Catalyst-free water-mediated N-Boc deprotection

A catalyst-free water-mediated N-Boc deprotection of N-Boc-amines is reported. In the absence of any additional reagents, the free amines were formed from a variety of aromatic and aliphatic N-Boc-amines as well as from some N-Boc-amino acid derivatives.     

A new access to substituted tetraethyl N-Boc 2-aminoethylidene-1,1-bisphosphonates and phosphonyl-substituted aza-Morita-Baylis-Hillman-type adducts

A general one-pot synthesis of substituted 2-aminoethylidene-1,1-bisphosphonates has been developed. The protocol involves base-induced addition of sodium tetraethyl methylenebisphosphonate to N-Boc imines generated in situ from N-Boc-α-amidoalkyl-p-tolylsulfones by the action of sodium hydride. The direct and efficient conversion of the title compounds into aza-Morita-Baylis-Hillman-type adducts has been also elaborated.     

Efficient, solventless N-Boc protection of amines carried out at room temperature using sulfamic acid as recyclable catalyst

A simple, rapid, and efficient protocol for the chemoselective N-Boc protection of amines using sulfamic acid as catalyst is described. N-Boc protection of various structurally diverse aliphatic, aromatic, alicyclic, and heterocyclic amines (1°, 2°, 3°) was carried out with (Boc)₂O using sulfamic acid as catalyst (5 mol %) at room temperature under solventless conditions. The advantages of this method are simplicity, shorter reaction times (1-15 min), a cost-effective catalyst, and excellent isolated yields (90-100%); it is also environmentally benign. Moreover, the combined use of ultrasound and sulfamic acid achieves a synergic effect that is especially marked in the N-Boc protection of deactivated (sterically hindered and electron-deficient) amines. The catalyst possesses distinct advantages: ease of handling, cleaner reactions, high activity, and excellent chemoselectivity.     

Highly regioselective Friedel-Crafts alkylation of indoles with α,β-unsaturated N-acylbenzotriazoles

The Friedel-Crafts alkylation rather than acylation of indoles was realized with α,β-unsaturated acylbenzotriazoles catalyzed by samarium(III) iodide under reflux in anhydrous THF. The reaction was highly regioselective, and a series of new 3-substituted indole derivatives were obtained in moderate to good yields with the potential to be further transformed into various indole derivatives due to the presence of active acylbenzotriazole moiety.     

Axially chiral phosphine-oxazoline ligands in silver(I)-catalyzed asymmetric Mannich reaction of N-Boc aldimines with trimethylsiloxyfuran

Axially chiral phosphine-oxazoline ligand L6 was found to be a fairly effective chiral ligand in silver(I)-catalyzed asymmetric Mannich reaction of N-Boc aldimines with trimethylsiloxyfuran to give the corresponding adducts in up to 97% yield, 7:1 dr and 86% ee (major diastereoisomer).     

Radiation synthesis and characterization of poly(N,N-dimethylaminoethyl methacrylate-co-N-vinyl 2-pyrrolidone) hydrogels

In this study, radiation synthesis and characterization of swelling behavior and network structure of poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA), and poly(N,N-dimethylaminoethyl methacrylate-co-N-vinyl 2-pyrrolidone) (P(DMAEMA-co-VP)), hydrogels were investigated. PDMAEMA and P(DMAEMA-co-VP) hydrogels in the rod forms were prepared by irradiating the ternary mixtures of DMAEMA/VP/cross-linking agent, ethyleneglycol dimethacrylate (EGDMA), by gamma rays at ambient temperature. In composition ranges where the three components were completely miscible, water was also added to the ternary mixture to provide the formation of homogeneous polymerization and gelation. The influence of irradiation dose, comonomer, VP, and cross-linking agent, EGDMA, content on the total percentage gelation and monomer conversion were investigated. The effect of pH and temperature on the swelling behavior of hydrogels have also been examined. Hydrogels showed typical pH response and temperature responses, such as low-pH and low temperature swelling and high-pH and high temperature deswelling. Polymer-solvent interaction parameter (χ) and enthalpy and entropy changes appearing in the χ parameter for the P(DMAEMA-co-VP)-water system were determined by using Flory-Rehner theory of swelling equilibrium. The negative values for ΔH and ΔS indicate that prepared pure PDMAEMA and P(DMAEMA-co-VP) hydrogels have lower critical solution temperature (LCST) and Flory-Rehner theory of swelling equilibrium provides a satisfactory agreement to the experimental swelling data of the hydrogels.     

An efficient and chemoselective Brønsted acidic ionic liquid-catalyzed N-Boc protection of amines

The first report of a Brønsted acidic ionic liquid, 1-methylimidazolium tetrafluoroborate [(HMIm)BF₄], catalyzed efficient and chemoselective N-Boc protection of various amines using (Boc)₂O is presented. Optically pure amino alcohols and amino acid esters were converted efficiently to their corresponding optically pure N-Boc derivatives. The reported method is mild, solvent-free and has the advantages of both homogeneous and heterogeneous catalysis with high product yields, selectivity and ease of product separation.     

A concise synthesis of asymmetrical N,N′-disubstituted guanidines

We present a new and concise method for the preparation of asymmetrical N,N′-disubstituted guanidines starting from thiourea via the reaction of N-Boc-protected N′-alkyl/aryl substituted thioureas with an amine in the presence of mercury(II) chloride and triethylamine.     

N,N′-Diisopropyl- and N,N′-dicyclohexylthiourea cadmium(II) complexes as precursors for the synthesis of CdS nanoparticles

Crystals of the cadmium(II) complexes of N,N-diisopropylthiourea and N,N-dicyclohexylthiourea were obtained and their X-ray single crystal structures determined. These complexes are air-stable, easy to prepare and inexpensive and decompose cleanly to give good quality crystalline CdS. The nanoparticles of CdS thus obtained showed quantum confinement effects in their optical spectra, with close to band-edge emission in luminescence experiments. The broad diffraction patterns observed are typical of nanodimensional particles. The variation of concentration of precursor-to-HDA ratio change the isolated materials from spheres to rod-shaped. TEM images showed agglomerates of needle-like plate of particles.     

Nano-ferrous ferric oxide (nano-Fe3O4): Powerful,reusable, and stable catalyst for N-Boc protection of amines

Nano-ferrous ferric oxide (nano-Fe₃O₄) efficiently catalyzed N-boc protection of amines in high yields and acceptable reaction times. Nano-Fe₃O₄ was applied as an efficient, green, heterogeneous and reusable magnetite catalyst. Clean reaction, simple purification, short reaction time and high yield were some other advantages of this compound.     

Efficient iodine catalyzed chemoselective synthesis of aminals—an access to N,N-acetals by the addition of lactams to N-acyl imines

A highly efficient protocol has been developed for the synthesis of aminals from γ-butyrolactam and benzaldehyde using iodine as Lewis acid catalyst. The attack of γ-butyrolactam nucleophile to intermediate N-acyliminium ion was more favorable, when aryl aldehyde bears the electron donating group (EDG). Iodine plays a key role in these reaction transformations. This current mild protocol is environmentally benign and cost-effective method for the synthesis of industrially and pharmaceutically useful scaffolds.     

Intramolecular C-H insertion in ring-expanded N-heterocyclic carbenes

Mild heating of the ring-expanded N-heterocyclic carbenes 7-Mes and 6-Mes results in intramolecular insertion of the carbene into an ortho-methyl C-H bond. In the presence of traces of acid, the resulting products ring-open to afford N-alkyl indoles.     

Facile synthesis of acyclic azanucleosides from N-pivaloyloxymethyl amides and sulfonamides: synthesis of aza-analogues of Ganciclovir

N-Pivaloyloxymethyl amides and sulfonamides, readily available from N-alkylation of both amides and sulfonamides with commercial chloromethyl pivaloate, were converted into acyclic azanucleosides via a one-pot base silylation/nucleoside coupling procedure.     

One-pot and microwave-assisted synthesis of N-sulfonylaziridines

A novel and efficient microwave-assisted one-step reaction was developed to synthesize chiral N-sulfonylaziridines by the reaction of different chiral amino alcohols and sulfonic chlorides. The newly developed microwave synthetic method has the advantage of reducing the reaction time from 24 to 0.5 h with improved yields (84-93%) and minimizing by-products.     

A practical synthesis of N-tosylimines of arylaldehydes

Synthesis of N-tosylimines of arylaldehydes was carried out by the reaction of arylaldehydes and p-toluenesulfonamide in methylene chloride in the presence of trifluoroacetic anhydride as a dehydrating agent.     

Electrochemical fluorination of N,N-dimethylperfluoroacylamides

The electrochemical fluorination (ECF) of N,N-dimethylperfluoroacylamides gives the corresponding perfluoro-N,N-dimethylacylamides in low yield. With increase of the number of carbon atoms in the perfluoroacyl radical the yield of the required perfluoro-N,N-dimethylacylamides is slightly increased.     

Diastereo- and enantioseparation of a N-Boc amino acid with a zwitterionic quinine-based stationary phase: Focus on the stereorecognition mechanism

A chiral chromatography method enabling the simultaneous diastereo- and enantioseparation of N^α-Boc-N⁴-(hydroorotyl)-4-aminophenylalanine [Boc-Aph(Hor)-OH, 1] was optimized with a quinine-based zwitterionic stationary phase. The polar-ionic eluent system consisting of ACN:MeOH:water—49.7:49.7:0.6 (v/v/v) with formic acid (4.0 mM) and diethylamine (2.5 mM), allowed the successful separation of the four acid stereoisomers: α_d,d-/d,l-1 = 1.08; α_d,l-/l,d-1 = 1.08; α_l,d-/l,l-1 = 1.40.     

N-Nosyl-α-amino acids in solution phase peptide synthesis

A highly efficient and practical synthesis of peptides in solution phase has been developed. The procedure is based on the use of p-nitrobenzenesulfonyl (nosyl) group for the protection of the amino function of α-amino acids. Every step of the procedure, protection of the amino function by the nosyl group, formation of the peptide bond, and removal of the sulfonamide group, is characterized by high yields and excellent purity of the final products. The described strategy allows the preparation of short peptide sequences keeping the chiral integrity of amino acid precursors. Compatibility of nosyl group with the side-chain protecting groups used in Fmoc-based strategy is demonstrated. The method here presented is an alternative strategy that could provide advantages for future peptide synthesis.     

Efficient synthesis of indoles using [3,3]-sigmatropic rearrangement of N-trifluoroacetyl enehydrazines

[3,3]-Sigmatropic rearrangement of N-trifluoroacetyl enehydrazines provides a novel method for the construction of indoles. N-Trifluoroacetyl enehydrazine having a cyclopentene ring smoothly underwent [3,3]-sigmatropic rearrangement followed by cyclization to give indolines in excellent yield. On the other hand, both cyclohexenyl N-trifluoroacetyl enehydrazine and acyclic N-trifluoroacetyl enehydrazine gave indoles in good yield. Additionally, the substituent effect on the benzene ring was also studied. The rearrangement of N-trifluoroacetyl enehydrazines proceeded smoothly even under either aqueous or solvent-free conditions.     

Novel synthesis of α-nitroalkenes from nitroalkanes via halogenation of intermediate N,N-bis(silyloxy)enamines

An approach to conjugated nitroalkenes via oxidation of N,N-bis(silyloxy)enamines with bromine or iodine in the presence of tetra-n-butylammonium acetate is described. The acetate ion plays a key role by acting as a mild desilylating reagent. This new strategy allows the synthesis of α-nitroalkenes from the corresponding nitroalkanes.