Practical Synthesis of N‐Alkyl‐N‐alkyloxycarbonylaminomethyl Prodrug Derivatives of Acetaminophen,Theophylline, and 6‐Mercaptopurine

We report a novel synthesis of N‐alkyl‐N‐alkyloxycarbonylaminomethyl (NANAOCAM) prodrugs of acetaminophen, theophylline, and 6‐mercaptopurine by alkylation of the corresponding drug molecule with N‐alkyl‐N‐alkyloxycarbonylaminomethyl chlorides in good yield. Most of the alkylating agents were efficiently synthesized by chloromethylation of N‐alkyl carbamic acid alkyl esters, which in turn were made from alkyl amines and alkyl chloroformates. In cases where the alkyl chloroformates were not available, synthesis of N‐alkyl carbamic acid alkyl esters was accomplished by converting an alcohol to a chloroformate or to an activated acylating agent such as acyl imidazoles or p‐nitrophenylcarbonate esters, followed by their reaction with alkyl amines.     

Computational Insight into Nickel‐Catalyzed Carbon–Carbon versus Carbon–Boron Coupling Reactions of Primary,Secondary, and Tertiary Alkyl Bromides

The nickel‐catalyzed alkyl–alkyl cross‐coupling (C?C bond formation) and borylation (C?B bond formation) of unactivated alkyl halides reported in the literature show completely opposite reactivity orders in the reactions of primary, secondary, and tertiary alkyl bromides. The proposed Ni^I/Ni^III catalytic cycles for these two types of bond‐formation reactions were studied computationally by means of DFT calculations at the B3LYP level. These calculations indicate that the rate‐determining step for alkyl–alkyl cross‐coupling is the reductive elimination step, whereas for borylation the rate is determined mainly by the atom‐transfer step. In borylation reactions, the boryl ligand involved has an empty p orbital, which strongly facilitates the reductive elimination step. The inability of unactivated tertiary alkyl halides to undergo alkyl–alkyl cross‐coupling is mainly due to the moderately high reductive elimination barrier.     

Nucleophilic substitution reactions using Polyacrylamide-Based phase transfer catalyst in organic and aqueous media

Poly [N-(2-aminoethyl) acrylamido] trimemethyl ammonium chloride was prepared and used as an effective heterogeneous phase-transfer catalyst. This modified polyacrylamide catalyzed nucleophilic displacement of alkyl halides for easy preparation of alkyl thiocyanates, alkyl cyanides, alkyl azides, and alkyl aryl ethers in high yields and short reaction times in organic and aqueous media under two-phase and triphase conditions. The catalyst can be recovered and reused several times.     

Synthesis of a wide range of thioethers by indium triiodide catalyzed direct coupling between alkyl acetates and thiosilanes

An indium triiodide-catalyzed substitution of the acetoxy group in alkyl acetates with thiosilanes provides access to a variety of thioethers. The method is efficient for a wide scope of acetates such as primary alkyl, secondary alkyl, tertiary alkyl, allylic, benzylic, and propargylic acetates.     

Dipole moments of some alkyl vinyl and alkyl propenyl ethers

Dipole moments of several alkyl vinyl and alkyl propenyl ethers have been determined by the Halverstadt-Kumler method in benzene solution at 293 K. The μ values depend on the bulkiness of the alkyl group present. In the alkyl vinyl ether series, a part of the varying μ values may be ascribed to changes in molecular geometry with varying bulkiness of the alkyl group. Other factors are clearly involved, since even in the alkyl (Z)-propenyl ether series μ values depend significantly on the alkyl group, although the geometry of the molecules remains essentially constant throughout the series. In the latter series, the total dipole moment is linearly related to the Taft's σ^*-values of the alkyl groups:μ/D=?(1.17±0.15)σ^*+(1.29±0.03). This suggests that the variation of μ with the alkyl radical follows from the changing polar character of the alkyl groups, which leads to changes in the value of the group moment μro.     

Synthesis and mycobacterial growth inhibition activities of bivalent and monovalent arabinofuranoside containing alkyl glycosides

Arabinofuranosides constitute one of the important components of cell wall structures of mycobacteria. With this importance of arabinofuranosides in mind, alkyl glycosides bearing arabinofuranoside trisaccharides were prepared, wherein the sugars were presented either in the monovalent or bivalent forms. Following the synthesis, the monovalent and bivalent alkyl glycosides were tested for their activities in a mycobacterial growth assay. The growth of the mycobacterial strain M. smegmatis was assessed in the presence of the alkyl glycosides and it was realized that the alkyl glycosides acted as inhibitors of the mycobacterial growth. The inhibition of the growth, caused by the above alkyl glycosides, was not observed for the arabinofuranose trisaccharide alone, without the alkyl groups, and for an alkyl glycoside bearing maltose as the sugar component.     

Copper‐Catalyzed Reductive Cross‐Coupling of Nonactivated Alkyl Tosylates and Mesylates with Alkyl and Aryl Bromides

A copper‐catalyzed reductive cross‐coupling reaction of nonactivated alkyl tosylates and mesylates with alkyl and aryl bromides was developed. It provides a practical method for efficient and cost‐effective construction of aryl–alkyl and alkyl–alkyl C?C bonds with stereocontrol from readily available substrates. When used in an intramolecular fashion, the reaction enables convenient access to various substituted carbo‐ or heterocycles, such as 2,3‐dihydrobenzofuran and benzochromene derivatives.     

Mass spectra of some high molecular weight tetra(alkyl)silanes

The mass spectra of tetra(alkyl)silanes having one short and three long alkyl groups were recorded (C₂₀? C₃₂). These silanes did not give molecular ions, and the dominant course of fragmentation involved the loss of alkyl groups, followed by elimination of alkenes. The loss of alkyl groups, followed by elimination of alkenes. The loss of alkyl groups followed the sequence iso-Pr>Et, Pr,… C₁₄H₂₉» Me. With alkyl groups longer than hexyl, a rearrangement was observed in which n-alkanes were eliminated from the base ion. When the alkyl group was hexyl, the alkane eliminated was methane; when the alkyl group was heptyl, ethane was expelled; with octyl, it was propane; and with decyl, n-pentane was expelled. Deuterium labeling showed that at least two modes of rearrangement were occurring.     

Photodegradation of polyfluorene and fluorene oligomers with alkyl and aromatic disubstitutions

The stability of fluorene-based compounds and polymers, especially at the bridged C-9 position under photoirradiation and thermal treatment, has claimed wide attention. We report the electronic, vibrational, and MALDI-TOF mass spectral combined studies for the fluorene oligomers with alkyl and aromatic substitutions under UV-light irradiation. The low-energy emission and the formation of ketonic defects after degradation highly depend on the proportion of alkyl substitution. The oligomer with fully aromatic substitution shows good stability, but when the proportion of alkyl substitution increases, their photostability rapidly decreases. The mass spectra show not only the mass of the fluorenone-fluorene trimer but also another new degradation product with a large mass (pristine oligomer plus 14) from alkyl oxidation, which testify to the assistance of alkyl side chain during degradation. We propose that the degradation of fluorene is a radical chain process propagated by alkyl side chains, and then the different stability between alkyl and aromatic substitution can be well explained.     

Iron-Catalyzed Reductive Cross-Coupling of Alkyl Electrophiles with Olefins

In terms of its abundance and its minimal toxicity, iron has advantages relative to other transition metals. Although alkyl–alkyl bond construction is central to organic synthesis, examples of iron-catalyzed alkyl–alkyl couplings of alkyl electrophiles are relatively sparse. Herein we report an iron catalyst that achieves cross-coupling reactions of alkyl electrophiles wherein olefins, in the presence of a hydrosilane, are used in place of alkylmetal reagents. Carbon–carbon bond formation proceeds at room temperature, and the method employs commercially available components (Fe(OAc)₂, Xantphos, and Mg(OEt)₂); interestingly, this set of reagents can be applied directly to a distinct hydrofunctionalization of olefins, hydroboration. Mechanistic studies are consistent with the generation of an alkyl radical from the alkyl electrophile, as well as with reversibility for elementary steps that precede carbon–carbon bond formation (olefin binding to iron and β-migratory insertion).     

环化橡胶光交联产物的降解动力学和十二烷基苯磺酸的增溶机理

本文研究了在烷基苯磺酸作用下,环化橡胶类感光性高分子光交联产物降解反应的动力学行为。测定了在链长不一的烷基苯磺酸作用下,降解反应的级数和降解反应的活化能,讨论了烷基的链长以及烷基链长不一的苯磺酸浓度对降解反应速率的影响,提出了降解反应的增溶机理,证实了十二烷基苯磺酸对环化橡胶类感光性高分子光交联产物的降解反应有较大的促进作用。     

Characterization of alkyl polyglycosides by both reversed-phase and normal-phase modes of high-performance liquid chromatography

Alkyl polyglycosides today represent the most important sugar surfactant. Nonionic sugar surfactants produced via different synthetic routes are mixtures of alkyl homologues, oligomers, anomers and isomers. Alkyl homologues and oligomers of alkyl mono- and diglucosides were separated by reversed-phase high-performance liquid chromatography (HPLC) with methanol-water as the mobile phase using a gradient elution. The gradient was optimized in respect to a simultaneous separation of alkyl glycosides according to their alkyl chain length and alkyl polyoxyethylene glucosides with regard to their length of the polyoxyethylene spacer. The separation of alkyl glycosides into alpha- and beta-anomers was carried out by normal-phase HPLC with isooctane-ethyl acetate (60:40, v/v)-2-propanol in the gradient mode. Light scattering detection was used. Matrix-assisted laser desorption ionization time-of-flight mass spectra of alkyl glucosides and dodecyl glucosides with oxyethylene spacer groups are presented.     

Photolysis of alpha-azidoacetophenones: direct detection of triplet alkyl nitrenes in solution

We report the first detection of triplet alkyl nitrenes in fluid solution by laser flash photolysis of alpha-azido acetophenone derivatives, 1. Alphazides 1 contain an intramolecular triplet sensitizer, which ensures formation of the triplet alkyl nitrene by bypassing the singlet nitrene intermediate. At room temperature, azides 1 cleave to form benzoyl and methyl azide radicals in competition with triplet energy transfer to form triplet alkyl nitrene. The major photoproduct 3 arises from interception of the triplet alkyl nitrene with benzoyl radicals. The triplet alkyl nitrene intermediates are also trapped with molecular oxygen to yield the corresponding 2-nitrophenylethanone. Laser flash photolysis of 1 reveals that the triplet alkyl nitrenes have absorption around 300 nm. The triplet alkyl nitrenes were further characterized by obtaining their UV and IR spectra in argon matrices. (13)C and (15)N isotope labeling studies allowed us to characterize the C-N stretch of the nitrene intermediate at 1201 cm(-)(1).     

The first palladium-catalyzed Sonogashira coupling of unactivated secondary alkyl bromides

A palladium-carbene catalyzed Sonogashira coupling of unactivated alkyl bromides with alkyl substituted alkynes is reported. For the first time, unactivated secondary alkyl halides were successfully employed in Sonogashira reactions.     

Iron‐Catalyzed Decarboxylative Alkyl Etherification of Vinylarenes with Aliphatic Acids as the Alkyl Source

Because of the lack of effective alkylating reagents, alkyl etherification of olefins with general alkyl groups has not been previously reported. In this work, a variety of alkyl diacyl peroxides and peresters generated from aliphatic acids have been found to enable the first iron‐catalyzed alkyl etherification of olefins with general alkyl groups. Primary, secondary and tertiary aliphatic acids are suitable for this reaction, delivering products with yields up to 97 %. Primary and secondary alcohols react well, affording products in up to 91 % yield.     

Influence of alkyl chain length on phosphate self-assembled monolayers

A series of alkyl phosphates with alkyl chain lengths ranging from C10 to C18 have been synthesized. Self-assembled monolayers (SAMs) of these molecules were prepared on titanium oxide surfaces by immersion of the substrates in alkyl phosphate solutions of 0.5 mM concentration in n-heptane/isopropanol. The SAMs were characterized by means of dynamic water contact angle (dCA) measurements, variable-angle spectroscopic ellipsometry (VASE), X-ray photoelectron spectroscopy (XPS), and polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS). A higher degree of order and packing density within the monolayers was found for alkyl phosphates with alkyl chain lengths exceeding 15 carbon atoms. This is reflected in a lower dCA hysteresis, as well as a film thickness measured by VASE and XPS close to the expected values for SAMs with an average alkyl chain tilt angle of 30 degrees to the surface normal. Additionally a shift of the symmetric and antisymmetric C-H stretching modes in the PM-IRRAS spectra to lower wave numbers was observed. These findings imply a higher two-dimensional crystallinity of the films derived from alkyl phosphates with a longer alkyl chain length.     

Reduction of organic halides with lanthanum metal: a novel generation method of alkyl radicals

Results of the reaction of alkyl halides with lanthanum metal have been shown. The reduction of alkyl iodide with 1/3 equiv of lanthanum metal efficiently proceeded to give the corresponding reductive dimerized products along with the formation of reduction and dehydroiodination products. In the case of alkyl bromides and chlorides, the reaction did not proceed under the same reaction conditions as that of alkyl iodides; however, the reaction was dramatically promoted by the addition of a catalytic amount of iodine. A reaction pathway including alkyl radicals was suggested.     

Langmuir monolayers of the long-chain alkyl derivatives of a nucleoside analogue and the formation of self-assembled nanoparticles

The long-chain alkyl derivatives of a nucleoside analogue-acyclovir were prepared in the paper. One is stearyl-glycero-succinyl-acyclovir (SGSA) with a single 18-carbon length (C18) alkyl chain. Another is dioctadecyl-aspartate-succinyl-acyclovir (DASA) with double C18 alkyl chains. They were prepared by the esterification of succinyl-acyclovir with the lipids, and sodium salts of them were also prepared. Guanine moieties and alkyl moieties bring the derivatives intermolecular hydrogen bonding and hydrophobic interaction in water separately. The forces are influenced by the number of alkyl chains and the charged state, and determine the solubility and the self-assembly behavior of the derivatives. The double alkyl-chain derivatives (DASA and DASA-Na) formed rigid Langmuir monolayers on air/water surface, while the single alkyl chain derivatives (SGSA and SGSA-Na) did not. However, cholesterol (Chol) could assist SGSA to form rigid monolayers through inserting into the alkyl chains of SGSA to mimic the second alkyl chain. SGSA self-aggregates in water were prepared by the injection method with tetrahydrofuran as solvent. Cuboid-like shape and nanoscale size demonstrated that SGSA self-aggregates were self-assembled nanoparticles. Shape, particle size, zeta potential and phase transition of the nanoparticles were characterized. And they showed an average size of 83.2 nm, a negative surface charge of -31.3-mV zeta potential and a gel-liquid crystalline phase transition of 50.38 degrees C. The formation mechanism of self-assembled nanoparticles was analyzed. Hydrophobic interaction of alkyl chains improves SGSA molecules to form bilayers, and then cuboid-like nanoparticles were obtained by layer-by-layer aggregation based on inter-bilayers hydrogen bonding. However, the charged guanine moieties make SGSA-Na lose the function of hydrogen bonding so that SGSA-Na only forms vesicles in water based on hydrophobic interaction. Strong hydrophobicity and wide-open rigid double alkyl chains of DASA and DASA-Na restrict self-assembly in water media, and no homogeneous suspensions were obtained. Therefore, the molecular self-assembly behavior of the long-chain alkyl derivatives of nucleoside analogues on water surface or in water media is determined by the number of alkyl chains and the charged state.     

Influence of alkyl chain length of alpha olefin sulfonates on surface and interfacial properties

Alpha olefin sulfonates (AOS) with various alkyl chain lengths have been used to investigate the influence of alkyl chain length on the interfacial properties at air–water, liquid paraffin–water, and parafilm–water interfaces. It was found that the critical micelle concentration decreased with increasing alkyl chain length, while the efficiency of reducing surface tension was inverse relationship with alkyl chain length. The diffusion coefficient obviously reduced with an increase of surfactant concentration and alkyl chain length. The C_14-16AOS shows better wettability and emulsification than C_16-18AOS and C_20-24AOS. For foaming properties, the foamability and foam stability dramatically decreased with increasing alkyl chain length.     

烷基-α-D-吡喃葡萄糖苷的合成与性能

以D-葡萄糖为原料,经全乙酰化、在SnCl_4催化下与脂肪醇糖苷化、脱保护3步反应合成了7种不同碳链长度的烷基-α-D-吡喃葡萄糖苷。利用核磁共振、表面张力仪和偏光显微镜等对其进行结构、表面张力和热致液晶等性能测试,结果表明,当烷基-α-D-吡喃葡萄糖苷烷基链长(n)为6~9时,均有发泡和乳化性能,其中正壬基-α-D-吡喃葡萄糖苷具有最佳的发泡和乳化性能;烷基糖苷(n=6~9)的表面张力(γ_(CMC))及临界胶束浓度(CMC)均比较低;饱和吸附量(Γ_(max))随烷基链的增长而减小,饱和吸附面积(A_(min))随烷基链增长而增大;形成胶束时的标准自由能(ΔG_(mic))和吸附自由能(ΔG_(ads))均为负值,其绝对值随烷基链增长而越来越大,其中正辛基-α-D-吡喃葡萄糖苷的表面活性最好;烷基糖苷(n=4~9)对皮肤均无急性刺激作用;所合成的烷基糖苷均具有热致液晶行为,随烷基链长的增加,液晶相的温度范围变宽,液晶相的稳定性越好。