Synthesis of New N‐(5‐Oxo‐2,5‐dihydro)pyrrol‐3‐yl Glycines and N‐(5‐Oxo‐2,5‐dihydro)pyrrol‐3‐yl Glycines Esters

Following our efforts towards the synthesis of new potential inhibitors of Xanthine Dehydrogenase (XDH), we describe here a general method for the preparation of N-(5-oxo-2,5-dihydro)pyrrol-3-yl glycines and N-(5-oxo-2,5-dihydro)pyrrol-3-yl glycine esters from glycine ethyl ester hydrochloride and various 4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylic acid esters and carbonitriles.     

Synthesis of 1,4‐Bis[(3‐Aryl)‐s‐triazolo(3,4‐b)‐(1,3,4)thiadiazole‐6‐yl]benzenes

Some 1,4‐bis[(3‐aryl)‐s‐triazolo[3,4‐b]‐[1,3,4]thiadiazole‐6‐yl]benzenes are readily accessible in high yields by reaction of 3‐aryl 4‐amino‐5‐mercapto‐1,2,4‐triazole with p‐phthalic acid.     

Spectrophotometric Determination of Nitrite in Water Samples with 4‐(1‐Methyl‐1‐Mesitylcyclobutane‐3‐yl)‐2‐Aminothiazole

Abstract

A simple, sensitive, and specific spectrophotometric method for the measurement of nitrite in water has been developed and optimum reaction conditions along with other analytical parameters have been evaluated. The azo dye, 4‐(1‐methyl‐1‐mesitylcylobutane‐3‐yl)‐2‐(p‐N,N‐dimethylazobenzene)‐1,3‐thiazole was synthesized with the reaction of 4‐(1‐methyl‐1‐mesitylcylobutane‐3‐yl)‐2‐aminothiazole and N,N‐dimethyl aniline in acidic medium. Obtained azo dye has been characterized by infrared (IR), ¹H nuclear magnetic resonance (NMR), and microanalysis methods. The dye shows an absorption maximum at 482 nm. The method is optimized for acid concentration, pH, amount of reagents required, time, and interfering species. All the determinations were carried out at this wavelength throughout the work. At an analytical wavelength of 482 nm, Beer's law is obeyed over the concentration range 0.05 to 2.00 µg nitrite per mL analyte. The molar absorptivity, Sandell's sensitivity, and relative standard deviation are 2.03×10⁴ L mol^?1 cm^?1±251.3 (95%), 2.28×10^?3 µg cm^?2, and 2.74% (n=10), respectively. The detection limit of the method is 0.012 µg ml^?1 of nitrite ion. The method was succesfully applied to the determination of nitrite in tap water and lake water.     

Electrochromic Properties of ‘Trimeric' Thiophene‐pyrrole‐thiophene Derivative Grown from Electrodeposited 6‐(2,5‐di(thiophen‐2‐yl)‐1H‐pyrrol‐1‐yl)hexan‐1‐amine and its Copolymer

A centrosymmetric polymer precursor, namely 6‐(2,5‐di(thiophen‐2‐yl)‐1H‐pyrrol‐1‐yl)hexan‐1‐amine (TPHA), was synthesized via a Knorr–Paal reaction using 1,4‐di(2‐thienyl)‐1,4‐butanedione and hexane‐1,6‐diamine. The resultant monomer was characterized by Nuclear Magnetic Resonance (¹H‐NMR). Electroactivity of TPHA was investigated via cyclic voltammetry. The electronic structure and the nature of electrochromism in P(TPHA) and its copolymer with EDOT, (P(TPHA‐co‐EDOT)), were examined via spectroelectrochemistry studies. P(TPHA) switches between claret red neutral state and blue oxidized state. Optical response times for coloring and bleaching processes of the P(TPHA) and P(TPHA‐co‐EDOT) were found as 2.1 s and 1.6 s, respectively.

The copolymer of TPHA was used to construct dual type polymer electrochromic devices (ECDs) against poly(3,4‐ethylenedioxythiophene) (PEDOT). Spectroelectrochemistry and electrochromic switching out of the devices were investigated.     

Synthesis of O‐β‐D‐Glucopyranosides of 7‐Hydroxy‐3‐(imidazol‐2‐yl)‐4H‐chromen‐4‐ones

The 7‐hydroxy‐3‐formyl‐4H‐chromen‐4‐one 1 reacted with various cyclic 1,2‐dicarbonyl compounds in the presence of ammonium acetate to furnish 7‐hydroxy‐3‐([4,5‐fused] imidazol‐2‐yl)‐4H‐chromen‐4‐ones 2a–f, which on glucosylation with α‐acetobromoglucose affords 2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranosyloxy‐3‐([4,5‐fused] imidazol‐2‐yl)‐4H‐chromen‐4‐ones 3a–f. 7‐O‐β‐D‐Glucopyranosyloxy‐3‐([4,5‐fused] imidazol‐2‐yl)‐4H‐chromen‐4‐ones 4a–f were prepared by deacetylation with anhydrous zinc acetate in absolute methanol. The structure of these new O‐β‐D‐glucosides was established on the basis of chemical, elemental, and spectral analysis. These compounds were evaluated for their in vitro biological activity.

     

Facile One‐Pot Synthesis of 3‐{2‐[5‐Hydroxy‐4‐(2‐hydroxy‐ethyl)‐3‐methyl‐pyrazol‐1‐yl]‐thiazol‐4‐yl}‐chromen‐2‐ones via a Three‐Component Reaction

Reaction of 3‐(2‐bromo‐acetyl)‐chromen‐2‐one with thiosemicarbazide and 2‐acetylbutyro lactone in anhydrous ethanol gave 3‐{2‐[5‐hydroxy‐4‐(2‐hydroxy‐ethyl)‐3‐methyl‐pyrazol‐1‐yl]‐thiazol‐4‐yl}‐chromen‐2‐one in good yields.     

Substituted Quinolinones,Part 11: Efficient Synthesis of Different 3‐(4‐Arylidene and Hetarylidene‐5‐oxopyrazolin‐3‐yl) quinolin‐2‐ones

Several 3‐(4‐arylidene and hetarylidene‐5‐oxopyrazolin‐3‐yl)quinolin‐2‐ones 6–26 were synthesized in an efficient methodology utilizing both pyrazolinylquinolinone 2 and its chromenylmethylene derivative 10. Compound 2 was derivatized by Knoevenagel condensation with different carbonyl compounds. Nucleophilic ring opening–ring closure (RORC) of the compound 10 furnished the desired 4‐methylenepyarzolinone bearing novel five‐, six‐, and seven‐membered heterocycles, in good yields.     

Convenient Synthesis of Substituted 5‐(Hydroxymethyl)‐8‐methyl‐3‐(4‐phenylquinazolin‐2‐yl)‐2H‐pyrano[2,3‐c]pyridin‐2‐ones

Abstract

Interaction of 2‐imino‐2H‐pyrano[2,3‐c]pyridin‐3‐carboxamide with substituted 2‐aminobenzophenones proceeds via recyclization mechanism leading to substituted 3‐(4‐arylquinazolyn‐2‐yl)‐2H‐pyrano[2,3‐c]pyridin‐2‐ones. Their reaction with acetic anhydride affords the O‐acylation products.     

The Structure of N‐(1‐Deoxy‐β‐D‐fructopyranos‐1‐yl)‐L‐proline Monohydrate (“D‐Fructose‐L‐proline”) and N‐(1,6‐Dideoxy‐α‐L‐fructofuranos‐1‐yl)‐L‐proline (“L‐Rhamnulose‐L‐proline”)

Nano n-propylsulfonated γ-Fe₂O₃ was found to be a highly efficient, reusable heterogeneous catalyst for the conversion of a range of monosaccharides and some of their derivatives to the corresponding O-isopropylidene derivatives in good to excellent yields by refluxing the reaction mixture in dry acetone. The magnetic property of the catalyst enabled its separation from the reaction mixture by a simple process of filtration along with the aid of an external magnet. The efficiency of the catalyst was found to be largely unaffected for at least up to six cycles of reuse, thus proving the new methodology to be environmentally rewarding besides being simple and facile in operation.     

Efficient Synthesis of 1‐(5′‐Acylamino‐1′,3′,4′‐thiadiazol‐2′‐yl)‐4‐acyl‐thiosemicarbazides

Acyl chlorides reacted with ammonium thiocyanate and carbonic dihydrazide under phase‐transfer catalysis to first afford 2,2′‐bis(acylaminothiocarbonyl)‐carbonic dihydrazides, which further cyclized in the presence of glacial acetic acid to efficiently give 1‐(5′‐acylamino‐1′,3′,4′‐thiadiazol‐2′‐yl)‐4‐acyl‐thiosemicarbazides in high yield.     

Synthesis and Characterization of Alkyl and Aryl‐(4‐methyl‐6‐nitro‐quinolin‐2‐yl)amines: X‐Ray Structures of Ethyl and Cyclohexyl‐(4‐methyl‐6‐nitro‐quinolin‐2‐yl)amine

Abstract

We have synthesized and characterized a series of alkyl and aryl‐(4‐methyl‐6‐nitro‐quinolin‐2‐yl)amines through a high‐yield, three‐step procedure starting from 4‐methylquinolin‐2‐ol. Nitration using concentrated nitric/sulfuric acids, followed by chlorination in phosphorus oxychloride, yielded 2‐chloro‐4‐methyl‐6‐nitro‐quinoline. All of the intermediates and aminated products have been characterized by multinuclear (¹H and ¹³C) NMR spectroscopy, elemental analysis, and, in the case of the two title compounds (ethyl and cyclohexyl‐(4‐methyl‐6‐nitro‐quinolin‐2‐yl)amine), a single crystal X‐ray structure was obtained to verify the nature of the new materials.     

Two‐Step Novel Synthesis of 2‐Amino‐6‐(1,3‐dioxo‐2,3‐dihydro‐1H‐inden‐2‐yl)‐4,7‐diphenyloxepine‐3‐carbonitrile and 5‐(1,3‐Dioxo‐2,3‐dihydro‐1H‐inden‐2‐yl)‐2‐imino‐6‐phenyl‐2H‐pyran‐3‐carbonitrile

Starting from indan‐1,3‐dione, a novel two‐step synthesis of the oxepine derivatives 5a,b and the pyran derivatives 7 and 8 under very simple reaction conditions is described.     

Synthesis of 4‐(Indol‐1‐yl)butanals via Rhodium‐Catalyzed Hydroformylation of 1‐Allylindoles

The rhodium‐catalyzed hydroformylation of new 1‐(β‐methallyl) indoles 1a–e carried out with Rh₄ (CO)₁₂ as the catalyst precursor, at 100 atm total pressure and 100°C, produces the 4-(indol‐1‐yl)‐3‐methylbutanals 2a–e as the sole products in high yields. The synthesized 4‐indolylbutanals are stable under the adopted conditions and are isolated and characterized here for the first time. The preparation of the starting 1‐allylindoles is described too.     

Solid‐State Synthesis of 4‐[(Indol‐3‐yl)‐arylmethyl]‐1‐phenyl‐3‐methyl‐5‐pyrazolones by Catalysis of Molecular Iodine

4‐[(Indol‐3‐yl)‐arylmethyl]‐1‐phenyl‐3‐methyl‐5‐pyrazolones could be smoothly and effectively obtained in good yields through the iodine‐catalyzed reactions under solid‐state conditions at room tempertaure. The three‐component approach in a one‐pot procedure was reported for the first time. A possible mechanism was suggested to elucidate the remarkable reaction selectivities.     

Microwave‐Promoted Efficient Synthesis of 3‐(5‐Arylfuran‐2‐yl)‐6‐aryl/aryloxymethylene‐1,2,4‐s‐Triazolo[3,4‐b]‐1,3,4‐thiadiazoles

A simple, rapid, and efficient method for the synthesis of substituted 1,2,4‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazoles under microwave irradiation conditions is reported, and a series of 3‐(5′‐aryl‐2′‐furyl)‐6‐aryl/aryloxymethylene‐1,2,4‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazoles was synthesized via this method.     

Synthesis of C‐Nucleoside Analogues Starting from 1‐(Methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)‐4‐phenyl‐but‐3‐yn‐2‐one

Abstract

1‐(Methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)‐4‐phenyl‐but‐3‐yn‐2‐one (4) was synthesized by the reaction of (methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)ethanal (2) with lithium phenylethynide and following oxidation. Compound 4 and hydrazine hydrate provided the 3(5)‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl‐methyl)‐5(3)‐phenyl‐1H‐pyrazole (5). The reactions of 4 with amidinium salts and a S‐methyl‐isothiouronium salt, respectively, furnished the pyrimidine C‐nucleoside analogues 6a–6c. Treatment of 4 with 2‐aminobenzimidazole afforded 2‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐ylmethyl)‐4‐phenyl‐benzo [4,5]imidazo[1,2‐a]pyrimidine (7a). Compound 4 and sodium azide yielded 2‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)‐1‐[5(4)‐phenyl‐1H(2H)‐1,2,3‐triazole‐4(5)‐yl]ethanone (8).     

Synthesis of (Methyl 3‐O‐Benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐d‐altropyranosid‐2‐yl)thiophene Derivatives as Precursors of New Iso‐C‐nucleoside Analogues

Treatment of 2‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐d‐altropyranosid‐2‐yl)ethanal (3) with malononitrile in the presence of aluminium oxide provided 2‐cyano‐4‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐d‐altropyranosid‐2‐yl)crotononitrile (4). Starting from 4, cyclization with sulphur and triethylamine yielded 2‐amino‐5‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐d‐altropyranosid‐2‐yl)thiophene‐3‐carbonitrile (5). Further cyclization could be achieved with triethyl orthoformate/ammonia to furnish 4‐amino‐6‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐d‐altropyranosid‐2‐yl)thieno[2.3‐d]pyrimidine (8).     

One‐Pot Synthesis of 2‐(1‐Alkyl/aralkyl‐1H‐benzimidazole‐2‐yl)‐quinoxaline Derivatives using Molecular Iodine

The title compound (5) has been prepared in one pot by refluxing 1‐(1‐alkyl/aralkyl‐1H‐benzimidazole‐2‐yl)‐ethanone (1) with substituted o‐phenylenediamine (2) in ethanol in the presence of iodine. Alternatively, 5 could also be prepared by treating 2‐bromo‐1‐(1‐ alkyl/aralkyl‐1H‐benzimidazole‐2‐yl)‐ethanone (3A) with 2 in refluxing ethanol. The formation of 5 from 1 and 2 probably occurs through the intermediacy of 3B (i.e., 3, X=I) and 4.     

Asymmetric Synthesis of (2S)‐1‐(3,4‐Dihydroxyphenoxy)‐3‐(3,′4′‐Dimethoxyphenoxy) Ethylamino‐2‐propanol hydrochloride (RO363)

Enantiomerically pure (S)‐RO363 was synthesized by using (R,R) Salen Co(III) complex for the resolution of terminal epoxide. The hydrolytic kinetic resolution process was carried out at room temperature in excellent enantioselectivity. The method can be applied for large‐scale preparation of (S) RO363.     

Regioselective Endocyclic Oxidation of Enantiopure 3‐Alkylpiperidines: Synthesis of (3S,5S)‐(‐)‐3‐Ethyl‐5‐Methylpiperidine

An efficient regioselective endocyclic oxidation of enantiopure 3‐alkylpiperidines 1(a–c) with bromine in acetic acid to generate the corresponding 5‐alkylpiperidin‐2‐ones 3(a–c) as main product is described. In addition, starting from 3a or 3b, the synthesis of (3S,5S)‐(‐)‐3‐ethyl‐5‐methylpiperidine 6 · HCl was achieved. Finally, the X‐ray single‐crystal analysis of compound 4 is reported.