Photoannelation Reactions of 3‐(Alk‐1‐ynyl)cyclohept‐2‐en‐1‐ones

Irradiation (350 nm) of the newly synthesized 3‐(alk‐1‐ynyl)cyclohept‐2‐en‐1‐ones 1 and 2 leads to the selective formation of tricyclic head‐to‐head dimers. In the presence of 2,3‐dimethylbuta‐1,3‐diene, the (monocyclic) enone 1 affords trans‐fused 7‐alkynyl‐bicyclo[5.2.0]nonan‐2‐ones as major photoproducts, whereas photocycloaddition of benzocyclohept‐5‐en‐7‐one 2 to the same diene gives preferentially the eight‐membered cyclic allene 16 via ‘end‐to‐end’ cyclization of the intermediate allyl‐propargyl biradical 22 . On contact with acid, cycloocta‐1,2,5‐triene 16 isomerizes to cycloocta‐1,3,5‐triene 18 .     

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.     

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 .     

Photocycloaddition Reactions of 5,5‐Dimethyl‐3‐(3‐methylbut‐3‐en‐1‐ynyl)cyclohex‐2‐en‐1‐one

The title cyclohexenone 1d undergoes photodimerization selectively at the exocyclic C?C bond to give a 1 : 1 mixture of 1,2‐dialkynyl‐1,2‐dimethylcyclobutanes 6 and 7 . On irradiation in the presence of 2,3‐dimethylbuta‐1,3‐diene, 1d affords bicyclo[8.4.0]tetradeca‐1,2,3,7‐tetraen‐11‐one 9 . This – formal – (6+4)‐cycloadduct undergoes quantitative isomerization to 3‐cycloheptadienyl‐2,5,5‐trimethylcyclohex‐2‐enone 11 on treatment with basic silica gel.     

Regioselective Synthesis of 6‐[Chloro(difluoro)methyl]salicylates by [3+3] Cyclocondensations of 1,3‐Bis(trimethylsilyloxy)buta‐1,3‐dienes with 1‐Chloro‐1,1‐difluoro‐4‐(trimethylsilyloxy)pent‐3‐en‐2‐one

The TiCl₄‐mediated [3+3] cyclocondensation of various 1,3‐bis(trimethylsilyloxy)buta‐1,3‐dienes with 1‐chloro‐1,1‐difluoro‐4‐(trimethylsilyloxy)pent‐3‐en‐2‐one provides a regioselective access to novel 6‐(chlorodifluoromethyl)salicylates (=6‐(chlorodifluoromethyl)‐2‐hydroxybenzoates) with very good regioselectivity. For selected products, it was demonstrated that the CF₂Cl group can be transformed to CF₂H and CF₂(Allyl) by free‐radical reactions.     

Reactions with 4‐Hydroxy‐2‐methylbutananilides: Unexpected Formation of a Cyclopropanecarboxamide

The successive treatment of the N,N‐disubstituted 4‐hydroxy‐2‐methylbutanamide 2a with lithium diisopropylamide (LDA) and diphenyl phosphorochloridate (DPPCl) led to the 1‐methylcyclopropanecarboxamide 10 in good yield. This base‐catalyzed cyclization offers a new approach to cyclopropanecarboxamides. Under similar conditions, the N‐monosubstituted 4‐hydroxy‐2‐methylbutanamide 2b gave the 3‐methylpyrrolidin‐2‐one 11 . The structure of the cyclopropanecarboxamide 10 was established by X‐ray crystallography.     

Electrocarboxylation of Acetophenone to 2‐Hydroxy‐2‐phenylpropionic Acid in the Presence of CO2

Electrocarboxylation of acetophenone with CO₂ to obtain 2‐hydroxy‐2‐phenylpropionic acid was carried out in acetonitrile solution containing 0.1 mol·L^?1 tetraethylammonium bromide. Influences of the nature of the electrodes, the working potential, the passed charge and the concentration of acetophenone on the electrocarboxylation were studied. After optimizing the synthetic parameters, the maximal isolated yield reached 73.0% on Mg‐stainless steel couple electrodes under potentiostatic electrolysis until 2.2 F·mol^?1 of charge was passed at 25 °C. The reduction of acetophenone was studied by cyclic voltammetry and the mechanism has been proposed on the basis of the results.     

One‐Pot Synthesis of 4‐(Alkylamino)‐1‐(arylsulfonyl)‐3‐benzoyl‐1,5‐ dihydro‐5‐hydroxy‐5‐phenyl‐2H‐pyrrol‐2‐ones via a Multicomponent Reaction

An effective route to novel 4‐(alkylamino)‐1‐(arylsulfonyl)‐3‐benzoyl‐1,5‐dihydro‐5‐hydroxy‐5‐phenyl‐2H‐pyrrol‐2‐ones 10 is described (Scheme 2). This involves the reaction of an enamine, derived from the addition of a primary amine 5 to 1,4‐diphenylbut‐2‐yne‐1,4‐dione, with an arenesulfonyl isocyanate 7 . Some of these pyrrolones 10 exhibit a dynamic NMR behavior in solution because of restricted rotation around the C? N bond resulting from conjugation of the side‐chain N‐atom with the adjacent α,β‐unsaturated ketone group, and two rotamers are in equilibrium with each other in solution ( 10 ? 11 ; Scheme 3). The structures of the highly functionalized compounds 10 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS), by elemental analyses, and, in the case of 10a , by X‐ray crystallography. A plausible mechanism for the reaction is proposed (Scheme 4).     

胆甾-4α-甲基-8-烯-3β，7α-二醇二乙酸酯的结构与性质研究

Lophenol, cholest-4α-methyl-7-en-3β-ol (1), obtained from Dracaena cochinchinensis (Lour.) S. C. Chen, was structurally modified. It was acetylated to protect 3β-hydroxyl group, and then oxidised by selenium dioxide in acetic acid to give cholest-4a-methyl-8-en-3β, Ta-diol diacetate (3). This compound 3 is unstable in chloroform solution or when heated and easily converted to a diene compound, cholest-4a-methyl-7,14-dien-3β-ol acetate (4). The structures of 3 and 4 were elucidated by means of IR, ^1H NMR, ^13C NMR and MS, and the absolute configuration of 3 was established by X-ray crystallography. The property of 3 was also discussed in this paper. Both 3 and 4 are new compounds and were reported for the first time.     

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.     

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).     

New Approaches to the Synthesis of 4‐(2‐Aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones and 3‐Ureidoindoles and a Study of Their Interconversion

3‐Alkyl/aryl‐3‐ureido‐1H,3H‐quinoline‐2,4‐diones ( 2 ) and 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) react in boiling concentrated HCl to give 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ). The same compounds were prepared by the same procedure from 2‐alkyl/aryl‐3‐ureido‐1H‐indoles ( 4 ), which were obtained from the reaction of 3‐alkyl/aryl‐3‐aminoquinoline‐2,4(1H,3H)‐diones ( 1 ) with 1,3‐diphenylurea or by the transformation of 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) and 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ) in boiling AcOH. The latter were converted into 1,3‐bis[2‐(2‐oxo‐2,3‐dihydro‐1H‐imidazol‐4‐yl)phenyl]ureas ( 5 ) by treatment with triphosgene. All compounds were characterized by ¹H‐ and ¹³C‐NMR and IR spectroscopy, as well as atmospheric pressure chemical‐ionisation mass spectra.     

Transferred multipolar atom model for 10β,17β‐dihydroxy‐17α‐methylestr‐4‐en‐3‐one dihydrate obtained from the biotransformation of methyloestrenolone

Biotransformation is the structural modification of compounds using enzymes as the catalysts and it plays a key role in the synthesis of pharmaceutically important compounds. 10β,17β‐Dihydroxy‐17α‐methylestr‐4‐en‐3‐one dihydrate, C₁₉H₂₈O₃·2H₂O, was obtained from the fungal biotransformation of methyloestrenolone. The structure was refined using the classical independent atom model (IAM) and a transferred multipolar atom model using the ELMAM2 database. The results from the two refinements have been compared. The ELMAM2 refinement has been found to be superior in terms of the refinement statistics. It has been shown that certain electron‐density‐derived properties can be calculated on the basis of the transferred parameters for crystals which diffract to ordinary resolution.     

Improved Synthesis of 2,2‐Arylmethylene Bis(3‐hydroxy‐5,5‐dimethyl‐2‐cyclohexene‐1‐one) and 1,8‐Dioxo‐octahydroxanthene Derivatives Catalyzed by Electrogenerated Base and Sulfuric Acid

An efficient method has been developed for the synthesis of 1,8‐dioxo‐octahydroxanthene derivatives in two‐step. In the first step, the electrogenerated base (EGB) catalyzed multicomponent transformation of dimedone and aromatic aldehydes in an undivided cell in the presence of sodium bromide as an electrolyte into 2,2′‐arylmethylene bis(3‐hydroxy‐5,5‐dimethyl‐2‐cyclohexene‐1‐one) at room temperature. In the second step, H₂SO₄ was employed as a dehydrating reagent for the cyclization process to give symmetrical heterocycles 1,8‐dioxo‐octahydroxanthene derivatives. Short reaction time, convenient work up, and using of inexpensive reagents, simple equipment, novel and eco‐friendly procedure make this strategy more useful for the preparation of xanthene derivatives.     

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.     

Structure and Thermal Stability of a Novel 2‐D Layered Copper(II) Coordination Polymer with the Bidentate Ligand 1, 2, 4‐Triazol‐5‐one

Single crystals of {[Cu(TO)₂(H₂O)₂](NO₃)₂}_n (TO: 1, 2, 4‐triazol‐5‐one) were grown by slow evaporation from aqueous solution. It crystallizes in the orthorhombic space group Pbca, with a = 7.082(1), b = 10.285(1), c = 17.911(3)Å, V = 1304.6(3)ų, Z = 4. The Cu^II distorted octahedra are bridged by bidentate TO ligands into infinite 2‐D interlaced rhombic grid‐like network planes, {[Cu(TO)₂(H₂O)₂]²⁺}_n. Hydrogen bonds, electrostatic interactions, and weak van der Waals' forces assemble these planes and the NO₃^— anions to a layered structure. The title compound decomposes at 153.4 °C to the final products, Cu(CN)₂ and CuO.     

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.     

Polymorphism in 3‐acetyl‐4‐hydroxy‐2H‐chromen‐2‐one

A new polymorph (denoted polymorph II) of 3‐acetyl‐4‐hydroxy‐2H‐chromen‐2‐one, C₁₁H₈O₄, was obtained unexpectedly during an attempt to recrystallize the compound from salt–melted ice, and the structure is compared with that of the original polymorph (denoted polymorph I) [Lyssenko & Antipin (2001). Russ. Chem. Bull. 50 , 418–431]. Strong intramolecular O—H...O hydrogen bonds are observed equally in the two polymorphs [O...O = 2.4263 (13) Å in polymorph II and 2.442 (1) Å in polymorph I], with a slight delocalization of the hydroxy H atom towards the ketonic O atom in polymorph II [H...O = 1.32 (2) Å in polymorph II and 1.45 (3) Å in polymorph I]. In both crystal structures, the packing of the molecules is dominated and stabilized by weak intermolecular C—H...O hydrogen bonds. Additional π–π stacking interactions between the keto–enol hydrogen‐bonded rings stabilize polymorph I [the centres are separated by 3.28 (1) Å], while polymorph II is stabilized by interactions between α‐pyrone rings, which are parallel to one another and separated by 3.670 (5) Å.     

Anionic polymerization of N,N‐dialkyl‐2‐methylenebut‐3‐enamide: Effect of alkyl substituents on polymerization behavior

Anionic polymerizations of three 1,3‐butadiene derivatives containing different N,N‐dialkyl amide functions, N,N‐diisopropylamide (DiPA), piperidineamide (PiA), and cis‐2,6‐dimethylpiperidineamide (DMPA) were performed under various conditions, and their polymerization behavior was compared with that of N,N‐diethylamide analogue (DEA), which was previously reported. When polymerization of DiPA was performed at ?78 °C with potassium counter ion, only trace amounts of oligomers were formed, whereas polymers with a narrow molecular weight distribution were obtained in moderate yield when DiPA was polymerized at 0 °C in the presence of LiCl. Decrease in molecular weight and broadening of molecular weight distribution were observed when polymerization was performed at a higher temperature of 20 °C, presumably because of the effect of ceiling temperature. In the case of DMPA, no polymer was formed at 0 °C and polymers with relatively broad molecular weight distributions (M_w/M_n = 1.2) were obtained at 20 °C. The polymerization rate of PiA was much faster than that of the other monomers, and poly(PiA) was obtained in high yield even at ?78 °C in 24 h. The microstructure of the resulting polymers were exclusively 1,4‐ for poly(DMPA), whereas 20–30% of the 1,2‐structure was contained in poly(DiPA) and poly(PiA). © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3714–3721, 2010     

Adding a Functional Handle to Nature′s Building Blocks: The Asymmetric Synthesis of β‐Hydroxy‐α‐Amino Acids

β‐Hydroxy‐α‐amino acids are not only used by synthetic chemists but are also found in natural products, many of which show anti‐microbial or anti‐cancer properties. Over the past 30 years, chemists have searched for many asymmetric routes to these useful building blocks. Initial attempts to synthesize these compounds utilized chiral auxiliaries and the reactions of glycine equivalents with aldehydes to form two stereocenters in one step. Other methods with the formation of specific intermediates or that were aimed at a specific amino acid have also been investigated. Asymmetric hydrogenation by dynamic kinetic resolution has emerged as a high‐yielding method for the synthesis of an array of modified amino acids with good stereoselectivity. More recently, amino‐acid functionalization and multicomponent reactions have increased the atom economy and simplified many long and difficult routes. In this Focus Review, many of the elegant syntheses of these compounds are explored. The applications of β‐hydroxy‐α‐amino acids in natural‐product synthesis are also mentioned.