Easy access to N-alkylation of N-unsubstituted [60]fulleropyrrolidines: reductive amination using sodium triacetoxyborohydride

[60]Fulleropyrrolidines were used as secondary amines to react with aldehydes through reductive aminations to afford N-alkylated derivatives. In spite of the very weak base activity of the nitrogen atom of N-unsubstituted [60]fulleropyrrolidines, this method was found to be efficient at the aid of sodium triacetoxyborohydride. Several N-alkylated derivatives were synthesized and fully characterized.     

Carbon-carbon bond formations at the benzylic positions of N-benzylxanthone imines and N-benzyldi-1-naphthyl ketone imine

Two N-benzyl imines are designed to allow for carbon-carbon bond formations at the aminated benzylic positions. Direct benzylic arylation reactions of N-benzylxanthone imine with aryl chlorides proceed under palladium catalysis in the presence of cesium hydroxide, yielding the corresponding benzhydrylamine derivatives. Alkylation reactions of N-benzyldi-1-naphthyl ketone imine with alkyl halides in the presence of potassium tert-butoxide afford the corresponding 1-phenylalkylamines in high yields. Conjugate addition of N-benzyldi-1-naphthyl ketone imine is also described.     

Synthesis of oxindoles via Cu-mediated reactions between N-phenylacrylamides and ethyl 2-bromo-2-methylpropionate

A novel way of synthesizing alkylated oxindoles via Cu-mediated atom transfer radical addition reaction between N-phenylacrylamides and ethyl 2-bromo-2-methylpropionate has been described. It was found that the use of N,N,N′,N′-1,1,2,2,-tetramethylethylenediamine as ligand was important for achieving good yields. Additionally, the use of DMSO as solvent and running the reaction at 130?°C were also crucial. In some cases, the product can be further brominated when the reaction temperature was raised to 150?°C.     

Trihaloacetaldehyde N,O-acetals: useful building blocks for dihalomethylene compounds

The reaction of trifluoroacetaldehyde N,O-acetals with more than 2 equiv of alkyllithiums at −78 °C resulted in regiospecific defluorinative alkylation with unusual regioselectivity to give α,α-difluoroketone N,O-acetals in excellent yield. In contrast, under similar conditions, trichloroacetaldehyde N,O-acetals gave simple mono-dechlorinated product without the alkyl transfer reaction from alkyllithiums to the generated intermediates.     

Highly dispersed potassium on alumina as a metalating agent. Alkylation of enolizable compounds

Highly dispersed potassium on alumina (K/Al₂O₃) acts as a metalating agent towards enolizable compounds and the intermediate organopotassium derivatives can be alkylated with primary alkyl bromides. The reaction conditions are dependent on the substrate. In particular, tetrahydrofuran is the solvent of choice for the metalation of nitriles and aldehydeN,N-dimethylhydrazones at ?60°C and of N-cyclohexyl ketimines at room temperature, whereas hexane must be used for ketones.     

2-Hydroxy-N,N,N-tributylethanaminium thiocyanate as solvent and reagent for the preparation of alkyl thiocyanates

2-Hydroxy-N,N,N-tributylethanaminium thiocyanate was utilized as both solvent and reagent for the conversion of alkyl halides to the corresponding alkyl thiocyanates in good yields under mild conditions.     

Asymmetric chemoenzymatic synthesis of N-acetyl-α-amino esters based on lipase-catalyzed kinetic resolutions through interesterification reactions

Several phenylalanine analogs have been synthesized through a four-step route starting from easily available ethyl acetamidocyanoacetate. In a first reaction, and making use of phase transfer catalysts, this compound reacted with several alkyl halides, being benzyltributylammonium chloride identified as the best one for the production of a series of quaternary amino acids in moderate to excellent yields (52–95%). Then, the corresponding N-acetyl-phenylalanine methyl and allyl ester derivatives were obtained through acidic hydrolysis, esterification, and N-acetylation. Rhizomucor miehei lipase was found as a versatile enzyme for the resolution of these amino esters, finding the best results through interesterification reactions with butyl butyrate in acetonitrile. A great influence in the stereoselectivity was found depending on the chemical structure of the compound, achieving for the non- or para-substituted in the phenyl ring excellent stereoselectivities, being moderate for the meta-nitro derivative, while the ortho-nitro amino ester did not react.     

Versatile, convenient synthesis of pyrimido[1,2,3-cd]purinediones

The alkylation of 3-substituted cycloalkylcarboxamido-6-aminouracil derivatives with 3-bromo-1-propanol followed by ring closure yields 1,3,8-trisubstituted xanthine derivatives bearing a polar hydroxyl group. Use of the more reactive 1,3-dibromopropane or homologous dibromoalkanes for the alkylation reaction results in simultaneous alkylation at N1 and the exocyclic amino group (N⁶) yielding imidazo-, pyrimido- and diazepino-pyrimidine derivatives. The pyrimidopyrimidine derivatives can subsequently be cyclised using hexamethyldisilazane at high temperature affording an easy, convenient and general access to tricyclic pyrimido[1,2,3-cd]purinediones. Alternatively, 3-substituted 6-amino-5-benzylideneaminouracil derivatives can be reacted with 1,3-dibromopropane followed by an oxidative cyclisation using thionyl chloride to obtain the desired tricyclic pyrimido[1,2,3-cd]purinediones, which are sterically fixed analogues of pharmacologically active purine derivatives.     

Buffer-induced, selective mono-C-alkylation of phloroglucinol: application to the synthesis of an advanced intermediate of catechin

A straightforward mono-selective and C-specific alkylation of phloroglucinol with activated alkyl halides is presented. The use of water as solvent limits the amount of over-alkylated by-products. Provided some minor changes in the experimental conditions, hydrophobic cinnamyl halides can also be reacted, thus giving a direct access to advanced intermediates of natural flavonoids.     

DBU-promoted alkylation of alkyl phosphinates and H-phosphonates

The alkylation of alkyl phosphinates and some H-phosphonate diesters is promoted by the base DBU. Only more reactive alkyl halides react in preparatively useful yields. However, the method provides easy access to important H-phosphinate building blocks, without the need for a protecting group strategy or metal catalysts. The reaction is conveniently conducted at, or below, room temperature. The preparation of methyl-H-phosphinate esters is particularly interesting as it avoids the heretofore more common use of methyldichlorophosphine MePCl₂.     

Aromatic systems with 10π electrons derived from 3a-azapentalene. XXXV Quaternary salts of 3-methyl-s-triazolo[4,3-α]benzimidazole

Quaternary salts with general structures 3 and 4 are obtained by reaction of 3-methyl-s-tríazolo [4,3-α]benzimidazole and its alkyl derivatives 1 and 2 (R ≠ H) with alkyl halides. Compound 1 quaternizes at N₁ and N₂, whereas 2 quaternizes only at N₉. Compounds 3 and 4 are useful models for the study of the sites of protonation in this series. Structures are unequivocally assigned by hydrolysis and dealkylation.     

Electrogenerated N-heterocyclic carbenes: N-functionalization of benzoxazolones

A simple electrochemical procedure for the N-acylation and N-alkylation of benzoxazol-2(3H)-ones has been set up via electrolysis of an ionic liquid containing a benzoxazolone followed by addition of saturated or unsaturated anhydrides or alkyl halides. The electrochemically induced N-functionalization of benzoxazol-2(3H)-ones works very well in all tested ionic liquids, avoiding the use of volatile organic solvents. The N-acyl and N-alkyl derivatives of benzoxazol-2(3H)-ones were isolated in good to excellent yields; moreover, the ionic liquid has been reused fivefold maintaining the high yield of the products.     

General methodology for the chemoselective N-alkylation of (2,2,6,6)-tetramethylpiperidin-4-ol: Contribution of microwave irradiation

A convenient method to access a broad variety of N-alkyl-(2,2,6,6)-tetramethylpiperidin-4-ol compounds is reported. The thermal treatment of a mixture of (2,2,6,6)-tetramethylpiperidin-4-ol and allyl or benzyl bromide derivatives gave the corresponding N–alkylated compounds in good yields while leaving the hydroxyl functional group intact. Whereas 40?h were needed to reach complete conversion, microwave irradiation allowed the reaction time to be reduced (20?min) and improved the yields in most cases.     

Ind-N-alkylation of rutaecarpine and synthesis of two novel related heterocyclic ring systems: Indolo[1′,2′:3,4]pyrazo[1,2-α]quinazoline and indolo[1′,2′:3,4] [1,4] diazepino[ 1,2-α]quinazoline

The failure to obtain the N-(13)alkylrutaecarpines ( 1d,e,f ) by heating rutaecarpine ( 1a ) with neat alkyl halides at 120° is discussed in comparison with the facile reaction with methyl iodide. In contrast, with alkyl halide-potassium carbonate in acetone, the corresponding N-(13)alkyl-rutaeearpines ( 1d-l ) are obtained in good yield. By use of 1,3-diiodopropane and 1,2-dibromo-ethane, this reaction provides a facile route to 12a and 13 which are derivatives of the heretofore unknown indolo[1,2′:3,4]pyrazo[1,2-α]quinazoline and indolo[1,2 :3,4][1,4]diazepino[1,2-α]quinazoline ring systems.     

Inorganic base-mediated stereoselective hydroamination of arylalkynes with imidazole: An efficient access to N-vinylimidazoles

A metal-free inorganic base-mediated highly stereoselective hydroamination of arylalkynes with imidazoles has been developed, and the corresponding N-vinylimidazoles were obtained in good yields and with moderate to excellent stereoselectivities (up to 99:1). For the electron rich alkynes, the reaction system of CsOH·H₂O/NMP/140?°C led to the predominant formation of E-addition products, while the reaction system of KOH/NMP/90?°C afforded the Z-isomers as the major product. The electron deficient alkynes furnished predominantly the E-addition products in both reaction systems. This study essentially provides a general and an efficient protocol for the synthesis of E-isomer of the N-vinylimidazoles.     

Synthesis of aryl benzyl NH-sulfoximines

Efficient synthesis and characterisation of a series of aryl benzyl NH-sulfoximines are described. While N-protected versions of aryl benzyl sulfoximines have been previously described, reports of their deprotection are very limited, presumably due to lability under the typically harsh deprotection conditions which can be employed with the less reactive aryl alkyl derivatives. Use of N-cyanosulfoximines as key intermediates overcomes these difficulties leading to an effective synthetic route to these compounds.     

Copper-doped silica cuprous sulfate: A highly efficient heterogeneous nano-catalyst for one-pot three-component synthesis of 1-H-2-substituted benzimidazoles from 2-bromoanilines,aldehydes, and [bmim]N3

A facile and highly efficient one-pot three-component synthesis of 1-H-2-substituted benzimidazole derivatives from readily available substrates catalyzed by copper-doped silica cuprous sulfate (CDSCS) is described. In this method, treatment of diverse 2-bromoanilines, aldehydes, and [bmim]N₃ in DMF at 110 °C in the presence of CDSCS as a highly efficient heterogeneous nano-catalyst affords the corresponding 1-H-2-substituted benzimidazoles in good to excellent yields. The CDSCS is an inexpensive and stable nano-catalyst that could be simply prepared, recovered and reused for many consecutive reaction runs without significant loss of its activity.     

Synthesis of 1,3-Dialkylimidazolium and 1,3-Dialkylbenzimidazolium Salts

A number of N-alkylimidazoles and N-alkylbenzimidazoles were synthesized by reactions of imidazole and benzimidazole with alkyl halides. The reaction rate increases by a factor of 2 to 3 under conditions of microwave activation. Subsequent treatment of the resulting N-alkylazoles with alkyl halides afforded the corresponding 1,3-dialkylimidazolium and 1,3-dialkylbenzimidazolium halides.     

Distannane mediated reaction of N-acyliminium ion pools with alkyl halides. A chain mechanism involving radical addition followed by electron transfer

Hexabutyldistannane was found to be an effective mediator allowing the reaction of N-acyliminium ion pools with alkyl halides. A chain mechanism involving the addition of an alkyl radical generated from an alkyl halide to an N-acyliminium ion followed by the one-electron reduction of the resulting radical-cation by distannane was proposed.     

Methylpyridylbenzimidazoles. Part I. Mono,bis-quaternary salts and related polymethyne dyes

The reaction of 2-(4-methyl-2-pyridyl)benzimidazole with long chain alkyl halides led to N-alkylation at the imidazole ring. The bases obtained were selectively quaternized at the azine and azole nitrogen atoms. The pyridinium salts gave the corresponding polymethyne dyes. Spectral (nmr and uv) and surface properties are briefly discussed.