Improved Synthesis of 1‐Hydroxy‐2,2,5,5‐tetramethyl‐3‐imidazoline 3‐Oxide (HTIO)

A simple, efficient, mild, and reproducible method for the synthesis of 1‐hydroxy‐2,2,5,5‐tetramethyl‐3‐imidazoline 3‐oxide is described. The method is based on the condensation of 2‐hydroxyamino‐2‐methylpropanal oxime with 2,2‐diethoxypropane in the presence of an equimolar quantity of acetic acid. Cost‐effectiveness of the condensation procedure could be also achieved by replacing 2,2‐diethoxypropane with less expensive 2,2‐dimethoxypropane.     

Improved Synthesis of Tetrakis(2‐thienyl)methane

Abstract

An improved synthesis of tetrakis(2‐thienyl)methanes, where an aromatic nucleophilic substitution is the key reaction for the introduction of the fourth 2‐thienyl group, has been developed, thus, reaction of tris(2‐thienyl)methyl anion with 2‐fluoro‐5‐cyanothiophene smoothly proceeded to give (5‐cyano‐2‐thienyl)‐tris(2‐thienyl)methane in good yield. Alkaline hydrolysis of the cyano group to carboxylic acid followed by decarboxylation at 180°C in quinoline in the presence of copper(I) oxide afforded the parent tetrakis(2‐thienyl)methane in 50% total yield from the trithienylmethane.     

Improved Syntheses of N‐Desmethylcitalopram and N,N‐Didesmethylcitalopram

An improved and efficient synthesis of N‐desmethylcitalopram (2) and N,N‐didesmethylcitalopram (3) is presented. The method involved N‐demethylation of citalopram (1) using 1‐chloroethyl chloroformate to give 2 in 87% yield. Synthesis of 3 was accomplished by alkylation of 8 with 1‐(3‐bromopropyl)‐2,2,5,5‐tetramethyl‐1‐aza‐2,5‐disilacyclopentane (9).     

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.     

Scalable Process for 4‐(2‐Hydroxy‐2‐methyl)‐ethyl‐benzylamine

The preparation of the title compound has been revisited and improved. Starting from inexpensive cuminonitrile, 4‐(2‐hydroxy‐2‐methyl)‐ethyl‐benzylamine is obtained in a scalable two‐step process with an overall yield of 55%.     

Improved Syntheses of (±)-Ar-Turmerone via Organotin Reagents

(±)-Ar-turmerone has been obtained alternatively from p-methylacetophenone and p-bromotoluene with ethoxymethyltributyltin or α-ethoxycrotyltributyltin and isobutenyltributyltin as key reagents. The overall yields lie in the range 49–60%.     

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.     

Oxidative Conversion of 3‐Alkoxyfurans to 2‐Hydroxy‐3(2H)‐furanones and 2‐Hydroxy‐2‐butene‐1,4‐diones with 2,3‐Dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) or Phenyltrimethylammonium Tribromide (PTAB) in t‐BuOH

2‐Alkoxy‐1,3,4‐triphenylfurans were oxidized to 3‐alkoxy‐2,4,5‐triphenyl‐ 2‐butene‐1,4‐diones with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) in t‐BuOH. In contrast, various 3‐alkoxy‐2,4,5‐triphenylfurans were directly converted to 2‐hydroxy‐3(2H)‐furanone with phenyltrimethylammonium tribromide (PTAB) in t‐BuOH. The oxidative ring opening of 3‐alkoxy‐2,5‐diphenylfurans to cis‐2‐hydroxy‐2‐butene‐1,4‐dione was also accomplished with PTAB in t‐BuOH under the same reaction conditions.     

Synthesis of 1‐(2‐Hydroxy‐phenyl)‐3‐piperidin‐1‐yl‐propenone by Ultrasonic Irradiation

Different 1‐(2‐hydroxy‐phenyl)‐3‐piperidin‐1‐yl‐propenones have been synthesized by ultrasonic activation from differently substituted 3‐formyl chromones and piperidine.     

One‐Pot Synthesis of 5‐Alkylfuran‐2(5H)‐ones

5‐Alkylfuran‐2(5H)‐ones can be efficiently obtained using a one‐pot approach, starting from methyl 3‐nitropropanoate and aldehydes, in ethyl acetate, with Amberlyst A‐21 as catalyst, in 60–90% overall yield.     

Syntheses of β－Hydroxy Ketones by Organosamarium

An organosamarium reagent was prepared via the reaction of a-bromoacetophenone with samarium. This organosamarium reagent reacted with aldehydes to give β-hydroxy ketones. A possible reaction process was suggested.     

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 4‐Hydroxy‐2‐methyl‐(2H)‐1,2‐benzothiazine‐3‐sulfonic Acid 1,1‐Dioxide

We report a convenient synthesis of 4‐hydroxy‐2‐methyl‐(2H)‐1,2‐benzothiazine‐3‐sulfonic acid‐1,1‐dioxide (6a) prepared in a novel one‐pot reaction. The synthesis involves two transformations starting from 2‐methyl‐2H‐1,2‐benzothiazin‐4‐(3H)‐one 1,1‐dioxide (7) with an overall yield better than that from the stepwise process, as well as the alternate procedure starting from saccharin (1). One‐pot synthesis of an important intermediate, saccharin‐N‐methane sulfonic acid (4), is also described.     

Improved Synthesis of 2‐(3H)Benzothiazolethiones under Microwave Irradiation

2‐(3H)Benzothiazolethiones (2‐mercaptobenzothiazole) are prepared by an improved method, which utilizes microwave‐assisted cyclization of the corresponding ortho‐haloanlines with potassium O‐ethyl dithiocarbonate. By using microwave irradiation, the relative reactivity of 2‐chloroanilines was greatly improved to the same level as that of 2‐fluoroanilines and 2‐bromoanilines.     

An Improved Preparation of 2,5-Dimethoxy-tetrahydrofuran

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Highly Regioselective One‐Pot Synthesis of 7‐Hydroxy‐6‐methylphthalide from 3‐Hydroxy‐4‐methylbenzylalcohol

7‐Hydroxy‐6‐methylphthalide 2 was synthesized with high regioselectivity and moderate yield using a novel one‐pot synthesis that employed 3‐hydroxy‐4‐methylbenzylalcohol 1 and formaldehyde in the presence of tin(IV) chloride as catalyst and triethylamine as base. The proposed mechanism of the formation of 2 involves ortho‐formylation followed by hemiacetal formation and oxidation.     

Improved and Highly Versatile Synthesis of 5‐Aryltropones

Abstract

The use of 5‐iodo‐2‐methoxytropone in palladium(0)‐catalyzed coupling reactions with a variety of arylboronic acids has resulted in significantly improved reaction yields and times for a sterically and electronically diverse series of novel 5‐aryltropones. In addition, the required 5‐iodo‐2‐methoxytropone was conveniently synthesized in excellent yield.     

Improved Syntheses of 3,17β-Diacetoxyestra-1,3,5(10)-Trien-6-One

improved syntheses of 3,17β-Diacetoxyestra-1,3,5(10)-trien-6-one 5 was achieved in 4 steps (respectively in 45% and 56% overall yield) from 19-nortestosterone 1.     

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).     

Improved Synthesis of C 2‐Symmetric 4,4′‐α,ω‐Alkylenedioxy‐bis(3‐methoxybenzaldehydes)

Abstract

An improved Williamson synthesis of C ₂‐symmetric 4,4′‐(α,ω‐alkylenedioxy)‐bis(3‐methoxybenzaldehydes) from vanillin is described. These dialdehydes are often insoluble in cold acetone, which renders their purification especially facile.