Microwave‐induced Stereoselectivity in Synthesis of trans‐4‐Aryl‐3‐methyl‐6‐oxo‐4,5,6,7‐tetrahydro‐2H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitriles

A facile synthesis of trans isomers of 4‐aryl‐3‐methyl‐6‐oxo‐4,5,6,7‐tetrahydro ‐ 2H ‐ pyrazolo[3,4‐b]pyridine‐5‐carbonitriles via three‐component condensation reaction of an aldehyde, 3‐amino‐5‐methylpyrazole and ethyl cyanoacetate in acetonitrile has been developed under microwave irradiation. This one‐pot reaction proceeds without any catalyst in short times and gives the product in high selectivities and high yields.     

Synthesis of 3‐Ω‐amino‐2‐thiohydantoins

In the reaction of ethyl isothiocyanatoacetate with diamines, followed by cyclization of the intermediate product, 3‐monosubstituted thiohydantoins have been obtained. It was found that the reaction course depends on the purity of the isothiocyanate used and also, in the case of dialkylaminoamines, the self‐cyclization occurs. Besides the dialkylamino derivatives of 3‐monosubstituted 2‐thiohydantoins also new monoalkylamino, amino and heterocyclic derivatives were synthesized. The aryldiazonium derivative of 3‐monosubstituted 2‐thiohydantoin yielded both respective phenol derivative after hydrolysis and the product of coupling with 2‐naphthol.     

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。     

Photoinduced and thermal reactions of α‐cyano‐β‐bromomethylcinnamide with 1‐benzyl‐1,4‐dihydronicotinamide

The photoinduced reaction of a mixture of (Z)‐α‐cyano‐β‐bromomethylcinnamide (1) and (E)‐α‐cyano‐β‐bromomethylcinnamide (2) with 1‐benzyl‐1, 4‐dihydronicotinamide produces a mixture of the (E)‐ and (Z)‐ isomers of α‐cyano‐β‐methylcinnamide (3 and 4). Using spin‐trapping technique for monitoring reactive intermediate, it is shown that the reaction proceeds via electron transfer‐debromination‐H abstraction mechanism. The thermal reaction of the same substrate with BNAH at 60°C in the dark gives three products: the (E)‐ and (Z)‐isomers of α‐cyano‐β‐methylcinnamide and a dehydrodimeric product; 2, 7‐dicyano‐3, 6‐diphenylocta‐2, 4, 6‐trien‐1, 8‐dioic amide (7). Based on product analysis, scavenger experiment and cyclic voltammetry, an electron transfer‐debromination‐disproportionation mechanism is proposed.     

Facile and Selective Synthesis of 4‐Methyl‐ and 4‐Phenylthiosemicarbazide (=N‐Methyl‐ and N‐Phenylhydrazinecarbothioamide) Derivatives of Benzil (=1,2‐Diphenylethane‐1,2‐dione)

A selective synthesis of 4‐methylthiosemicarbazide (=N‐methylhydrazinecarbothioamide; 4a ) derivatives by reaction with benzil (=1,2‐diphenylethane‐1,2‐dione; 3 ) is described. The reaction conditions determined the condensation product formed. The most important factor was the acid used: in the presence of conc. HCl solution, the open‐chain 2 : 1 compound 1a was exclusively obtained, whereas in the presence of 2M HCl, the cyclic 1 : 1 condensation product 2a was formed. The alcohol used, the presence of H₂O, and the time of heating were additional crucial factors. The new cyclic compound 2a with a MeO group was exclusively formed when working under high‐dilution conditions. The reaction with the 4‐phenyl derivative 4b gave new cyclic compounds as the major products under all conditions used (Scheme).     

An Unprecedented Synthesis of 3,3‐Disubstituted Isochroman‐1,4‐diones Using Nitrones as Oxygen Atom Donors

A one‐pot reaction of ninhydrin, N‐methyl‐C‐phenyl nitrone, and secondary amine leading to the unprecedented synthesis of 3,3‐disubstituted isochroman‐1,4‐diones is described here. In this reaction, nitrone acts as an oxygen atom donor producing an imine as a side product. The mild reaction conditions, the flexibility of the secondary amines that can be used, the novelty of the product, and the good yields are the highlights of this reaction.     

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 15‐Cyano‐12‐oxopentadecano‐15‐lactone and 15‐Cyano‐ 12‐oxopentadecano‐15‐lactam

15‐Cyano‐12‐oxopentadecano‐15‐lactone was synthesized in 59% total yield starting from 2‐nitrocyclododecanone by Michael addition to acrylaldehyde, followed by reaction with trimethylsilylcyanide, hydrolysis, ring‐expansion, and Nef reaction. A two‐step, one‐pot synthesis of intermediate 2‐hydroxy‐4‐(1‐nitro‐2‐oxycyclododecyl)butanenitrile from 3‐(1‐nitro‐2‐oxocyclododecyl)propanal was developed and the conditions for the Nef reaction were studied. 15‐Cyano‐12‐oxopentadecano‐15‐lactam was synthesized in 40% total yield starting from 2‐nitrocyclododecanone by Michael addition to acrylaldehyde, followed by Strecker reaction, ring‐expansion, and Nef reaction. The conditions for the Strecker and Nef reactions were studied. The structures of the target compounds, intermediates, and by‐product were characterized by IR, ¹H‐ and ¹³C‐NMR, and elemental analysis or MS.     

Cyclization of 4‐Phenylthiosemicarbazide with Phenacylbromide Revisited. Formation of 1,3,4‐Thiadiazines and of Isomeric 1,3‐Thiazoles

The cyclization of 4‐phenylthiosemicarbazide with phenacylbromide, carried out in refluxing ethanol, afforded 1,3,4‐thiadiazine 1 as the major product. In contrast to a previous report, 2‐phenylimino‐4‐phenyl‐2,3‐dihydro‐1,3‐thiazol‐3‐amine ( 2 ) and not 2‐hydrazono‐3,4‐diphenyl‐2,3‐dihydro‐1,3‐thiazole ( 8 ) was formed as a side‐product. This product is the main product when the reaction is carried out in concentrated hydrochloric acid. Our findings were independently confirmed by independent syntheses of the isomeric products and by a thorough study of their reactivity. It is important to note that the product distribution of the cyclization of thiosemicarbazides with haloketones strongly depends on the substitution pattern and on the reaction conditions.     

Hydroarylation of 2‐Aryloxybut‐1‐en‐3‐ynes via Pd/Acid‐Catalyzed C−H Bond Activation: A Concise Synthesis of 2,3‐Bismethylene‐2,3‐dihydrobenzofurans

An intramolecular exo ‐hydroarylation of 2‐aryloxy‐1,4‐disilylbut‐1‐en‐3‐ynes via ortho ‐C−H bond activation under palladium(0) and acid catalysis was found to give 2,3‐bis(silylmethylidene)‐2,3‐dihydrobenzofurans. The two silyl groups present probably promoted the reaction and played a key role in stabilizing the diene moiety in the product. The products readily led to functionalized condensed cycles by a Diels–Alder reaction.     

An Upstream By‐product from Ester Activation via NHC‐Catalysis Catalyzes Downstream Sulfonyl Migration Reaction

A sequential reaction combining N‐heterocyclic carbene (NHC) and N‐hydroxyphthalimide (NHPI) catalysis allowed for the upstream by‐product NHPI, which was generated in the NHC‐catalyzed cycloaddition reaction, to act as the catalyst for a downstream nitrogen‐to‐carbon sulfonyl migration reaction. Enantiomeric excess of the major product in the cycloaddition reaction remained intact in the follow‐up sulfonyl migration reaction.     

溴化镁催化的1,2,3,4-四氢吡啶酮无溶剂合成研究

An efficient and environmentally friendly procedure for the one-pot synthesis of tetrahydropyrimidinones from aldehydes, β-diketones and urea/thiourea by using magnesium bromide as an inexpensive and easily available catalyst under solvent-free conditions was described. Compared with the classical Biginelli reaction conditions, this new method has the advantage of good to excellent yields (74%-94%) and short reaction time (45-90 min). The structure of the Biginelli reaction product from β-diketone, salicylaldehyde and urea has been proposed to possess an oxygen-bridge by cyclization (intramolecular Michael-addition).     

An Environment‐friendly Synthesis of 2,3‐Disubstituted‐2‐iminothiazoline‐4‐ones

A series of 2,3‐substituted‐2‐iminothiazoline‐4‐ones derivatives have been synthesized via an improved method including an auto‐catalyzed reaction. This method avoided using any extra catalyst except for the reaction material. This method has been successful in both the aromatic substituted 2‐iminothiazolines and the alkyl substituted 2‐iminothiazolines. The special product with a hydroxyl group on the 2‐iminogroup of 1,3‐thiazoline‐4‐ones has also been obtained unexpectedly. The possible mechanism has been proposed for the special process of dealkylation and hydroxylation. This method offered a special way to afford the 2‐hydroxyimino‐substituted thiazoline‐4‐one derivatives in an efficient and eco‐friendly way. The mechanism of the transformation under acid condition has also been proposed.     

New trans/cis tetrahydroisoquinolines. 1. trans‐2‐benzyl‐3‐(l‐methyl‐1h‐pyrrol‐2‐yl)‐4‐substituted‐1,2,3,4‐tetrahydroisoquinolin‐1‐ones and corresponding tetrahydroisoquinolines

The reaction of homophthalic anhydride and N‐(1‐methyl‐1H‐pyrrol‐2‐yl‐methylidene)‐benzylamine in boiling benzene afforded as a main product the expected substituted trans‐1,2,3,4‐tetrahydroisoquinoline‐4‐carboxylic acid 5 . The carboxylic group of 5 was transformed in four steps into cyclic amino‐methyl groups yielding numerous new tetrahydroisoquinolinones 11a‐j incorporating a given fragment of pharmacological interest. Reduction of 11a‐j was studied.     

Reaction of 2‐Alkoxy‐4,5‐diphenyl‐1,3‐oxazin‐6‐one with different alcohols and elucidation of the products

Reaction of 2‐methoxy‐4,5‐diphenyl‐1,3‐oxazin‐6‐one 1a with methanol was studied, and the product of the reaction was determined by spectroscopic data and X‐ray analysis. In addition, a series of (Z)‐alkyl 3‐(alkoxycarbonylamino)‐2,3‐diphenylacrylate 4 was synthesized and characterized. J. Heterocyclic Chem., (2012).     

Hydroaluminierung: Synthese,Struktur und Eigenschaften von 1‐Methyl‐cis‐1‐azonia‐5‐alabicyclo[3.3.0]octan und des Alan‐triallylamin‐Adduktes

Hydro‐Alumination: Synthesis, Structure, and Properties of 1‐Methyl‐ cis ‐1‐azonia‐5‐alabicyclo[3.3.0]octane and of the Alan‐triallylamine Adduct The alan‐N‐methyl‐diallylamine adduct ( I ) was obtained by the reaction of N,N‐diallyl‐methyl‐ammoniumchloride with LiAlH₄. Subsequently the reaction product was transformed by intramolecular hydro‐alumination reaction into bis(1‐methyl‐cis‐1‐azonia‐5‐alabicyclo[3.3.0]octane) ( II ). In contrast to I , the bis(alan‐triallylamine) adduct ( III ) does not undergo an analogous hydro‐alumination reaction. The compounds I , II and III were characterized by MS, IR, ¹H‐, ¹³C‐ and ²⁷Al‐NMR spectroscopy, and the X‐ray structures of II and III are reported and discussed.     

Gold‐Catalyzed Formal C−C Bond Insertion Reaction of 2‐Aryl‐2‐diazoesters with 1,3‐Diketones

The transition‐metal‐catalyzed formal C−C bond insertion reaction of diazo compounds with monocarbonyl compounds is well established, but the related reaction of 1,3‐diketones instead gives C−H bond insertion products. Herein, we report a protocol for a gold‐catalyzed formal C−C bond insertion reaction of 2‐aryl‐2‐diazoesters with 1,3‐diketones, which provides efficient access to polycarbonyl compounds with an all‐carbon quaternary center. The aryl ester moiety plays a crucial role in the unusual chemoselectivity, and the addition of a Brønsted acid to the reaction mixture improves the yield of the C−C bond insertion product. A reaction mechanism involving cyclopropanation of a gold carbenoid with an enolate and ring‐opening of the resulting donor–acceptor‐type cyclopropane intermediate is proposed. This mechanism differs from that of the traditional Lewis‐acid‐catalyzed C−C bond insertion reaction of diazo compounds with monocarbonyl compounds, which involves a rearrangement of a zwitterion intermediate as a key step.     

A kinetic study of the high temperature rearrangement of 4‐ethyl‐3,5‐diphenyl‐4H‐1,2,4‐triazole

The kinetics of the thermal rearrangement 4‐ethyl‐3,5‐diphenyl‐4H‐1,2,4‐triazoles, 1 , to the corresponding 1‐ethyl‐3,5‐diphenyl‐1‐alkyl‐1H‐1,2,4‐triazoles, 2 , was studied in 15‐Crown‐5 and octadecane at 330 °C. The reaction was very slow in octadecane but proceed well in 15‐Crown‐5. The reaction order for the reaction was not constant but changed from an initial second order rate law towards a first order rate law as the reaction progressed. This was confirmed by the concentration dependent reaction order, n_c, which was larger than the time dependent rate law, n_t. The rationale for the observation was, that at high substrate concentrations the reaction order was second order while at lower concentrations a competing solvent assisted reaction plays an increasing important role. The data were in agreement with a mechanism in which the neutral 4‐alkyl‐triazoles in an intermolecular nucleophilic displacement reaction form a triazolium triazolate, which in a subsequent nucleophilic reaction gives the observed product.     

Bromination of Cycloparaphenylenes: Strain‐Induced Site‐Selective Bis‐Addition and Its Application for Late‐Stage Functionalization

Bromination of [n ]cycloparaphenylenes (CPPs) is herein reported. Small [n ]CPPs (n <8) underwent a bis‐bromine addition reaction with high site selectively to produce tetrabromo adducts in moderate to excellent yields. Theoretical calculations revealed that thermodynamic stability dictates both the reactivity and site selectivity of the reaction. The addition product was further converted into the octabromo product by a FeBr₃‐catalyzed site‐selective bromination reaction. The tetra‐ and octabromine adducts were then transformed into mono‐ to tetrabromo CPPs, which were further converted into several CPP derivatives. Therefore, bromination and subsequent transformations provide a path for late‐stage functionalization of CPPs.     

Spectrofluorimetric and Spectrophotometric Determination of Oxamniquine in Pharmaceuticals and Biological Fluids via Derivatization with 4‐Chloro‐7‐Nitrobenzo‐2‐oxa‐1,3‐Diazole (NBD‐Cl)

Spectrophotometric and spectrofluorimetric methods were developed for the determination of oxamniquine (OXM). Both methods are based on coupling with 4‐chloro‐7‐nitrobenzo‐2‐oxa‐1,3‐diazole (NBD‐Cl) in borate buffer of pH 7.6, and the reaction product was measured at 400 nm (Method I). The same product was measured by spectrofluorimetry at 480 nm upon excitation at 400 nm (Method II). The absorbance and the fluorescence intensity were enhanced by addition of sodium dodecyl sulphate (SDS). The absorbance‐concentration plot is rectilinear over the range of 5–25 μg/mL with an LOD of 0.31 μg/mL. The fluorescence‐concentration plot is linear over the range of 0.2–1.2 μg/mL with an LOD of 0.03 μg/mL. Both methods were applied to the analysis of capsules, and the results were in good agreement with those obtained using the official method. The method was applied to spiked human plasma; the mean % recovery (n = 5) is 101.05 ± 1.65. A proposal of the reaction pathway is presented.