Showing papers on "Alkylation published in 2003"

Preparation of 1-Butyl-3-Methyl Imidazolium-Based Room Temperature Ionic Liquids

Abstract: P 1-Butyl-3-methylimidazolium tetrafluoroborate 1-Butyl-3-methylimidazolium hexafluorophosphate R 1-Butyl-3-methylimidazolium chloride Potassium hexafluorophosphate P 1-Butyl-3-methylimidazolium hexafluorophosphate Keywords: heterocycles, five-membered, two nitrogens; halogen compounds, chlorine compounds; alkylation, N-alkylation; 1-chlorobutane, irritant, possible carcinogen; 1-chlorobutane; heterocycles, five-membered, two nitrogens; halogen compounds, fluorine compounds; replacement reactions, halogen by various groups; heterocycles, five-membered, two nitrogens; halogen compounds, fluorine compounds; replacement reactions, halogen by various groups

Design of N-Spiro C2-Symmetric Chiral Quaternary Ammonium Bromides as Novel Chiral Phase-Transfer Catalysts: Synthesis and Application to Practical Asymmetric Synthesis of α-Amino Acids

Abstract: A series of C2-symmetric chiral quaternary ammonium bromides 10 and 11 have been designed as a new, purely synthetic chiral phase-transfer catalyst, and readily prepared from commercially available optically pure 1,1‘-bi-2-naphthol as a basic chiral unit. The details of the synthetic procedures of each requisite chiral binaphthyl subunit have been disclosed, and the structures of the assembled N-spiro chiral quaternary ammonium bromides 11a and 11f were unequivocally determined by single-crystal X-ray diffraction analysis. The reactivity and selectivity of these chiral ammonium bromides as chiral phase-transfer catalysts have been evaluated in the asymmetric alkylation of the benzophenone Schiff base of glycine ester 7 under mild liquid−liquid phase-transfer conditions, and the optimization of the reaction variables (solvent, base, and temperature) has also been conducted. Further, the scope and limitations of this asymmetric alkylation have been thoroughly investigated with a variety of alkyl halides, in...

Mechanistic Studies of Nickel(II) Alkyl Agostic Cations and Alkyl Ethylene Complexes: Investigations of Chain Propagation and Isomerization in (α-diimine)Ni(II)-Catalyzed Ethylene Polymerization

Abstract: The synthesis of a series of (α-diimine)NiR2 (R = Et, nPr) complexes via Grignard alkylation of the corresponding (α-diimine)NiBr2 precursors is presented. Protonation of these species by the oxonium acid [H(OEt2)2]+[BAr‘4]- at low temperatures yields cationic Ni(II) β-agostic alkyl complexes which model relevant intermediates present in nickel-catalyzed olefin polymerization reactions. The highly dynamic nature of these agostic alkyl cations is quantitatively addressed using NMR line broadening techniques. Trapping of these complexes with ethylene provides cationic Ni alkyl ethylene species, which are used to determine rates of ethylene insertion into primary and secondary carbon centers. The Ni agostic alkyl cations are also trapped by CH3CN and Me2S to yield Ni(R)(L)+ (L = CH3CN, Me2S) complexes, and the dynamic behavior of these species in the presence of varied [L] is discussed. The kinetic data obtained from these experiments are used to present an overall picture of the ethylene polymerization mech...

Soft antimicrobial agents: synthesis and activity of labile environmentally friendly long chain quaternary ammonium compounds.

Abstract: A series of soft quaternary ammonium antimicrobial agents, which are analogues to currently used quaternary ammonium preservatives such as cetyl pyridinium chloride and benzalkonium chloride, were synthesized. These soft analogues consist of long alkyl chain connected to a polar headgroup via chemically labile spacer group. They are characterized by facile nonenzymatic and enzymatic degradation to form their original nontoxic building blocks. However, their chemical stability has to be adequate in order for them to have antimicrobial effects. Stability studies and antibacterial and antiviral activity measurements revealed relationship between activity, lipophilicity, and stability. Their minimum inhibitory concentration (MIC) was as low as 1 microg/mL, and their viral reduction was in some cases greater than 6.7 log. The structure-activity studies demonstrate that the bioactive compounds (i.e., MIC for Gram-positive bacteria of <10 microg/mL) have an alkyl chain length between 12 and 18 carbon atoms, with a polar headgroup preferably of a small quaternary ammonium group, and their acquired inactivation half-life must be greater than 3 h at 60 degrees C.

Secondary benzylation using benzyl alcohols catalyzed by lanthanoid, scandium, and hafnium triflate

Abstract: The combination of a secondary benzyl alcohol and a metal triflate (e.g., La, Yb, Sc, and Hf triflate) in nitromethane was a highly effective secondary-benzylation system. Secondary benzylation of carbon (aromatic compounds, olefins, an enol acetate), nitrogen (amide derivatives), and oxygen (alcohols) nucleophiles was carried out with a secondary benzyl alcohol and 0.01−1 mol % of a metal triflate in the presence of water. Secondary benzyl alcohols and nucleophiles bearing acid-sensitive functional groups (e.g., tert-butyldimethylsilyloxy and acetoxy groups and methyl and benzyl esters) could be used for alkylation. Hf(OTf)4 was the most active catalyst for this alkylation, and trifluoromethanesulfonic acid (triflic acid, TfOH) was also a good catalyst. The catalytic activity of metal triflates and TfOH increased in the order La(OTf)3 < Yb(OTf)3 < TfOH < Sc(OTf)3 < Hf(OTf)4. A mechanistic study was also performed. The reaction of 1-phenylethanol (4a) in the presence of Sc(OTf)3 in nitromethane gave an eq...

Comparison of the Electrical Properties and Chemical Stability of Crystalline Silicon(111) Surfaces Alkylated Using Grignard Reagents or Olefins with Lewis Acid Catalysts

Abstract: Four methods were used to functionalize crystalline Si(111) surfaces with alkyl groups (C_nH_(2n+1), n = 1, 2, 6, 8): chlorination with PCl_5 followed by alkylation with C_nH_(2n+1)MgX (X = Cl, Br), chlorination with Cl_2(g) followed by alkylation with C_nH_(2n+1)MgX, Lewis acid-mediated reduction of a terminal alkene, and anodization in diethyl ether containing 3.0 M CH_3MgI. The chemical properties of each surface were characterized as a function of time exposed to air using X-ray photoelectron spectroscopy, and the electrical properties of the various surfaces were probed using time-resolved radio frequency (rf) photoconductivity decay methods. Both chlorination/alkylation routes produced alkylated Si surfaces that displayed low ( 600 h of exposure to air. Surfaces functionalized through this route also displayed a significantly lower rate of oxidation than did unalkylated, H-terminated or Cl-terminated Si(111) surfaces. In contrast, surfaces modified by the Lewis acid-catalyzed reduction of 1-hexene and 1-octene exhibited high S values (S > 400 cm s^(-1)) when initially exposed to air and oxidized as rapidly as H-terminated Si(111) surfaces. Methyl-terminated Si(111) surfaces functionalized by anodization in a solution of CH_3MgI in ether exhibited stable, albeit high, S values (460 cm s^(-1)), indicating that the surface had been partially modified by the anodization process. The fractional monolayer coverage of oxide on the alkylated surface after exposure to air was determined for each functionalization technique. Although all four of the functionalization routes studied in this work introduced alkyl groups onto the Si surface, subtle changes in the extent and quality of the alkyl termination are significant factors in determining the magnitude and degree of chemical and electrical passivation of the resulting functionalized Si surfaces.

Asymmetric Friedel-Crafts Reactions: Catalytic Enantioselective Addition of Aromatic and Heteroaromatic C-H Bonds to Activated Alkenes, Carbonyl Compounds, and Imines

Abstract: The development and scope of catalytic enantioselective addition of aromatic and heteroaromatic C-H bonds to α,β-unsaturated alkenes, carbonyl compounds, and imines are presented. α,β-Unsaturated alkenes, 4-substituted 2-oxo-3-butenoate esters and alkylidene malonates react with indoles, furans and electron-rich aromatic compounds in the presence of chiral bisoxazoline-copper(II) complexes to give the Friedel-Crafts alkylation adduct in moderate to high yields and with up to >99.5% ee. Chiral bisoxazoline-copper(II) complexes can also catalyze the enantioselective addition of especially electron-rich aromatic compounds to activated carbonyl compounds such as glyoxylates and trifluoropyruvate to give e.g. optically active aromatic mandelic acid esters in good yields and enantioselectivities. Electron-rich aromatic compounds and heteroaromatic compounds react in an enantioselective fashion with activated N-protected α-imino esters to give optically active aromatic and heteroaromatic u-amino acid derivatives using chiral BINAP-copper(I) complexes as the catalyst.

Alpha-imino esters: versatile substrates for the catalytic, asymmetric synthesis of alpha- and beta-amino acids and beta-lactams.

Abstract: The catalytic asymmetric addition of organic nucleophiles to alpha-imino esters has emerged as one of the most promising and intensely investigated routes to optically enriched alpha- and beta-amino acid derivatives and beta-lactams. The importance of alpha-imino esters stems not only from the vast appeal of the potential product classes,(1) but also from their remarkable reactivity as highly electrophilic imines. With each passing year, the number of publications concerning the asymmetric alkylation of imino esters grows significantly. The asymmetric alkylation of imines(2) and N,O-acetals has been in itself a subject of intense interest.(3) In this Account, we wish to illustrate our contribution to this timely field, as well as to highlight the seminal contributions of others.

Palladium-catalyzed asymmetric addition of pronucleophiles to allenes.

Abstract: Simple additions are the most atom economic way to effect alkylations. The ability to effect the hydrocarbonation of allenes asymmetrically then becomes a highly efficient alkylation protocol. The first example of such a protocol involves the ability of a palladium(0) catalyst derived from palladium trifluoroacetate dimer and the bis-2-diphenylphosphinobenzamide of trans-1,2-diamininocyclohexane to catalyze additions to benzyloxyalkene. Various substituted Meldrum's acids including hydroxy Meldrum's acid react well in the presence of 1 mol % trifluoroacetic acid to give one regioisomer with ee's ranging from 82 to 99%. Switching to azlactones to access unusual quarternary amino acids requires somewhat more basic conditions. Thus, use of 2 mol % potassium alpha-butoxide and 20 mol % hippuric acid leads to a smooth reaction to produce a simple regiosomer. This nucleophile raises the question of facial selectivity with respect to both the nucleophile and the electrophile. Excellent diastereoselectivity (dr 13-20:1) and enantioselectivity (85-94% ee) are obtained. Thus, a new approach for asymmetric allylic alkylations of carbon pronucleophiles by simple additions provides a very efficient, more atom economic strategy for asymmetric C-C bond formation.

The Michael addition of indoles to alpha,beta-unsaturated ketones catalyzed by CeCl3.7H2O-NaI combination supported on silica gel.

Abstract: Alkylation of indoles by means of the Michael addition has been the subject of a number of investigation. It is well established that regioselectivity in the additions of indoles to electron-deficient alkenes is strongly controlled by the reaction medium. In a continuation of the work on developing greener and cleaner technologies, the cerium(III) chloride heptahydrate and sodium iodide combination supported on silica gel catalyzes the alkylation of various indoles with α,β-unsaturated ketones giving 3-(3-oxoalkyl)indole derivatives in good yields. The substitution on the indole nucleus occurred exclusively at the 3-position, and N-alkylation products have not been observed.

Palladium-catalyzed nucleophilic benzylic substitutions of benzylic esters.

Abstract: A palladium complex generated in situ from [Pd(eta3-C3H5)(cod)]BF4 and DPPF is a good catalyst for benzylic alkylation of benzyl methyl carbonate with the carbanion of dimethyl malonates. The catalytic reaction is applicable to a wide range of the benzylations of benzylic esters with malonates. The catalytic activity was heavily affected by the bite angle of the bidentate phosphine ligand on palladium. DPEphos ligand is superior to DPPF in the case of palladium-catalyzed benzylic amination of benzylic esters.

Method for manufacturing alkylate oil with composite ionic liquid used as catalyst

Abstract: The present invention pertains to a method for manufacturing alkylate oil using a composite ionic liquid as catalyst. A mixture of isobutane and C4 olefins is used as the raw material, and a composite ionic liquid is used as catalyst to carry out an alkylation reaction. The alkane/olefin ratio in the raw material is higher than 1:1. In the composition of the aforementioned composite ionic liquid catalyst, the cations come from a hydrohalide of an alkyl-containing amine or pyridine, while the anions are composite coordinate anions coming from two or more metal compounds. One of the metal compounds is an aluminum compound, while other metal compounds are compounds of Group IB and Group IIB elements of the Periodic Table and the transition metals. The present invention also provides a design of static mixer reaction apparatus that can realize the aforementioned manufacturing method. The method of the present invention increases the selectivity of the alkylation reaction to give the alkylation product a relatively high octane number and further increase the product yield. Also, the manufacturing operation is simplified, and the cost can be reduced. This method is an environmentally friendly method that will not pollute the environment.

Reversible infertility in male mice following oral administration of alkylated imino sugars: a non-hormonal approach to male contraception

Abstract: The present invention provides a method by which to reversibly render male mammals infertile. Thus, the disclosed N-substituted imino compounds, and pharmaceutical compositions thereof, completely impair the fertility of male mammals, but exhibit no effect on that of female mammals, and are thus useful as male contraceptives. Particularly efficacious compounds are imino sugars derived from N-alkylated piperidines of the formulae: wherein R 2 is can be a linear or branched C 1-18 alkyl, C 2-18 alkenyl or alkynyl; or aralkyl; which may be optionally substituted with one or more of —OH; —F; —Cl; —Br; —I; —NH 2 ; alkyl- and dialkylamino; linear or branched C 1-6 alkyl, C 2-6 alkenyl and alkynyl; aralkyl; linear or branched C 1-6 alkoxy, aryloxy; aralkoxy; —CN, —NO 2 , —COOH, —COO(alkyl); —COO(aryl); —C(O)NH(C 1-6 alkyl); —C(O)NH(aryl); sulfonyl; (C 1-6 alkyl)sulfonyl; arylsulfonyl; sulfamoyl, (C 1-6 alkyl)sulfamoyl; (C 1-6 alkyl)thio; (C 1-6 alkyl)sulfonamide; arylsulfonamide; —NHNH 2 ; and —NHOH.

A Highly Enantioselective Phosphabicyclooctane Catalyst for the Kinetic Resolution of Benzylic Alcohols

Abstract: A new class of chiral phosphines belonging to the P-aryl-2-phosphabicyclo[3.3.0]octane family (PBO) has been prepared by enantioselective synthesis starting from lactate esters and 2,2-dimethylcyclopentanone enolate 5. A selective enolate alkylation method has been developed for preparation of 9 and 10 using a chelating ester substituent in the triflate alkylating agent 11. Subsequent conversion to the PBO catalysts 2 and 39 relies on a diastereoselective cyclization from the cyclic sulfate 17 and LiPHAr to afford the more hindered endo-aryl phosphines. These phosphines function as efficient catalysts for the kinetic resolutions of aryl alkyl carbinols by benzoylation (16, 21, 22) or iso-butyroylation in the case of the less hindered aryl alkyl carbinol substrates. With o-substituted aryl alkyl carbinols, the enantioselectivities exceed 100, and s = 380 ± 10 has been demonstrated in the case of methyl mesityl carbinol. The PBO-catalyzed acylations probably involve a P-acylphosphonium carboxylate intermedi...

Aromatic Nucleophilic Substitution or CuI-Catalyzed Coupling Route to Martinellic Acid

Abstract: Condensation of β-amino ester 8b with triflate 7 gives N-aryl amino ester 11, which is converted into 2-substituted 4-oxoquinoline 4 using an intramolecular Dieckmann reaction as the key step. CuI-mediated coupling of β-amino ester 8a with 1,4-diiodobenzene followed by an intramolecular acylation and Pd-catalyzed carbonylation provide another manner to 4. Alkylation of 4 and subsequent reductive amination deliver the cyclic imine 14, which is transformed into triamine 3 by ordinary operations. Guanylation of 3 under mild condition followed by deprotection results in the synthesis of martinellic acid 1.

Synthesis of α-Amino Acids via Asymmetric Phase Transfer-Catalyzed Alkylation of Achiral Nickel(II) Complexes of Glycine-Derived Schiff Bases

Abstract: Achiral, diamagnetic Ni(II) complexes 1 and 3 have been synthesized from Ni(II) salts and the Schiff bases, generated from glycine and PBP (7) and PBA (11), respectively, in MeONa/MeOH solutions. The requisite carbonyl-derivatizing agents pyridine-2-carboxylic acid(2-benzoyl-phenyl)-amide 7 (PBP) and pyridine-2-carboxylic acid(2-formyl-phenyl)-amide 11 (PBA) were readily prepared from picolinic acid and o-aminobenzophenone or picolinic acid and methyl o-anthranilate, respectively. The structure of 1 was established by X-ray crystallography. Complexes 1 and 3 were found to undergo C-alkylation with alkyl halides under PTC conditions in the presence of beta-naphthol or benzyltriethylammonium bromide as catalysts to give mono- and bis-alkylated products, respectively. Decomposition of the complexes with aqueous HCl under mild conditions gave the required amino acids, and PBP and PBA were recovered. Alkylation of 1 with highly reactive alkyl halides, carried out under the PTC conditions in the presence of 10% mol of (S)- or (R)-2-hydroxy-2'-amino-1,1'-binaphthyl 31a (NOBIN) and/or its N-acyl derivatives and by (S)- or (R)-2-hydroxy-8'-amino-1,1'-binaphthyl 32a (iso-NOBIN) and its N-acyl derivatives, respectively, gave rise to alpha-amino acids with high enantioselectivities (90-98.5% ee) in good-to-excellent chemical yields at room temperature within several minutes. An unusually large positive nonlinear effect was observed in these reactions. The Michael addition of acrylic derivatives 37 to 1 was conducted under similar conditions with up to 96% ee. The (1)H NMR and IR spectra of a mixture of the sodium salt of NOBIN and 1 indicated formation of a complex between the two components. Implications of the association and self-association of NOBIN for the observed sense of asymmetric induction and nonlinear effects are discussed.

Enantioselective synthesis of alpha-alkyl-beta,gamma-unsaturated esters through efficient cu-catalyzed allylic alkylations.

Abstract: A method for enantioselective Cu-catalyzed allylic substitution between various alkylzincs and alpha,beta-unsaturated carboxylic esters that bear a gamma-phosphate is reported. These transformations afford alpha-alkyl-beta,gamma-unsaturated carbonyls with regioselectivities of 7:1 to >20:1 (S(N)2':S(N)2) and in 87-97% ee. The utility of the method is illustrated by a convergent total synthesis of topoisomerse II inhibitor (R)-elenic acid.