An Easy Access to Construct Some Fused 1,2,4‐Triazines with Ring Junction Nitrogen Systems and Their Biological Evaluation

The chemical reactivity of 4‐amino‐6‐benzyl‐3‐mercapto‐1,2,4‐triazine‐5(4H )‐one ( 1 ) towards various aliphatic or/and mono and bis aromatic carboxylic acid derivatives to give the corresponding fused heterocyclic systems, 1,3,4‐thiadiazoles 4 , 5 , 6 , which incorporating 1,2,4‐triazine nucleus was achieved. Moreover, compound 1 was subjected to react either with halo acetic acids or bromo ester to afford the respective fused nitrogen ring junction systems, thiadiazole 2 and 3 , or thiadiazine 7 . However, the tetracyclic ring system 9 was furnished through condensation reaction of isatine with triazine 1 . In addition, some of the new synthesized compounds were evaluated as an antioxidant and antitumor agents.     

Recent Progress in the Chemistry of 2-Tosylacetonitrile

This review is a broad overview of the chemistry of 2-tosylacetonitrile, which considered as a very reactive synthetic compound. The synthetic methods are reported. The reactions of the title compound lead to the preparation of a variety of heterocyclic ring systems, such as five- and six-membered ring systems containing one, two, or three heteroatoms. The reaction mechanisms are discussed.     

An Easy Access to Construct Some New Fused 1,2,4‐Triazines with Ring Junction Nitrogen Systems and Their Biological Evaluation

The chemical reactivity of 4‐amino‐6‐benzyl‐3‐mercapto‐1,2,4‐triazine‐5(4H )‐one ( 1 ) towards various aliphatic or/and mono and bis aromatic carboxylic acid derivatives to give the corresponding fused heterocyclic systems, 1,3,4‐thiadiazoles 4 , 5 , 6 , which incorporating 1,2,4‐triazine moiety was achieved. Moreover, compound 1 was subjected to reaction either with halo acetic acids or bromo ester to afford the respective fused nitrogen ring junction systems, thiadiazole 2 and 3 or thiadiazine 7 . However, while the tetracyclic ring system 9 was furnished through condensation reaction of isatine with triazine 1 . In addition, some of the new synthesized compounds were evaluated as an antioxidant and antitumor agents.     

A New Pathway to Synthesize Cyclomercurated Ferrocenylimines Containing Heterocyclic Ring

The cyclomercurated ferrocenylimines containing heterocyclic ring were prepared by the condensation of cyclomercuration of acylferrocene with the appropriate heterocyclic amine.This procedure provides an efficient method for the synthesis of cyclomerucurated ferrocenylimines containing heterocyclic ring which are difficultly synthesized by the conventional method.The reaction mechanism is proposed.     

Reactions of 3-formylchromone with active methylene and methyl compounds and some subsequent reactions of the resulting condensation products

This review presents a survey of the condensations of 3-formylchromone with various active methylene and methyl compounds, e.g. malonic or barbituric acid derivatives, five-membered heterocycles, etc. The utilisation of the condensation products for the synthesis of different heterocyclic systems, which is based on the ability of the gamma-pyrone ring to be opened by the nucleophilic attack is also reviewed. Finally, the applications of microwave irradiation as an unconventional method of reaction activation in the synthesis of condensation products is described and the biological activity of some chromone derivatives is noted.     

Assessment of the regioselectivity in the condensation reaction of unsymmetrical o-phthaldialdehydes with alanine

One approach for the synthesis of isoindolinones, a privileged bioactive heterocyclic core structure, involves a condensation reaction of o-phthaldialdehydes with a suitable nitrogen-containing nucleophile. This fascinating reaction is revisited here in the context of the use of o-phthaldialdehydes that contain additional substituents in the aromatic ring leading to a detailed analysis of the regioselectivity of the reaction. Eleven monosubstituted o-phthaldialdehydes were synthesised and reacted with alanine. The regioselectivity observed across the eleven substrates led to the design of a disubstituted substrate that reacted with very high control. A gram-scale reaction followed by esterification gave one major regioisomer in high yield. In addition, the regioselectivity observed on reaction of two novel monodeuterated substrates led to an increased mechanistic understanding.     

Synthesis of nitrogen heterocycles by condensation of the conjugate base of open-chain reissert compound analogs with vinyltriphenylphosphonium bromide (schweizer's salt)

Reaction of the conjugate base of several open-chain Reissert compound analogs with vinyltriphenylphosphonium bromide is shown to afford a convenient route to substituted pyrroles. The condensation is a two-step process involving an initial reversible addition to form an unstabilized Wittig reagent followed by an intramolecular Wittig reaction upon the carbonyl group of the tertiary amide functionality with concomitant elimination of HCN. Several applications to the synthesis of 1,2,5-trisubstituted pyrroles are presented, together with attempts to expand this methodology to the synthesis of other heterocyclic systems.     

Ab initio study of the mechanism of forming a spiro‐heterocyclic ring compound involving Si and Ge from dichlorosilylene germylidene(Cl2SiGe:) and formaldehyde

The mechanism of the cycloaddition reaction between singlet dichlorosilylene germylidene (Cl₂Si?Ge:) and formaldehyde has been investigated with the CCSD(T)//MP2/6‐31G* method. From the potential energy profile, it could be predicted that the reaction has one dominant reaction pathway. The reaction rule presented is that the two reactants first form a four‐membered Si‐heterocyclic ring germylene through the [2 + 2] cycloaddition reaction. Because of the 4p unoccupied orbital of Ge atom in the four‐membered Si‐heterocyclic ring germylene and the π orbital of formaldehyde forming a π→p donor–acceptor bond, the four‐membered Si‐heterocyclic ring germylene further combines with formaldehyde to form an intermediate. Because the Ge atom in intermediate undergoes sp3 hybridization after transition state, then, the intermediate isomerizes to a spiro‐heterocyclic ring compound involving Si and Ge via a transition state. © 2012 Wiley Periodicals, Inc.     

Synthesis of thionaphtheno [3, 2-b] pyrrole

The interest shown in the preparation of new heterocyclic systems, and functional derivatives of them, led us to synthesize a new condensed ring system, which included the thionaphthene and pyrrole ring systems.     

On triazoles XVI. The reaction of 5-amino-1,2,4-triazoles with β- and γ-oxo esters. A novel N-carbonylation reaction

5-Amino-1,2,4-triazoles reacted with alifatic β-oxo-esters to yield besides the unexpected 1,2,4-triazolo-[1,5-a]-1,3,5-benzotriazepin-5-one derivative 7 either the corresponding esters 5 and 6 or a 1:2 condensation product 8. To the contrary alicyclic and heterocyclic β-oxo-esters formed in the above reaction only derivatives 7. The proposed mechanism of the formation of 7 involving a novel N-carbonylation reaction was proved by the isolation of the by-products and the intermediate of the reaction. Repeating the above reaction with a γ-oxo-ester, namely the ethyl levulinate, derivatives 17 and 18 , respectively, representing two new ring systems were obtained.     

Solid‐Phase Synthesis of Structurally Diverse Heterocycles by an Amide–Ketone Condensation/N‐Acyliminium Pictet–Spengler Sequence

An efficient approach for the solid‐phase synthesis of structurally diverse heterocyclic compounds is presented. Under acidic reaction conditions, peptidic levulinamides undergo intramolecular ketone–amide condensation reactions to form cyclic N‐acyliminium intermediates. In the presence of a tethered nucleophile, a second cyclization reaction results in the formation of a fused bicyclic ring system. The scope of the methodology was demonstrated by several combinations of substituted ketones and nucleophiles, the latter conveniently originating from amino acids with functionalized side chains, such as tryptophan, substituted phenylalanines, and cysteine. The cyclization sequence provides diastereomerically pure products in high yields. In one extension of the methodology, the resulting relative stereochemistry of the products enables the formation of bridged ring systems by a unique cyclative release mechanism.     

Synthesis of heterocyclic analogs of chalcone containing the selenophene ring

Crotonaldehyde-type condensation using alkaline or acid catalyst is used to synthesize 14 chalcone analogs containing in addition to the selenophene ring, a number of other heterocyclic groups. A Michael adduct is shown to be formed by reaction of 2-acetylselenophene with 2-pyridine aldehyde.     

Synthesis of purinobenzodiazepine and purinobenzotriazocine derivatives,two new heterocyclic ring systems

The preparation of two new heterocyclic ring systems, purinobenzodiazepine and purinobenzotriazocine derivatives by the condensation of 8-aminotheophylline or 8-hydrazinotheophylline with o-carboxybenzaldehyde or o-carboxyacetophenone is described.     

Ab initio study of mechanism of cycloaddition reaction between H2Ge = Ge: and acetone

The mechanism of the cycloaddition reaction between singlet H₂Ge = Ge: and acetone has been investigated with CCSD(T)//MP2/6-31G* method. From the potential energy profile, it could be predicted that the reaction has two competitive dominant reaction pathways. The reaction rule presented is that the two reactants firstly form a four-membered Ge-heterocyclic ring germylene through the [2 + 2] cycloaddition reaction. Because of the 4p-unoccupied orbital of Ge atom in the four-membered Ge-heterocyclic ring germylene and the π-orbital of acetone forming a π → p donor–acceptor bond, the four-membered Ge-heterocyclic ring germylene further combines with acetone to form an intermediate. Because the Ge atom in intermediate happens sp³ hybridization after transition state, then, intermediate isomerizes to a spiro-Ge-heterocyclic ring compound via a transition state. Simultaneously, the ring strain of the four-membered Ge-heterocyclic ring germylene makes it isomerize to a twisted four-membered ring product.     

Reactions of 1,2-bis(trifluoroacetyl)benzene with nucleophiles leading to heterocyclic compounds

The reaction of 1,2-bis(trifluoroacetyl)benzene (II) with ammonia, hydrazine, hydroxylamine and L-alanine has been investigated and the resulting heterocyclic compounds fully characterized on the basis of spectral data. The reaction of II with $\text{o}$-aminophenol and $\text{o}$-phenylenediamine led to the formation of tetracyclic compounds XI and XII respectively. The structure of compound XII has been further supported by single crystal X-ray crystallography. Our studies reveal the potential of the diketone II as a valuable synthon for the synthesis of a variety of heterocyclic systems with trifluoromethyl substituents.     

Solvent‐Specific C―N Bond Formation: Synthesis of Novel Ninhydrin–Creatinine Heterocyclic Condensation Products

Novel ninhydrin–creatinine heterocyclic condensation products ( 3–5 ) were synthesized under different solvent conditions. The compound 2‐(2‐amino‐1‐methyl‐4‐oxo‐4,5‐dihydro‐1H‐imidazol‐5‐yl)‐2‐hydroxy‐1H‐ind‐ene‐1,3(2H)‐dione ( 3 ) was formed by reacting ninhydrin ( 1 ) with creatinine ( 2 ) in the presence of sodium acetate in acetic acid. The same reactants afforded the zwitterionic compound 4 when the reaction was carried out in water, and a novel oxadiazine ring system (product 5 ) was generated when benzene was used as solvent.     

Uncommon expansion of piperidine ring into hydroazocine ring in reactions of some piperidine β-acyl derivatives with acetylenecarboxylic acids esters

Cyclohexanone condensation with formaldehyde and methylamine led to the formation of 4ahydroxy-2-methyloctahydrospiro[isoquinoline-4,1'-cyclohexan]-2'-one whose structure was established by means of X-ray diffraction (XRD) analysis. This spiro compound reacted with acetylenecarboxylic acids esters with unexpected conversion of its piperidine ring into a hexahydroazocine cycle. The uncommon expansion reaction of the β-acyl-substituted piperidine ring into a hexahydroazocine cycle is confirmed by the analogous conversion of 4-hydroxy-1-methyl-4-phenylpiperidin-3-yl(phenyl)methanone into azocine derivative at treating with methyl propiolate.     

Synthesis of novel heterocycles related to the dynemicin a ring skeleton

Studies directed towards the construction of the CDE ring framework of dynemycin A ( 1 ) are reported. A series of quinoline based dienophiles containing an activating group (e.g. 5 , Scheme 1), reacted with acyclic dienes (e.g. 4 , Scheme 1) in a Diels-Alder fashion under increased pressure to afford a variety of heterocyclic systems related to the CDE skeleton of dynemycin A. Reaction of dienophile 15 with cyclic diene 29 led to the novel hetereocycle 34 whereas attempted decarbonylation of 41 led to a novel rhodium-promoted intramolecular carbonylation of the terminal acetylene furnishing compound 43 .     

Synthesis and structure of pyrazolo[5,1-a]isoindol-8-ones from Aromatic Ortho Diesters

The title compounds 2 , have now been shown to arise in certain cases from condensation of aromatic ortho-diesters with ketone, where formerly only indeno[1,2-c]pyrazol-4(1H)-ones 3 have been reported from such reaction. Heretofore 2 was obtained in a less direct fashion from phthalaldehydic acid esters. When hetero-aromatic diesters were employed, new heterocyclic ring systems as represented by 2a,b ,c were prepared for the first time. Structures of 2 have been verified from detailed ¹H and ¹³C nmr studies, while representative intermediates 4–9 in the condensation of diesters to 2 have been isolated and identified.     

新型含巴比妥酸的芳香酰腙类化合物的合成、晶体结构及抑菌活性

在微波辅助下,1,3-二甲基-5-醛基巴比妥酸与芳氧基/芳胺基乙酰肼及含氮杂环乙酰肼缩合制备新型酰腙化合物,并对其抑菌活性进行评价的研究。 新化合物的结构经过元素分析、红外光谱、核磁共振谱、质谱和X射线单晶衍射等技术手段确认。 体外的抑菌活性实验显示,部分目标化合物呈现出优于环丙沙星的抑菌活性。 经过构效关系分析表明,当芳基为含氮杂环时,所形成的化合物抗菌活性与芳基为苯环时相比明显较强,抑菌活性最强的酰腙化合物2t对金黄色葡萄球菌的最小抑菌浓度(MIC)值为0.8 g/L,对大肠杆菌的最小抑菌浓度(MIC)值为1.6 g/L。