Design,Synthesis, and Evaluation of 3‐((4‐(t‐Butyl)‐2‐(2‐benzylidenehydrazinyl)thiazol‐5‐yl)methyl)quinolin‐2(1H)‐ones as Neuraminidase Inhibitors

A series of novel 3‐((4‐(t‐butyl)‐2‐(2‐benzylidenehydrazinyl)thiazol‐5‐yl)methyl)quinolin‐2(1H)‐ones ( 7a – 7z ) were designed, synthesized and evaluated for their ability of inhibiting neuraminidase (NA) of in?uenza H1N1 virus. Some compounds displayed moderate influenza NA inhibitory activity. Compound 7l with the scaffold of 2‐(2‐(2‐methoxybenzylidene)hydrazinyl)thiazole was the best one, exhibiting moderate NA inhibitory activity with IC₅₀ of 44.66 µmol/L. Structure‐activity relationship showed that compounds with methoxy or hydroxy groups at the ortho position, fluorine and nitro groups at the meta position and chlorine and bromine groups at the para position of phenyl ring were more active. Docking study indicated that compound 7l has important interactions with some key residues (including Asp151, Glu119, Arg292, Tyr406, and Asn347) and binds to 430‐cavity adjacent to NA active site.     

Enantiospecific Synthesis of (R)‐3‐Amino‐4‐(2,4,5‐trifluorophenyl)butanoic Acid Using (S)‐Serine as a Chiral Pool

Starting from (S)‐serine, a new method was developed for the synthesis of the β‐amino acid part of sitagliptin in ten steps and with an overall yield of 30%. The crucial step of the synthesis was the ring opening of N‐ and O‐protected (R)‐aziridin‐2‐methanol with (2,4,5‐trifluorophenyl)magnesium bromide to give N‐ and O‐protected (R)‐2‐amino‐3‐(2,4,5‐trifluorophenyl)propan‐1‐ol.     

Synthesis of (4Z)‐4‐(Arylmethylidene)‐5‐ethoxy‐1,3‐oxazolidine‐2‐thiones by the Reaction of Ethyl (2Z)‐3‐Aryl‐2‐isothiocyanatoprop‐2‐enoates with Organolithium Compounds

A convenient one‐pot method for the preparation of (4Z)‐4‐(arylmethylidene)‐5‐ethoxy‐1,3‐oxazolidine‐2‐thiones 2 and 3 from ethyl (2Z)‐3‐aryl‐2‐isothiocyanatoprop‐2‐enoates 1 , which can be easily prepared from ethyl 2‐azidoacetate and aromatic aldehydes, has been developed. Thus, these α‐isothiocyanato α,β‐unsaturated esters were treated with organolithium compounds, including lithium enolates of acetates, to provide 5‐substituted (4Z)‐4‐(arylmethylidene)‐5‐ethoxy‐1,3‐oxazolidine‐2‐thiones, 2 , and 2‐[(4Z)‐(4‐arylmethylidene)‐5‐ethoxy‐2‐thioxo‐1,3‐oxazolidin‐5‐yl]acetates, 3 .     

Embryotoxicity studies of tri‐n‐butyltin(IV) complexes of 5‐[(E)‐2‐(aryl)‐1‐diazenyl]‐2‐hydroxybenzoic acid and 2‐[(E)‐2‐(3‐formyl‐4‐hydroxyphenyl)‐1‐diazenyl] benzoic acid on sea urchin development

The toxicity studies of free 5‐[(E)‐2‐(aryl)‐1‐diazenyl]‐2‐hydroxybenzoic acid and 2‐[(E)‐2‐(3‐formyl‐4‐hydroxyphenyl)‐1‐diazenyl]benzoic acid and their tri‐n‐butyltin(IV) complexes were evaluated by using sea urchin early developmental stages as recommended model organisms for toxicity tests. The novel complexes, as the parent tri‐n‐butyltin(IV) chloride (TBTCl), caused mitosis block and induced high embryonic mortality in sea urchin. Copyright © 2005 John Wiley & Sons, Ltd.     

One‐Pot Synthesis of N,N‐Disubstituted (Z)‐4‐(Halomethylidene)‐4H‐3,1‐benzothiazin‐2‐amines from 2‐(2,2‐Dihaloethenyl)phenyl Isothiocyanates and Secondary Amines

We have developed a one‐pot procedure for the preparation of N,N‐disubstituted (Z)‐4‐(halomethylidene)‐4H‐3,1‐benzothiazin‐2‐amines 3 from 2‐(2,2‐dihaloethenyl)phenyl isothiocyanates 1 , easily accessible from known 2‐(2,2‐dihaloethenyl)benzenamines by a three‐step sequence, and secondary amines. Thus, the isothiocyanates 1 react with secondary amines to afford the corresponding thiourea derivatives, of which the treatment with NaH provides the desired products.     

Effect of Medium Acidity and Photostability of 3‐(4‐Dimethylamino‐phenyl)‐1‐(2,5‐dimethyl‐thiophen‐3‐yl)‐propenone (DDTP): A New Green Emitting Laser Dye

On the line of a previous work on the spectral properties of some of heteroaryl chalcone, the effect of medium acidity and photoreactivity of 3‐(4‐dimethylamino‐phenyl)‐1‐(2,5‐dimethyl‐thiophen‐3‐yl)‐propenone (DDTP) has been investigated in dimethylformamide and in chloromethane solvents such as methylenechloride, chloroform and carbon tetrachloride. The dye solution (ca. 5×10⁻⁴ mol·L⁻¹ in DMF) gives a good laser emission in the range 470–560 nm with emission maximum at 515 nm upon pumping by nitrogen laser (λ_ex=337.1 nm). The laser parameters such as gain coefficient (α), emission cross section (δ_e) and half life energy (E_1/2) at maximum laser emission are also determined.     

Synthesis of 2‐Aryl‐2,3‐dihydro‐1,8‐naphthyridin‐4(1H)‐ones by Deprotective Cyclization of N‐{3‐[(2E)‐3‐Arylprop‐2‐enoyl]pyridin‐2‐yl}‐2,2‐dimethylpropanamides in Water

A new and convenient method for the preparation of 2‐aryl‐2,3‐dihydro‐1,8‐naphthyridin‐4(1H)‐ones 4 has been developed. Thus, N‐{3‐[(2E)‐3‐arylprop‐2‐enoyl]pyridin‐2‐yl}‐2,2‐dimethylpropanamides 3 are synthesized from commercially available pyridin‐2‐amine using an easily performed three‐step sequence and are subjected to cyclization with deprotection under acidic conditions in H₂O to give the desired products. Similarly, 2‐aryl‐2,3‐dihydro‐1,7‐naphthyridin‐4(1H)‐ones 8 and 2‐aryl‐2,3‐dihydro‐1,6‐naphthyridin‐4(1H)‐ones 12 can be prepared from pyridin‐3‐amine and pyridin‐4‐amine, respectively.     

Synthesis of 4‐Arylisocoumarins (=4‐Aryl‐1H‐2‐benzopyran‐1‐ones) through Acidic Hydrolysis of (Z)‐2‐(1‐Aryl‐2‐methoxyethenyl)benzaldehydes,Followed by Oxidation

4‐Arylisocoumarins (=4‐aryl‐1H‐2‐benzopyran‐1‐ones) 6 were prepared from 2‐(1‐aryl‐2‐methoxyethenyl)‐1‐bromobenzenes 1 . Successive treatment of these bromo styrenes with BuLi and 1‐formylpiperidine gave a mixture of (E)‐ and (Z)‐2‐(1‐aryl‐2‐methoxyethenyl)benzaldehydes 2 . Hydrolysis of (Z)‐isomers with conc. HBr, followed by pyridinium chlorochromate (PCC) oxidation of the resulting 1H‐2‐benzopyran‐1‐ol derivatives 4 (and 5 ), afforded the desired products.     

The Synthesis of (4E)‐N‐(4‐chlorophenyl)‐5‐substituted‐2‐diazo‐3‐oxopent‐4‐enoic Acid Amides

The (4E)‐N‐(4‐chlorophenyl)‐5‐(3‐chlorophenyl)‐2‐diazo‐3‐oxopent‐4‐enoic acid amides 5a˜j were synthesized with N‐(4‐chlorophenyl)‐2‐diazo‐3‐oxobutyramide 4 from p‐chloroaniline and various arylaldehydes. The yielded products 5a˜j were investigated with NMR, MS, IR, and X‐ray crystallographic techniques.     

Formation and Molecular Structure of an Ion Pair Iron (II) Compound Derived from 2,6‐Bis‐ [1‐(2,6‐dibromophenylimino) ‐ethyl] pyridine and 2‐Acetyl‐6‐[1‐(2, 6‐dibromophenylimino)‐ethyl] pyridine

Two novel tridentate ligands of 2,6‐bis‐[l‐(2,6‐dibromophenylimino) ethyl] pyridine (L₁) and2‐acetyl‐6‐[1‐(2,6‐dibromophenylimino) ethyl] pyridine (L2) have been synthesized. The iron(II) complex of L₁ and L₂ has been characterized with the crystal structure of [Fe(L₁)(L₂)]²⁺ [FeCl₄]² CH₂Cl₂ [monoclinic, P2₁ (#11), a = 1.0562(4), b = 2.0928(4), c = 1.2914(2) nm, β = 100.12°, V = 2.810(1) nm³ D_c = 1.879 g/cm³ and Z = 2].     

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 three‐dimensional ZnII coordination framework: poly[[μ2‐(E)‐1,2‐bis(pyridin‐4‐yl)ethene][μ4‐(E)‐2,2′‐(diazene‐1,2‐diyl)dibenzoato][μ2‐(E)‐2,2′‐(diazene‐1,2‐diyl)dibenzoato]dizinc(II)]

In the title coordination polymer, [Zn₂(C₁₄H₈N₂O₄)₂(C₁₂H₁₀N₂)]_n, the asymmetric unit contains one Zn^II cation, two halves of 2,2′‐(diazene‐1,2‐diyl)dibenzoate anions (denoted L²⁻) and half of a 1,2‐bis(pyridin‐4‐yl)ethene ligand (denoted bpe). The three ligands lie across crystallographic inversion centres. Each Zn^II centre is four‐coordinated by three O atoms of bridging carboxylate groups from three L²⁻ ligands and by one N atom from a bpe ligand, forming a tetrahedral coordination geometry. Two Zn^II atoms are bridged by two carboxylate groups of L²⁻ ligands, generating a [Zn₂(CO₂)₂] ring. Each loop serves as a fourfold node, which links its four equivalent nodes via the sharing of four L²⁻ ligands to form a two‐dimensional [Zn₂L₄]_n net. These nets are separated by bpe ligands acting as spacers, producing a three‐dimensional framework with a 4⁶6⁴ topology. Powder X‐ray diffraction and solid‐state photoluminescence were also measured.     

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).     

Synthesis of 3‐(ω‐Hydroxyalkoxy)isobenzofuran‐1(3H)‐ones by Trifluoroacetic Acid‐Mediated Lactonization of tert‐Butyl 2‐(1,3‐Dioxol‐2‐yl)‐ or 2‐(1,3‐Dioxan‐2‐yl)benzoates

An efficient two‐step method for the preparation of 3‐(2‐hydroxyethoxy)‐ or 3‐(3‐hydroxypropoxy)isobenzofuran‐1(3H)‐ones 3 has been developed. Thus, the reaction of 1‐(1,3‐dioxol‐2‐yl)‐ or 1‐(1,3‐dioxan‐2‐yl)‐2‐lithiobenzenes, generated in situ by the treatment of 1‐bromo‐2‐(1,3‐dioxol‐2‐yl)‐ or 1‐bromo‐2‐(1,3‐dioxan‐2‐yl)benzenes 1 with BuLi in THF at ?78°, with (Boc)₂O afforded tert‐butyl 2‐(1,3‐dioxol‐2‐yl)‐ or 2‐(1,3‐dioxan‐2‐yl)benzoates 2 , which can subsequently undergo facile lactonization on treatment with CF₃COOH (TFA) in CH₂Cl₂ at 0° to give the desired products in reasonable yields.     

Efficient Synthesis of (3E)‐3‐[Amino(aryl)methylidene]chromane‐2,4‐diones (=(3E)‐3‐[Amino(aryl)methylene]‐2H‐1‐benzopyran‐2,4(3H)‐diones) via a Three‐Component Reaction

The Michael‐type addition of a 4‐hydroxycoumarin (=4‐hydroxy‐2H‐1‐benzopyran‐2‐one) 1 to a β‐nitrostyrene (=(2‐nitroethenyl)benzene) 2 in the presence of AcONH₄ leads to substituted (3E)‐3‐[amino(aryl)methylidene]chroman‐2,4‐diones (=(3E)‐3‐[amino(aryl)methylene]‐2H‐1‐benzopyran‐2,4(3H)‐diones) 4 (Table 1). High yields, short reaction time, and easy workup are advantages of this novel one‐pot three‐component reaction.     

Synthesis and Herbicidal Activity of Novel N‐(2‐Fluoro‐5(3‐methyl‐2,6‐dioxo‐4‐(trifluoromethyl)‐2,3‐dihydro‐pyrimidin‐1(6H)‐yl)phenyl)‐2‐phenoxyacetamide Derivatives

Thirteen novel N‐(2‐fluoro‐5‐(3‐methyl‐2,6‐dioxo‐4‐(trifluoromethyl)‐2,3‐dihydropyrimidin‐1(6H)‐yl)phenyl)‐2‐phenoxy)acetamides were designed and synthesized utilizing 4‐fluoro‐aniline and ethyl 3‐amino‐4,4,4‐trifluoro‐but‐2‐enoate as starting materials. The chemical structures of all compounds were confirmed by ¹H NMR, IR, mass spectrum and elemental analyses. Subsequently, the herbicidal activities of the as‐prepared compounds were evaluated in the greenhouse. Bioassay results indicated that most of compounds had better herbicidal activities against dicotyledonous weeds. Among all the tested compounds, compounds 4a – 4i showed good herbicidal activities at both pre‐emergence and post‐emergence treatment against two or three kinds of dicotyledonous weeds, such as Abutilon theophrasti Medic, Amaranthus ascendens L, and Chenopodium album L at the dosage of 75 g ai/ha.     

Ring Opening of 2‐(Benzylamino)‐2H‐1,4‐benzoxazin‐3(4H)‐ones and 2‐Bromo‐2H‐1,4‐benzoxazin‐3(4H)‐ones

Substituted 2‐(benzylamino)‐2H‐1,4‐benzoxazin‐3(4H)‐ones are unstable under alkaline and acidic conditions, undergoing opening of the benzoxazinone ring. 2‐Bromo‐2H‐1,4‐benzoxazin‐3(4H)‐ones show similar degradation under alkaline conditions, while replacement of Br at C(2) to give 2‐hydroxy‐2H‐1,4‐benzoxazin‐3(4H)‐ones was observed only under mild alkaline conditions. Mechanisms of ring opening and degradation to 2‐aminophenol derivatives are proposed.     

Transformations of Methyl 2‐[(E)‐2‐(Dimethylamino)‐1‐(methoxycarbonyl)ethenyl]‐1‐methyl‐1H‐indole‐3‐carboxylate

A simple and efficient synthesis of novel 2‐heteroaryl‐substituted 1H‐indole‐2‐carboxylates and γ‐carbolines, compounds 1 – 3 , from methyl 2‐(2‐methoxy‐2‐oxoethyl)‐1‐methyl‐1H‐indole‐3‐carboxylate ( 4 ) by the enaminone methodology is presented.     

Hydriodic Acid‐Mediated Cyclization of α‐Substituted Secondary 2‐Ethenylbenzamides: Synthesis of 2‐Substituted 2,3‐Dihydro‐3,3‐dimethyl‐1H‐isoindol‐1‐ones and 3,3‐Disubstituted (E)‐1‐(Arylimino)‐1,3‐dihydroisobenzofurans

A new and facile method for the preparation of 2‐substituted 2,3‐dihydro‐3,3‐dimethyl‐1H‐isoindol‐1‐ones 3 and 3,3‐disubstituted (E)‐1‐(arylimino)‐1,3‐dihydroisobenzofurans 6 has been developed. Thus, treatment of N‐alkyl(or aryl)‐2‐(1‐methylethen‐1‐yl)benzamides 2 with concentrated hydriodic acid (HI) in MeCN at room temperature afforded 3 . Similar treatment of N‐aryl‐2‐(1‐phenylethen‐1‐yl)benzamide 5 with concentrated HI at 0° afforded 6 .     

A One‐Pot Biginelli Synthesis of 6‐Unsubstituted 5‐Aroylpyrimidin‐2(1H)‐ones and 6‐Acetyl‐1,2,4‐triazin‐3(2H)‐ones

The three‐component Biginelli‐like cyclocondensation reaction of enamines 1 , urea, and aldehydes in dioxane/acetic acid efficiently afforded the corresponding 6‐unsubstituted 3,4‐dihydropyrimidin‐2(1H)‐ones 2 in good yields (Scheme 1, Table). The corresponding reaction of azaenamine (=hydrazone) 7 with benzaldehyde and urea afforded 6‐acetyl‐1,2,4‐triazin‐3(2H)‐ones in good yields (Scheme 3).