1-chlorobutane Research Articles

Liquid-chromatographic determination of erlotinib (OSI-774), an epidermal growth factor receptor tyrosine kinase inhibitor

A high-performance liquid-chromatographic (HPLC) assay with UV detection has been developed for the quantitative determination of erlotinib (OSI-774) in human plasma. Quantitative extraction was achieved by a single-solvent extraction involving a mixture of acetonitrile and n-butyl chloride (1:4, v/v). Erlotinib and the internal standard hydrochloride salt (OSI-597) were separated on a column packed with Nova-Pak C18 material and a mobile phase composed of acetonitrile and water, pH 2.0 (60:40, v/v). The column effluent was monitored with dual UV detection at wavelengths of 348 nm (erlotinib) and 383 nm (OSI-597). The calibration graph was linear in the range of 100–4500 ng/ml, with values for accuracy and precision ranging from 87.9 to 96.2% and 2.13 to 5.10%, respectively, for three different sets of quality control samples. The developed method was successfully applied to study the pharmacokinetics of erlotinib in a cancer patient at the recommended daily dose of 150 mg.

Indication of molecular oscillations during free electron transfer: reaction of butyl chloride parent ions with benzyltrimethylsilanes

Molecular oscillations are accompanied with electron density fluctuations mainly of the higher occupied orbitals. This is particularly marked for rotational motions of large substituents of aromatic molecules. Hence, the extremely rapid and non-adiabatic free electron transfer from benzyltrimethylsilanes to n-butyl chloride parent radical cations affords the existence of different short-living molecular conformers. This is indicated by a characteristic pattern of transient products including metastable radical cations and fragment radicals derived from a dissociative and very unstable ionisation product.

Second Virial Coefficient of Oligo- and Poly(α-methylstyrene)s. Effects of Chain Stiffness, Chain Ends, and Three-Segment Interactions

The second virial coefficient A2 was determined from light scattering measurements for atactic oligo- and poly(α-methylstyrene)s (a-PαMS) with the fraction of racemic diads fr = 0.72 over a wide range of weight-average molecular weight Mw from 6.48 × 102 to 5.46 × 106 in cyclohexane at 30.5 °C (ϑ) and in toluene at 25.0 °C, and for Mw ≥ 2 × 105 in 4-tert-butyltoluene at 25.0 °C, in n-butyl chloride at 25.0 °C, and in cyclohexane at 35.0, 45.0, and 55.0 °C. It is shown that the observed characteristic features of A2 at ϑ, which is denoted by A2,ϑ, as a function of Mw in cyclohexane at ϑ, i.e., a sharp increase with decreasing Mw for small Mw and a rather long-tailed negative region for large Mw, may be well explained by the theory that takes account of the effects of chain ends and also of three-segment interactions. It is also shown that the observed dependence of A2 on Mw in toluene may be quantitatively explained by the theory that takes account of the effects of chain stiffness, local chain conformatio...

Electrophilic Addition of Butyl Chloride to 2‐Allylphenol in the Presence of Sulfur Trioxide.

Electrophilic Addition of Butyl Chloride to 2‐Allylphenol in the Presence of Sulfur Trioxide.

The effect of inert salts on the structure of the transition state in the SN2 reaction between thiophenoxide ion and butyl chloride.

The effect of inert salts on the structure of the transition state has been determined by measuring the secondary alpha deuterium and the chlorine leaving group kinetic isotope effects for the S(N)2 reaction between n-butyl chloride and thiophenoxide ion in both methanol and DMSO. The smaller secondary alpha deuterium isotope effects and very slightly larger chlorine isotope effects found in both solvents when the inert salt is present suggests that the S(N)2 transition state is tighter and more product-like, with a shorter S-C(alpha) and very a slightly longer C(alpha)-Cl bond when the added salt is present. The salt effect on the reaction in methanol where the reacting nucleophile is the solvent-separated ion-pair complex is much greater than the salt effect on the reaction in DMSO where the reacting nucleophile is the free ion. This greater change in transition-state structure found when the inert salt is present in methanol is consistent with the solvation rule for S(N)2 reactions. The greater change in the S-C(alpha) bond is predicted by the bond strength hypothesis. A rationale for the changes found in transition-state structure when the inert salt is present is suggested for both the free-ion and the ion-pair reactions.

Antithetical product situation in the femtosecond and nanosecond photoionization of sterically hindered phenols in non-protic solvents

The photoionization of sterically hindered phenols in acetonitrile or n-butyl chloride solution gives apparently contradictory results performing biphotonic ionization with femtosecond as well as nanosecond UV lasers: in the first case phenol radical cations were found whereas in the latter one only phenoxyl radicals were detected. This is explained by non-resonant and resonant ionization pathways. Furthermore, the deprotonation rate of the phenol radical cations in acetonitrile in the presence of water traces could be determined as to be diffusion controlled ((3 to 7 )×10 9 dm 3 mol −1 s −1) which could not be observed till now because of its extreme p K a value of ≪−1.

The effect of HMPA on the reactivity of epoxides, aziridines, and alkyl halides with organolithium reagents.

A kinetic study of the effect of added HMPA cosolvent on the reaction of 2-lithio-1,3-dithiane (1), bis(phenylthio)methyllithium (2), and bis(3,5-bistrifluoromethylphenylthio)methyllithium (3) with methyloxirane (propylene oxide), N-tosyl-2-methylaziridine, and the several alkyl halides (BuCl, BuBr, BuI, allyl chloride) was carried out. Widely varied rate effects of HMPA on these SN2 substitutions were observed, ranging from >108 rate increases for 1 and butyl chloride to >103 rate decreases for 3 and methyloxirane. These reactions appear to go through separated ion pair intermediates, so a key effect is the ease of ion pair separation of the lithium reagent (3 > 2 > 1). Because 3 is already almost fully separated in THF, HMPA has no effect on the rate of halide substitution, but a large reduction is observed with the epoxide as substrate, a consequence of strong lithium assistance to the ring opening which is suppressed when excess HMPA is present. When ion pair separation is difficult (1), modest rate increases (104) are seen for epoxide opening, but very large increases are seen for aziridine (106) and alkyl halide reactions (108), for which lithium assistance is much less important. Reagent 2 shows more complicated behavior in reaction with the epoxide: 1-2 equiv of HMPA causes a small rate increase, while larger amounts cause a large rate decrease. Here the rate-accelerating effects of SIP formation are more nearly balanced with the rate-retarding effects of suppression of lithium catalysis.

Determination of the docetaxel vehicle, polysorbate 80, in patient samples by liquid chromatography–tandem mass spectrometry

A new simple method was developed for the quantitative determination of the docetaxel (Taxotere) vehicle, polysorbate 80 (Tween 80), in human plasma. Calibration curves were constructed in the range of 1–100 μg/ml, using paclitaxel (0.01 m M) as internal standard, and were analyzed using a power fit with equal weighting. Sample pretreatment involved a one-step extraction with acetonitrile– n-butyl chloride (1:4, v/v). The analytes were separated on a Waters X-Terra MS column (50×2.1 mm I.D.) packed with 3.5-μm ODS material, and eluted with methanol–water (9:1, v/v) containing 0.1% formic acid. The column effluent was monitored by tandem mass spectrometry with electrospray ionization. The overall extraction efficiency was 50–60%, with values for precision and accuracy of ≤16% and <15% relative error, respectively. Our current method is ∼60–100-fold more sensitive than previous assays, and will be used to define Tween 80 disposition in patients receiving Taxotere.

Balance of the Deactivation Channels of the First Excited Singlet State of Phenols: Effect of Alkyl Substitution, Sterical Hindrance, and Solvent Polarity

On the basis of laser flash photolysis with detection by picosecond and nanosecond emission as well as absorption spectroscopy, a quantitative description is given of all the deactivation channels of the first excited singlet state of phenols ArOH(S1) such as fluorescence, intersystem crossing to the triplet system (ISC), chemical dissociation into radicals, and radiationless internal conversion (IC). For this purpose, various phenols with different alkyl substitution patterns (mono to 3-fold substitution with methyl and /or tert-butyl groups) were studied in solvents of increasing polarity: cyclohexane, n-butyl chloride, tetrahydrofuran, ethanol, methanol, acetonitrile, and water. The fluorescence lifetimes of the phenols were found to range from a few tens of picoseconds up to a few nanoseconds, correlating with fluorescence quantum yields between 10-1 and 10-3, at room temperature. With a probability less than 0.1, the photodissociation of ArOH(S1) was found to be nearly unaffected by changing the type of solvent. As a result of the ISC the triplet yields amount to 0.2−0.3, with smaller values in nonpolar and the larger ones in polar media. As a very marked exception, sterically hindered phenols (2,6-di-tert-butyl substituted) behave quite differently: they exhibit extremely short living fluorescences, show no ISC, and, radiationless, are only deactivated by internal conversion. This complete physical energy dissipation makes the sterically hindered phenols ideal light quenchers.

Viscosity- and Hydrodynamic-Radius Expansion Factors of Oligo- and Poly(α-methylstyrene)s in Dilute Solution

The intrinsic viscosity [η] was determined for 23 samples of atactic oligo- and poly(α-methylstyrene)s (a-PαMS), each with the fraction of racemic diads fr = 0.72, in the range of weight-average molecular weight Mw from 4.12 × 102 to 5.46 × 106 in three good solvents, toluene, 4-tert-butyltoluene, and n-butyl chloride, at 25.0 °C. The translational diffusion coefficient D was also determined from dynamic light-scattering measurements for 17 a-PαMS samples in the range of Mw from 1.04 × 103 to 3.22 × 106 under the same solvent conditions. It was found that the values of [η] in toluene and n-butyl chloride are appreciably smaller than the previous ones of [η]ϑ in cyclohexane at 30.5 °C (ϑ) in the oligomer region in which the intramolecular excluded-volume effect may be ignored, while those of [η] in 4-tert-butyltoluene are only slightly larger than the latter there because of the dependence on solvent of the hydrodynamic chain (bead) diameter. The disagreement in toluene and n-butyl chloride may be regarded as arising from the so-called specific interaction between polymer and solvent molecules, and therefore the viscosity-radius expansion factor αη in these solvents was calculated after removing its contribution. On the other hand, the values of the hydrodynamic radius RH defined from D in the three good solvents were found to agree well with the previous ones of RH,ϑ in cyclohexane at ϑ in the oligomer region, and therefore the hydrodynamic-radius expansion factor αH could be calculated straightforwardly. It was then found that both plots of αη and αH against the scaled excluded-volume parameter z̃ for a-PαMS in the three good solvents along with those for atactic polystyrene and atactic and isotactic poly(methyl methacrylate)s previously studied form their respective single-composite curves, confirming the validity of the quasi-two-parameter scheme that all expansion factors are functions only of z̃ irrespective of the differences in polymer species (chain stiffness and local chain conformation) and solvent condition.

Kinetics and Mechanism of Monomolecular Heterolysis of Commercial Organohalogen Compounds: XXX. 1 Correlation Analysis of Solvation Effects in Heterolysis of tert -Butyl Chloride

Quantitative analysis of the effect of solvent parameters on the rate of heterolysis of tert-butyl chloride was performed; the reaction rate is fairly described by the polarity, polarizability, and electrophilicity parameters or by the ionizing ability parameter, while the nucleophilicity of the solvent has no rate effect. A negative effect of nucleophilic solvation was revealed in protic solvents.

A rapid and sensitive high-performance liquid chromatography-electrospray ionization-triple quadrupole mass spectrometry method for the quantitation of oxycodone in human plasma.

A sensitive method for the determination of oxycodone concentrations in plasma by high-performance liquid chromatography (HPLC)-electrospray ionization-triple quadrupole mass spectrometry is described. The method is rugged, reliable, selective, and rapid with a run time of 2 min. One milliliter of plasma is made basic and extracted with 2-mL duplicate portions of 2% isoamyl alcohol in n-butyl chloride. The combined extracts are then evaporated to dryness, reconstituted in 100 microL of the mobile phase (15% methanol-85% water containing 0.1% acetic acid), and injected onto the HPLC. The limit of quantitation is 1 ng/mL, and the estimated limit of detection is 33 pg/mL (signal-to-noise = 3). Standard curves are linear over the range of 1 to 100 ng/mL with all correlation coefficient values greater than 0.9989. The method is used to determine the concentration of oxycodone in human plasma following the intravenous infusion of doses ranging from 5 to 15 mg in which the analysis of over 3000 plasma samples is required.

SN2, E2 reactions of butylchlorides on NaY zeolite: A potential method for studying the formation and reactivity of alkoxy species on the zeolite surface

The adsorption and reaction of n-butyl, sec-butyl, isobutyl and tert-butyl chlorides over NaY zeolite was studied by infrared spectroscopy. All the chlorides reacted almost instantaneously with the zeolite, giving rise to CH2 and CH3 bands in the infrared spectra. A band at approximately 1640 cm−1, ascribed to CC vibration, was observed in all experiments, its intensity being dependent upon the structure of the chloride. For tert-butyl chloride the intensity is greatest, and bands at 3550 and 3061 cm−1, ascribed to the acidic OH and olefinic CH, respectively, were observed. The intensity of the olefinic band is weaker in secondary and especially primary chlorides. Calculations at the B3LYP/6-31+G** level, using a T3 cluster to represent the zeolite active site, indicated that, for the secondary and primary chlorides, the formation of the alkoxy species, through an SN2 type reaction mechanism, is lower in energy relative to proton elimination, through an E2 type mechanism. The opposite was observed for the tert-butyl chloride, in agreement with the experimental results. The method can be useful for generating alkoxide species, especially primary and secondary ones, and for studying their reactivity on the zeolite surface.

Electrophilic addition of butyl chloride to 2-allylphenol in the presence of sulfur trioxide

Electrophilic addition of butyl chloride to 2-allylphenol in the presence of sulfur trioxide

Discrete ionization of two different short-living conformers of selenophenol by rapid free electron transfer to solvent parent radical cations

In the pulse radiolysis of solutions of selenophenol in n-butyl chloride, selenophenol radical cations and phenylselenyl radicals are generated as direct products of the ion–molecule reaction between the solvent parent radical cations and selenophenol. This effect is explained with an electron-transfer phenomenon where in each encounter situation the electron jump proceeds so extremely rapid that different transient conformers of the scavenger molecule must be taken into account, differing in the phases of the molecular torsion vibration of the C–SeH bond. Quantum-chemical calculations resulted in a very low activation energy of less than 1 kcal mol −1 for the rotation of this bond and a favored geometry where the Se–H group is twisted against the aromatic moiety by an angle of 90°.

Quantitative analysis of fentanyl in rat plasma by gas chromatography with nitrogen–phosphorus detection

A sensitive assay method was developed to determine fentanyl, an opiate agonist, in rat plasma by gas chromatography with nitrogen–phosphorus detection. For the pretreatment of plasma samples, sodium hydroxide was added to denature protein and n-butyl chloride was used to extract fentanyl. The calibration curve was linear within the concentration range 0.5 to 50 ng/ml ( r=0.9997). The limit of detection was 0.1 ng/ml, and 0.5 ng/ml could be quantified with acceptable precision. Furthermore, fentanyl could be determined in only 200 μl of rat plasma. The method has been successfully applied to an intramuscular pharmacokinetic study at a dose of 10 μg/kg. Therefore, the current method is a valuable analytical tool for investigating the pharmacokinetics of fentanyl at low clinical doses.

Postmortem tissue concentrations of venlafaxine

Venlafaxine is a phenethylamine antidepressant which inhibits both serotonin and norepinephrine reuptake and is structurally unrelated to the serotonin reuptake inhibitors (SSRIs). Its major metabolite, O-desmethylvenlafaxine (ODV), also inhibits serotonin reuptake. Although metabolized by the cytochrome P-450 (CYP) system, venlafaxine inhibits CYP 2D6 and 3A4 to a far lesser extent than do the SSRIs. Mechanisms of drug action are reviewed and evaluated in the investigation of 12 fatalities occurring over a 6-month-period where venlafaxine was detected. Venlafaxine and ODV were identified by liquid chromatography–mass spectrometry (LC–MS) using atmospheric pressure ionization (API) electrospray in positive mode following an n-butyl chloride extraction. Postmortem tissue concentrations studied in each of 12 postmortem cases for venlafaxine and ODV, were 0.1–36 and <0.05–3.5 mg/l (peripheral blood), <0.05–22 and <0.05–9.9 mg/kg (liver), <0.05–10 and <0.05–1.5 mg/l (vitreous), <0.05–53 and <0.05–6.8 mg/l (bile), <0.05–55 and <0.05–21 mg/l (urine), respectively, and 0.1–200 mg of venlafaxine in the gastric contents. Venlafaxine was typically present with other drugs, including other antidepressants, alcohol, and benzodiazepines. The potential for interaction with each drug is discussed. Over the 6-month-period of this study, there were no deaths ascribed solely to venlafaxine intoxication.

Gyration-Radius Expansion Factor of Oligo- and Poly(α-methylstyrene)s in Dilute Solution

The mean-square radius of gyration 〈S2〉 was determined from small-angle X-ray scattering and light scattering measurements for atactic oligo- and poly(α-methylstyrene)s (a-PαMS) with the fraction of racemic diads fr = 0.72 in toluene at 25.0 °C, in 4-tert-butyltoluene at 25.0 °C, and in n-butyl chloride at 25.0 °C in the range of weight-average molecular weight from 1.04 × 103 to 5.46 × 106. The gyration-radius expansion factor αS was then evaluated from the values of 〈S2〉 so determined along with those of 〈S2〉ϑ previously determined for the same samples in cyclohexane at 30.5 °C (ϑ). It is shown that the plots of αS against the scaled excluded-volume parameter z for a-PαMS along with those for atactic polystyrene (a-PS) and atactic and isotactic poly(methyl methacrylate)s previously studied form a single-composite curve, confirming the validity of the quasi-two-parameter scheme that all expansion factors are functions only of z irrespective of the differences in polymer species (chain stiffness and loc...

Simultaneous determination of mono-, di-, and tributyltin in sediments by isotope dilution analysis using gas chromatography--ICPMS.

A mixed spike containing 119Sn-enriched monobutyltin (MBT), dibutyltin (DBT), and tributyltin (TBT) was prepared by direct butylation of 119Sn-enriched tin metal using a 1:3 molar excess of butyl chloride with iodide and triethylamine as catalysts. The isotopic composition of the different tin species in the spike solution was determined by gas chromatography- ICPMS after aqueous ethylation using sodium tetraethylborate. Reverse isotope dilution analysis was used for the characterization of the spike by means of natural MBT, DBT, and TBT standards. No species transformation was evident during derivatization from the reverse isotope dilution experiments based on the measured isotope ratios both before and after spiking. The mixed spike was applied to the simultaneous analysis of MBT, DBT, and TBT in certified reference materials, PACS-2 and CRM 646, with satisfactory results.

Active‐center equilibrium in Ziegler–Natta butadiene polymerization

AbstractThe Ziegler–Natta‐catalyzed polymerization of 1,3‐butadiene was investigated at a low aluminum alkyl/cobalt (Al/Co) ratio using two different soluble catalyst systems: cobalt(II) octanoate/diethylaluminum chloride/water and cobalt(II) octanoate/methylaluminoxane/tert‐butyl chloride. When the active‐center concentration was determined by the number‐average molecular weight technique, it was found that the percentage of active cobalt depended on the Al/Co ratio. Subsequently, an equilibrium reaction was proposed to be Co + 2Al ⇌ CoAl2, where Co is cobalt(II) octanoate, Al is either of the aluminum alkyl‐activator species, and CoAl2 is the active catalyst. © 2001 John Wiley &amp; Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2256–2261, 2001