Regioselective reaction of 5,6-dialkyl-2-halopyridine-3,4-dicarbonitriles with ammonia

The reaction of 5,6-dialkyl-2-halopyridine-3,4-dicarbonitriles with alcoholic ammonia under elevated pressure gave 5,6-dialkyl-2-aminopyridine-3,4-dicarbonitriles as a result of nucleophilic replacement of the halogen atom by amino group. 6,7-Dialkyl-4-halo-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diimines were formed in analogous reaction at room temperature in the presence of potassium carbonate.     

Favorskii-Umlagerung in Gegenwart von 3,4-Dimethoxyfuran: 11endo-oxa-tricyclo [4.3.1.12,5]undec-3-en-10-on und Derivate

Favorskii -rearrangement in the presence of 3,4-dimethoxyfuran: preparation of 3,4-dimethoxy 11 endo -oxo-tricyclo [4.3.1.1^2,5]undec-3-en-10-one and any derivatives On treatment with sodiumhydride of 2-chloro-cyclohexanone in the presence of 3,4-dimethoxyfuran, a possible intermediate of the Favorskii-rearrangement has been trapped as 3,4-dimethoxy-11endo-oxa-tricyclo [4.3.1.1^2,5]undec-3-en-10-one ( 3 ). This new compound contains a highly nucleophilic double bond. It can be cleaved in high yield by ozonolysis to 2exo, 4exo-bis (methoxycarbonyl)-3-oxabicyclo [3.3.1]nonan-9-one ( 4 ). Addition of chlorine to 3 occurs in stereoselective exo-cis-manner to the crystalline 3exo, 4exo-dichloro-3endo,4endo-dimethoxy 11endo-oxa-tricyclo [4.3.1.1^2,5]undecan-10-one ( 5 ). Silver ion assisted hydrolysis of 5 , followed by thermal treatment of the intermediate hydrates, leads to the red 11endo-oxa-tricyclo [4.3.1.1^2,5]undecan-3,4, 10-trione ( 6 ), and methanolysis to 3,3,4,4-tetramethoxy-11endo-oxa-tricyclo [4.3.1.1^2,5]undecan-10-one ( 8 ). By photolytic decarbonylation, 8 is converted into 3,3,4,4-tetramethoxy-10-oxa-tricyclo-[4.3.1^2,5.0]decan ( 9 ).     

The synthesis of pyrazolo[3,4-d]pyridazines. Photochemical cyclization to pyrazolo[3,4-d]pyridazin-4(5H)-ones with subsequent functionalization

The synthesis of 1,3-disubstituted and 1,3,5-trisubstituted 1H-pyrazolo[3,4-d]pyridazin-4(5H)-ones is conveniently performed by photochemical cyclization. Functionalization of the former compounds leading to the formation of 1,4-disubstituted and 1,3,4-trisubstituted 1H-pyrazolo[3,4-d]pyridazines is smoothly effected through pertinent nucleophilic substitutions.     

Synthesis of thieno[3,4-d]-1,3-dithiol-2-one derivatives

A series of mono-substituted and bis-substituted derivatives of thieno [3,4-d]-1,3-dithiol-2-one were prepared through halogenation, chloromethylation, and subsequent nucleophilic substitution reactions. Compounds were characterized by NMR, FT-IR, and HRMS.     

Recent progress on catalytic [1,3]-oxygen rearrangement reactions from nitrogen to carbon atoms

[1,3]-Rearrangement reactions of an oxygen atom from a nitrogen atom to a carbon atom is an ideal way to synthesize highly elaborate molecules in which nitrogen and oxygen functionalities are vicinally arranged. Recently, it has been disclosed that this intriguing transformation takes place in the presence of Lewis acidic metal catalysts. In this digest, we summarize recent findings on the catalytic [1,3]-oxygen rearrangement reactions, such as direct [1,3]-rearrangement of N-oxygenated enamines and anilines, as well as π-acidic metal-catalyzed cascade reaction involving the [1,3]-rearrangement process.     

Au-catalyzed synthesis of (1Z,3E)-2-pivaloxy-1,3-dienes from propargylic pivalates

Propargylic pivalates with electronically unbiased internal alkynes are selectively transformed into (1Z,3E)-2-pivaloxy-1,3-dienes containing various functionalities. The unusual selectivity of 1,2-acyloxy migration over the structurally preferred 3,3-rearrangement is realized. This reaction is highly stereoselective and offers rapid access to dienes for one-pot intra-/intermolecular Diels-Alder reactions either under thermal conditions or with Lewis acid catalysis.     

Anion-anion assembly: a new class of anionic supramolecular polymer containing 3,4-dichloro-2,5-diamido-substituted pyrrole anion dimers

Two molecules containing two 2,5-diamido,3,4-dichloropyrrole units linked via 1,3- or 1,4-substituted benzene rings have been synthesized. The pyrrole groups in these compounds deprotonate in the presence of tetrabutylammonium fluoride and form pyrrole anion dimers via NH...N- hydrogen bonds. This dimerization process results in the formation of polyanionic chains linked via an unusual "orthogonal" hydrogen-bonding array.     

An unusual Mannich type reaction of tertiary aromatic amines in aqueous micelles

An efficient, unusual Mannich type reaction of tertiary aromatic amines, formaldehyde and 1,3-dicarbonyl compounds is described in aqueous micelles catalyzed by boric acid to afford dialkylaminoarylated 1,3-dicarbonyls. In this unusual Mannich type reaction, tertiary aromatic amines react with formaldehyde to generate an N-alkyl-N-(4-methylenecyclohexa-2,5-dienylidene)alkylaminium intermediate (aza quinone methide), which undergoes nucleophilic addition with 1,3-dicarbonyl compounds. The reaction is highly regioselective, and exclusively para functionalized products are formed in high yields.     

Convenient Synthesis of 3,4-bis(Alkylthio) Thiophenes

A variety of symmetrically substituted 3,4-dithioether-thiophenes were prepared by the acid catalyzed nucleophilic substitution of 3,4-di(methoxy)thiophene with the appropriate thiol.     

1,3-Dioxopyrrolo[3,4-b]porphyrins: synthesis and chemistry

A novel 1,3-dioxopyrrolo[3,4-b]porphyrin (2) has been synthesized in 70% yield following a [4 + 2] cycloaddition reaction of pyrrolo[3,4-b]porphyrin 1 with (1)O(2). The new imide was used as a template to other 1,3-dioxopyrrolo[3,4-b]porphyrins and to the corresponding open counterparts. The UV/vis absorption spectra of the new compounds show significant red-shifts when compared with those of the nonsubstituted analogues. The structure of an imide derivative was confirmed by single-crystal X-ray diffraction.     

A novel dilithiation approach to 3,4-dihydro-2H-1,3-benzothiazines, 3,4-Dihydro-2H-1,3-benzoxazines,and 2,3,4,5-tetrahydro-1,3-benzothiazepines

3,4-Dihydro-2H-1,3-benzothiazines 4, 3,4-dihydro-2H-1,3-benzoxazines 9, and 2,3,4,5-tetrahydro-1,3-benzothiazepines 6 were synthesized by directed ortho-lithiation of thiophenols and phenols and by side-chain lithiation of substituted thiophenols, respectively, in one-pot by reacting with N,N-bis[(benzotriazol-1-yl)methyl]amines 3 as 1,3-biselectrophile synthons.     

Synthesis of 3,4-alkoxythieno[2,3-b]thiophene derivatives. The first block copolymer associating the 3,4-ethylenedioxythieno[2,3-b]thiophene (EDOThT) unit with 3,4-ethylenedioxythiophene (EDOT) moieties

The synthesis of 3,4-alkoxythieno[2,3-b]thiophene derivatives has been developed from the readily accessible dimethyl or diethyl 3,4-dihydroxythieno[2,3-b]thiophenedicarboxylates. The yields for the dialkoxy derivatives were strongly dependent both on the base and the alkylating agent used for the nucleophilic substitutions. A trimer associating the new 3,4-ethylenedioxy-thieno[2,3-b]thiophene unit with 3,4-ethylenedioxythiophene moieties has been synthesized and electropolymerized.     

Novel reactions of 6,7-dimethoxy-3,4-dihydroisoquinoline and 3,4-dihydro-β-carboline with dipolarophiles

New reactions of 6,7-dimethoxy-3,4-dihydroisoquinoline and 3,4-dihydro-β-carboline with various electron-deficient olefins are described. ‘One-pot’ generation and cycloaddition of the 1,3- and 1,4-dipoles formed from these heterocycles with a range of alkene dipolarophiles affords cycloadducts in good yields with high regio- and stereoselectivity.     

Unexpected cycloadducts from 1,3-dipolar cycloaddition of 3,4-dehydromorpholine N-oxide to N-cinnamoyl piperidines—first report of the novel formation of 2:1 cycloadducts

A series of unexpected cycloadducts along with normal cycloadducts have been isolated from the 1,3-dipolar cycloaddition of 3,4-dehydromorpholine N-oxide to piperidides of cinnamic acid and para-substituted cinnamic acids and these were analyzed by X-ray crystallography to reveal novel solid-state structures. At first, 1:1 cycloadducts were formed which underwent in situ nucleophilic attack by another reduced nitrone moiety. A plausible iminium-oxonium ion mechanism has been proposed.     

Cycloadditionen von 3,4-Dimethoxyfuran an Dienophile

On cycloaddition reactions with 3,4-dimethoxyfuran We describe new cycloadditions of 3,4-dimethoxyfuran (3,4-DF, 1 ) with various dienophiles. In contrast to furan, the reaction of 3,4-DF with maleic anhydride gives exo- and endo-adducts at approximately the same rate. The thermodynamically more stable product is again the exo-product. Less active dienophiles lead also to mixtures of exo- and endo-adducts, except for citraconic anhydride (methylmaleic anhydride) which forms only the adduct with an endo-methyl group. Dimethylmaleic anhydride could not be reacted with 3,4-DF. All adducts with 3,4-DF contain a hidden 1,2-dicarbonyl group in the form of an endiolether. Its pronounced nucleophilic character allows a series of further additions. Noteworthy are the stereospecific cis-additions of halogens and the preparation of several acetals. Ozonolysis of the enolether in 4 allows the preparation of the hitherto unknown 2r, 3trans, 4trans, 5cis-tetrahydrofuran tetracarboxylic acid and derivatives thereof ( 5 and 6 ).     

Chemical transformations of trisubstituted pyrazolo[3,4-d]pyrimidines and their 1-ribosides

A number of 3,4,6-trisubstituted pyrazolo[3,4-d]pyrimidines and their 1-ribosides were synthesized from 3-cyano-4,6-dimethylmercaptopyrazolo [3,4-d]pyrimidine. The cyano group was converted to thiocarbamoyl, imido ester, carboxamidoximno, carboxamidrazono, carboxy, and amidino groups. The 4-methylmercapto group was replaced by mercapto, methoxy, amino, and hydrazino groups. The reactivities of methylmercapto and 3-cyano groups in substituted pyrazolo [3,4-d] pyrimidines and the corresponding nucleosides with respect to nucleophilic agents were compared. The introduction of a ribose residue in the 1 position facilitates nucleophilic addition to the 3-cyano group and replacement of the 4-methylmercapto group. High resistance of the 6-methylmercapto group to the action of nucleophilic agents and higher reactivity of the cyano groups as compared with methylmercapto groups were observed. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 243–250, February, 1980.     

Electrophilically Activated Nitroalkanes in Synthesis of 3,4-Dihydroquinozalines

Nitroalkanes activated with polyphosphoric acid serve as efficient electrophiles in reactions with various nucleophilic amines. Strategically placed second functionality allows for the design of annulation reactions enabling preparation of various heterocycles. This strategy was employed to develop an innovative synthetic approach towards 3,4-dihydroquinazolines from readily available 2-(aminomethyl)anilines.     

Rearrangement of some chlorosubstituted 3-amino-3,4-dihydro-1-hydroxycarbostyrils in hydrogen halide acids

The general conditions and results of rearrangement studies of the 5-, 6-, 7-, and 8-chloro-substituted 3-amino-3,4-dihydro-1-hydroxycarbostyrils in concentrated hydrochloric and hydro-bromic acids to the corresponding dihalosubstituted 3-amino-3,4-dihydrocarbostyrils have been described. The 5-, 7- and 8-chlorocarbostyrilhydroxamic acids undergo nucleophilic displacement by either chloride or bromide ion preferentially at the 6-position to form the respective 5,6-, 6,7- and 6,8-dihalolactams. However, with the 3-amino-6-chloro-3,4-dihydro-1-hydroxycarbo-styril where the 6-position is blocked, nucleophilic displacement by halide ions occurs at the 8-position to afford the 6,8-dihalolactams. The 6,8-dichloro- and 6,8-dibromolactams were also prepared by alternative halogenation procedures for purposes of comparison with the rearrangement products.     

Intramolekulare 1,3-dipolare Cycloadditionen mit alkenyl-substituierten 3,4-Diarylsydnonen

Intramolecular 1,3-Dipolar Cycloaddition Reactions of Alkenyl-substituted 3,4-Diarylsydnones The 3,4-diarylsydnones 1 and 12a–e with an allyl or alkenyloxy substituent on the N(3)-phenyl group have been synthesized by classical methods starting from 2-allylaniline and the corresponding alkenyloxyanilines, respectively (Schemes 2 and 3). Whereas the allyl-substituted sydnone 1 undergoes an intramolecular 1,3-dipolar cycloaddition at room temperature in solution to yield 13 (Scheme 4), the alkenyloxy-substituted sydnones 12a–e are thermally stable. On irradiation of 1 and 12a–d , formation of the fused dihydropyrazoles 2 and 14a–d (Schemes 1 and 5) is observed. In the case of 12d , the yield of 14d is very low, and the symmetric 1,2,3-triazole 15a has been isolated as the main product. A very likely reaction mechanism for the formation of the photoproducts involves decarboxylation of the sydnones to give a nitrile-imine which undergoes an intramolecular 1,3-dipolar cycloaddition onto the C?C bond.     

Salts of alkyl-substituted 3,4-dihydroiso-quinolines with 2-acetylcyclopentane-1,3-dione

Reactions of alkyl-substituted 3,4-dihydroisoquinolines, with 2-acetylcyclopentane-1,3-dione were used to prepare 3,4-dihydroisoquinolinium 2-acetylcyclopentane-1, 3-dionates, which could not be converted into ABCD-tetracyclic derivatives of the 8-azagonane series (benzo[a]cyclopentano[f]quinolizines). The salts obtained were studied and characterized by physicochemical methods. It was shown by combining the NMR and H/D-isotope exchange methods that for 1-alkyl-3,4-dihydroisoquinolines and their salts in solutions, an imine-enamine (iminium-enaminium), and for the 2-acetylcyclopentane-1,3-dione anion, a keto-enol tautomeric equilibrium takes place.Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus', Minsk 220141. Chemical Engineering Institute, Russian Academy of Sciences, Perm'614000. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 681–690, May, 1998.