A novel four-component tandem protocol for the stereoselective synthesis of highly functionalised thiazoles

The reaction of bis(aroylmethyl) sulfides with aromatic aldehydes and ammonium acetate in 1:2:1 molar ratio under solvent-free microwave irradiation afforded predominantly a series of thiazoles, viz., 1-aryl-2-[5(Z)-5-arylmethylidene-2,4-diaryl-2,5-dihydrothiazol-2-yl]ethanones stereoselectively. This reaction presumably occurs via a Knoevenagel condensation-Michael addition-cyclocondensation-ring opening-ring closing Michael addition sequence. The intermediacy of (Z,Z)-2,2′-thiobis(1,3-diarylprop-2-en-1-ones) in the above transformation is demonstrated by their conversion to the thiazoles upon reaction with ammonium acetate under solvent-free microwave irradiation.     

Stereospecific synthesis of new 2,3,4,5-piperidinetetracarboxylic acids and 2,3,5-piperidinetricarboxylic acids

Diels-Alder adducts of 1,2-dihydropyridine with maleic and acrylic acid derivatives were stereospecifically converted by way of RuO₄ oxidation into new r-2,c-3,c-4,c-5-piperidinetetracarboxylic acid, r-2,t-3,t-4,c-5-piperidinetetracarboxylic acid, r-2,c-3,c-5-piperidinetricarboxylic acid, and r-2,t-3,c-5-piperidinetricarboxylic acid.     

Application of ortho-chloro-β-aroylthioamides in synthesis(II): an efficient one-pot, three-component synthesis of tricyclic thiochromeno[2,3-b]pyridine derivatives

Tricyclic thiochromeno[2,3-b]pyridine derivatives have been successfully synthesized in an unusual one-pot multicomponent cascade reaction from ortho-halo-β-aroylthioamides, Meldrum's acid, and aromatic aldehydes. The reaction presumably proceeds via Knoevenagel condensation-Michael addition-cyclocondensation-decarboxylation-rearrangement-intramolecular S_NAr reaction sequence. High bond forming efficiency of this reaction makes it attractive for the synthesis of thiochromeno[2,3-b]pyridine derivatives in a single step operation.     

(l)-Proline-catalysed novel tandem reactions of 1-substituted piperidin-4-ones with (E)-4-arylbut-3-en-2-ones: N-substituent mediated product selectivity and synthesis of novel nitrogen heterocycles

(l)-Proline-catalysed reaction of 1-alkyl/aralkylpiperidin-4-ones with (E)-4-arylbut-3-en-2-ones furnishes novel isoquinoline derivatives, with two or three rings, in good yields via tandem Robinson annulation-Michael addition(s) sequences, while the reaction of 1-arylpiperidin-4-ones with (E)-4-arylbut-3-en-2-ones affords 3-azabicyclo[3.3.1]nonan-9-ones via a tandem Michael addition-aldol reaction sequence.     

Application of N,3-diaryl-3-oxo-propanethioamide in synthesis: an efficient and mild domino approach to highly substituted fused chromenones

A convenient and rapid synthesis of hitherto unknown 3-aroyl-4-aryl-2-phenylamino-4H-benzo[g]chromene-5,10-diones in high yield from β-aroyl-thioacetanilide, aromatic aldehyde, and 2-hydroxy-1,4-naphthoquinone via InCl₃ catalyzed one-pot three-component tandem Knoevenagel condensation–Michael addition–intramolecular cyclization–elimination reaction sequence is disclosed for the first time. This domino protocol has been used to obtain highly substituted pyrano[3,2-c]chromen-5(4H)-ones and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-ones from N,3-diaryl-3-oxo-propanethioamide, aromatic aldehyde, and 4-hydroxycoumarine or dimedone under mild reaction conditions. A plausible reaction mechanism is proposed. The 4H-pyrano[3,2-c]chromen-5-one and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-one derivatives possessing 3-(2-chlorobenzoyl)-2-phenylamino-substituents further cyclized under basic conditions to yield penta-cyclic 7,13-diaryl-5,14-dioxa-13-aza-benzo[a]naphthacen-6,8(7H,13H)-dione and tetra-cyclic 6,12-diaryl-3,3-dimethyl-3,4-dihydro-2H-chromeno[2,3-b]quinolin-1,11(6H,12H)-dione, respectively.     

A facile tandem protocol for the regioselective synthesis of novel thienobenzothiazepines

A series of new 3-benzyl-1,10-diaryl-4H,10H-thieno[3,4-c][1,5]benzothiazepines has been synthesised regioselectively from the reaction of 5-aryl-2,4-bis(arylmethylidene)dihydro-3-thiophenones with o-aminothiophenol in the presence of acetic acid. This transformation presumably occurs via a tandem Michael addition-condensation-isomerisation sequence.     

The Mannich-type interaction of sulfur-containing CH acids with formaldehyde and primary amines

One-pot reactions of dimethyl sulfonyldiacetate and N-methyl-2r,6c-di(methoxycarbonyl)-3t,5t-diphenyltetrahydro-1,4-thiazine 1,1-dioxide with formaldehyde and primary amines lead to derivatives of 9-thia-3,7-diazabicyclo[3.3.1]nonane 9,9-dioxide resulted from decarboxylation of the ester groups at the positions 1 and 5. The effects of the reaction conditions and structure of the starting reagents on the yields of 9-thia-3,7-diazabicyclo[3.3.1]nonane 9,9-dioxides were studied.     

Tandem versus single C-C bond forming reaction under palladium-copper catalysis: regioselective synthesis of α-pyrones fused with thiophene

We herein report a highly convenient protocol for rapid construction of α-pyrone fused with thiophene. This includes one-pot and regioselective synthesis of 4,5-disubstituted and 5-substituted thieno[2,3-c]pyran-7-ones, 6,7-disubstituted and 6-substituted thieno[3,2-c]pyran-4-ones. The synthesis of thieno[2,3-c]pyran-7-ones involves palladium mediated cross coupling of 3-iodothiophene-2-carboxylic acid with terminal alkynes in a simple synthetic operation. The coupling-cyclization reaction was initially studied in the presence of Pd(PPh₃)₂Cl₂ and CuI in a variety of solvents. 5-Substituted 4-alkynylthieno[2,3-c]pyran-7-ones were isolated in good yields when the reaction was performed in DMF. Similarly, 6-substituted 7-alkynylthieno[3,2-c]pyran-4-ones were synthesized via palladium-catalyzed cross coupling of 2-bromothiophene-3-carboxylic acid with terminal alkynes. A tandem C-C bond forming reaction in the presence of palladium catalyst rationalizes the formation of coupled product in this apparently three-component reaction. The cyclization step of this coupling-cyclization-coupling process occurs in a regioselective fashion to furnish products containing six-membered ring only. This sequential C-C bond forming reaction however, can be restricted to the formation of single C-C bond by using 10% Pd/C-Et₃N-CuI-PPh₃ as catalyst system in the cross coupling reaction. 5-Substituted thieno[2,3-c]pyran-7-ones were obtained in good yields when the coupling reaction was performed under this condition. Some of the compounds synthesized were tested in vitro for their anticancer activities.     

Microwave assisted synthesis of indole-annulated dihydropyrano[3,4-c]chromene derivatives via hetero-Diels-Alder reaction

An efficient two-step synthesis of indole-annulated dihydropyrano[3,4-c]chromene derivatives is achieved via Knoevenagel condensation of O-propargylated salicylaldehyde derivatives with indolin-2-ones followed by a microwave-assisted intramolecular-hetero-Diels-Alder reaction of the resulting (Z)-3-(2-(prop-2-ynyloxy)benzylidene)indolin-2-ones in the presence of 20 mol % CuI in acetonitrile.     

Microwave-assisted combinatorial synthesis of hexa-substituted 1,4-dihydropyridines scaffolds using one-pot two-step multicomponent reaction followed by a S-alkylation

A sequential one-pot two-step protocol for microwave-assisted synthesis of Hantzsch-type hexa-substituted 1,4-dihydropyridines has been developed. The three-component reactions of beta-aroylthioamides with aldehydes and acetonitrile derivatives produce the intermediates in situ followed by a S-alkylation to afford hexa-substituted 1,4-dihydropyridines. The reaction presumably proceeds via a Knoevenagel condensation-Michael addition-cyclocondensation-rearrangement-S N2 reaction sequence. Target compounds were obtained in high yields and simply purified by recrystallization. The novel method is complementary to the classical Hantzsch synthesis in that it is well-suited to the preparation of hexa-substituted 1,4-dihydropyridines.     

Four component tandem Knoevenagel–Michael strategy for the assembly of arylaldehydes,N,N'-dimethylbarbituric acid, 4-hydroxy-6-methyl-2H-pyran-2-one and morpholine into unsymmetrical scaffold with three different heterocyclic rings

A new type of four component tandem Knoevenagel–Michael reaction has been found consisting in the assembly of benzaldehydes, N,N'-dimethylbarbituric acid, 4-hydroxy-6-methyl-2H-pyran-2-one and morpholine in alcohols, other organic solvents or water at room temperature without catalyst or any other additives, which results in the selective formation of unsymmetrical scaffold with three different heterocyclic rings in 63–98% yields. The crystal structure of morpholinium 5-[(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)(4-nitrophenyl)methyl]-1,3-dimethyl-2,6-dioxo-1,2,3,4-tetrahydropyrimidin-6-olate has been confirmed by X-ray diffraction.     

Flavonoids. 41. Stereospecific synthesis of 2,3-dihydro-c-3-substituted-t-3-methyl-r-2-phenyl-4H-1-benzopyran-4-ones

The synthesis of 2,3-dihydro-t-3-mesyloxy-c-3-methyl-r-2-phenyl-4H-1-benzopyran-4-one (1) is described. The reaction of mesylate 1 with various nucleophiles, first of all O- and N-nucleophiles, yields the corresponding 2,3-dihydro-c-3-substituted-t-3-methyl-r-2-phenyl-4H-1-benzopyran-4-ones 2b, 7b, 9, 10, 12, 14 and 18 . Azide 14 is a useful intermediate for the synthesis of flavonoids 15–17 .     

Synthesis of 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones from 4-aryl-3-carbethoxy-6-(trifluoromethyl)-2-pyrones and their reaction with sodium azide leading to new carbostyril derivatives

Treatment of ethyl 4-aryl-6-(trifluoromethyl)-2-oxo-2H-pyran-3-carboxylates, prepared from 4,4,4-trifluorobutane-1,3-diones, PCl₅ and sodium diethyl malonate, with sulfuric acid afforded the intramolecular Friedel–Crafts acylation products, 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones, from which 2-(trifluoromethyl)-6H-pyrano[3,4-c]quinoline-4,5-diones were obtained via the Schmidt reaction in moderate yields. The latter reacted with sodium azide to give 2-oxo-4-(5-trifluoromethyl-1,2,3-triazol-4-yl)-1,2-dihydroquinoline-3-carboxylic acids in good yields.     

Flavonoids. 43 [1,2]. Deprotonation-initiated aryl migration with sulfur dioxide extrusion: A route to 2,3-dihydro-2,3-diaryl-3-hydroxy-4H-1-benzopyran-4-ones

Treatment of trans-2,3-dihydro-2-aryl-3-nosyloxy-4H-1-benzopyran-4-ones with various bases afforded 2,3-dihydro-r-2-aryl-t-3-hydroxy-c-(4-nitrophenyi)-4H-1-benzopyran-4-ones in a deprotonation-initiated aryl migration followed by sulfur dioxide extrusion. In the presence of hydroxide and methoxide ions a secondary ring cleavage has also been observed. However, the reaction of trans-2,3-dihydro-2-aryl-3-nosyloxy-4H-1-benzopyran-4-ones with cyanide ions gave 2,3-dihydro-r-2-aryl-t-4-cyano-c-3,c4-epoxy-4H-1-benzopyrans in a carbonyl attack of cyanide followed by an internal substitution reaction.     

Prins-Reaktionen mit Arylaldehyden, 3. Mitt.

By reaction of excess benzaldehyde with cyclohexene in presence of sulfuric acid besider-2,c-4-diphenyl-(t-4aH,c-8aH)-hexahydro-4H-1,3-benzodioxin (2) andr-4-phenyl-(t-4aH,c-8aH)-hexahydro-4H-1,3,2-benzodioxathiin-2,2-dioxide (3),trans-2-benzyloxycyclohexyl phenyl ketone (5) and (E)-3-benzylidene-1-cyclohexenyl phenyl ketone (6) are obtained. The formation of5 and6 is shown to proceed via an acid catalyzedCannizzaro reaction of benzaldehyde.

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2. Mitt.:H. Griengl undK. P. Geppert, Mh. Chem.107, 675 (1976).     

4-alkyl-6-amino-4-N 3,N 5-diaryl-2-thioxo-1,2,3,4-tetrahydropyridine-3,5-dicarboxamides: I. Tandem synthesis and alkylation. Molecular and crystal structure of 6-allylsulfanyl-2-amino-4-isobutyl-N 3,N 5-di-m-tolyl-3,4-dihydropyridine-3,5-dicarboxamide

4-Alkyl-6-amino-4-N ³,N ⁵-diaryl-2-thioxo-1,2,3,4-tetrahydropyridine-3,5-dicarboxamides were obtained via tandem synthesis involving the Knoevenagel reaction, Michael reaction and intramolecular condensation. Alkylation of the obtained dicarboxamides proceeds regioselectively at the S atom to form the corresponding thioethers. Structure of 6-allylsulfanyl-2-amino-4-isobutyl-N ³,N ⁵-di-m-tolyl-3,4-dihydropyridine-3,5-dicarboxamide was uniquely determined by XRD analysis.     

Synthesis of 6-aryl- and 5-aroylcomanic acids from 5-aroyl-2-carbethoxy-4-pyrones via a deformylative rearrangement and ring-opening/ring-closure sequence

The reaction of 1-aryl-2-(dimethylaminomethylene)butane-1,3-diones with diethyl oxalate in the presence of sodium hydride in THF gave ethyl 5-aroyl-4-oxo-4H-pyran-2-carboxylates, from which 4-oxo-6-aryl-4H-pyran-2-carboxylic acids (6-arylcomanic acids) were obtained in high yields via acid-catalyzed deformylative rearrangement. 5-Aroyl-4-oxo-4H-pyran-2-carboxylic acids (5-aroylcomanic acids) were prepared via а ring-opening/ring-closure sequence by the reaction of 5-aroyl-2-carbethoxy-4-pyrones with piperidine and subsequent basic hydrolysis and acidification.     

The reaction of manganese carbonyl with tert-butylisocyanide: Synthesis and characterization of cis- and trans-[Mn(BuNC)4(CN)(CO)]

The reaction of Mn₂(CO)₁₀ with tert-butyl isocyanide in the presence of 10 bar of carbon monoxide leads to the formation of cis- and trans-[Mn(^tBuNC)₄(CN)(CO)], 1a and 1b, in good yields together with [Mn(^tBuNC)₆]CN (2), as a minor product. Nevertheless, the reaction pathway highly depends on the reaction conditions. An interesting side-product is obtained, if chloroform is used during the workup procedure. Compound 3 is composed of cationic [Mn(^tBuNC)₅(CO)] units as well as dinuclear anionic [Mn(^tBuNC)₄(CO)(μ-CN)MnCl₃] moieties. If no additional CO pressure is applied to the system, the organic product N,N′-di-tert-butyl-3,5-bis-tert-butylimino-4-phenyl-cyclopent-1-ene-1,2-diamine (4), is formed in considerable amount. Compound 4 most probably is produced via a double benzylic C-H activation of the solvent toluene and the oligomerization of four isocyanide moieties. The reaction of 1b with Co(NO₃)₂ leads to the isolation of the trinuclear cyanide bridged coordination compound {[Mn(^tBuNC)₄) (CO) (μ-CN)]₂Co(NO₃)₂}, 5, in which the cobalt atoms are tetrahedrally surrounded by the two cyanide ligands and the η¹-coordinated nitro groups. In contrast to the reaction of 1b, treatment of the dicyano complexes cis- or trans-[Ru(^tBuNC)₄(CN)₂] with Co(NO₃)₂ results in the formation of the coordination polymers {[Ru(^tBuNC)₄(CN)₂]Co(NO₃)₂}_n, 7 (trans) and 9 (cis). All new compounds are characterized by X-ray diffraction experiments.     

MOF‐promoted Three‐component Synthesis of Functionalized Pyrano[3,2‐c]chromen under Mild Conditions

A convenient and efficient route for synthesis of various derivatives of 3‐benzoyl‐4‐phenyl‐2‐(trifluoromethyl)pyrano[3,2‐c]chromen‐5(4H)‐one has been used via tandem Knoevenagel condensation–Michael addition and intramolecular cyclization sequence. These products have been synthesized in the presence of catalytic amount of metal–organic framework (MOF) and potassium carbonate as one‐pot, three‐component reaction. MOF catalyst has been separated easily with external magnet, and high purity of products has been obtained after washing with ethanol. This protocol has advantages of simplicity, mild condition, and high yield. More importantly, MOF has been easily recycled for three times.     

Comparison of free and metal coordinated 1,4-disubstituted-1,4-diaza-1,3-butadienes : Crystal and molecular structures of 1,4-dicyclohexyl-1,4-diaza-1,3-butadiene and trans-[dichloro(triphenylphosphine)(1,4-di-tert-butyl- 1,4-diaza-1,3-butadiene)palladium(II)]

The crystal and molecular structures of c-Hex-DAB (c-hexyl-NC(H)C(H)N-c-hexyl; DAB = 1,4-diaza-1,3-butadiene) and of trans-[PdCl₂(PPh₃)(t-Bu-DAB)] are reported. Crystals of c-Hex-DAB are monoclinic with space group C_2/c and cell constants: a = 24.70(1), b = 4.660(2), c = 12.268(3)Å, β = 107.66(4)°, Z = 4. The molecule has a flat E-s-trans-E structure with bond lengths of 1.258(3)Å for the CN double bond and 1.457(3)Å for the central CC′ bond. These bond lengths and the NC-C′ angle of 120.8(2)° indicate that the C- and N-atoms are purely sp²-hybridized and that there is little or no conjugation within the central DAB skeleton. Crystals of trans-[PdCl₂(PPh₃)(t-Bu-DAB)] are triclinic with space group P-1 and cell constants: a = 17.122(3), b = 18.279(3), c = 10.008(5)Å, α = 96.77(2), β = 95.29(3), γ = 109.79(2). Z = 4. The t-Bu-DAB ligand is coordinated to the metal via one lone pair only. In this 2e; σ-N coordination mode the E-s-trans-E conformation of the free DAB-ligand is still present and the bonding distances within the DAB-ligand are hardly affected. [CN: 1.261(10)Å; CC′: 1.479(10)Å (mean).] The PdN-, NC- and central CC′-bond lengths are compared with those found in other metal -R-DAB complexes.