Synthesis of (E)‐ and (Z)‐5‐(Bromomethylene)furan‐2(5H)‐one by Bromodecarboxylation of (E)‐2‐(5‐Oxofuran‐2(5H)‐ylidene)acetic Acid

(E)‐ and (Z)‐5‐(bromomethylene)furan‐2(5H)‐one have been prepared starting from the commercially available adduct between furan and maleic anhydride. A bromodecarboxylation reaction is a key step in the synthesis. The reaction gives the (E)‐ or (Z)‐5‐(bromomethylene)furan‐2(5H)‐one as the major product, dependent on the method used in the bromodecarboxylation.     

Synthesis of (±)‐ar‐Macrocarpene

An efficient first synthesis of the sesquiterpene ar‐macrocarpene, an irregular sesquiterpene isolated from Cupressus macrocarpa foliage, starting from 3‐methylcyclohexenone has been described, which confirmed the structures of macrocarpenes.     

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.     

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.     

Efficient Synthesis of 2‐(N‐Substituted)‐2‐imidazolines and 2‐(N‐Substituted)‐1,4,5,6‐tetrahydropyrimidines

A general method for the preparation of 2‐(N‐Substituted)‐2‐imidazolines and 2‐(N‐Substituted)‐1,4,5,6‐tetrahydropyrimidines is described. These heterocycles can be synthesized from their respective anilines with 2‐chloro‐2‐imidazoline or 2‐chloro‐1,4,5,6‐tetrahydropyrimidine, generated in situ from imidazolidin‐2‐one and tetrahydropyrimidin‐2(1H)‐one activated by dimethyl chlorophosphate, in good to excellent yields.     

Application of Sulfinyl bis(2,4‐dihydroxythiobenzoyl) in the Synthesis of N‐Substituted 2‐Amino‐5‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazoles

One‐stage synthesis of N‐substituted 2‐amino‐5‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazoles is described. The compounds were prepared by the reaction of the sulfinyl bis(2,4‐dihydroxythiobenzoyl) (STB) with 4‐substituted 3‐thiosemicarbazides. STB was obtained from 2,4‐dihydroxybenzenecarbodithioic acid and thionyl dichloride. The structure of compounds was confirmed by IR, ¹H NMR, ¹³C NMR, and EI‐MS data.     

Synthesis,Characterization and Photocrosslinking Properties of Poly(1‐(4‐Methacrylamidophenyl)‐1‐(4‐nitrophenyl)prop‐1‐en‐3‐one)

The phenylmethacrylamide monomer, 1‐(4‐methacrylamidophenyl)‐1‐(4‐nitrophenyl)prop‐1‐en‐3‐one (MPNP) containing a photosensitive group was synthesized by reacting 4‐nitrocinnamoylaniline with methacryloyl chloride in the presence of triethylamine at 0–5°C. The functional monomer, MPNP was polymerized in ethyl methyl ketone (EMK) under nitrogen atmosphere at 70°C using benzoyl peroxide (BPO) as the initiator. The synthesized polymer was characterized by UV, IR, ¹H‐NMR and ¹³C‐NMR spectroscopy. The molecular weight data of the polymer as obtained from gel permeation chromatography suggests a higher tendency for chain termination by radical recombination than disproportionation. The thermal studies of the polymer were obtained from thermogravimetric analysis. The glass transition temperature of the polymer was determined by differential scanning calorimetry. The solubility of the polymer was tested in various organic solvents at room temperature. The photosensitivity of the polymer was investigated in various solvents in the presence and absence of triplet photosensitizers. The effect of the different solvents nature and concentration on the rate of photocrosslinking of the polymer were also examined for using the polymer as negative photoresist materials.     

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.     

Synthesis of Analogues of (1 → 6)‐Branched (1 → 3)‐Glucohexaose

Abstract

β‐D‐Galp‐(1 → 3)‐[β‐D‐Galp‐(1 → 6)‐]α‐D‐Glcp‐(1 → 3)‐β‐D‐Glcp‐(1 → 3)‐[α‐D‐Manp‐(1 → 6)‐]D‐Glcp 16 and β‐D‐Galp‐(1 → 3)‐[β‐D‐Glcp‐(1 → 6)‐]α‐D‐Glcp‐(1 → 3)‐β‐D‐Glcp‐(1 → 3)‐[α‐D‐Manp‐(1 → 6)‐]D‐Glcp 18 were synthesized as the analogues of the immunomodulator β‐D‐Glcp‐(1 → 3)‐[β‐D‐Glcp‐(1 → 6)‐]α‐D‐Glcp‐(1 → 3)‐β‐D‐Glcp‐(1 → 3)‐[β‐D‐Glcp‐(1 → 6)‐]D‐Glcp through coupling of trisaccharide donors 8 and 13 with trisaccharide acceptor 14 followed by deprotection, respectively.     

Effect of Triton‐X‐100 Solvent in the Micellar Catalysis of the Aquation of Tris(2‐nitroso‐1‐naphtholate) Ferrate (II)

The effect of triton‐X‐100 micelles on the aquation of Fe(C₁₀H₆N₂O)₃ ²⁺ has been investigated with triton‐X‐100 as solvent. In liquid triton‐X‐100, over a range of [H₂O] _T (0.0–3 M), significant rate enhancement factors of 50–150 are observe. Acid inhibits the rate of aquation at fixed [H₂O] _T . A mechanism based on effective solvent participation in a chemical environment similar to that in reversed micelles is proposed in liquid triton‐X‐100 with dispersed water pockets. This mechanism predicts direct H₂O substitution into the coordination sphere of Fe(C₁₀H₆N₂O)₃ ²⁺ in the highly polar water pockets or cavities where the Fe (II) complex molecules are solubilized. Changes in the tumbling rate, structure, and activity of water are suggested to account for the observed changes in the rate of aquation as a function OH [H₂O] _T . All k _ψ–[H₂O] _T profiles are structured and exhibit maxima with k _ψ(max) shifted to progressively higher [H₂O] _T as the fixed concentration [H⁺] _T is increased.     

Improved Syntheses of 5‐Hydroxy‐2‐Pyridones (2,5‐Dihydroxypyridines)

Improved syntheses of 5-hydroxy-2-pyridone, 6-chloro-5-hydroxy-2-pyridone, 2,5-dihydroxynicotinic acid, and three methyl-substituted 5-hydroxy-2-pyridones are reported.     

Amino Acids as a Chiral Pool: Synthesis of (S)‐and (R)‐2‐N‐Carbomethoxy‐5‐aminoindane from (S)‐ and (R)‐Phenylalanines

Enantioselective syntheses of (R)‐and (S)‐2‐N‐carbomethoxy‐5‐aminoindanes from (R)‐ and (S)‐phenylalanines, respectively, are described. A Friedel–Crafts reaction employing N‐carbomethoxy phenylalanine leads to chiral 2‐N‐carbomethoxy‐1‐indanone, which is diastereoselectively reduced to 1‐hydroxy‐2‐N‐carbomethoxyindane. After protection of the hydroxyl group, a regioselective nitration gives a 6‐nitroindane intermediate, which upon hydrogenation affords (R)‐or (S)‐2‐N‐carbomethoxy‐5‐aminoindane.     

Antibacterial Activities of New (E) 2‐Cyano‐3‐(3′,4′‐dimethoxyphenyl)‐2‐propenoylamide Derivatives

(E) 2‐Cyano‐3‐(3′,4′‐dimethoxyphenyl)‐2‐propenoyl chloride (2) underwent mono‐ and binucleophilic displacement with hydrazines, amines, ureas, and aromatic bifunction amines to give new 2‐propenoyl hydrazines (4 and 5), 2‐propenoylamide (6, 7, 12, 13, 15, 17, 19, 21), and 2‐thiol propenoate (22–24). Some of these products were cyclized to give novel heterocyclic derivatives (8, 10, 14, 16, and 20).     

Efficient Synthesis of N‐Oxide Derivatives: Substituted 2‐(2‐(Pyridyl‐N‐oxide)methylsulphinyl)benzimidazoles

Different substituted 2‐chloromethylpyridyl derivatives (6a–d) were oxidized with mCPBA to give the respective 2‐chloromethylpyridine‐N‐oxide derivatives (7a–d) at low temperature, which on condensation with 2‐mercapto‐1H‐benzimidazole (8a–c) in the presence of aprotic solvents give the 2‐[[(pyridin‐2‐yl‐1‐oxide)methyl]sulfanyl]‐1H‐benzimidazole (9a–d) in good yield. Finally, 9a–d oxidized with mCPBA in chlorinated solvent gives a mixture of 2‐[[(pyridin‐2‐yl‐1‐oxide)methyl]sulfonyl]‐1H‐benzimidazole (3a–d, 10%) and 2‐[[(pyridin‐2‐yl‐1‐oxide) methyl]sulfinyl]‐1H‐benzimidazole (4a–d, 90%) derivatives.     

Synthesis of (±)‐12‐Methoxyherbertenediol Dimethyl Ether

Efficient total synthesis of (±)‐12‐methoxyherbertenediol dimethyl ether and 12‐homoherbertenediol was accomplished starting from vanillin employing a Claisen rearrangement–RCM reaction–based approach.     

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.     

Synthesis and Crystallographic Study of1,6‐bis‐(N‐phenothiazinyl)‐2,4‐hexadiyne

1,6‐bis‐(N‐phenothiazinyl)‐2,4‐hexadiyne (I) was synthesized in high yield by oxidative coupling of N‐propargyl phenothiazine. Grown from methylene chloride‐hexane solution, I is a monoclinic crystal, space group C2/c a=14.9500(18) Å; b=13.5512(15) Å; c=12.0116(10) Å; β=102.628(9)° Å; V=2374.6(4) ų. The intermolecular distances and arrangement of I in the unit cell preclude the usual diacetylene reactivity. Nevertheless, heating of I at 145°C results in decomposition of I to phenothiazine and a dark brown solid. In addition, cation‐radicals of I were prepared by oxidation with nitrosonium tetrafluoroborate and iodine to give stable ion‐radical salts.     

Novel Synthesis of 5‐Substituted‐3‐phenylindole‐2‐(1,2,4‐triazole) Derivatives

Various substituted 3‐phenylindole 2‐carboxylates (1a–c) were prepared according to the literature methods. These carboxylates (1a–c) on reaction with thiosemicarbazide yielded 5‐substituted‐3‐phenylindol‐2‐(1,2,4‐triazole‐3‐thione) (2a–c) on refluxing in pyridine for 8 h. The 5‐substituted‐3‐phenylindole‐2‐[1,2,4‐triazolo‐3‐thioacetic acid] (3a–c) were prepared from 5‐substituted‐3‐phenyl indole‐2‐[1,2,4‐triazole‐3‐thione] (2a–c) on reaction with an appropriate alkylating agent and sodium acetate in acetic acid. Further, (3a–c) were reacted with acetic anhydride to bring about a cyclocondensation reaction to yield 5‐substituted‐3‐phenylindol‐2‐thiazolo(2,3‐b)‐triazole (4a–c). The 5‐substituted‐3‐phenylindole‐2‐[1,2,4‐triazolo‐3‐acetic acid] (3a–c) were reacted with o‐phenylenediamino dihydrochloride in ethylene glycol to yield 5‐substituted‐3‐phenylindole‐1,2,4‐triazolo‐3′‐yl‐thiomethyl)benzimidazoles (5a–c).     

Expeditious Synthesis of New 3,4,6‐Trihydroxythiepanes from d‐(‐)‐Quinic Acid

We report herein that the new seven‐membered‐ring thiosugars (thiepanes) have been synthesized from d‐(‐)‐quinic acid. The key feature of the synthesis involves the thiocyclization of protected hexane‐1,2,3,5,6‐pentanol derivatives. The subsequent step of acidic removal of protecting groups is critical in the reaction conditions to obtain the required 3,4,6‐trihydroxythiepanes. During the course of studies, the unexpected trihydroxythiopyrans are formed because of the ring contractions of their corresponding trihydroxythiepanes under various conditions.     

Practical Synthesis of (±)‐Venlafaxine

A practical total synthesis of antidepressant (±)‐venlafaxine is disclosed.