Microwave‐assisted Synthesis of 6‐{(5‐Aryl‐1,3,4‐oxadiazol‐2‐yl)methyl}‐6H‐indolo[2,3‐b]quinoxalines

An efficient and convenient synthesis of a new series of 2‐{(6H‐indolo[2,3‐b]quinoxalin‐6‐yl)methyl}‐5‐aryl‐1,3,4‐oxadiazoles from readily available 1,2‐diaminobenzene and isatins under microwave irradiation conditions was disclosed. The 6‐{(5‐aryl‐1,3,4‐oxadiazol‐2‐yl)methyl}‐6H‐indolo[2,3‐b]quinoxalines were also prepared by the thermal cyclo‐condensation reaction of 2‐(6H‐indolo[2,3‐b]quinoxalin‐6‐yl)acetohydrazides with carboxylic acids in refluxing POCl₃. The microwave‐assisted synthesis was rapid and resulted in higher yield of the products at lower operating temperature with reduced waste generation in comparison with the thermal reaction protocol.     

Separation and Retention Behavior of Aromatic Carboxylic Acid Isomers by High‐Performance‐Liquid‐Chromatography Using β‐Cyclodextrin Bonded Phase with Diamine‐s‐Triazine Moiety

A β‐cyclodextrin (β‐CD) bonded phase with diamine‐s‐triazine moiety was prepared. The separation and retention behavior of the isomers of five aromatic carboxylic acids, including toluic acid, aminobenzoic acid, nitrobenzoic acid, hydroxybenzoic acid, and naphthoic acid were investigated by a high‐performance liquid chromatography (HPLC) using the β‐CD bonded phase prepared. The influence of mobile phase pH in the range of 2.7‐3.6 on the retention of these analytes was examined. The isomers of the aromatic carboxylic acids, with the exception of nitrobenzoic acid, were optimally and effectively separated at pH 2.7, while the three isomers of nitrobenzoic acid could be well separated at pH 3.3. Compared with the chromatographic results obtained previously on the amine‐s‐triazine‐β‐CD bonded phase, the retention factors of the isomers of aromatic carboxylic acid on the diamine‐s‐triazine‐β‐CD bonded phase increase to a relatively much greater extent. Thus, the functionality of the spacer arm of the bonded phase playing an important role in the retention of aromatic carboxylic acid isomers is demonstrated. The results also imply that the hydrogen‐bonding interaction and the mechanism of anion exchange sorption as well may contribute significantly to the retention mechanisms.     

A Facile and Efficient Synthesis of Arylsulfonamido‐Substituted 1,5‐Benzodiazepines and N‐[2‐(3‐Benzoylthioureido)aryl]‐3‐oxobutanamide Derivatives

A facile and efficient synthesis of 1,5‐benzodiazepines with an arylsulfonamido substituent at C(3) is described. 1,5‐Benzodiazepine, derived from the condensation of benzene‐1,2‐diamine and diketene, reacts with an arylsulfonyl isocyanate via an enamine intermediate to produce the title compounds of potential synthetic and pharmacological interest in good yields (Scheme 1). In addition, reaction of benzene‐1,2‐diamine and diketene in the presence of benzoyl isothiocyanate leads to N‐[2‐(3‐benzoylthioureido)aryl]‐3‐oxobutanamide derivatives (Scheme 2). This reaction proceeds via an imine intermediate and ring opening of diazepine. The structures were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this type of cyclization is proposed (Scheme 3).     

A General,Activator‐Free Palladium‐Catalyzed Synthesis of Arylacetic and Benzoic Acids from Formic Acid

A new catalyst for the carboxylative synthesis of arylacetic and benzoic acids using formic acid (HCOOH) as the CO surrogate was developed. In an improvement over previous work, CO is generated in situ without the need for any additional activators. Key to success was the use of a specific system consisting of palladium acetate and 1,2‐bis((tert‐butyl(2‐pyridinyl)phosphinyl)methyl)benzene. The generality of this method is demonstrated by the synthesis of more than 30 carboxylic acids, including non‐steroidal anti‐inflammatory drugs (NSAIDs), under mild conditions in good yields.     

Synthesis,characterization and spectral studies of various newer 4‐benzyloxy‐1H‐indole‐2‐carboxylic acid (arylidene)‐hydrazides

4‐Benzyloxyindole‐2‐carboxylic acid hydrazide reacts with aromatic and heterocyclic aldehydes in alcoholic medium in refluxing conditions to give 4‐benzyloxy‐1H‐indole‐2‐carboxylic acid (arylidene)‐hydrazides, important synthetic intermediates for the synthesis of a newer class of pharmacologically active compounds. We describe here the synthesis of various 4‐benzyloxy‐1H‐indole‐2‐carboxylic acid (arylidene)‐hydrazides by conventional as well as microwave irradiation techniques. The structures of these compounds have been confirmed by spectroscopic techniques (FTIR, NMR and MS). Some of the interesting features of the electron impact mass spectral fragmentation pattern of these compounds are also discussed.     

Highly efficient AgNO3‐catalyzed approach to 2‐(benzo[d]azol‐2‐yl)phenols from salicylaldehydes with 2‐aminothiophenol, 2‐aminophenol and benzene‐1,2‐diamine

A new, convenient and efficient AgNO₃‐catalyzed strategy for the preparation of 2‐(benzo[d]azol‐2‐yl)phenol derivatives in good to excellent yields (63–98%) is described. The reaction proceeds via condensation/intramolecular nucleophilic addition/oxidation process between substituted salicylaldehydes and 2‐aminothiophenol, 2‐aminophenol or benzene‐1,2‐diamine under mild reaction conditions. Notably, this reaction utilizes cheap AgNO₃ as a readily available and low‐cost benign oxidant at low catalyst loadings with excellent functional group tolerance.     

A General,Activator‐Free Palladium‐Catalyzed Synthesis of Arylacetic and Benzoic Acids from Formic Acid

A new catalyst for the carboxylative synthesis of arylacetic and benzoic acids using formic acid (HCOOH) as the CO surrogate was developed. In an improvement over previous work, CO is generated in situ without the need for any additional activators. Key to success was the use of a specific system consisting of palladium acetate and 1,2‐bis((tert‐butyl(2‐pyridinyl)phosphinyl)methyl)benzene. The generality of this method is demonstrated by the synthesis of more than 30 carboxylic acids, including non‐steroidal anti‐inflammatory drugs (NSAIDs), under mild conditions in good yields.     

Preparations of Saturated N‐P‐N Type Secondary Phosphine Oxides and their Applications in Cross‐Coupling Reactions

A series of cyclohexane‐1,2‐diamine ( 3a – 3d ) and benzene‐1,2‐diamine derivatives ( 3e – 3h ) were pre‐ pared. Followed by hydrolysis, the reaction of 3a – 3c with PCl₃ successfully led to the formation of cor‐ responding metastable saturated heteroatom‐substituted secondary phosphine oxides (HASPO 4a – 4c ), a tautomer of the saturated heteroatom‐substituted phosphinous acid (HAPA). Whereas ambient‐stable diamine‐coordinated palladium complexes were obtained, HAPA‐coordinated palladium complexes were not successfully synthesized. The molecular structures of HASPO 4c , Pd(OAc)₂(3a) , PdBr₂(3b) and Pd(OAc)₂(3c) and [Cu(NO₃)(3d)⁺][NO₃ ^? ] were determined by single‐crystal X‐ray diffraction method. Catalysis of in‐situ Suzuki‐Miyaura cross‐coupling reactions for aryl bromides and phenylboronic acid using diamine 3a as ancillary ligand showed that the optimized reaction condition at 60 °C is the combination of 2 mmol % 3a /3.0 mmol KOH/1.0 mL 1,4‐dioxane/1 mmol % Pd(OAc)₂. Moreover, moderate reactivity was observed when using aryl chlorides as substrates (supporting infor‐ mation). When diamine 3d was employed in Heck reaction, good tolerance of functional groups of aryl bromides were observed while using 4‐bromoanisole and styrene as substrates. The optimized condi‐ tion for Heck reaction at 100 °C is 3 mmol % 3d /3.0 mmol CsF/1.0 mL toluene/3 mmol % Pd(OAc)₂. In general, cyclohexane‐1,2‐diamine derivatives exhibited better catalytic properties than those of benzene‐1,2‐diamines.     

Two‐Step Synthetic Route to 10‐Substituted Isoalloxazines

10‐Substituted isoalloxazines were synthesized in two steps starting from 1,2‐phenylenediamine. Monoalkylation of the diamine resulted in 2‐amino‐N‐alkylanilines, which were subsequently condensed with alloxan in boric acid and acetic acid to give 10‐substituted isoalloxazines.     

Phenacyl esters as a new photocleavable linker in liquid-phase chemistry

PEG-supported 2-methylphenacyl ester as a new photocleavable linker is reported. The photocleavage based on an efficient intramolecular hydrogen abstraction was carried out with 280-366 nm UV irradiation in benzene or methanol to give the corresponding carboxylic acid in high yields and purities. The linker was suitable for aliphatic and aromatic carboxylic acids as well as protected amino acids.     

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.     

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.     

Ultrasound‐Promoted Catalyst‐Free Synthesis of 2,2′‐(1,4‐Phenylene)bis[1‐acetyl‐1,2‐dihydro‐4H‐3,1‐benzoxazin‐4‐one] Derivatives

A convenient approach to 2,2′‐(1,4‐phenylene)bis[1‐acetyl‐1,2‐dihydro‐4H‐3,1‐benzoxazin‐4‐one] derivatives 4 was explored employing the one‐pot condensation of anthranilic acids (=2‐aminobenzoic acids) 1 with terephthalaldehyde (=benzene‐1,4‐dicarboxaldehyde; 2 ) under ultrasound‐irradiation conditions (Scheme 1). The reactions proceeded smoothly in the presence of excess Ac₂O in the absence of any other catalyst and solvent to afford the respective products in high yields.     

Synthesis and Reactions of 3‐Methylthiazolo[3,2‐a]Benzimidazole‐2‐Carboxylic Acid Hydrazide: Synthesis of Some New Pyrazole, 1,3‐Thiazoline, 1,2,4‐Triazole and 1,2,4‐Triazolo[3,4‐b]‐1,3,4‐Thiadiazine Derivatives Pendant to Thiazolo[3,2‐a]Benzimidazole Moiety

The reaction of 3‐methylthiazolo[3,2‐a]benzimidazole‐2‐carboxylic acid ethyl ester (1) with hydrazine hydrate gives the hydrazide 2 which reacts with CS₂/KOH to afford the potassium salt 3. Treatment of 3 with l‐aryl‐2‐bromoethanones 4a,b afforded the 1,3‐thiazoline derivatives 6a,b, respectively, while the reaction of 3 with hydrazine hydrate afforded 1,2,4‐triazole‐3‐thione derivative 9. The reaction of 9 with l‐aryl‐2‐bromoethanones 4a,b and with hydrazonyl chlorides 11a,b gave the 1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazine derivatives 10a,b and 12a,b, respectively. Treatment of hydrazide 2 with phenyl isothiocyanate in refluxing benzene gave the thiosemicarbazide derivative 16. The latter reaction gave 1,3,4‐oxadiazole derivative 17 when benzene was replaced by DMF. Cyclization of the thiosemicarbazide derivative 16 with NaOH resulted in the formation of the 1,2,4‐triazole‐3‐thione derivative 18.     

A Simple One‐Pot Synthesis of Fully Substituted 1H‐Pyridone[1,2‐a]‐Fused‐1,3‐Diazaheterocycles

An efficient procedure for the synthesis of 7‐(aryl)‐8‐nitro‐2,3,6,7‐tetrahydroimidazo[1,2‐a]pyridinones, 8‐(aryl)‐9‐nitro‐3,4,7,8‐tetrahydropyridone[1,2‐a]pyrimidines and 9‐(aryl)‐10‐nitro‐2,3,4,5,8,9‐hexahydropyridone[1,2‐a]diazepine via one‐pot three component reaction of diamine, nitroketene dithioacetal (1,1‐bis(methylsulfanyl)‐2‐nitroethene), and coumarine‐3‐ carboxylic acid derivatives in EtOH under reflux conditions is reported. The advantages of this procedure are simplicity, easy purification, good yields, and catalyst‐free conditions. All products were confirmed by ¹H‐ and ¹³C‐NMR, IR, MS, and X‐ray crystal structure analyses.     

An Efficient Synthesis for Some New Heterocyclic Compound‐fused Oxindole Derivatives

An efficient and rapid procedure for the synthesis of novel oxindole derivatives is described. The process employs a condensation reaction of 3‐(bis(methyl thio)methylene)indolin‐2‐one and dinucleophiles such as 1,2‐phenylene diamine, propylene diamine, 2‐aminoethanol, ethylene‐1,2‐dithiol, 2‐mercaptoethanol, (1S,2S)‐cyclohexane‐1,2‐diamine, 2‐aminoethanthiol, 2,3‐diaminomaleonitrile, 2‐aminobenzenethiol, (3,4‐diaminophenyl)(phenyl)methanone, and ethane‐1,2‐diole in the presence of triethylamine under solvent‐free conditions at 60°C.     

A new polymorph of benzene‐1,2‐diamine: isomorphism with 2‐aminophenol and two‐dimensional isostructurality of polymorphs

A new crystalline form of benzene‐1,2‐diamine, C₆H₈N₂, crystallizing in the space group Pbca, has been identified during screening for cocrystals. The crystals are constructed from molecular bilayers parallel to (001) that have the polar amino groups directed to the inside and the aromatic groups, showing a herringbone arrangement, directed to the outside. The known monoclinic form and the new orthorhombic polymorph exhibit two‐dimensional isostructurality as the crystals consist of nearly identical bilayers. In the monoclinic form, neighbouring bilayers are generated by a unit translation along the a axis, whereas in the orthorhombic form they are generated by a c‐glide. Moreover, the new form of benzene‐1,2‐diamine is essentially isomorphous with the only known form of 2‐aminophenol.     

Synthesis and Antibacterial Activity of s‐Triazoles,s‐Triazolo[3,4‐b]‐1,3,4‐thiadiazines and s‐Triazolo[3,4‐b]‐1,3,4‐thiadiazoles of 5‐Methylisoxazole

The condensation of 4‐amino‐5‐mercapto‐3‐(5‐methylisoxazol‐3‐yl)‐1,2,4‐triazole with substituted phenacyl bromide, aldehydes, p‐bromophenylisothiocyanate, aromatic carboxylic acids and oxalic acid, is described. The antibacterial activity of representative compounds was evaluated.     

Generation and reactivity of 3‐carbethoxy‐5‐phenyl‐5H,7H‐thiazolo[3,4‐c]oxazol‐4‐ium‐1‐olate

3‐Carbethoxy‐5‐phenyl‐5H,7H‐thiazolo[3,4‐c]oxazol‐4‐ium‐1‐olate was generated from (2R,4R)‐N‐ethoxyoxalyl‐2‐phenylthiazolidine‐4‐carboxylic acid and its reactivity studied. This münchnone showed low reactivity as dipole although from the reaction with dimethyl acetylenedicarboxylate the corresponding (3R)‐3‐phenyl‐17H,3H‐pyrrolo[1,2‐c]thiazole‐5,6,7‐tricarboxylate could be isolated. The thermolysis of (2R,4R)‐N‐ethoxyoxalyl‐2‐phenylthiazolidine‐4‐carboxylic acid in refluxing acetic anhydride led to the synthesis of N‐(1‐ethoxycarbonyl‐2‐phenylvinyl)‐2‐phenyl‐4‐thioxo‐1,3‐thiazolidine. The structure of methyl (2R,4R)‐N‐ethoxyoxalyl‐2‐phenylthiazoliddine‐4‐carboxylate was determined by X‐ray crystallography.     

Isocyanide‐Based Three‐Component Synthesis of Highly Substituted 1,6‐Dihydro‐6,6‐dimethylpyrazine‐2,3‐dicarbonitrile, 3,4‐Dihydrobenzo[g]quinoxalin‐2‐amine,and 3,4‐Dihydro‐3,3‐dimethyl‐quinoxalin‐2‐amine Derivatives

A novel and efficient isocyanide‐based multicomponent reaction between alkyl or aryl isocyanides 1 , 2,3‐diaminomaleonitrile ( 2 ), naphthalene‐2,3‐diamines ( 6 ) or benzene‐1,2‐diamine ( 9 ), and 3‐oxopentanedioic acid ( 3 ) or Meldrum's acid ( 4 ) or ketones 7 was developed for the ecologic synthesis, at room temperature under mild conditions, of 1,6‐dihydropyrazine‐2,3‐dicarbonitriles 5a – 5f in H₂O without using any catalyst, and of 3,4‐dihydrobenzo[g]quinoxalin‐2‐amine and 3,4‐dihydro‐3,3‐dimethyl‐quinoxalin‐2‐amine derivatives 8a – 8g and 10a – 10e , respectively, in the presence of a catalytic amount of p‐toluenesulfonic acid (TsOH) in EtOH, in good to excellent yields (Scheme 1).