Chemoselective Route for Synthesis of N‐Aryl‐3‐oxochromeno[2,3‐c]pyrazole‐2(3H)‐carbothioamide Derivatives

A chemoselective route for the synthesis of chromeno[2,3‐c]pyrazole‐2(3H)‐carbothioamide derivatives by a five‐component reaction of salicylaldehyde, malononitrile, NH₂NH₂?H₂O, aryl isothiocyanate, and H₂O in EtOH/AcOH mixture is reported. This new protocol has the advantages of high yields, short reaction times, ease of operation, and simple purification. All structures were confirmed by IR, ¹H‐ and ¹³C‐NMR, and MS analyses. A plausible mechanism for this type of reaction is proposed (Scheme 2).     

Poly[bis[μ2‐3‐(pyridin‐4‐yl)benzoato‐κ3N:O,O′]lead(II)]

In the title compound, [Pb(C₁₂H₈NO₂)₂]_n, the Pb atom sits on a crystallographic C₂ axis and is six‐coordinate, ligated by two chelating carboxylate groups from two 3‐(pyridin‐4‐yl)benzoate (L) ligands and by two N atoms from another two ligands. Each ligand bridges two Pb^II centres, extending the structure into a corrugated two‐dimensional (4,4) net. The ligand L is conformationally chiral, with a torsion angle of 27.9 (12)° between the planes of its two rings. The torsion angle has the same sense throughout the structure, so that the extended two‐dimensional polymer is homochiral. Investigation of the thermal stability shows that the network is stable up to 613 K. In the absence of any stereoselective factor in the preparation of the compound, the enantiomeric purity of the crystal studied, based only on the torsional conformation of the ligand, implies that the bulk sample is a racemic conglomerate.     

Regioselective Synthesis of the 5,6‐Dihydro‐4H‐furo[2,3‐c]pyrrol‐4‐one Skeleton: A New Class of Compounds

We hereby report the first preparation of the 5,6‐dihydro‐4H‐furo[2,3‐c]pyrrol‐4‐one ( 3 ) and its derivatives starting from methyl 3‐(methoxycarbonyl)furan‐2‐acetate ( 8 ). The ester functionality connected to the methylene group was regiospecifically converted to the desired monohydrazide 9 . Conversion of 9 into the acyl azide 10 followed by Curtius rearrangement gave the corresponding isocyanate derivative 11 (Scheme 2). Reaction of 11 with different nucleophiles produced urethane and urea derivatives (Scheme 3). Intramolecular cyclization reactions provided the target compounds (Scheme 5). Removal of the amine‐protecting group formed the title compound 3 .     

Synthesis and in vitro Antibacterial Activities of 5‐(2,3,4,5‐Tetrahydro‐1H‐chromeno[2,3‐d]pyrimidin‐5‐yl)pyrimidione Derivatives

A series of novel 5‐(2,3,4,5‐tetrahydro‐1H‐chromeno[2,3‐d]pyrimidin‐5‐yl)pyrimidione derivatives have been synthesized from substituted salicylaldehydes and barbituric acid or 2‐thiobarbituric acid in water catalyzed by phase transfer catalysis of triethylbenzyl ammonium chloride (TEBA). Elemental analysis, IR, ¹H NMR, and ¹³C NMR elucidated the structures of all the newly synthesized compounds. In vitro antimicrobial activities of synthesized compounds have been investigated against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa. These newly synthesized derivatives exhibited significant in vitro antibacterial activity.     

Synthesis of Furo[2,3‐d]pyridazin‐4(5H)‐one and Its N(5)‐Substituted Derivatives

We report the efficient preparation of furo[2,3‐d]pyridazin‐4(5H)‐one and its N‐substituted derivatives starting from methyl 2‐methylfuran‐3‐carboxylate. The Me group was converted to the aldehyde group, which was then condensed with hydrazine derivatives. Then, the ester functionalities were hydrolyzed to the corresponding acids, followed by treatment with SOCl₂ to give N‐substituted furopyridazinone derivatives.     

Facile Synthesis of Naphtho[2,3‐d]thiazoles,Naphtho[2,3‐e][1,3,4]thiadiazines and Bis(naphtho[2,3‐d]thiazolyl)copper(II) Derivatives from Heteroylthiosemicarbazides

A one step synthesis protocol for the conversion of heteroylthiosemicarbazides and 2,3‐dichloro‐1,4‐naphthoquinone to naphtho[2,3‐d]thiazoles, naphtho[2,3‐e][1,3,4]thiadiazines as well as bis(naphtho[2,3‐d]thiazolyl)copper(II) derivatives is described. The products were conclusively confirmed by single crystal X‐ray analyses. A mechanism for the formation of the products is presented.     

A New Four‐Component Reaction for the Synthesis of Spiro[4H‐indeno[1,2‐b]pyridine‐4,3′‐[3H]indoles]

A new four‐component synthesis of spiro[4H‐indeno[1,2‐b]pyridine‐4,3′‐[3H]indoles] and spiro[acenaphthylene‐1(2H),4′‐[4H‐indeno[1,2‐b]pyridines] by the reaction of indane‐1,3‐dione, 1,3‐dicarbonyl compounds, isatins (=1H‐indole‐2,3‐diones) or acenaphthylene‐1,2‐dione, and AcONH₄ in refluxing toluene in the presence of a catalytic amount of pyridine is reported.     

A Facile One‐Pot Synthesis of Functionalized 1,5‐Dihydro‐2H‐[1]benzopyrano[2,3‐b]pyridin‐5‐ones

The highly reactive 1 : 1 intermediate generated in the reaction between dialkyl acetylenedicarboxylate (=but‐2‐ynedioic acid dialkyl ester) 4 and triphenylphosphine was trapped by 2‐amino‐4‐oxo‐4H‐1‐benzopyran‐3‐carboxaldehydes 5 to yield highly functionalized dialkyl‐1,5‐dihydro‐5‐oxo‐1‐phenyl‐2H‐[1]benzopyrano[2,3‐b]pyridine‐2,3‐dicarboxylates in high yield.     

A Simple Synthesis of 2‐{(Arylmethylidene)hydrazinylidene]‐3‐hydroxy‐4H‐furo[3,2‐c]pyran‐4(3H)‐ones

A simple synthesis of 2‐hydrazinylidene‐3‐hydroxy‐4H‐furo[3,2‐c]pyran‐4‐ones is described. A mixture of (isocyanoimino)(triphenyl)phosphorane, an aromatic aldehyde, and dehydroacetic acid (=3‐acetyl‐2‐hydroxy‐6‐methyl‐4H‐pyran‐4‐one) undergo a 1 : 1 : 1 addition reaction under mild conditions to afford the title compounds in excellent yields.     

A Convenient Synthesis of 2,3‐Dihydro‐4H‐thiopyrano[2,3‐b]‐, ‐[2,3‐c]‐, or ‐[3,2‐c]pyridin‐4‐ones by the Reaction of the Corresponding 1‐(Chloropyridinyl)alk‐2‐en‐1‐ones with NaSH

2,3‐Dihydro‐4H‐thiopyrano[2,3‐b]pyridin‐4‐ones 4 were prepared by a three‐step sequence from commercially available 2‐chloropyridine ( 1 ). Thus, successive treatment of 1 with ⁱPr₂NLi (LDA) and α,β‐unsaturated aldehydes gave 1‐(2‐chloropyridin‐3‐yl)alk‐2‐en‐1‐ols 2 , which were oxidized with MnO₂ to 1‐(2‐chloropyridin‐3‐yl)alk‐2‐en‐1‐ones 3 . The reactions of 3 with NaSH?n H₂O proceeded smoothly at 0° in DMF to provide the desired thiopyranopyridinones. Similarly, 2,3‐dihydro‐4H‐thiopyrano[2,3‐c]pyridin‐4‐ones 8 and 2,3‐dihydro‐4H‐thiopyrano[3,2‐c]pyridin‐4‐ones 12 were obtained starting from 3‐chloropyridine ( 5 ) and 4‐chloropyridine ( 9 ), respectively.     

Synthesis,Anticancer, and QSAR Studies of 2‐Alkyl(aryl,hetaryl)quinazolin‐4(3H)‐thione's and [1,2,4]Triazolo[1,5‐c]quinazoline‐2‐thione's Thioderivatives

Considering the frightening high level of mortality from cancer, studies of anticancer agents are vital nowadays. The 24 thioderivatives of 2‐alkyl(aryl)‐quinazolin‐4(3H)‐thiones and 20 thioderivatives of [1,2,4]triazolo[1,5‐c]quinazoline‐2‐thiones were synthesized and evaluated for preliminary in vitro anticancer activity with subsequent in silico QSAR analysis. The substance 18 had the best results inhibiting growth of eight cancer cell lines: CCRF‐CEM of leukemia; SF‐539, SNB‐75, and U251 of CNS cancer; 786, RXF393, and UO‐31 of renal cancer; and MDA‐MB‐231/ATCC of breast cancer (?31.50 – 47.41% of cell growth) with low procancer effect. Calculated QSAR‐models for CCRF‐CEM of leukemia, T‐47D and HS 578T of breast cancer, and mean cell growth demonstrated good rate of anticancer activity prediction (r² = 0.7 – 0.8,  = 0.5 – 0.7).     

One‐pot Combinatorial Synthesis of Benzo[4,5]imidazo‐[1,2‐a]thiopyrano[3,4‐d]pyrimidin‐4(3H)‐one Derivatives

A series of novel fused tetracyclic benzo[4,5]imidazo[1,2‐a]thiopyrano[3,4‐d]pyrimidin‐4(3H)‐one derivatives were synthesized via the reaction of aryl aldehyde, 2H‐thiopyran‐3,5(4H,6H)‐dione, and 1H‐benzo[d]imidazol‐2‐amine in glacial acetic acid. This protocol features mild reaction conditions, high yields and short reaction time.     

Synthesis of 3‐Alkoxybenzo[c]thiophen‐1(3H)‐ones by Hydrolysis of N‐Substituted 3‐Alkoxybenzo[c]thiophen‐1(3H)‐imines Derived from 1‐Bromo‐2‐(dialkoxymethyl)benzenes and Isothiocyanates

A convenient procedure for the preparation of a new type of thiophthalides, 3‐alkoxybenzo[c]thiophen‐1(3H)‐ones 4 and 9 has been developed. Thus, 1‐(dialkoxymethyl)‐2‐lithiobenzenes, generated by Br/Li exchange between 2‐bromo‐1‐(dialkoxymethyl)benzenes 1 and 6 , and BuLi, react with isothiocyanates to afford N‐substituted 2‐(dialkoxymethyl)benzothioamides 2 and 7 , which, on treatment with a catalytic amount of TsOH?H₂O, give N‐substituted 3‐alkoxybenzo[c]thiophen‐1(3H)‐imines 3 and 8 . The latter are hydrolyzed under acidic conditions to the desired products 4 and 9 , respectively.     

新型2-氨基-呋喃并[2,3-d]嘧啶-4(3H)-酮衍生物的合成及抗肿瘤活性

报道应用aza-Wittig反应,采用易得的原料,在温和的条件下,以78%～90%的产率有效的合成了新型2-氨基-呋喃并[3,2-d]嘧啶-4(3H)-酮衍生物5,其结构经IR,1H NMR,MS和元素分析确认.为进一步得到结构确认,化合物5c经X射线衍射分析证实.运用噻唑蓝(MTT)标准法对化合物5进行了体外抗肿瘤活性的测定,其中5f对肺癌细胞A459的IC50值为18.4μmol/L,显示出潜在良好的抗肿瘤活性.     

Synthesis,Reactions, Characterization and Biological Evaluation of 2,3′‐Bipyridine Derivatives (III)

1‐Pyridin‐3‐yl‐3‐(2‐thienyl of 2‐furyl)prop‐2‐en‐1‐ones 1a , 1b reacted with 2‐cyanoethanethioamide 2 to afford the corresponding 4‐(thiophen‐2‐yl or furan‐2‐yl)‐6‐sulfanyl‐2,3′‐bipyridine‐5‐carbonitriles 3a , 3b . The synthetic potentiality of compounds 3a , 3b were investigated in the present study via their reactions with several active halogen containing compounds 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 5 , 5a , 5b . Our aim here is the synthesis of 4‐(2‐thienyl or 2‐furyl)‐6‐pyridin‐3‐ylthieno[2,3‐b]pyridin‐3‐amines 6a , 6b , 6c , 6d , 6e , 6g , 6h , 6i , 6j , 6k , 6l , 6m , 6n ,via 6‐(alkyl‐thio)‐4‐(2‐thienyl or 2‐furyl)‐2,3′‐bipyridine‐5‐carbonitriles 5a , 5b , 5c , 5d , 5e , 5i , 5j , 5k , 5l , 5m . The structures of all newly synthesized heterocyclic compounds were elucidated by considering the data of IR, ¹H‐NMR, mass spectra, as well as that of elemental analyses. Anti‐cancer, anti‐Alzheimer, and anti‐COX‐2 activities were investigated for all the newly synthesized heterocyclic compounds.     

Synthesis and Structure of 2‐Substituted Thieno[3′,2′:5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐one Derivatives

A series of new 2‐substituted 3‐(4‐chlorophenyl)‐5,8,9‐trimethylthieno[3′,2′: 5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐ones 8 were synthesized via an aza‐Wittig reaction. Phosphoranylideneamino derivatives 6a or 6b reacted with 4‐chlorophenyl isocyanate to give carbodiimide derivatives 7a or 7b , respectively, which were further treated with amines or phenols to give compounds 8 in the presence of a catalytic amount of EtONa or K₂CO₃. The structure of 2‐(4‐chlorophenoxy)‐3‐(4‐chlorophenyl)‐5,8,9‐trimethylthieno[3′,2′: 5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐one ( 8j ) was comfirmed by X‐ray analysis.     

A two‐dimensional cadmium(II) coordination polymer based on 5‐(pyridin‐4‐yl)isophthalic acid: poly[[tetraaquabis[μ3‐5‐(pyridin‐4‐yl)isophthalato]dicadmium(II)] pentahydrate]

The title Cd^II compound, {[Cd₂(C₁₃H₇NO₄)₂(H₂O)₄]·5H₂O}_n, was synthesized by the hydrothermal reaction of Cd(NO₃)₂·4H₂O and 5‐(pyridin‐4‐yl)isophthalic acid (H₂L). The asymmetric unit contains two crystallographically independent Cd^II cations, two deprotonated L²⁻ ligands, four coordinated water molecules and five isolated water molecules. One of the Cd^II cations adopts a six‐coordinate octahedral coordination geometry involving three O atoms from one bidentate chelating and one monodentate carboxylate group of two different L²⁻ ligands, one N atom of another L²⁻ ligand and two coordinated water molecules. The second Cd^II cation adopts a seven‐coordinate pentagonal–bipyramidal coordination geometry involving four O atoms from two bidentate chelating carboxylate groups of two different L²⁻ ligands, one N atom of another L²⁻ ligand and two coordinated water molecules. Each L²⁻ ligand bridges three Cd^II cations and, likewise, each Cd^II cation connects to three L²⁻ ligands, giving rise to a two‐dimensional graphite‐like 6³ layer structure. These two‐dimensional layers are further linked by O—H...O hydrogen‐bonding interactions to form a three‐dimensional supramolecular architecture. The photoluminescence properties of the title compound were also investigated.     

Synthesis of Novel Polyfunctionally Substituted Thieno[2,3‐c]pyridazines

4‐Cyano‐5,6‐dimethylpyridazin‐3‐(2H)‐thione 3b was used as a key intermediate for the synthesis of novel polysubstituted thieno[2,3‐c]pyridazines.     

Synthesis and Fungicidal Activity of (E)‐5‐[1‐(2‐Oxo‐1‐oxaspiro[4,5]dec/non‐3‐en‐3‐yl)ethylidene]‐2‐aminoimidazolin‐4‐one Derivatives

The novel fungicidal agents, (E )‐5‐[1‐(2‐oxo‐1‐oxaspiro[4,5]dec/non‐3‐en‐3‐yl)ethylidene]‐2‐aminoimidazolin‐ 4‐one derivatives, were designed and synthesized in moderate to excellent yields in four steps using α ‐hydroxyketone and diketene as raw materials and characterized by HR‐ESI‐MS , ¹H NMR and X‐ray diffraction. The preliminary bioassay showed that some of these compounds, such as 5e , 6a , 6e , and 7 h exhibit 87.8%, 91.3%, 89.9% and 87.8% inhibition rates against Sclerotinia scleotiorum , 3b , 3c , 4c and 7 h exhibit 96.4%, 92.5%, 90.3% and 76.9% inhibition rates against Phytophthora capsici at the concentration of 50 µg/mL , respectively. These compounds exhibited significant fungicidal activities against S. scleotiorum and P. capsici with EC₅₀ values of 2.56–11.60 µg/mL , and compounds 6e and 7 h exhibited weak inhibition against the spore germination of S. scleotiorum , while the spore germination of P. capsici was strongly inhibited by compound 7 h solution. Scanning electron microscopy (SEM ) and transmission electron microscopy (TEM ) observation indicated that compound 7 h had a significant impact on the structure and function of the hyphal cell wall of P. capsici mycelium.     

A Novel and Efficient Synthesis of 3‐[(4,5‐Dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐chromen‐2‐ones (=3‐[(4,5‐Dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐1‐benzopyran‐2‐ones)

An efficient one‐pot synthesis of 3‐[(4,5‐dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐chromen‐2‐one (=3‐[(4,5‐dihydro‐1H‐pyrrol‐3yl)carbonyl]‐2H‐1‐benzopyran‐2‐one) derivatives 4 by a four‐component reaction of a salicylaldehyde 1 , 4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one, a benzylamine 2 , and a diaroylacetylene (=1,4‐diarylbut‐2‐yne‐1,4‐dione) 3 in EtOH is reported. This new protocol has the advantages of high yields (Table), and convenient operation. The structures of these coumarin (=2H‐1‐benzopyran‐2‐one) derivatives, which are important compounds in organic chemistry, were confirmed spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this reaction is proposed (Scheme 2).