Showing papers on "Alkylation published in 1996"

Alkylation of Si Surfaces Using a Two-Step Halogenation/Grignard Route

Abstract: Despite the fact that H-terminated, HF-etched Si crystals are the starting point for construction of most contemporary electronic devices,1 little is known about the chemical reactions of H-terminated Si surfaces under ambient temperature and pressure.2,3 Functionalization of Si without partial oxidation and/or formation of electrical defects is potentially important in fabricating improved electronic devices4,5 as well as in measurement of charge transfer rate constants at semiconductor/ liquid contacts.6 One recently described approach involves the reaction of HF-etched Si(111) with olefins and organic diacyl peroxides, in which formation of a self-assembled (near)monolayer of Si-alkyls was hypothesized.2 We report here an alternative strategy to functionalize HF-etched Si surfaces involving halogenation and subsequent reaction with alkyl Grignard or alkyl lithium reagents. We report vibrational spectroscopic and temperature programmed desorption data which confirm that the alkyl groups are bonded covalently to the Si surface, and we demonstrate that such overlayer formation can impede the undesirable oxidation of Si in a variety of environments while providing surfaces of high electrical quality. The H-terminated Si surface7 was first exposed to PCl5 for 20-60 min at 80-100 °C, in chlorobenzene with benzoyl peroxide as the radical initiator.8,9 Upon chlorination, the XP survey spectra (Figure 1) showed peaks at 270.2 ( 0.4 binding electron volts, BeV, (Cl 2s) and 199.3 ( 0.4 BeV (Cl 2p), indicating that this procedure yielded Cl on the surface. The high-resolution XP spectrum of the Si 2p peak of this surface displayed, in addition to the substrate Si signal, an additional peak located at 0.98 ( 0.12 BeV higher in binding energy (Figure 2) whose position and intensity was consistent with the formation of a surface Si-Cl bond.10 Auger electron spectra

Low temperature ionic liquids

Abstract: A low temperature molten ionic liquid composition comprising a mixture of a metal halide and an alkyl-containing amine hydrohalide salt is described which is useful as a catalyst and a solvent in alkylation, arylation and polymerization reactions or as an electrolyte for batteries. The metal halide is a covalently bonded metal halide which can contain a metal selected from the group comprised of aluminum, gallium, iron, copper, zinc, and indium, and is most preferably aluminum trichloride. The alkyl-containing amine hydrohalide salt may contain up to three alkyl groups, which are preferably lower alkyl, such as methyl and ethyl.

Improved process for the synthesis of 2'-o-substituted pyrimidines and oligomeric compounds therefrom

Abstract: Improved processes for the synthesis of 2'-O-substituted pyrimidine nucleosides and oligomeric compounds having these nucleosides are disclosed. The synthetic processes feature alkylation of a 2,2'-anhydropyrimidine nucleoside or a 2S,2'-anhydropyrimidine nucleoside with a weak nucleophile in the presence of a Lewis acid.

Isobutane/2-butene alkylation on zeolite beta: Influence of post-synthesis treatments

Abstract: The influence of the framework and extraframework composition of zeolite beta on its activity, selectivity, and deactivation behavior during the alkylation of isobutane with 2-butene has been studied by submitting a H-beta sample to different post-synthesis treatments. The parent Hβ sample was prepared by calcination, conventional NH4+ exchange, and further calcination of a commercial TEA-beta. These treatments were seen to produce some framework dealumination with formation of dispersed cationic extraframework aluminum (EFAL) species. The Hβ was then dealuminated by two chemical treatments (hydrochloric acid and ammonium hexafluorosilicate) and by steam calcination, the former procedures leading to almost EFAL-free catalysts. Furthermore, Hβ was also treated with the required amount of ammonium hexafluorosilicate (HFS) in order to remove EFAL species generated during the activation of the parent TEA-beta sample. The catalysts were characterized by XRD, N2 adsorption-desorption isotherms,27Al and29Si MAS-NMR, XPS, and IR spectroscopy with adsorption-desorption of pyridine. In general, dealumination of Hβ leads to less active, selective, and stable catalysts for isobutane/butene alkylation. The chemically dealuminated EFAL-free catalysts were much more active than the steamed sample, which was attributed to the presence of both cationic EFAL compensating framework charge and condensed type EFAL blocking acid sites in the latter catalyst. Furthermore, elimination of EFAL in Hβ by HFS treatment also decreased the alkylation activity of the zeolite, suggesting a synergistic effect of dispersed cationic EFAL species with framework hydroxyls of Hβ to form Bronsted acid sites of enhanced acid strength.

Cu-catalyzed alkylation and Fe catalyzed alkenylation of organomanganese reagents

Abstract: Two new selective C-C bond formation procedures are described; the Cu- catalyzed alkylation of organomanganese chlorides by alkyl halides and the Fe- catalyzed alkenylation of organomanganese chlorides by alkenyl halides. These reactions have a large scope and give high yields under mild conditions (rt, 1 h). They are highly chemoselective and allow the preparation of numerous functionalized molecules. In both cases, the presence of NMP as cosolvent (THFNMP) is determinant. For preparative organic chemistry, these two reactions compare favorably to the other related procedures since they are very easy to carry out and involve no toxic or expensive product. The Fe-catalyzed reaction is the first general Fe-catalyzed alkenylation procedure of preparative interest since no excess of alkenyl halides is required and even alkenyl chlorides can be used successfulIy.

Kinetic Analysis of Isobutane/Butene Alkylation over Ultrastable H−Y Zeolite

Abstract: The alkylation of isobutane withtrans-2-butene over ultrastable Y-type zeolites has been studied. It is well-known that this reaction is accompanied by a rapid deactivation of the catalyst. The objective of our study is to elucidate the route to catalyst deactivation so that the means of mitigating this problem can be identified. Using the initial reaction rate data, evidence has been found for a Bronsted acid mechanism. Under liquid-phase conditions, the reaction has been found to be severely diffusion limited. Using a kinetic model that accounts for the effect of diffusion, it was found that alkylation over this catalyst suffers from slow hydride transfer relative to olefin addition. This gives rise to a rapid formation of C12 + carbocations. The formation of these cations has been tied to catalyst deactivation, using a mathematical model for the reaction. On the basis of the insight gained from the experiments and modeling work, optimal reactor and catalyst design issues are examined. It is inferred from the reaction mechanism and confirmed experimentally that alkylation under pulsed flow conditions yields higher trimethylpentane/dimethylhexane ratios and slower rates of deactivation. It is suggested that the cause of the slow rate of hydride transfer is steric hindrance. Strategies for relieving this steric hindrance are proposed.

Practical Syntheses of Enantiomerically Enriched γ-Lactones and γ-Hydroxy Ketones by the Alkylation of Pseudoephedrine Amides with Epoxides and Their Derivatives

Abstract: Pseudoephedrine amide enolates are shown to undergo efficient alkylation reactions with epoxides as electrophiles. Reactions with monosubstituted epoxides are subject to stereochemical matching such that the pairing leading to the 1,3-syn diastereomer is a highly selective, synthetically useful process, while the pairing forming the 1,3-anti diastereomer is not. Reactions with the 1,1-disubstituted epoxide isobutylene oxide are also highly diastereoselective and synthetically useful, but ethylene oxide exhibits poor diastereoselectivity. As an alternative to the use of ethylene oxide, 2-(tert-butyldimethylsilyloxy)ethyl iodide is shown to undergo highly diastereoselective and efficient alkylation reactions with pseudoephedrine amide enolates. Interestingly, epoxides and alkyl halides are found to attack opposite π-faces of pseudoephedrine amide enolates. The products of each of these alkylation reactions are transformed efficiently into γ-lactones by acidic hydrolysis and into methyl ketones by the additi...

Nonstabilized Alkyl Complexes and Alkyl‐Cyano‐Ate Complexes of Iron(II) and Cobalt(II) as New Reagents in Organic Synthesis

Abstract: Alkyl transition metal reagents are being increasingly used for alkylations in organic synthesis. They have various advantages over alkyllithium and alkyl-magnesium reagents including higher selectivity, lower basicity, and—as long as the transition metal is not in its highest oxidation state—their willingness to undergo oxidative addition with electrophiles. Alkyl derivatives of FeII and CoII, which are not stabilized by special ligands but still can be easily handled, are in many cases superior to the well-known alkyl–CuI and -MnII reagents and can also undergo unexpected reactions. The introduction of alkyl-cyanoate complexes of FeII and CoII, the cyanide ligands of which (in contrast to neutral π-acidic ligands) do not reduce the reactivity, has led to further advances. Reaction mechanisms will be discussed and comparisons will be made with alkylating reagents containing CuI, MnII, NiII, or TiIV as well as with Pd-catalyzed coupling reactions. Furthermore, it will be shown that super-ate FeII complexes are almost certainly the reactive species in highly selective catalytic alkylations.

Doping-Induced Layered Structure in N-Alkylated Polyanilines

Abstract: The influence of various organic dopants on the structure of N-alkylated polyanilines substituted with alkyl side chains of different lengths and at different degrees of alkylation has been studied by FT-IR, UV-Visible spectroscopies, and X-ray diffraction. The results show that the protonation as seen for polyaniline emeraldine base can be achieved successfully through the doping method in our experiments. The conductivities of the doped polymers decrease with increasing the length of side chains and the degree of alkylation. The polyanilines doped with methanesulfonic acid (MSA), toluenesulfonic acid (TSA), and dodecylbenzenesulfonic acid (DBSA) induce a co-operative effect with the alkyl side chains on the formation of layer order. Small dopants distort the layered structure and prevent the crystallization of the side chains. The interaction of the alkyl side chains and alkyl group in DBSA assist in the development of the layered structure.

Exploratory Synthetic Studies of the α-Methoxylation of Amides via Cuprous Ion-Promoted Decomposition of o-Diazobenzamides†

Abstract: A convenient nonelectrochemical amide oxidation method has been developed. The process involves a cuprous ion-promoted decomposition of o-diazobenzamides like 4, generated in situ from the corresponding o-aminobenzamides, to give N-acyliminium ion intermediate 9 via a 1,5-H-atom transfer, followed by metal-catalyzed oxidation of the resulting α-amidyl radical. The transformation produces α-methoxybenzamides 15 in good yields. An attempt was made to apply this oxidation method to a total synthesis of the alkaloid (−)-anisomycin (16). Scalemic o-aminobenzamide pyrrolidine derivatives 18a/18b underwent oxidation to give α-methoxylated amide substrates 19a/19b, respectively, in good yields. However, alkylation of the N-acyliminium intermediate 20 with (p-methoxybenzyl)magnesium chloride gave the undesired anti-compounds 22a/22b as the major products. The amide oxidation exhibits good regioselectivity with many unsymmetrical 2-substituted piperidine and pyrrolidine systems. In general, it appears that the larg...

Total synthesis of (-)-tetrahydropalmatine via chiral formamidine carbanions : unexpected behavior with certain ortho-substituted electrophiles

Abstract: A method has been developed by alkylation of chiral lithioformamidines to construct protoberberine alkaloids with a C(9) and C(10) D-ring substitution pattern. This ring pattern was established using an ortho-substituted hydroxymethylbenzene electrophile protected as a silyl ether to ultimately provide (-)-tetrahydropalmatine in 88% ee. Additionally, we have discovered limitations with ortho-substituted electrophiles in the asymmetric formamidine alkylation. These electrophiles have the potential to disrupt the lithium formamidine chelate and cause the selectivity in the alkylation to be uncharacteristically low. The total synthesis of (+/-)-canadine and (-)-tetrahydropalmatine along with the limitations to the formamidine alkylation technology are delineated herein.

Regioselective Enolization and Alkylation of 4-Oxo-N-(9-phenylfluoren-9-yl)proline: Synthesis of Enantiopure Proline−Valine and Hydroxyproline−Valine Chimeras

Abstract: The regioselective enolization of 4-oxo-N-(9-phenylfluoren-9-yl)proline benzyl ester (5) followed by alkylation with different alkyl halides has been used to synthesize a variety of β-alkylproline derivatives. In particular, enolization of 5 with 400 mol % of KN(SiMe3)2 and alkylation with iodomethane provided 3,3-dimethyl-4-oxo-N-(9-phenylfluoren-9-yl)proline benzyl ester (7a) in excellent yield. Subsequent hydride reduction of ketone 7a and protecting group exchange by hydrogenation in the presence of di-tert-butyl dicarbonate provided enantiopure (2S,4R)- and (2S,4S)-3,3-dimethyl-4-hydroxy-N-(BOC)prolines 2. Hydroxyproline−valine chimeras (2S,4R)- and (2S,4S)-2 are each synthesized from hydroxyproline in six steps and 27% respective overall yield. Deoxygenation of 3,3-dimethyl-4-hydroxy-N-(9-phenylfluoren-9-yl)proline benzyl esters 9 via their conversion to xanthates 10 followed by tributylstannane-mediated reduction provided 3,3-dimethyl-N-(9-phenylfluoren-9-yl)proline benzyl ester (11) in excellent y...

A New Strategy for the Synthesis of alpha-Difluoromethyl-Substituted alpha-Hydroxy and alpha-Amino Acids.

Abstract: A new method for the preparation of alpha-chlorodifluoromethyl-, alpha-bromodifluoromethyl-, and alpha-difluoromethyl-substituted alpha-hydroxy and alpha-amino acid esters 11, 19-21 is described. The key step of the synthesis is the regioselective alkylation of ketones 5, 7-9 and imines 16-18 with C-nucleophiles. The ketones 7-9 are readily available from 3,3,3-trifluorolactate 1 by a five-step procedure. Subsequent removal of the protecting groups from 19-21 provides the corresponding free amino acids 25, 26, 28.

Synthesis and potent anti-HIV-1 activity of novel 6-benzyluracil analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine.

Abstract: Ethyl 2-alkyl-4-aryl-3-oxobutyrates were synthesized from the corresponding arylacetonitriles and 2-bromo esters. Condensation of the butyrates with thiourea followed by treatment with chloroacetic acid afforded the 5-alkyl-6-(arylmethyl)uracils. Condensation of the uracils with acetals using trimethylsilyl triflate (TMS triflate) as a catalyst gave acyclic 5-alkyl-6-(arylmethyl)uracil derivatives. 6-Benzyl-5-ethyluracil was also condensed with methyl 5-O-(tert-butyldiphenylsilyl)-2-deoxy-3-O-(phenoxythiocarbonyl+ ++)-alpha,beta-D-erythro-pentofuranoside, followed by Barton reduction and deprotection, to give the anomers of 6-benzyl-5-ethyl-2',3'-dideoxyuridine. Alkylation of the uracils with alkyl chloromethyl sulfides gave new thio analogues of HEPT. All new N1-substituted uracils were tested for activity against HIV-1, and the thio analogues were found extremely potent.

Synthesis, Chemical Properties, and Preliminary Evaluation of Substituted CBI Analogs of CC-1065 and the Duocarmycins Incorporating the 7-Cyano-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one Alkylation Subunit: Hammett Quantitation of the Magnitude of Electronic Effects on Functional Reactivity

Abstract: The synthesis of 7-cyano-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (CCBI), a substituted CBI derivative bearing a C7 cyano group, is described in efforts that establish the magnitude of potential electronic effects on the functional reactivity of the agents. The CCBI alkylation subunit was prepared by a modified Stobbe condensation/Friedel−Crafts acylation for generation of the appropriately functionalized naphthalene precursors followed by 5-exo-trig aryl radical−alkene cyclization for synthesis of the 1,2-dihydro-3H-benz[e]indole skeleton and final Ar-3‘ alkylation for introduction of the activated cyclopropane. The most concise approach provided the CCBI subunit and its immediate precursor in 14−15 steps in superb overall conversions (15−20%). Resolution of an immediate CCBI precursor and its incorporation into both enantiomers of 34−39, analogs of CC-1065 and the duocarmycins, are detailed. A study of the solvolysis reactivity and regioselectivity of N-BOC-CCBI (25) revealed that introduction...

Cytochrome P450 metabolic dealkylation of nine N-nitrosodialkylamines by human liver microsomes

Abstract: The metabolic dealkylation of nine nitrosodialkylamines, including five symmetrical (nitrosodimethylamine, nitrosodiethylamine, nitrosodipropylamine, nitrosodibutylamine and nitrosodiamylamine) and four asymmetrical nitrosodialkylamines (nitrosomethylethylamine, nitrosomethylpropylamine, nitrosomethylbutylamine and nitrosomethylamylamine), was investigated in 14 samples of human liver microsomes. All these nitrosodialkylamines were dealkylated to aldehydes that were separated by reversed phase HPLC and UV detected as dinitrophenylhydrazones. As the length of the alkyl chain increased from methyl to pentyl, dealkylation of symmetrical nitrosodialkylamines became less efficiently catalyzed by cytochrome P450. Conversely, oxidation of the methyl moiety of asymmetrical nitrosomethylalkylamines increased with the size of the alkyl moiety, while dealkylation of the longer alkyl group decreased. N-Dealkylase activities were significantly correlated with P450 activities measured in human liver microsomes. These catalytic activities involve CYP2A6 (coumarin 7-hydroxylation), CYP2C (mephenytoin 4-hydroxylation and tolbutamide hydroxylation), CYP2D6 (dextromethorphan O-demethylation), CYP2E1 (chlorzoxazone and p-nitrophenol hydroxylation) and CYP3A4 (nifedipine oxidation). By using 10 heterologously expressed P450s, it was shown that nitrosodimethylamine was mainly demethylated by CYP2E1. However, such enzyme specificity was lost with increasing size of the alkyl group. Therefore, the chain length of the alkyl group of nitrosodialkylamines determined the P450 involved in its oxidation. All these results emphasize that the catalytic site of P450 2E1 has a geometric configuration such that only small molecules like nitrosodimethylamine fit favorably within the putative active site of the enzyme. Furthermore, there is good evidence that P450s other than P450 2E1, such as P450 2A6, 2C8/2C9/2C19 and 3A4, are involved in the metabolism of nitrosodialkylamines bearing bulky alkyl chains.

The effect of sulfation conditions and activation temperature of sulfate-doped ZrO2, TiO2 and SnO2 catalysts during isobutane/2-butene alkylation

Abstract: The activity, selectivity, and deactivation behavior of sulfated ZrO 2 , TiO 2 and SnO 2 catalysts during the liquid phase alkylation of isobutane with 2-butene at 32°C have been studied as a function of the sulfate source, i.e., sulfuric acid and ammonium sulfate, sulfate concentration, and calcination temperature. It has been shown that, for each metal oxide, the optimum calcination temperature giving maximum activity depends on both the source of sulfur and the sulfur concentration used during the impregnation step. Moreover, when the most active preparations of each sulfated oxide are compared, it is shown that the initial activity decreases in the order: SO 4 2− /ZrO 2 ⩾ SO 4 2− /TiO 2 SO 4 2− /SnO 2 , which is the expected trend of acid strength. However, owing to the higher strength of the acid sites, the former two catalysts present a very high initial cracking activity, thus affording low selectivities to the desired trimethylpentanes (TMP). It has also been shown that a certain loss of sulfates (between 0 and 30% of the initial sulfates for most of the preparations) takes place during the alkylation reaction on the three sulfated metal oxides. Sulfate decomposition is suggested to occur by chemical interaction of the butene molecules present in the feed with some surface sulfates.

Synthesis of Enantiomerically Pure Thiocrown Ethers Derived from 1,1‘-Binaphthalene-2,2‘-diol

Abstract: Synthetic methodology is given for the preparation of two different types of thiocrown ethers from optically pure 1,1‘-binaphthalene-2,2‘-diol (10). The conceptually simplest approach starts from optically pure 10 itself, which is alkylated (4 equiv of K2CO3 in DMF at 110 °C) with 2-chloroethanol followed by mesylation to provide 2,2‘-bis(2-(mesyloxy)ethoxy)-1,1‘-binaphthyl (14). When allowed to react with ethane-1,2-dithiol, propane-1,3-dithiol, 1,4,7-trithiaheptane, 1,4,8,11-tetrathiaundecane, 2,2-dimethylpropane-1,3-dithiol, 2-(mercaptomethyl)-1-propene-3-thiol, and 1,2-benzenedithiol in the presence of Cs2CO3 in DMF at 60 °C the corresponding thiocrown ethers 22−25, 28, 30, and 32 are formed in 30−54% yields. Test reactions were carried out to establish that no racemization occurs during alkylation under these conditions. Reaction of optically pure 10 with tetrahydropyranyl (THP)-protected 3-chloropropanol under similar conditions for the preparation of 14 proceeded more sluggishly but cleanly. Remova...

Synthesis and Properties of Substituted CBI Analogs of CC-1065 and the Duocarmycins Incorporating the 7-Methoxy-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (MCBI) Alkylation Subunit: Magnitude of Electronic Effects on the Functional Reactivity.

Abstract: The synthesis of 7-methoxy-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (MCBI), a substituted CBI derivative bearing a C7 methoxy group para to the C4 carbonyl, is described in efforts that establish the magnitude of potential electronic effects on the chemical and functional reactivity of the agents. The core structure of the MCBI alkylation subunit was prepared by a modified Stobbe condensation/Friedel−Crafts acylation for generation of the appropriately functionalized naphthalene precursors (15 and 20) followed by 5-exo-trig aryl radical−alkene cyclization (24 → 25, 32 → 33) for completion of the synthesis of the 1,2-dihydro-3H-benz[e]indole skeleton and final Ar-3‘ alkylation of 28 for introduction of the activated cyclopropane. Two approaches to the implementation of the key 5-exo-trig free radical cyclization are detailed with the former proceeding with closure of 24 to provide 25 in which the required product functionalization was introduced prior to cyclization and the latter with Tempo trap...

Chirospecific Syntheses of Conformationally Constrained 7-Azabicycloheptane Amino Acids by Transannular Alkylation.

Abstract: A new method is reported for the chirospecific preparation of optically pure 1-carboxy-7-azabicycloheptane amino acids for the generation of peptidomimetics as conformational probes. The method allows for the multigram preparation of these amino acid analogues through use of a thiolactam sulfide contraction and a transannular alkylation sequence as the key C−C bond-forming steps, starting from l-glutamic acid. The route provides access to two common intermediates, 7-(benzyloxycarbonyl)-1-carboxy-7-azabicyclo[2.2.1]-3-heptane and (1S,4R)-7-(benzyloxycarbonyl)-1-carboxy-7-azabicyclo[2.2.1]-3-heptanone tert-butyl ester, for elaboration to symmetrical and chiral amino acid homologues, respectively. Decarboxylation of the C-1 carboxy unit of the latter intermediate also demonstrated the applicability of the method for a short, chirospecific preparation of a (+)-epibatidine intermediate, (1S,4R)-7-(tert-butyloxycarbonyl)-1-carboxy-7-azabicyclo[2.2.1]-3-heptanone.