About the intermediacy of 1,2-dihydroquinazolinium salts in the Friedländer-Borsche synthesis of quinolinium salts in acidic medium

Spontaneously or under various heating conditions, 2-alkyl- or 2-aryl-(iminoalkyl)benzenamines react with ketones and triflic acid (1:1:1) to give quinolinium salts. When working under milder thermal conditions, intermediate 1,2-dihydroquinazolinium derivatives can be isolated or detected in solution but decompose upon standing or heating to give the corresponding quinolinium salts.     

Syntheses of dibenzo[b,e][1,4]dioxin derivatives via iron complexes, and further functionalizations via directed metallation

Double nucleophilic aromatic substitution reactions between (cyclopentadienyl)(η⁶-1,2-dichlorobenzene)iron(1 + ) salts and substituted 1,2benzenediols have been carried out under mild conditions to prepare [η⁶-dibenzo[b,e][1,4]dioxin]iron(1 + ) complexes functionalized in the 1- or 2-position with an alkyl, aldehyde, carboxylic acid, methoxycarbonyl, carboxamide, or hydroxy group. 3-Methyl- and 4-methyl-(η⁶-1,2-dichlorobenzene)iron complexes were treated with substituted 1,2-benzenediols to effect functionalization of both aromatic rings of the heterocycle. The dibenzodioxin ligands were liberated routinely by irradiation with ultraviolet light. Directed deprotonation of the free functionalized dibenzodioxins with an alkyllithium reagent followed by quenching with a variety of electrophiles yielded further derivatives, including two new isoindolone systems.     

Reaktionen und Verknüpfungen von 1,2-Diaza-3-sila-5-cyclopentenen

Reactions and Bridging of 1,2-Diaza-3-sila-5-cyclopentenes 1,2-Diaza-3-sila-5-cyclopentenes react with butyllithium to give lithium salts. In reactions of the lithium salts with halosilanes ( 1–7 ), trimethyltinchloride (8) or methyliodide ( 9 ) substituted compounds are obtained by LiHal elimination. Bromosuccinimide brominates the methylene group of the ring system ( 10 ). Bridging of 1,2-diaza-3-sila-5-cyclopentenes by boryl and silyl groups are described ( 11–13 ). In the reaction of trifluorophenylsilane with lithiated 1 , 2-tert.-butyl-4-lithio-3,3,5-trimethyl-4-fluorodimethylsilyl-1,2-diaza-3-sila-5-cyclopentene, which is stable in solution, a second substitution takes place ( 14 ). The thermal elimination of LiF from lithiated 1 leads to the formation of the spirocyclic compound 15 . The n.m.r. and mass spectra of the compounds are reported.     

Regioselective reduction of 3-substituted N-acylpyrazinium salts toward the synthesis of 1,2-dihydropyrazines

The regioselective reduction of 3-substituted N-acylpyrazinium salts with n-Bu(3)SnH has been developed for the synthesis of 3-substituted 1,2-dihydropyrazines in yields of 56-94%. Substitution of the pyrazinium salts with electron-donating groups favors the formation of the 1,2-isomers as a result of their better stability over the 1,6-isomers. Under mild acidic conditions, 3-methoxy substituted 1,2-dihydropyrazine was easily hydrolyzed in excellent yield to Δ(5)-2-oxopiperazine.     

Carbodiimide-mediated preparation of the tricyclic pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine ring system and its application to the synthesis of the potent antitumoral marine alkaloid variolin B and analog

A total synthesis of the marine alkaloid variolin B has been completed in 13 steps in an overall yield of 6.5% from 3-formyl-4-methoxypyridine. Our approach is based on the sequential formation of the 7-azaindole ring, the tricyclic pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine ring system, and finally installation of the 2-aminopyrimidine ring at C5. The required 7-azaindole ring appropriately substituted is formed by a modified indole synthesis involving a nitrene insertion process (two steps). Formation of the annelated pyrimidine ring is achieved by two routes both involving a carbodiimide-mediated cyclization process, which allow incorporation of the amine functionality at C9 of the core tricyclic (six steps). Installation of the northeast 2-aminopyrimidine ring at C5 is performed using the Bredereck protocol (three steps). Ultimate, thermal decarboxylation with concomitant O-methyl deprotection and further N-benzyl deprotection by the action of triflic acid completed the synthesis of the target natural product variolin B.     

Synthesis of substituted disulfonyl-containing polycyclic azines with the bridgehead nitrogen atom. Effects of the structure of 3-substituted pyridinium ylides on the regioselectivity of their reactions with <Emphasis Type="Italic">E</Emphasis>-1,2-di(alkylsulfonyl)-1,2-dichloroethenes

Heating the substituted pyridinium and isoquinolinium salts with E-1,2-di(alkylsulfonyl)-1,2-dichloroethenes in either chloroform or acetone in the presence of three-fold excess of Et₃N gave high yields of substituted 1,2-di(alkylsulfonyl)indolizines and 1,2-di(alkylsulfonyl) pyrrolo[2,1-a]isoquinolines, respectively. Effects of the structure of 3-substituted pyridinium ylides on the regioselectivity of their reaction with E-1,2-di(alkylsulfonyl)-1,2-dichloroethenes were revealed. It was shown that the presence of electron-releasing and electron-withdrawing substituents in the pyridinium ylide favors the formation of 8-substituted and 6-substituted 1,2-(dialkylsulfonyl)indolizines, respectively.     

Synthesis of some 7-substituted 3-chloro-3,4-dihydro-1-hydroxycarbostyrils by the reduction cyclization of α-chloro-β-(4-substituted-2-nitrophenyl)propionic acids

A new method was developed for the synthesis of some 7-substituted 3-chloro-3,4-dihydro-l-hydroxycarbostyrils 3c-g in which α-chloro-β-(4-substituted-2-nitrophenyl)propionic acids 2c-g were reductively cyclized by catalytic hydrogenation over platinum-on-carbon sulfided catalyst. In particular, this method was applied to α-chloro-β-(2-nitrophenyl)propionic acids bearing 4-methyl 2c , 4-ethyl 2d , 4-ethoxy 2e , 4-(n-butyl 2f and 4-phenyl 2g substituents to afford good yields of the corresponding 7-methyl 3c , 7-ethyl 3d , 7-ethoxy 3e , 7-(n-butyl) 3f , and 7-phenyl 3g substituted 3-chloro-3,4-dihydro-l-hydroxycarbostyrils. The various 4-substituted α-chloro-β-(2-nitrophenyl)propionic acids 2c-q were synthesized by reacting the in situ diazotized salts of the appropriate 4-substituted-2-nitroanilines in aqueous acetone with acrylic acid in the presence of cuprous chloride and hydrochloric acid. All compounds prepared in this study were characterized by microanalytical and ir and nmr spectral data.     

Substituted 3-and 5-formylpyridin-2-ones in the synthesis of 1-aryl-1, 6-naphthyridinone derivatives

New 1-aryl-6-[2-(dimethylamino)vinyl]4-oxo-1,4-dihydropyrimidine-5-carbonitriles and 4-arylamino-2-oxo-1,2-dihydropyridine-3-carbonitriles containing electron-withdrawing substituents in the benzene ring were synthesized from enamino amides and dimethylformamide dialkylacetals. The influence of various dimethylformamide acetals on the yield of 3-(4-chloro-anilino)-2-cyano-5-(dimethylamino)penta-2,4-dienoic acid N-(dimethylamino)methyl-ideneamide was investigated in the reaction of these acetals with 3-(4-chloroanilino)-2-cyanocrotonamide. New 4-arylamino-5-formyl-2-oxo-1,2-dihydropyridine-3-carbonitriles and 4-arylamino-2-oxo-1,2-dihydropyridine-3-carbaldehydes containing electron-withdrawing substituents in the benzene ring were synthesized. The latter compounds were converted into new substituted l,6-naphthyridinones by the action of various CH acids. A new approach to the synthesis of 4-(4-fluoroanilino)-5-formyl-2-oxo-1,2-dihydropyridine-3-carbonitrile using dimethylformamide diisopropylacetal under mild conditions was developed. The comparative reactivity of the formyl group in the reactions of 4-arylamino-5-formyl-2-oxo-1,2-dihydropyridine-3-carbonitriles and in 4-arylamino-2-oxo-1,2-dihydropyridine-3-carb-aldehydes with malononitrile was determined using HPLC.     

Triflic Acid Mediated Cascade Cyclization of Aryldiynes for the Synthesis of Indeno[1,2‐c]chromenes: Application to Dye‐Sensitized Solar Cells

A new triflic acid (TfOH)‐mediated cascade cyclization of ortho‐anisole‐substituted aryldiynes is described for the construction of indeno[1,2‐c]chromenes. The cascade cyclization proceeds through an unusual TfOH‐induced alkyne‐alkyne cyclization followed by nucleophilic attack of the methoxy group on the benzylidene cation, which is completely different to the cyclization of ortho‐aniline‐ or ortho‐thioanisole‐substituted aryldiynes. A new class of organic dyes with the indeno[1,2‐c]chromene framework as both donor and π‐linker were synthesized. These compounds exhibit high photovoltaic performances in dye‐ sensitized solar cells (DSCs).     

Pd-catalyzed cross-coupling reactions of halogenated 1-phenylpyrazol-3-ols and related triflates

1-Phenyl-1H-pyrazol-3-ol was used as a versatile synthon for the preparation of various 1-phenyl-1H-pyrazole derivatives substituted at C-3 and C-4 of the pyrazole nucleus and at the phenyl ring para-position. Treatment of 1-phenyl-1H-pyrazol-3-ol with triflic anhydride in the presence of base gave 3-trifloyloxy pyrazole, while bromination and iodination yielded the corresponding halogenated derivatives. The obtained scaffolds were used in carbon-carbon bond forming Pd-catalyzed cross-coupling reactions to yield (het)aryl- and carbo-functionally substituted 1-phenyl-1H-pyrazoles.     

Asymmetric synthesis of anti-homopropargylic alcohols from aldehydes and chiral sulfonimidoyl substituted bis(allyl)titanium complexes through generation and elimination of novel chiral alkylidenecarbene (dimethylamino)sulfoxonium ylides

A new method for the asymmetric synthesis of anti-configured homopropargylic alcohols 1 is described, which features the addition of chiral sulfonimidoyl substituted bis(allyl)titanium complexes 3 to aldehydes, the methylation of sulfonimidoyl substituted homoallylic alcohols 2 at the N-atom, and the elimination of alkenyl (dimethylamino)sulfoxonium salts 7 with LiN(H)tBu. The reaction of isopropyl, cyclohexyl, and methyl substituted allylic titanium complexes 3a-c with benzaldehyde, p-bromobenzaldehyde, p-chlorobenzaldehyde, p-methoxybenzaldehyde, (E)-3-phenylpropenal, and phenylpropynal afforded with high regio- and diastereoselectivities the anti-configured sulfonimidoyl substituted homoallylic alcohols 2a-j, respectively. Only one allylic unit of the titanium complexes 3a-c was transferred in the case of unsaturated aldehydes, and the starting allylic sulfoximines 2a-g were recovered in approximately 50% yield. The methylation of the silyl protected alkenyl sulfoximines 6a-j with Me(3)OBF(4) gave in practically quantitative yields the (dimethylamino)sulfoxonium salts 7a-j, respectively. Salts 7a-e, 7g, 7h, and 7j delivered upon treatment with 2 equiv of LiN(H)tBu the enantio- and diastereomerically pure saturated and unsaturated alkynes 9a-e, 9g, 9h, and 9j, respectively, in high yields. Besides the alkynes the sulfinamide 8 (96% ee) was isolated. Aminosulfoxonium salts 9f and 9i, which carry a CC triple bond, also suffered an elimination under these conditions but did not yield the corresponding diynes. Elimination of salts 7a-e, 7g, 7h, and 7j proceeds most likely through deprotonation at the alpha-position with formation of the novel alkylidenecarbene aminosulfoxonium ylides 19a-e, 19g, 19h, and 19j, respectively. The ylides 19a-e, 19g, 19h, and 19j presumably eliminate sulfinamide 8 with generation of the chiral nonracemic (beta-siloxyalkylidene)carbenes 20a-e, 20g, 20h, and 20j, which suffer a 1,2-H-shift with formation of alkynes 9. Support for the formation of the putative alkylidenecarbenes 20 as intermediates comes from the elimination of the beta-methyl substituted aminosulfoxonium salt 24, which delivered the enantio- and diastereomerically pure 2,3-dihydrofuran derivative 28 upon treatment with LiN(H)tBu in high yield. Here, the putative (beta-siloxyalkylidene)carbene 26 suffers a 1,5-O,Si bond insertion rather than a 1,2-Me shift. Methylation of the alkenyl sulfoximine 6a at the alpha-position with formation of 13 was achieved through deprotonation of the former with formation of the alpha-lithioalkenyl sulfoximine 11a and its treatment MeI. Reaction of the alpha-methylated alkenyl aminosulfoxonium salt 14a with LiNiPr(2) at low temperatures gave the enantio- and diastereomerically pure anti-configured homoallenylic alcohol derivative 15, while reaction of the salt with LiNiPr(2) or LiN(H)tBu at higher temperatures afforded the enantio- and diastereomerically pure nonterminal homopropargylic alcohol derivative 17. Deprotonation of the alkenyl (dimethylamino)sulfoxonium salts 7a and 7b with nBuLi afforded the novel alkylidenecarbene aminosulfoxonium ylides 19a and 19b, respectively, which upon treatment with MeI yielded the methylated aminosulfoxonium salts 14a and 14b, respectively.     

Reaction of oligomethylene di(3-oxobutanoate) with 1,1-disubstituted alkenes and molecular oxygen in the presence of manganese(II and/or IE) acetate

The reactions of 1,1-disubstituted ethenes with oligomethylene di(3-oxobutanoate) in the presence of manganese(II and/or III) acetate and atmospheric oxygen yielded an ω-(3-oxobutanoyloxy)alkyl 6,6-diaryl-3-hydroxy-3-methyl-1,2-dioxane-4-carboxylate, oligomethylene di(6,6-diaryl-3-hydroxy-3-methyl-1,2-dioxane-4-carboxylate)s, ω-hydroxyalkyl 6,6-diaryl-3-hydroxy-3-methyl-1,2-dioxane-4-carboxylates, an ω-(3-oxobutanoyloxy)alkyl 5,5-diaryl-2-methyl-4,5-dihydrofuran-3-carboxylate, oligomethylene di(5,5-diaryl-2-methyl-4,5-dihydrofuran-3-carboxylate)s, ω-hydroxyalkyl 5,5-diaryl-2-methyl-4,5-dihydrofuran-3-carboxylates, and an ohgomethylene diester bearing a substituted 1,2-dioxane ring and a substituted 4,5-dihydrofuran ring. The reaction of the 1,2-dioxan-3-ols with acid gave the corresponding compounds bearing furan rings. The reaction of 1,1,6,6-tetraaryl-1,5-hexadienes with oligomethylene di(3-oxobutanoate) in the presence of manganese(III) acetate yielded macrocyclic diesters bearing two 4,5-dihydrofuran rings.     

Neue modifizierte Polycarbosilane

Poly(allymethylsilyene-co-benzylidene) is obtained by treatment of allymethyldichlorosilane with α,α-dibromotoluene and magnesium as reducing agent. The polymer reacts with triflic acid under substitution of the allyl group to give the triflate derivative. The conversion of this compound with element hydrogen compounds and triethylamine or with lithium salts leads to numerous new functionally substituted polycarbosilanes. The modified polymers have been characterised by NMR spectroscope (²⁹ Si, ¹³C,¹H).     

Novel trialkylsilyl(germyl)-substituted thienyl- and furylbenzimidazoles and their N-substituted derivatives – synthesis,structure and cytotoxic activity

The reaction of 1,2-phenylenediamine with a variety of silicon- or germanium-containing 2-furaldehydes or 2-thienylcarbaldehydes in DMFA gave the corresponding benzimidazole derivatives in moderate yields (36–49%) in the presence of sodium hydrogen sulfite. As a result, a new series of silyl, germyl substituted hetarylbenzimidazoles were synthesized and their in vitro cytotoxicity was studied. The quaternisation of N-substituted benzimidazoles by heating with various alkyl, allyl and propargyl chlorides and bromides leads to the formation of benzimidazolinium salts. Potential cytotoxic activity of synthesized new benzimidazoles and benzimidazolinium salts was tested in vitro on two monolayer tumour cell lines: MG-22A (mouse hepatoma), HT-1080 (human fibrosarcoma) and normal mouse fibroblasts (NIH 3T3) and compared with corresponding benzimidazoles.     

Synthesis of 2‐(1‐methyl‐1,2,5,6‐tetrahydropyridin‐3‐yl)benzimidazoles

A useful approach for the synthesis of pharmacologically active tetrahydropyridinylbenzimidazoles is described. 2‐Pyridin‐3‐ylbenzimidazoles 3a‐d have been synthesized by condensation of 3‐pyridinecarbox‐aldehyde 1 with substituted 1,2‐phenylenediamines 2a‐d following oxidative cyclization with iodobenzene diacetate. Methylation of 3a‐d with iodomethane and potassium hydroxide, subsequent formation of methylpyridinium salts 4a‐d and 7a‐d and reduction thereafter afforded tetrahydropyridinylbenzimidazoles 5a‐d and 8a‐d .     

Studies on K2CO3-catalyzed 1,4-addition of 1,2-allenic ketones with diethyl malonate: controlled selective synthesis of beta,gamma-unsaturated enones and alpha-pyrones

The K2CO3 (10 mol %)-catalyzed 1,4-addition reaction of diethyl malonate with various substituted 1,2-allenic ketones leading to polyfunctionalized beta,gamma-unsaturated enones 3 or 4 was studied. With 3-unsubstituted 1-substituted-1,2-allenyl ketones, the highly selective formation of beta,gamma-unsaturated enones 4 was observed; with 1,2-allenyl ketones bearing one or two 3-substituents in the allenyl group, only beta,gamma-unsaturated enones 3 with an unmigrated carbon-carbon double bond were produced; with 3-monosubstituted-1,2-allenyl ketones Z-beta,gamma-unsaturated enones 3 were formed with excellent stereoselectivity (E:Z > 96:4); with propadienyl ketones, mixtures of beta,gamma-unsaturated enones 3 and 4 were formed. alpha-Pyrone derivatives were synthesized via the K(2)CO(3)-catalyzed or -promoted reaction of 1,2-allenic ketones with diethyl malonate via a sequential Michael addition-carbon-carbon double bond migration-lactonization process.     

1,2‐Diaza‐3‐silacyclopent‐5‐ene – Synthese und Reaktionen

1,2‐Diaza‐3‐silacyclopent‐5‐ene – Synthesis and Reactions The dilithium salt of bis(tert‐butyl‐trimethylsilylmethylen)ketazine ( 1 ) forms an imine‐enamine salt. 1 reacts with halosilanes in a molar ratio of 1:1 to give 1,2‐diaza‐3‐silacyclopent‐5‐enes. Me₃SiCH=CCMe₃ [N(SiR,R′)‐N=C‐C]HSiMe₃ ( 2 ‐ 7 ). ( 2 : R,R′ = Cl; 3 : R = CH₃, R′ = Ph; 4 : R = F, R′ = CMe₃; 5 : R = F, R′ = Ph; 6 : R = F, R′ = N(SiMe₃)₂; 7 : R = F, R′ = N(CMe₃)SiMe₃). In the reaction of 1 with tetrafluorosilane the spirocyclus 8 is isolated. The five‐membered ring compounds 2 ‐ 7 and compound 9 substituted on the silicon‐fluoro‐ and (tert‐butyltrimethylsilyl) are acid at the C(4)‐atom and therefore can be lithiated. Experiments to prepare lithium salts of 4 with MeLi, n‐BuLi and PhLi gave LiF and the substitution‐products 10 ‐ 12 . 9 forms a lithium salt which reacts with ClSiMe₃ to give LiCl and the SiMe₃ ring system ( 13 ) substituted at the C(4)‐atom. The ring compounds 3 ‐ 7 and 10 ‐ 12 form isomers, the formation is discussed. Results of the crystal structure and analyses of 8 , 10 , 12 , and 13 are presented.     

Research on a number of substituted arylamides of dithiocarboxylic acids

Dithiomalonic acid diarylamldes are cyclized to 3,5-diarylamino-1,2-dithiolium halides by oxidation with an equivalent amount of bromine (iodine) in chloroform solution; the same amides are cyclized to 4-bromo-3,5-diarylamino-1,2-dithiolium bromides with excess bromine and to 3-arylamino-5-arylimino-1,2-dithiols in alkaline media with potassium ferricyanide. The behavior of the synthesized substituted 1,2-dithiols with respect to various reagents was studied.     

1,2-fused pyrimidines. V. Synthesis of 1-alkyl or phenyl-2H-dipyrido-[1,2-a:2′,3′-d]pyrimidine-2,5(1H)-diones

The reaction of 2-[(N-acyl, N-alkyl or phenyl)amino]-4H-pyrido[1,2-a]pyrimidin-4-ones 8a-g with the N,N-dimethylformamide/phosphorus oxychloride Vilsmeier reagent 1 (95°, 90 minutes) afforded 1-alkyl or phenyl-2H-dipyrido[1,2-a:2′,3′-d]pyrimidine-2,5(1H)^?diones, 3-alkyl substituted or not, 10a-g . The starting compounds 8 were prepared by treating 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones N-alkyl substituted 7a,b or N-phenyl substituted 4 with excess anhydrides (130°, 7 hours) when the 2-(alkylamino) derivatives 7 were used in the reaction, compounds 8 were obtained along with very small amounts of 3-acyl-2-(alkylamino)-4H-pyrido[1,2-a]pyrimidin-4-ones 9 .     

Synthesis of substituted 4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazolines and 4-oxo-3,4-dihydroquinazoline-2-thioles

We have developed a liquid-phase synthesis of combinatorial libraries of new disubstituted 4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazolines and trisubstituted 4-oxo-3,4-dihydroquinazoline-2-thioles. The former were prepared using two general procedures: (i) cyclization of substituted methyl anthranilates with isothiocyanates, or (ii) cyclization of substituted 2-(methylcarboxy)benzeneisothiocyanates with primary amines or hydrazines. 4-Oxo-3,4-dihydroquinazoline-2-thioles were prepared by S-alkylation of disubstituted 4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazolines with alkyl or aryl halides. The hydrolysis of methyl benzimidazo[1,2-c]quinazoline-6(5H)-thione-3-carboxylate led to the corresponding acid. This acid was utilized in the synthesis of new benzimidazo[1,2-c]quinazoline-6(5H)-thione-3-carboxamide and S-substituted 6-mecaptobenzimidazo[1,2-c]quinazoline-3-carboxamide libraries.