Use of the Pictet-Spengler reaction for the synthesis of 1,4-disubstituted-1,2,3,4-tetrahydro-β-carbolines and 1,4-disubstituted-β-carbolines: formation of γ-carbolines

Microwave-assisted conjugate addition of indole on nitro-olefins furnished nitro compounds, which were reduced to tryptamines. Further, by using Pictet-Spengler condensation, new 1,4-disubstituted-1,2,3,4-tetrahydro-β-carbolines were synthesized in diastereoselective manner. Dehydrogenation of the tetrahydro-β-carbolines produced new 1,4-disubstituted-β-carbolines. As a new observation, in some of the cases, Pictet-Spengler condensation and dehydrogenation gave two products, namely 1,4-disubstituted-β-carbolines and 1,4-disubstituted-γ-carbolines. A mechanism is proposed for this observation.     

Synthesis of 2-imino-4-thiazolines, 2-imino-4-alkoxythiazolidines,thiazoles and 4-imidazolin-2-ones from α-halomethyl ketimines

A variety of heterocycles, including 3,4-disubstituted-2-imino-4-thiazolines, 3,4-disubstituted-4-methoxy-2-iminothiazolidines, 2,4-disubstituted-thiazoles, 2-amino-4-substituted-thiazoles and 1,5-disubstituted-4-imidazolin-2-ones, were synthesized from α-chloromethyl and α-bromomethyl ketimines by condensation with potassium thiocyanate, thiourea, ammonium thiocyanate and potassium cyanate.     

Ring contraction synthesis of 2,5-disubstituted-3-arylamino-4-cyanopyrroles from 2,6-disubstituted-4-arylamino-5-cyanopyrimidines

A method for synthesis of 2,5-disubstituted-3-arylamino-4-cyanopyrroles from newly synthesised 2,6-disubstituted-4-arylamino-5-cyanopyrimidines by treatment with zinc and acetic acid, the yields being up to 80%, is developed.     

Novel methods for the synthesis of 5-substituted-3-carboxy-2,5- and 4,5-dihydrothiophenes and 5-substituted 2- and 3-sulfolenes

Various approaches to the syntheses of 5-substituted-3-carbomethoxy-2,5-dihydrothiophenes and their product sulfolenes, required as synthetic precursors for tangutorine, are described. An efficient route to 3,5-disubstituted-4,5-dihydrothiophenes and hence 3,5-disubstituted-2-sulfolenes by radical chemistry is also described.     

syn-2,3-Disubstituted-2,3-dihydro-1,4-benzoxathiin rings: preparation from quinone ketals and 2-mercaptoethanols

A general method for the preparation of syn-2,3-disubstituted-2,3-dihydro-1,4-benzoxathiin rings from 2-mercaptoethanols and quinone ketals is presented. This ring system is produced by Michael addition of a 2-mercaptoethanol to a quinone ketal, followed by cyclization of the initial Michael adduct, and subsequent aromatization to afford a syn-2,3-disubstituted-1,4-benzoxathiin in fair to good chemical yield. Several chiral syn-2,3-disubstituted-2,3-dihydro-1,4-benzoxathiin rings were prepared with this method from enantioenriched 2-mercaptoethanols. No loss of enantiopurity was observed.     

Novel and Efficient Cyclization Procedure for the Synthesis of 2,5-Disubstituted-1,3,4-thiadiazoles Without Using Any Ring-Closing Reagents

A novel method for the synthesis of 2,5-disubstituted-1,3,4-thiadiazoles via direct ring closure of 1,6-disubstituted-2,5-dithioureas in dimethylformanide without using any ring-closing reagents has been accidentally discovered. Repeated and extended experiments confirmed that this is a very simple and efficient way to synthesize these kinds of fine chemicals. A series of novel 2,5-disubstituted-1,3,4-thiadiazoles have been synthesized via this method in good yields.     

A novel traceless route to synthesize 3,5-disubstituted-1,2,4-triazoles on PEG6000

A novel traceless route to 3,5-disubstituted-1,2,4-triazoles has been described, which allows the incorporation of two elements of diversity. This method provided a library of 3,5-disubstituted-1,2,4-triazoles with high yields and purity.     

Synthesis of 1,3-disubstituted-2-amino-5-hydroxyindoles by reductive aromatization

Reductive aromatization and demethylation of 1,3-disubstituted-2-amino-5-oxo-7a-methyl-5,7a-dihydroindoles with zinc, pyridine and a trace of water yields 1,3-disubstituted-2-amino-5-hydroxyindoles. Simple derivatives of the 5-hydroxy substituent are described.     

Three-component coupling of alkynes, Baylis-Hillman adducts and sodium azide: a new synthesis of substituted triazoles

A three-component coupling was used to prepare a series of 1,4-disubstituted-1,2,3-triazoles from the corresponding acetylated Baylis-Hillman adducts, sodium azide and terminal alkynes. This one-pot reaction further increases the efficacy of ‘Click’ synthesis and diversifies the preparation of multi-functional 1,4-disubstituted-1,2,3-triazoles.     

Selective synthesis of 2,3-disubstituted-2H-isoindol-1-ylphosphonate and 2,3-disubstituted-1,2-dihydroiso-quinolin-1-ylphosphonate via metal-tuned reaction of alpha-amino (2-alkynylphenyl)methylphosphonate

Palladium(II)-catalyzed reaction of alpha-amino (2-alkynylphenyl)methylphosphonate provides a novel and efficient route to 2,3-disubstituted-2H-isoindol-1-ylphosphonate via 5-exo-cyclization and [1,5]-H shift; while 2,3-disubstituted-1,2-dihydroisoquinolin-1-ylphosphonate is afforded through 6-endo-cyclization utilizing silver triflate as catalyst.     

Electrosynthesis of 3-chloro-1,4-disubstituted-2(1H)- quinolinones and 3,3-dichloro-4-hydroxy-1,4-disubstituted- 3,4-dihydro-2(1H)-quinolinones,as well as a new convenient process to dioxindoles

Cathodic reduction of N-(2-acyl(or aroyl)phenyl)-2,2,2,-trichloro-N-alkylacetamide at -1.2 V (vs SCE) under aprotic conditions yields 3-chloro-1,4-disubstituted-2(1H)-quinolinones (1) as the major product. When the reaction is carried out at -0.8 V (vs SCE), 3,3-dichloro-4-hydroxy-1,4-disubstituted-3,4-dihydro-2(1H)-quinolinones (2) and 1,4-disubstituted-1,4-dihydro-quinoline-2,3-dione (3) are formed. Ring contraction of 2 and 3 in aqueous sodium hydroxide resulted in the formation of 3-hydroxy-1,3-dihydroindol-2-ones (5). The most plausible reaction mechanisms are proposed.     

Traceless liquid-phase synthesis of 3-alkylamino-4,5-disubstituted-1,2,4-triazoles on polyethylene glycol (PEG)

A liquid-phase route to 3-alkylamino-4,5-disubstituted-1,2,4-triazoles has been developed, which permits the incorporation of three elements of diversity. The heterocycle was constructed upon PEG6000 (soluble polymer) modified by 4-hydroxy-2-methoxybenzaldehyde, from which a traceless cleavage could be realized with TFA/CH₂Cl₂. This method provided a library of 3-alkylamino-4,5-disubstituted-1,2,4-triazoles with reasonable yields and excellent purity.     

Facile solid phase synthesis of 1,2-disubstituted-6-nitro-1,4-dihydroquinazolines using a tetrafunctional scaffold

Solid phase synthesis of 1, 2-disubstituted-6-nitro-1,4-dihydroquinazolines is described. The new tetrafunctional scaffold N-Alloc-3-amino-3-(2-fluoro-5-nitrophenyl)propionic acid was prepared by nitration of 3-amino-3-(2-fluorophenyl)propionic acid. The scaffold was anchored to Rink resin via its carboxylic group and treated with primary amines to displace the arylfluorine followed by cyclization with aryl isothiocyanates in the presence of DIC upon Alloc deprotection to afford 1,2-disubstituted-6-nitro-1,4-dihydroquinazolines in high yield.     

The condensation products of 2,3,6-trisubstituted-1,4-naphthoquinones with 2-aminothiophenol

The 2,6-disubstituted-, 3,6-disubstituted-5H-benzo[a]phenothiazin-5-one derivatives and 7-substituted-benzo[a] [1,4]benzothiazino[3,2-a]phenothiazine derivatives were prepared by the condensation of 2,3,6-trisubstituted-1,4-naphthoquinones with 2-aminothiophenol. The resulting compounds were subjected to reduction, dehalogenation and condensation with aniline. Some of the condensation intermediates were isolated and the reaction mechanism was also investigated.     

Synthesis of 2,5-disubstituted-3-cyanoindoles

An efficient synthesis of 2,5-disubstituted-3-cyanoindoles is described. This approach utilizes a highly selective iodination together with the modified Madelung reaction to generate an intermediate which can be readily transformed to more fully elaborated 2,5-disubstituted-3-cyanoindole templates that were previously difficult to access. Detailed examples and utility of this approach are presented herein.     

Synthesis of 6-amino-5-cyano-1,4-disubstituted-2(1H)-pyrimidinones via copper-(I)-catalyzed alkyne-azide 'click chemistry' and their reactivity

In this paper we present the room temperature synthesis of a novel serie of 1,4-disubstituted-1,2,3-triazoles 4a-l by employing the (3+2) cycloaddition reaction of pyrimidinones containing alkyne functions with different model azides in the presence of copper sulphate and sodium ascorbate. To obtain the final triazoles, we also synthesized the major precursors 6-amino-5-cyano-1,4-disubstituted-2(1H)-pyrimidinones 3a-r from ethyl 2,2-dicyanovinylcarbamate derivatives 2a-c and various primary aromatic amines containing an alkyne group. The triazoles were prepared in good to very good yields.     

One-pot synthesis of 4,5-disubstituted 1,2,3-(NH)-triazoles using terminal acetylenes, carbon monoxide, aryl iodides, and sodium azide

A one-pot method for the synthesis of 4,5-disubstituted-1,2,3-(NH)-triazoles via carbonylative Sonogashira reaction/1,3-dipolar cycloaddition of terminal acetylenes, carbon monoxide, aryl iodides, and sodium azide was developed. A series of new 4,5-disubstituted-1,2,3-(NH)-triazoles were prepared readily under mild conditions.     

A Convenient Synthesis of 3,5-Disubstituted 2-Acetylindoles

An easy synthesis of 3,5-disubstituted-2-actylindoles by the HC1 cyclization of the corresponding phenylhydrazones is described.     

The ring opening of 3,4-dichloro-1,2,5-thiadiazole with metal amides. A new synthesis of 3,4-disubstituted-1,2,5-thiadiazoles

We have developed a new synthesis of 3,4-disubstituted-1,2,5-thiadiazoles. The methodology is based on the ring opening of readily available 3,4-dichloro-1,2,5-thiadiazole with metal amides to afford a stable synthon, which is then transformed into the 3,4-disubstituted-1,2,5-thiadiazole derivatives via two consecutive reactions with O-, S-, N- or C-nucleophiles.     

Studies on Fragrance Raw Materials of α-Terpineol Analogues

Thirty four α-substituted or α, α-disubstituted-( 1-methylcyclohexen-4-yl )methanols and α-substituted or α,α-disubstituted-(4-methylcyclohexyl) methanols weresynthesized. Thirty two of them are new compounds. 1H NMR and IR spectra of allthe compounds were determined, MS spectra of some of them were obtained as well.The characteristic odors were evaluated.Keywords Fragrance raw materials,α-Terpineol analogues, Synthesis, Structuredetermination