellent yield (74-98%) and high purity. (III) reacts in acetic anhydride at room temperature to give 3-aryl-4-formylsydnone oxime O-acetate (IV). A convenient method for the synthesis of 3-aryl-4-cyanosydnone (V) is to dehydrate (III) with acetic anhydride at reflux. When (IV) was refluxed with acetic anhydride, (V) was similarly obtained. Another convenient method to prepare (V) from (III), dehydration with thionyl chloride at room temperature, was also investigated.     

Über siliciumschwefel-verbindungen : III. Neue organylthiosilane

Novel organylthio(alkoxy)silanes (I, II, III and XII) and organylthio(diethylamino)silanes (IV, V) are described. They were prepared by treating lithium or lead thiolates with the corresponding chlorosilanes or by cleavage of dimethylbis(diethylamino)silane with thiols. Phenylthiosilanes (Me₃SiSPh, III and XIII) furthermore can be obtained by reaction of chlorosilanes with benzenethiol in the presence of tertiary amines. The SiS bond of Me₃SiSPh is cleaved by chlorosilanes like Me₂Si(NEt₂)Cl or Me₂Si(OPr)Cl. This reaction is a convenient route to prepare compounds I and IV. The physical and chemical properties of the novel compounds were investigated.     

Synthesis of Certain S-Triazole and s-Triazolo[3,4-B] 1,3,4-Thiadiazole Derivatives of Expected Pharmacological Activity

Reaction of the newly prepared 3-(2-thienyl)-4-amino-s-triazole-5-thione (I) with different alkyl kalides and aromatic aldehydes afforded the corresponding thioethers and arylidene derivatives (II and III), respectively. Attempt ring closure of (I) with acetic anhydride produced the unexpected triacetyl derivative (IV). The synthesis of certain 3-(2-thienyl)-6-substituted-s-triazolo[3,4-b] 1,3,4-thiadiazoles (V and VII) was described. IR, NMR and mass spectral analyses of the prepared compounds were discussed.     

Heterocyclic tautomerisms. I. An investigation of the 2-arylbenzothiazoline-2-(benzylideneamino)thiophenol tautomerism. Part 1

A definite tautomeric relationship has been found between 2-arylbenzothiazolines (I) and 2-(benzylideneamino)thiophenols (II). In a reaction characteristic of the closed ring structure (I), 2-arylbenzothiazolines were oxidized in high yield with benzoyl peroxide to the corresponding 2-arylbenzothiazoles (III). Reactions characteristic of the open ring structure (II) include the formation of the potassium salt of the open ring structure (IV) by reaction of 2-arylbenzothiazolines with potassium t-butoxide in toluene and oxidation of 2-arylbenzothiazolines to bis-[2-(benzylideneamino)phenyl] disulfides (V) by hydrogen peroxide in methanol.     

Acetylenic ketones. Part VI. Reaction of aroylphenylacetylenes with hydrazine derivatives

The reaction of aroylphenylacetylenes (I) with acyl- or aroylhydrazines (II) gave ω-aroyl-acetophenone-N-acyl or N-aroylhydrazones (IV). The latter gave upon treatment with methanolic potassium hydroxide and with acetic anhydride in the presence of sodium acetate, the corresponding pyrazoles (V) and the N-acetylpyrazoles (VII and VIII), respectively. The acetylenic ketones ( 1 ) also reacted with methylhydrazine and 1,1-dimethylhydrazine to give 5-aryl-1-methyl-3-phenylpyrazoles (XII), and 1,1-dimethylhydrazine derivatives (XIII), respectively. When the latter compounds were heated with acetic anhydride, they gave the N-methylpyrazoles (XII).     

Reaction of thioxophosphorane sulfenyl bromides with ethyl vinyl ether: Mechanistic and synthetic aspects

The mechanistic and synthetic aspects of the addition reaction of thioxophosphorane sulfenyl bromide with ethyl vinyl ether were studied in detail by NMR techniques. It has been found that the regiospecific, primary product of the reaction, 1-bromo-1-ethoxy-2S(dialkoxythiophosphoryl)ethane I, is unstable and undergoes slow decomposition to give four compounds. The formation of thiophosphoryl derivatives, vinyl ethers II and III, aldehyde IV, and the symmetrical hemiacetal anhydride V, has been considered in terms of a carbocation intermediate. By choice of the appropriate reaction conditions, the aldehyde IV can be obtained in very high yield.     

Reaction of 2-carboxy-1-methylindole-3-acetic acid anhydride with amines and with S-methylisothiosemicarbazide

2-Carboxy-1-alkylindole-3-acetic acid anhydrides (I) condensed with S-methylisothiosemicarbazide in DMF to form 5,11-dihydro-6-methyl-2-methylthioindolo[3′,2′:4,5]pyrido[1,2-b]-s-triazol-5-one (II). Compound II underwent ring opening on refluxing with sodium hydroxide solution to give IV. The anhydride I reacted with primary amines in benzene to give 2-carboxy-1-alkylindole-3-acetanilide derivatives (VI) which yielded l-methylindole-3-acetic acid by decarboxylation followed by hydrolysis. Compound II oxidised to the diketo compound X which could be prepared by the hydrolysis of the azomethine derivative IX with acetic acid-hydrochloric acid mixture. Compound II reacted with benzyl chloride to yield the dibenzyl derivative XII, condensed with p-chlorobenzaldehyde to form the 11-p-chlorobenzylidene derivative XI and coupled with arenediazonium salt to give the 11-arylhydrazone derivatives XIII.     

Synthesis of nonactin (author's transl)]

Synthesis of Nonactin. The macrotetrolide antibiotic nonactin (I), containing four units of a C₁₀ hydroxy acid, has been synthesized starting from two adequately protected derivatives (III and IV) of nonactic acid (II). The 32-membered ring of the macrotetrolide is built up by a sequence of condensation and deprotection steps leading first to a product with two, and subsequently to one with four nonactic acid residues (VIII) which is then cyclized in the presence of Ag⁺-ions. Two reactions forming ester bonds have been developed to condense the hydroxy acids and to effect the final cyclization. In one the activation of the carboxyl group is achieved by conversion into the mixed anhydride with 2,4,6-trimethylbenzene sulfonyl chloride in pyridine. In the other the Ag⁺-ion induced reaction of a S-(2-pyridyl) hydroxy carbothioate is used to form the corresponding macrocyclic lactone. In the case of nonactin the ring closure is promoted by the coordinating effect of Ag⁺-ions present in the reaction mixture.     

Metallacycloalkanes : II. Reactions of α,α′-bipyridyl-5-nickela-3,3,7,7-tetramethyl-trans-tricyclo[4.1.0.02,4]heptane

The title compound (II) underwent reductive elimination on treatment with maleic anhydride, tetracyanoethylene or triphenylphosphite to give 3,3,6,6,-tetramethyl-trans-tricyclo[3.1.0.0^2,4]hexane (III). With triphenylphosphite bi(2,2-dimethylcyclopropyl) (V) and 1-(2,2-dimethylcyclopropyl)-3-methyl-1,3-butadiene (VI) were also formed. Acidolysis of II with either HCl, malonic acid or methanol gave V. An intermediate complex α,α′-bipyridyl(phenoxy)-3-nickel-1,1′-bi-(2,2′-dimethylcyclopropyl) (VIII) was isolated by reaction of II with phenol. Methylene dibromide reacts with II to give III and 3,3,7,7-tetramethyl-trans-tricyclo[4.1.0.0^2,4]heptane (IV). With triethylaluminum and II complete exchange of the alkyl groups occurred and V was released on hydrolysis. Trifluoroborane diethyl ether and II gave 3,3,6,6-tetramethylcyclohexa-1,4-diene in a rearrangement-displacement reaction. The cyclodimerisation of 3,3-dimethylcyclopropene (I) to III catalysed by II and the fact that II can be recovered from the reaction mixture provides strong evidence for the intermediacy of metallacyclopentanes in these transition-metal-catalysed [2π + 2π] cyclo-additions.     

Synthesis of sterically hindered aromatic dialdehydes

A study was carried out on the formylation of a series of aromatic compounds containing two mesitylene or durene residues [dimesityl (I), dimesitylmethane (II), 1,2-dimesitylethane (III), 1,6-dimesitylhexane (IV), dimesityl sulfide (V), 1,1-dimesitylethylene (VI), 1,1-dimesityl-1-butene (VII), and didurylmethane (VIII)] by the action of dichloromethyl methyl ether (DCM) in the presence of A1C1₃ and TiCl₄. The corresponding dialdehydes are the major products. The formylation products when the reaction is carried out in the presence of A1C1₃ in the case of (I) and (V) contain significant amounts of monoaldehydes, while partial cleavage of the substrates with the formation of products containing only one benzene ring is observed in the case of (II) and (VIII) in addition to formylation.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1700–1703, July, 1991.     

Nucleophilic substitution in 1,2,3-thiadiazoles

By reactions of nucleophilic substitution of the halogen atom in 5-halo-1,2,3-thiadiazoles (IV), we have obtained 5-amino- (I, V), hydrazino-(VI, VII, IX, X), and mercapto- (VIII) 1, 2, 3-thiadiazoles. We show that upon reaction with amines, a mixture of 5-amino-1, 2, 3-thiadiazoles (I) and 5-mercapto-1, 2, 3-triazoles (II) is formed, and also the reaction product of compounds I and IV,: the selectivity of this process depends only on the type of solvent.Organic Synthesis Technology Department, Urals State Technical University—UPI, Ekaterinburg 620002. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 554–559, April, 1994. Original article submitted February 28, 1994.     

Reaction of phthaloylasparic anhydride with o-phenylenediamine in solution and spectral analysis of the reaction products

The ring-opening addition reaction of phthaloylasparic anhydride (I) with o-phenylenediamine (II) in a solution is affected by the polarity of the solvent used. At the molar ratio of 1:1, I and II undergo a β-oriented ring-opening reaction in polar solvents, such as DMF, DMAC, and DMSO; while in weaker polar solvents, such as dioxane and tetrahydrofuran, α-orientation predominates. By heating in a solvent mixture of DMF and xylene, the ring-opening products undergo condensation, and are converted into two isomers. One is methanol soluble 3-phthalimido-3-(2)benzimidazolylpropanoic acid (V) resulting from the α-oriented ring-opening reaction, the other is the sparingly soluble (in DMF) 2-phthalimido-3-(2)benzimidazolylpropanoic acid (VI) resulting from the β-oriented ring-opening reaction. The soluble V can be precipitated as cotton-like crystals from methanol and chloroform. When treated with acetic anhydride, V and VI are converted to other isomers, namely 3-phthalimidobenzimidazopyrrolone (VII) and 2-phthalimidobenzimidazopyrrolone (VIII). The isomers were identified by spectral analysis.     

New synthesis of 2-amino-3-cyano-4,5-tetramethylenethiophene

We have shown that 2-amino-3-cyano-4,5-tetramethylenethiophene (IV) is formed in the reaction of cyclohexanethione (I) with malononitrile (II) and sulfur in the presence of triethylamine. The reaction proceeds through a step involving the formation of cyclohexylidenemalononitrile (III) and occurs via attack by the malononitrile anion on the sulfur atom of the thiocarbonyl group of I. Δ^2,α-Bornanylmalononitrile (V) was similarly obtained from thiocamphor and II; the latter reaction cannot be realized with camphor because of the steric hindrance of the carbonyl carbon atom.     

The Mechanism of Schiff Base Formation of Some Arylidenes-p-Aminosalicylic Acid

Formation of a series of Schiff bases derived from p-aminosalicylic acid I and various aromatic aldehydes has been studied kinetically in ethanol medium in presence of piperidine as a basic catalyst. The order of the reaction is determined to each reactant by following the concentration of the Schiff base formed during the reaction. The reaction is Kinetically third-order in the presence of low concentration of piperidine, first-order to each of I , aldehyde and piperidine. On the other hand, in presence of ≥5×10^?4 M of piperidine the order of the reaction changed to second-order, thus much the reaction is independent of piperidine concentration. The rate determining step is suggested to be the dehydration of the carbinolamine intermediate step 4. Variation in reaction rate constants with the different substituent of the aromatic aldehyde, with substituents of aromatic amine and with the nature of the hydroxylic organic solvents as reaction medium are studied and discussed.     

Reaction of certain isocyanates with azomethines. Evidence for a new heterocyclic adduct

The preparation of triazinone (I) from certain isocyanates and N-alkyl azomethines was found to proceed easily without catalyst, particularly in refluxing chlorobenzene. The physical and chemical properties, including n.m.r. spectra of the oily triazinones, are contrasted with the newly discovered solid adducts arising from low temperature reaction of azomethine and chlorophenyl isocyanates. From stoichiometry of the reaction, elemental analysis, molecular weight of the products, and spectral analyses, the new materials (II) were found to incorporate two isocyanate and three azomethine moieties in their molecular make-up. The relative merits are considered for assigning II a molecular structure arising from a complex between a four and six-membered ring (III, IV) versus a ten-membered ring system (V, VI, VIa).     

Transformations of kurchi alkaloids—I The action of nitrous acid on holarrhimine

Holarrhimine (I), 18-hydroxy-3β,20-diamino-5-pregnene, was treated with nitrous acid under different conditions. From the reaction mixtures several crystalline products were isolated and characterized as 3β-hydroxy-18-20β-oxido-5-pregnene (II), the nitrate ester of II (III), 3β-nitro-18-20β-oxido-5-pregnene (IV), 6-methoxy-18-20β-oxido-3,5-cyclopregnane (V) and 3β,18-dihydroxy-20-amino-5-pregnene (VII). On treatment with boron trifluoride and acetic anhydride compounds II, IV, V and an unidentified compound (VI) gave the same triacetate 3β,18,20-triacetoxy-5-pregnene (VIII).     

Reaction of (bromodifluoromethyl)phenyldimethylsilane with organometallic reagents

A new fluorine-containing organosilicon compound, (bromodifluoromethyl)-phenyldimethylsilane (II), was synthesized by the N-bromosuccinimide (NBS) bromination of difluoromethyl)phenyldimethylsilane (I), which was prepared from phenyldimethylsilyllithium and chlorodifluoromethane. Compound II reacted with dimethyl sulfoxide to give dimethyl sulfide and phenyldimethylfluorosilane in quantitative yield. The reaction of II with nucleophiles, such as sodium ethoxide, Grignard or lithium reagents, afforded products arising from cleavage of the carbonsilicon bond. In contrast, the reaction of II with Grignard reagents in the presence of appropriate catalysts (Group VIII transition metal salts or complexes) afforded the homo-coupling product of II, 1,2-bis-(phenyldimethylsilyl)-1,1,2,2-tetrafluoroethane (IV), in excellent yield. The silver(I) salt-catalyzed reaction of II with ethylmagnesium bromide gave the cross-coupling product, (1,1-difluoropropyl)phenyldimethylsilane (V) as well as III and IV. When cuprous bromide was employed as catalyst, the reaction of II with ethylmagnesium bromide afforded 1-phenyldimethylsilyl-1-propene (VI) and 3-phenyldimethylsilyl-2-pentene (VII) as main products.     

Stereoselective synthesis of 2-dienyl-substituted piperidines using an eta4-dienetricarbonyliron complex as the stereocontrolling element in a double reductive amination cascade

In the presence of NaBH(OAc)(3), a 1,5-keto-aldehyde, contained within a side-chain of an eta(4)-dienetricarbonyliron complex, undergoes a double reductive amination sequence with a series of primary amines, to provide the corresponding piperidine products in good to excellent yield. The dienetricarbonyliron complex functions as a powerful chiral auxiliary in this cascade process, exerting complete control over the stereoselectivity of the reaction, with the formation of a single diastereoisomeric product. The sense of stereoinduction has been confirmed by X-ray crystallography. Removal of the tricarbonyliron moiety can be effected with CuCl(2) to afford the corresponding 2-dienyl-substituted piperidine in excellent yield. Attempted extension of this cyclisation strategy to the corresponding azepane ring system using a 1,6-keto-aldehyde as the cyclisation precursor was unsuccessful; in this case, the reaction stopped after a single reductive amination on the aldehyde to provide an acyclic keto-amine product.