Studies in Thio‐Claisen Rearrangement: Regioselective Synthesis of Thiopyrano[2,3‐b]pyran‐2‐ones and Thieno[2,3‐b]pyran‐2‐ones

Abstract

4‐Mercapto‐6‐methyl‐2‐pyrone was alkylated with different allylic and propargylic halides under phase transfer catalyzed condition in the presence of TBAB or BTEAC catalyst in chloroform–aqueous NaOH (1%) at room temperature. The S‐alkylated thiopyran‐2‐ones were then refluxed in quinoline or in chlorobenzene to give 4‐chloromethylthiopyrano[2,3‐b]pyran‐2‐one and 4‐hydroxymethylthiopyrano[2,3‐b]pyran‐2‐one or several thieno[2,3‐b]pyran‐2‐ones.     

Green Procedure for the Synthesis of Phthalazino[2,3‐b]phthalazine‐5,7,12,14‐tetraones

Different novel phthalazino[2,3‐b]phthalazine‐5,7,12,14‐tetraones were synthesized in a simple and environmentally benign method from the reaction of phthalic anhydrides with semicarbazide or thiosemicarbazide using montmorillonite K‐10 clay as solid heterogeneous acidic catalyst and microwaves under solvent‐free conditions in good yields and short reaction times. Products were characterized by the elemental analysis, IR, NMR, and mass spectrometry.     

Synthesis of 4‐Methyl Pyrrolo[2,3‐b]xanthone,a Novel Ring System

A short, high yielding synthesis of a novel substituted pyrrolo[2,3-b]xanthone has been developed. The synthesis begins with a copper catalyzed Ullmann coupling reaction followed by and intramolecular Friedel-Crafts acylation reaction to establish the xanthone core structure. After a regioselective nitration, a Leimgruber-Batcho synthesis establishes the final pyrrole ring.     

Novel Method for the Synthesis of 6,12‐Dihydro‐2‐Methylindolo[2,3‐ b]Carbazol‐6‐Ones

A novel method for the synthesis of 6,12‐dihydro‐2‐methylindolo[2,3‐b]carbazol‐6‐ones was developed from 1‐oxo‐2,3,4,9‐tetrahydro‐1H‐carbazol‐1‐one through methyl 6‐methyl‐2‐(1‐oxo‐2,3,4,9‐tetrahydro‐1H‐carbazol‐2‐yl)oxoacetate in good yields. This method provides an alternative path for the synthesis of this product using 2‐hydroxy methylene‐2,3,4,9‐tetrahydro‐1H‐carbazol‐1‐one.     

Synthesis of Novel Classes of Pyrido[2,3‐d]‐pyrimidines,Pyrano[2,3‐d]pyrimidines,and Pteridines

6‐Amino‐5‐formyluracils 1 and 5‐formyl‐6‐hydroxyuracils 4 react with Meldrum's acid 2 in the presence of piperidine as catalyst under thermolytic conditions to afford 6‐carboxy‐2,4,7‐trioxopyrido[2,3‐d]pyrimidines 3 and 6‐carboxy‐2,4,7‐trioxopyrano[2,3‐d]pyrimidines 5 in good yield. Under identical conditions, 6‐amino‐5‐nitrosouracils 6 react with 2 to afford pteridine‐6‐carboxylic acids 7 in good yields.     

Synthesis of Novel 5‐Trifluoromethyl‐2,4,7‐Trisubstituted Pyrido[2,3‐d]Pyrimidines

Abstract

Novel pyrido[2,3‐d]pyrimidines (2,4) were synthesized by reacting 2‐amino‐3‐cyano‐4‐trifluoromethyl‐6‐substituted pyridines (1) with Grignard reagent followed by condensation with anhydride/chloroacetylchloride/aromatic aldehyde.     

Nickel‐Catalyzed Electrochemical Synthesis of Dihydro‐Benzo[b]thiophene Derivatives

Abstract

The intramolecular electrochemical reductive cyclization of ortho‐haloaryl allyl thioethers catalyzed by Ni(II) complexes associated to cyclam ligands affords dihydro‐benzo[b]thiophene derivatives in moderate to good yields.     

Green Synthesis of Pyrano[2,3‐d]‐pyrimidine Derivatives in Ionic Liquids

Pyrano[2,3‐d]pyrimidine derivatives were synthesized in high yields by a condensation reaction between arylmethylidenemalononitrile and barbituric acid using room‐temperature ionic liquids such as 1‐n‐butyl‐3‐methylimidazolium tetrafluoroborate ([BMIm]BF₄) or 1‐butylpyridinium tetrafluoroborate ([BPy]BF₄) as solvents under neutral conditions.     

Synthesis of Some Novel Fluorinated Pyrazolo[3,4‐b]Pyridines

Abstract

Reaction of 5‐amino‐3‐substituted pyrazoles (1a–c) and 5‐amino‐1,3‐disubstituted pyrazoles (1d–i) with fluorinated‐β‐diketones (2) results in the formation of the single isomer of pyrazolo[3,4‐b]pyridines (4a–h). A one‐pot procedure for the synthesis of title compounds starting from α‐cyanoacetophenones along with a possible mechanistic pathway for the formation of the title compounds is described.     

Synthesis of Thiazolo[2,3‐c]‐s‐triazoles Using Poly[(4‐diacetoxyiodo)styrene]

Abstract

Arenecarbaldehyde‐4‐arylthiazol‐2‐ylhydrazones underwent ring closure with poly[(4‐diacetoxyiodo)styrene] (PSDIB) to 3,5‐diarylthiazolo[2,3‐c]‐s‐triazoles in dichloromethane.     

Synthesis of 7‐Sulfamoyl‐substituted 2‐Oxo‐2,3,4,5‐tetrahydro‐1H‐benzo[b]azepines

Sulfochlorination of 2‐оxo‐2,3,4,5‐tetrahydro‐1H‐benzo[b]azepine led to regioselective formation of the corresponding 7‐chlorosulfonyl derivative. Starting from this reagent, a large number of substituted 2‐oxo‐7‐sulfamoyl‐2,3,4,5‐tetrahydro‐1H‐benzo[b]azepines were obtained. This approach is amenable to combinatorial production of the title compounds, which possess promising therapeutic potential.     

Synthesis of 2,3‐Dihydro‐4H‐furo[3,2‐c] chromen‐4‐ones and 2,3‐Dihydronaphtho[2,3‐b]furan‐4,9‐diones by the Radical Cyclizations of Hydroxyenones with Electron-Rich Alkenes using Manganese(III) Acetate

We have obtained dihydrofurans 3a–j in the radical cyclization of 4‐hydroxycoumarin 1a and 2‐hydroxy‐1,4‐naphtoquinone 1b with electron rich alkenes 2a–i by manganese(III) acetate. Methods A and B, which have different molar ratios were studied comparatively in these reactions, and we observed that method B (molar ratio 2:1:3) gave the best results. Treatment of 4‐hydroxycoumarin 1a and electron rich alkenes 2a–e gave 2,3‐dihydro‐4H‐furo[3,2‐c]chromen‐4‐ones 3a–e in 36–86% yields by the method B. Under the same conditions, the reactions of 2‐hydroxy‐1,4‐naphtaquinone 1b with conjugated alkenes 2b and 2f–i afforded 2,3‐dihydronaphtho[2,3‐b]furan‐4,9‐diones 3f–j in an excellent yields.     

Synthesis of Benzo[b]benzo[2,3‐d]thiophen‐6,9‐diones via Palladium(II) Acetate–Mediated Cyclization of 5‐Arylthiocyclohexa‐2,5‐diene‐1,4‐diones

Palladium(II)‐mediated oxidative cyclization of 5‐arylthiocyclohexa‐2,5‐diene‐1,4‐diones 4 giving biologically important benzo[b]benzo[2,3‐d]thiophene‐6,9‐diones 2 has been performed with a stoichiometric amount of palladium(II) acetate in distillated acetic acid.     

A Convenient Approach to the Synthesis of Dialkyl 5‐Oxo‐1,2‐dihydro‐5H‐chromeno [4,3‐b]pyridine‐2,3‐dicarboxylates

Coumarin and its analogs are considered privileged scaffolds in the current synthetic and pharmacological research. The chemical behavior of enaminocarbaldehydes of the coumarin moiety under intramolecular Wittig reaction conditions in the presence of triphenylphosphine and dimethyl or diethyl acetylenedicarboxylates has been studied, resulting in the isolation of a series of dimethyl and diethyl 5‐oxo‐1,2‐dihydro‐5H‐chromeno[4,3‐b]pyridine‐2,3‐dicarboxylates in good to high yields.     

Thermolysis and [3+2]‐Cycloaddition Reactions of 2,3‐Diferrocenyl‐ and 2,3,‐Diruthenocenylcyclopropenones

Abstract

2,3‐Diferrocenyl‐ and 2,3‐diruthenocenylcyclopropenone undergo thermolysis at ～180°C with opening of the small ring via ketenocarbenes. Intramolecular transformation of the latter occurs with elimination of CO to yield dimetallocenylacetylenes. Alternatively, they enter into 1,3‐dipolar cycloaddition reactions with C≡C or C?C multiple bonds to give cyclopentadienone or cyclopentenone derivatives, respectively.     

Synthesis of Fused Tetrazolo[1,5‐c] pyrrolo[3,2‐e]pyrimidines and Their Reductive Conversion to New 4‐Aminopyrrolo[2,3‐d]pyrimidines

Some new 7,9‐substituted 7H‐1,2,3,4‐tetrazolo[1,5‐c]pyrrolo[3,2‐e]pyrimidines 5 have been synthesized either by diazotization of 4‐hydrazino‐5,7‐disubstituted‐7H‐pyrrolo[2,3‐d]pyrimidines 4 obtained by hydrazinolysis of 4‐chloro‐5,7‐disubstituted 7H‐pyrrolo[2,3‐d]pyrimidines 3 or via a substitution reaction between 3 and sodium azide. 5,7‐Disubstituted‐7H‐pyrrolo[2,3‐d]pyrimidin‐4(3H)‐ones 2 were obtained by cyclocondensation of 1,4‐disubstituted 2‐amino‐3‐cyanopyrroles 1 with formic acid, which, on chlorination using phosphorus oxychloride, afforded 3. 2‐Amino‐3‐cyanopyrroles 1 were synthesized from the reaction between (2-bromo-1-(4-fluorophenyl) ethylidene) propanedinitrile and substituted aromatic amines under Gewald reaction conditions. A novel route for the synthesis of 4‐amino‐5,7‐disubstituted‐7H‐pyrrolo[2,3‐d]pyrimidines 6 by the reductive ring cleavage of 5 has been reported.     

Synthesis of 2,3‐Dihydroxy‐1‐Epilupinine

The 1,3‐dipolar cycloaddition of unsaturated D‐threo‐hexaldonolactone 3 and a six‐membered cyclic nitrone 11 led to a single adduct 15, which could be transformed into (1S, 2S, 3S, 9aS)‐2,3‐dihydroxy‐1‐hydroxymethyl‐quinolizidine 28 related to epilupinine via a reaction sequence involving rearrangement of the six‐membered lactone ring into a five‐membered one, removal of the terminal carbon atom from the sugar chain, cleavage of the N‐O bond, and the intramolecular alkylation of the nitrogen atom.      

A Neat and Rapid Synthesis of 2‐Aryloxymethylene‐6‐Arylimidazo[2,1‐b]‐1,3,4‐Thiadiazole Under Microwave Irradiation

A neat and rapid procedure is reported for the synthesis of a variety of 2‐aryloxymethylene‐6‐arylimidazo[2,1‐b]‐1,3,4‐thiadiazole (3a–3r) by condensation reaction of 2‐amino‐5‐aryloxymethylene‐1,3,4‐thiadiazole (1a–1f) with ω‐bromoacetophenone (2a–2c) in ethanol solvent under microwave irradiation, which yielded a series of novel compounds. The yields are good to excellent. The procedure is simple and does not need any added catalyst or dehydrating reagent. Moreover, the crystals do not require further purification to give the products.     

Three‐Component One‐Pot Synthesis of 1,4‐Dihydropyrano[2,3‐c]pyrazole Derivatives in Aqueous Media

Abstract

6‐Amino‐5‐cyano‐4‐aryl‐1,4‐dihydropyrano[2,3‐c]pyrazoles were synthesized by three‐component reaction of aromatic aldehydes, malononitrile, and 3‐methyl‐1‐phenyl‐2‐pyrazolin‐5‐one using triethylbenzylammonium chloride (TEBA) as catalyst in aqueous media. The reaction has the advantages of good yield, less pollution, ease of separation, and of being environment friendly.     

Photoinduced [4?+?2] cycloaddition reactions of benzo[b]thiophene-2,3-dione with alkenes

[4?+?2]-Photocycloadditions of benzo[b]thiophene-2,3-dione with electron-rich and electron-deficient alkenes have been described. Olefins preferentially add at both carbonyl groups to give the head-to-head [4?+?2] cycloadducts, i.e., dioxanes only. Comprehensive molecular orbital calculations at DFT-B3LYP level have been carried out to address the mechanism as well as regiochemical course of the reaction.