Synthesis of 1,3‐Dihydro‐3‐oxo‐2‐benzofuran‐1‐carboxylates via Intramolecular Cyclization of 2‐[2‐(Dimethoxymethyl)phenyl]‐ 2‐hydroxyalkanoates Followed by Oxidation

A novel and efficient method for the preparation of 1,3‐dihydro‐3‐oxo‐2‐benzofuran‐1‐carboxylates 4 under mild conditions has been developed. Thus, the reaction of [2‐(dimethoxymethyl)phenyl]lithiums, generated easily from 1‐bromo‐2‐(dimethoxymethyl)benzenes 1 , with α‐keto esters gives the corresponding 2‐[2‐(dimethoxymethyl)phenyl]‐2‐hydroxyalkanoates 2 . The TsOH‐catalyzed cyclization of these hydroxy acetals is followed by the oxidation of the resulting cyclic acetals 3 with PCC to give the desired products in satisfactory yields. The reaction of [2‐(dimethoxymethyl)‐4,5‐dimethoxyphenyl]lithium with (MeOC?O)₂, followed by treatment with NaBH₄ or organolithiums, affords 2‐[2‐(dimethoxymethyl)‐4,5‐dimethoxyphenyl]‐2‐hydroxyalkanoates 6 , which can similarly be transformed into the corresponding 1,3‐dihydro‐3‐oxo‐2‐benzofuran‐1‐carboxylates 7 in reasonable yields.     

Synthesis of 4‐fluoroalkyl‐2H‐pyrido [1, 2‐a] pyrimidin‐2‐ones from 2, 2‐dihydropolyfluoroalkanoic acids

In the presence of N, N′‐dicyclohexylcarbodiimide, 2‐aminopyridine and its derivatives (2) condensed with 2, 2‐di‐hydropolyfluoroalkanoic adds (1) to give the corresponding amides. Subsequent intramolecular Micheal addition‐elimination reactions of the fluorine‐containing amides under basic conditions gave 4‐fluoroalkyl‐2H‐pyrido[1,2‐a]pyrimidin‐2‐ones (3) in good yields.     

Facile Synthesis of Substituted Ethyl 2‐(Chloromethyl)‐2‐hydroxy‐2H‐1‐benzopyran‐3‐carboxylates

Ethyl 2‐(chloromethyl)‐2‐hydroxy‐2H‐chromene‐3‐carboxylates 2a – 2j have been synthesized by reaction of substituted salicylaldehydes with ethyl 4‐chloro‐3‐oxobutanoate, in the presence of piperidine in CH₂Cl₂ at room temperature, in good yields.     

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 .     

Liquid‐Phase Synthesis of 2‐Methyl‐2‐Aryloxypropanoic Acid Derivatives from Polyethylene Glycol) Supported 2‐Bromo‐2‐Methylpropanoate

An efficient liquid‐phase synthesis of 2‐methyl‐2‐aryloxypropanoic acid derivatives with good yields and high purity on soluble polyethylene glycol (PEG) has been developed by treatment of PEG‐bound 2‐bromo‐2‐methylpropanoate with phenoxides in the presence of a catalytic amount of NBu₄I and KI, and subsequent cleavage from the PEG.     

Synthesis of 3‐Aryl‐2‐methoxyinden‐1‐one (Z)‐Phenylhydrazones via Hydrobromic Acid‐Mediated Cyclization of 2‐(1‐Aryl‐2‐methoxyethenyl)benzaldehyde Phenylhydrazones

2‐(1‐Aryl‐2‐methoxyethenyl)benzaldehydes 2 , obtained by successive treatment of 1‐(1‐aryl‐2‐methoxyethenyl)‐2‐bromobenzenes 1 with BuLi and 1‐formylpiperidine, were transformed to the corresponding phenylhydrazones 3 on treatment with PhNHNH₂. When these hydrazones were allowed to react with conc. HBr, cyclization, followed by dehydrogenation with air occurred, furnished 3‐aryl‐2‐methoxyinden‐1‐one (Z)‐phenylhydrazones 4 .     

固相β-环糊精包结物诱导7-羟基-2-甲氧基-2-甲基色满的不对称合成

研究了室温下间苯二酚和甲基乙烯基酮分别与β-环糊精（ β-CD）形成包结物后的几种不同固相反应,结果表明包结物A（间苯二酚/β-CD）与包结物B（甲基乙烯基酮/β-CD）反应能够很好地得到目的产物,产率及ee值分别为82.8%和78.4%;间苯二酚与包结物B反应仅得到低光学活性产物（ee值为19.5%）;包结物A与甲基乙烯基酮反应却没有得到手性目的产物。以熔点、X-粉末衍射、固相核磁碳谱及ROESY多种方法对所形成的包结物进行了表征,包结物中主客体的比例（1：1）通过¹H NMR (400 MHz)得以确定,文章对固相环加成反应的机制也进行了初步探讨。     

Alternative Synthesis of 2‐Hydroxy‐3,5,5‐trimethylcyclopent‐2‐en‐1‐one

The 2‐hydroxy‐3,5,5‐trimethylcyclopent‐2‐en‐1‐one ( 1 ) was synthesized in 42% yield by rearrangement of epoxy ketone 10 on treatment with BF₃⋅Et₂O under anhydrous conditions. Intermediate 10 was available from the known enone 8 , either via direct epoxidation (60% H₂O₂, NaOH, MeOH; yield 50%), or via reduction to the corresponding allylic alcohol 14 (LiAlH₄, THF), followed by epoxidation ([VO(acac)₂], ^tBuOOH) and reoxidation under Swern conditions, in 37% total yield.     

Synthesis and Cytotoxicity of 6‐Pyrrolidinyl‐2‐(2‐Substituted Phenyl)‐4‐Quinazolinones

In our continuing search for potential anticancer candidates, 2‐(3‐methoxyphenyl)‐6‐pyrrolidinyl‐4‐quinazolinone ( JJC‐1 ) was selected as the lead compound. Starting 5‐pyrrolidinyl‐2‐aminobenzamide was prepared using standard methodology from 5‐chloro‐2‐nitrobenzoic acid by reaction with SOCl₂, NH₃, pyrrolidine, and H₂. The starting benzamide then was reacted with 2‐substituted benzaldehyde or benzoyl chloride in N,N‐dimethylacetamide (DMAC) in the presence of NaHSO₃ at 150 °C. Thermal cyclodehydration/dehydrogenation gave the target 6‐pyrrolidinyl‐2‐(2‐substituted phenyl)‐4‐quinazolinones ( 15–22 ). These target compounds were assayed for their cytotoxicity in vitro against six cancer cell lines, including human monocytic leukemia cells (U937), mouse monocytic leukemia cells (WEHI‐3), human hepatoma cells (HepG2, Hep3B) and human lung carcinoma cells (A549, CH27). Most of them exhibited significant cytotoxic effect toward U937 and WEHI‐3 cells, with EC₅₀ values ranging from 0.30 to 10.10 μM. Compound 19 was investigated further for its action mechanisms. Preliminary findings indicated that compound 19 induced G2/M arrest and apoptosis on U937 cells.     

Photocycloaddition Reactions of 2‐(Alk‐3‐en‐1‐ynyl)cyclohex‐2‐enones

The newly synthesized 2‐(alk‐3‐en‐1‐ynyl)cyclohex‐2‐enones 4 undergo photodimerization (chemo‐ and regio‐)selectively at the exocyclic C?C bond to give diastereoisomeric mixtures of 1,2‐dialkynyl‐1,2‐dimethylcyclobutanes. On irradiation of 4 in the presence of 2‐chloroacrylonitrile, cyclobutane formation occurs again (chemo‐ and regio‐)selectively at the exocyclic C?C bond to afford diastereoisomeric mixtures of 2‐alkynyl‐1‐chloro‐2‐methylcyclobutanecarbonitriles. Similarly, compounds 4 undergo photoaddition to 2,3‐dimethylbuta‐1,3‐diene exclusively at the exocyclic C?C bond to afford mixtures of [2+2] and [4+2] cycloadducts.     

Synthesis of 4‐((2‐hydroxynaphthalen‐1‐yl)(aryl)methyl)‐5‐methyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐ones using nano‐Zn‐[2‐boromophenyl‐salicylaldimine‐methylpyranopyrazole]Cl2 nanoparticles

Nano‐Zn‐[2‐boromophenyl‐salicylaldimine‐methylpyranopyrazole]Cl₂ (nano‐[Zn‐2BSMP]Cl₂) as a nanoparticle Schiff base complex and a catalyst was introduced for the solvent‐free synthesis of 4‐((2‐hydroxynaphthalen‐1‐yl)(aryl)methyl)‐5‐methyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐ones by the multicomponent condensation reaction of various aromatic aldehydes, β‐naphthol, ethyl acetoacetate, and phenyl hydrazine at room temperature.     

Polymorphism of 3‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐yl)‐ and 3‐[5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl]‐2H‐chromen‐2‐ones

This study of 3‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐yl)‐2H‐chromen‐2‐one, C₁₇H₁₀N₂O₃, 1 , and 3‐[5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl]‐2H‐chromen‐2‐one, C₁₆H₉N₃O₃, 2 , was performed on the assumption of the potential anticancer activity of the compounds. Three polymorphic structures for 1 and two polymorphic structures for 2 have been studied thoroughly. The strongest intermolecular interaction is stacking of the `head‐to‐head' type in all the studied crystals. The polymorphic structures of 1 differ with respect to the intermolecular interactions between stacked columns. Two of the polymorphs have a columnar or double columnar type of crystal organization, while the third polymorphic structure can be classified as columnar‐layered. The difference between the two structures of 2 is less pronounced. Both crystals can be considered as having very similar arrangements of neighbouring columns. The formation of polymorphic modifications is caused by a subtle balance of very weak intermolecular interactions and packing differences can be identified only using an analysis based on a study of the pairwise interaction energies.     

Crystallographic report: Dimethyl‐2‐phenylethan‐2‐olamine cyanoborane

The structure of the title compound reveals the geometry around the boron atom to be tetrahedral, and the B? C?N moiety has a bent geometry. Copyright © 2005 John Wiley & Sons, Ltd.     

Synthesis of 2‐Mercaptobenzaldehyde, 2‐Mercaptocyclohex‐1‐enecarboxaldehydes and 3‐Mercaptoacrylaldehydes

A novel one‐pot approach for the preparation of 2‐mercaptobenzaldehyde, 2‐mercaptocyclohex‐1‐enecarboxaldehydes and 3‐mercaptoacrylaldehydes [(Z)‐3‐mercapto‐2‐methyl‐3‐phenylacrylaldehyde, 3‐mercapto‐3‐(o‐tolyl)acrylaldehyde)] starting from ortho‐bromobenzaldehyde, 2‐chlorocyclohex‐1‐enecarbaldehydes, (Z)‐3‐chloro‐2‐methyl‐3‐phenylacrylaldehyde and 3‐chloro‐3‐(o‐tolyl)acrylaldehyde is reported. The reaction of sulfur with the Grignard reagent of the acetal for the protection of the aldehyde group affords the title compounds through hydrolysis with dilute hydrochloric acid in high yields.     

Eight New 2‐(2‐Phenylethyl)chromone (=2‐(2‐Phenylethyl)‐4H‐1‐benzopyran‐4‐one) Derivatives from Aquilaria malaccensis Agarwood

Eight new and eight known 2‐(2‐phenylethyl)chromone (=2‐(2‐phenylethyl)‐4H‐1‐benzopyran‐4‐one) derivatives, i.e., 1 – 8 and 9 – 16 , respectively, together with the two known sesquiterpenoids 17 and 18 were isolated from a 70% MeOH extract of Aquilaria malaccensis (AM) agarwood chips. Their structures were determined based on extensive spectroscopic analysis and comparison with reported data.     

Nucleophilic Substitution on Porphyrin Ring： Synthesis of 2-（2-Hydroxynaphthyl）-5,10,15,20-tetraphenylporphyrin

The reactions of 2-nitro-5,10,15,20-tetraphenylporphyrin （1） and its Ni （Ⅱ） （2）, Cu （Ⅱ） （3）, Zn （Ⅱ） （4） complexes with sodium 2-naphthoxide have been investigated in different solvents for preparing 2-substituted porphyrins. 2-（2-Hydroxynaphthyl）-5,10,15,20-tetraphenyl porphyrin （5） and its Ni （Ⅱ） （6）, Cu （Ⅱ） （7）, Zn （Ⅱ） （8） complexes were obtained in 72%, 78%, 81% and 65% yields in 2-naphthol at 150 ℃ respectively. The same products were also obtained in other protic solvents such as diglycol and diglycol monomethyl ether. When the reactions proceeded in aprotic solvent DMF at 150 ℃, besides 5 （70%）, 6 （34%）, 7 （54%） and 8 （50%）, the corresponding 2-（2-naphythoxy）-5, 10,15,20-tetraphenylporphyrin （9）, and its Ni （Ⅱ） （10）, Cu （Ⅱ） （11）, Zn （Ⅱ） （12） complexes were also obtained in minor, 40%, 18% and 2% yields respectively, but only 5, 6, 7, 8 were found at room temperature in DMF or DMSO. These reactions axe much faster than those of 1-4 with sodium phenoxide. The formation of C-coupling products 5-8 was proposed via SRN 1 mechanism.     

Liquid-Phase Synthesis of Methyl （2Z）-2-Arylsulfonylmethyl-2-alkenoates from PEG-Supported a-Phenylselenopropionate

Treatment of lithio derivativ e of novel PEG-supported a-phenylselenopropionate with aldehydes, followed by oxidation-elimination with 30% hydrogen peroxide, formed Baylis-Hillman products, which were then reacted with sodium arylsulfinate. The resulting sulfonylated products were cleaved from the PEG efficiently affording methyl （2Z）-2-arylsulfonylmethyl-2-alkenoates in good yields and high purities.     

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.     

The Stereoselective Total Synthesis of (6S)‐5,6‐Dihydro‐6‐[(2R)‐2‐hydroxy‐6‐phenylhexyl]‐2H‐pyran‐2‐one via Prins Cyclization

The stereoselective total synthesis of an antiproliferative and antifungal α‐pyrone natural product (6S)‐5,6‐dihydro‐6‐[(2R)‐2‐hydroxy‐6‐phenylhexyl]‐2H‐pyran‐2‐one is described. The key steps involved are the Prins cyclization, Mitsunobu reaction, and ring‐closing metathesis reaction.     

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.