Isobutyric Anhydride Research Articles

Hyperbranched Polymer Functionalized Carbon Dots with Multistimuli-Responsive Property.

The pyrolysis of a hyperbranched polyethylenimine (PEI) and glycerol mixture under microwaves generated the carbon dot (CD) functionalized with PEI (CD-PEI). Isobutyric amide (IBAm) groups were attached to CD-PEI through the amidation reaction of isobutyric anhydride and the PEI moiety, which resulted in the thermoresponsive CD-PEI-IBAm's. CD-PEI-IBAm's were not only thermoresponsive but also responded to other stimuli, including inorganic salt, pH, and loaded organic guests. The cloud point temperature (Tcp) of the aqueous solutions of CD-PEI-IBAm's could be modulated in a broad range through changing the number of IBAm units of CD-PEI-IBAm or varying the type and concentration of the inorganic salts, pH, and loaded organic guests. All the obtained CD-PEI-IBAm's were photoluminescent, which could be influenced a little or negligibly by the added salts, pH, and the organic guests encapsulated.

Theoretical Prediction of Selectivity in Kinetic Resolution of Secondary Alcohols Catalyzed by Chiral DMAP Derivatives

The mechanism of esterification of the secondary alcohol 1-(1-naphthyl)ethanol 9 by isobutyric anhydride catalyzed by 4-pyrrolidinopyridine (PPY, 11) and a series of single enantiomer atropisomeric 4-dialkylaminopyridines 8a-g has been studied computationally at the B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) level. Comparison of the levels of enantioselectivity predicted computationally with the results obtained experimentally allowed the method to be validated. The value of the approach is demonstrated by the successful prediction that a structural modification of an aryl group within the catalyst from phenyl to 3,5-dimethylphenyl would lead to improved levels of selectivity in this type of kinetic resolution (KR) reaction, as was subsequently verified following synthesis and evaluation of this catalyst (8d). Experimentally, the selectivity of this type of KR is found to exhibit a significant deuterium isotope effect (for 9 vs d(1)-9).

Synthesis of thermoresponsive hyperbranched polyamidoamine and the molecular weight, pH, and anion sensitive thermoresponsive properties thereof

Hyperbranched polyamidoamine (HPAMAM) polymers, chemically analogous to the commercially available PAMAM dendrimer, were modified with isobutyric anhydride to result in isobutyramide (IBAm) terminated HPAMAMs (HPAMAM-IBAm). The aqueous solutions of HPAMAM-IBAm polymers had the lower critical solution temperature (LCST). The lower molecular-weight HPAMAM-IBAm exhibited higher LCST and the LCST difference was around 18 °C for one pseudo-generation variation. Further, the hyperbranched thermoresponsive polymers exhibited much lower LCSTs than the corresponding dendrimers with similar molecular weight. The LCST of HPAMAM-IBAm was pH sensitive. At pH below 10, the LCST increased significantly upon decreasing the pH, whereas, at pH above 10, the LCST decreased slowly with an increasing pH value. Nine sodium salts were used to measure the anion effect on the LCST of HPAMAM-IBAm. It was found that the LCST could also be modulated up or down in a broad range by simply adding a small amount of different kinds of inorganic anions. The specific ranking of inorganic anions in salting-out HPAMAM4-IBAm polymer was in accordance with the well-known Hofmeister series.

Acylation of p-xylene over zeolites

Zeolites differing in structure and acidity were tested in liquid phase acylation of p-xylene. Hexanoyl chloride, propionic anhydride and isobutyric anhydride were used as acylating agents. The highest conversions of acylating agent were achieved over large pore zeolites USY (66.3%) and Beta (58.2%). It was found that acylation of p-xylene proceeds only over large pore zeolites Beta and USY. Selectivities to monoacylated p-xylene obtained over USY zeolite decreased in the order: propionic anhydride 78.0% > hexanoyl chloride 67.2% > isobutyric anhydride 33.1%. Diacylated product was formed over zeolite USY with all acylating agents tested but only with hexanoyl chloride over zeolite Beta. It was found that the optimum Si/Al ratio of zeolite Beta for p-xylene acylation with propionic anhydride is 25, while for isobutyric anhydride is 19. Conversion of isobutyric anhydride decreased with increasing isobutyric anhydride concentration and increased with increasing amount of catalyst.

Hydrolysis of Isobutyric Anhydride: Effect of Partial Miscibility of Reactants on Kinetics

Hydrolysis of isobutyric anhydride suffers from the mass transfer issues associated with the inherent partial miscibility of the participating reactants in a certain concentration−temperature space. Hence, activity-based models are developed and used to describe the phase equilibrium behavior and the kinetics. In this work, the experimental and modeling approaches employed to study the kinetics in the single- and two-phase regions are presented. The solvation effects or the effect of autocatalysis on the rate of hydrolysis are studied. A discussion on the use of external acid catalysts/autocatalysis to enhance the rate of this reaction, especially in the two-phase region, and its application as a potential hazard identification tool is also presented.

Organocatalysis with azahelicenes: the first use of helically chiral pyridine-based catalysts in the asymmetric acyl transfer reaction

The successful utilisation of a helicene-based organocatalyst in acylative kinetic resolution of racemic secondary alcohol was described. Employing rac-1-phenylethanol, optically pure (–)-(M)-2-aza[6]helicene (5–20 mole %), isobutyric anhydride and N-ethyldiisopropylamine in chloroform at 22–40 °C, an asymmetric acyl transfer reaction took place overwhelming the uncatalysed background process. Moderate reactivity as well as selectivity factor (s = 9, 10) were observed. An effective control of the enantiodiscriminating step in acylative kinetic resolution by the helically chiral organocatalyst was proven for the first time.

Chemistry of hetero analogs of isoflavones 26. Synthesis of 2-alkyl derivatives of 3-(thiazol-2-yl)-and 3-(benzothiazol-2-yl)chromones

Treatment of substituted 2-(2,4-dihydroxyphenacyl)thiazole and 2-(2,4-dihydroxyphenacyl)benzothiazole with propionic and isobutyric anhydrides gives the substituted 2-ethyl-and 2-isopropyl-7-acyloxychromones. The use of pivaloyl chloride gives 1-pivaloyloxy-2-hetarylstyrene derivatives.

Regioselective Acylation of Octyl β-d-Glucopyranoside by Chiral 4-Pyrrolidinopyridine Analogues

Chiral 4-pyrrolidinopyridine (PPY) analogues with dual functional side chains consisting of indole units have been prepared from TRANS-4-hydroxy- L-proline. Treatment of octyl β- D-glucopyranoside with isobutyric anhydride in the presence of the catalysts gave the 6- O-acylate as the major product via acylation of a primary hydroxyl group. On the other hand, the 4- O-acylate was obtained as the major product in 66% regioselectivity via acylation of the secondary hydroxyl group at C-4 on treatment of octyl β- D-glucopyranoside with isobutyric anhydride in the presence of a PPY catalyst. Use of isobutyryl chloride instead of isobutyric anhydride in the presence of the catalyst gave the 6- O-acylate in 87% regioselectivity.

A Catalytic One-Step Process for the Chemo- and Regioselective Acylation of Monosaccharides

An organocatalytic method for the chemo- and regioselective acylation of monosaccharides has been developed. Treatment of octyl beta-D-glucopyranoside with isobutyric anhydride in the presence of 10 mol % of a C2-symmetric chiral 4-pyrrolidinopyridine catalyst (1) at -50 degrees C gave the 4-O-isobutyryl derivative as the sole product in 98% yield. Thus, chemoselective acylation, favoring a secondary hydroxyl group in the presence of a free primary hydroxyl group, and regioselective acylation, favoring one of three secondary hydroxyl groups, took place with perfect selectivity. A competitive acylation between octyl beta-D-glucopyranoside and a primary alcohol (2-phenylethanol) with 1.1 equiv of isobutyric anhydride in the presence of 1 gave the 4-O-isobutyrate of octyl beta-D-glucopyranoside with 99% regioselectivity in 98% yield, which indicates that acylation of the secondary hydroxyl group at C(4) of the carbohydrate proceeds in an accelerative manner. A possible mechanism, involving multiple hydrogen-bonding between 1 and the monosaccharide, is proposed for the chemo- and regioselective acylation.

Formation of dihydrouracils via cyclization of N-substituted 3-thioureidopropanoic acids and facile desulfurization

Cyclization of N-3 substituted 3-thioureidopropanoic acids in isobutyric anhydride at high temperature resulted in the unexpected formation of N-3, N-1-substituted dihydrouracils, as confirmed by thorough spectroscopic characterization. A mechanism based on the identification of intermediates observed at lower reaction temperatures is proposed.

Regioselective acylation of 6-O-protected octyl β- d-glucopyranosides by DMAP catalysis

Regioselectivity of acylation of 6-O-protected octyl β- d-glucopyranosides was investigated. Treatment of octyl 6- O-methyl-β- d-glucopyranoside with isobutyric anhydride in the presence of DMAP in toluene at −40 °C gave 3- O-isobutyryl derivative in >99% regioselectivity. Similar treatment of octyl 6- O-TBS-β- d-glucopyranoside at −20 °C also gave 3- O-isobutyryl derivative in >99% regioselectivity.

Reliable and fast quantitative analysis of active ingredient in pharmaceutical suspension using Raman spectroscopy

The concentration of acetaminophen in a turbid pharmaceutical suspension has been measured successfully using Raman spectroscopy. The spectrometer was equipped with a large spot probe which enabled the coverage of a representative area during sampling. This wide area illumination (WAI) scheme (coverage area 28.3 mm 2) for Raman data collection proved to be more reliable for the compositional determination of these pharmaceutical suspensions, especially when the samples were turbid. The reproducibility of measurement using the WAI scheme was compared to that of using a conventional small-spot scheme which employed a much smaller illumination area (about 100 μm spot size). A layer of isobutyric anhydride was placed in front of the sample vials to correct the variation in the Raman intensity due to the fluctuation of laser power. Corrections were accomplished using the isolated carbonyl band of isobutyric anhydride. The acetaminophen concentrations of prediction samples were accurately estimated using a partial least squares (PLS) calibration model. The prediction accuracy was maintained even with changes in laser power. It was noted that the prediction performance was somewhat degraded for turbid suspensions with high acetaminophen contents. When comparing the results of reproducibility obtained with the WAI scheme and those obtained using the conventional scheme, it was concluded that the quantitative determination of the active pharmaceutical ingredient (API) in turbid suspensions is much improved when employing a larger laser coverage area. This is presumably due to the improvement in representative sampling.

Modular Design of Pyridine-Based Acyl-Transfer Catalysts

Derivatives of 3,4-diaminopyridine have been synthesized and studied as catalysts for acyl-transfer reactions. The design of these catalysts is guided by the stability of their acetyl intermediates as determined through theoretical calculations at the B3LYP/6-311 + G(d,p)//B3LYP/6-31G(d) level of theory. The most promising catalysts have been synthesized through a three- to five-step synthesis starting from 3,4-diaminopyridine. The catalytic activity has been determined for the acylation of 1-ethynylcyclohexanol with acetic anhydride at 23 °C and with isobutyric anhydride at 40 °C. For both reactions, the catalytic activity depends dramatically on the substitution pattern of the diaminopyridines. Best results are obtained with catalysts containing alkyl substituents at both amine nitrogens.

Kinetic resolution of racemic alcohols catalyzed by minimal artificial acylases derived from l-histidine

The artificial acylases, tert-butyldiphenylsilyl ether and tris(trimethylsilyl)silyl ether of N(π)-methyl- N(α)-(2,4,6-triisopropylbenzenesulfonyl)- l-histidinol, are simple and small molecules, which contain only one chiral carbon center that originates from natural l-histidine. Asymmetric acylation of racemic secondary alcohols with isobutyric anhydride induced by these artificial acylases gave optically active isobutyrates and optically active alcohols with an S( k fast-reacting enantiomer/ k slow-reacting enantiomer) value of up to 132. One hydrogen bonding interaction between a sulfonamidyl group of the catalysts and a substrate should be essential for inducing the high level of kinetic resolution through catalytic asymmetric acylation. Furthermore, a reusable polystyrene-bound artificial acylase was developed to examine its practicality.

A new non-invasive, quantitative Raman technique for the determination of an active ingredient in pharmaceutical liquids by direct measurement through a plastic bottle

The concentration of an active pharmaceutical ingredient (povidone) in a commercial eyewash solution has been measured directly through a plastic (low-density polyethylene: LDPE) container using a wide area illumination (WAI) Raman scheme. The WAI scheme allows excitation using a 6 mm laser spot (focal length: 248 mm) that is designed to cover a wide sample area. As a result, it has the potential to improve the reliability Raman measurements by significantly enhancing representative sample interrogation, thus improving the reproducibility of sampling. It also decreases the sensitivity of sample placement with regard to the excitation focal plane. Simultaneously, isobutyric anhydride was placed in front of the bottles to use for a synchronous external standard configuration. This helps to correct the problematic variation of Raman intensity from the inherent fluctuation in laser power. Using the WAI Raman scheme combined with the synchronous standard method, the povidone concentration was successfully measured with spectral collection that was performed through a plastic barrier. The conventional Raman scheme was difficult to employ for the same purpose because of the degraded spectral reproducibility resulting from the smaller laser illumination area and the sensitivity of such an approach to the position of the sample bottle. The result from this study suggests that the WAI scheme exhibits a strong potential for the non-destructive quantitative analysis of pharmaceuticals measured directly in plastic containers. Preliminary work also shows that similar measurements can also be made in glass bottles. If implemented, this technique could be utilized as a simple and rugged method for quality assurance of final products in a manner consistent with Process analytical technology (PAT) requirements.

Zinc perchlorate hexahydrate [Zn(ClO 4) 2·6H 2O] as acylation catalyst for poor nucleophilic phenols, alcohols and amines: Scope and limitations

Commercially available zinc perchlorate hexahydrate [Zn(ClO 4) 2·6H 2O] was found to be a highly efficient catalyst for acylation of electron deficient phenols, sterically hindered alcohols and electron deficient and sterically hindered amines. The acetylated derivatives were obtained in excellent yields under solvent-free conditions and at room temperature. However, the reaction of highly electron deficient and sterically hindered phenol, e.g., 2,4-dinitrophenol required heating at 80 °C. In case of reactions with alkoxy or dialkoxy benzylic alcohols, a complex product mixtures were formed containing the corresponding dibenzylic ethers. The catalyst was found to be of general use with respect to other acylating agents such as propionic, iso-butyric, pivalic, benzoic and chloroacetic anhydrides. However, the rate of acylation was influenced by the steric and electronic factors of the anhydrides and followed the order Ac 2O > (PhCO) 2O > (EtCO) 2O > ( i PrCO) 2O > ( t BuCO) 2O ≫ (ClCH 2CO) 2O. Benzoylation and pivalation of phenols (including electron deficient phenols), dihydric phenol and sterically hindered alcohol afforded excellent yields. The catalytic activity of various zinc compounds was found to be of the order Zn(ClO 4) 2·6H 2O > ZnI 2 ∼ ZnBr 2 > ZnCl 2 ≫ Zn(OAc) 2 > ZnCO 3 and was parallel to the acidic strength of the corresponding protic acids.

New Class of Pyridine Catalyst Having a Conformation Switch System: Asymmetric Acylation of Varioussec-Alcohols

We have developed a new class of pyridine catalyst for asymmetric acylation of sec-alcohols having a conformation switch system in which interconversion between self-complexation and uncomplexation is induced by acylation and deacylation steps, respectively. Kinetic resolution of various sec-alcohols is performed by the asymmetric acylation with isobutyric anhydride using 0.05 to 0.5 mol % catalyst 1a with s values of up to 30. In addition, dl-diols are also resolved in a similar manner in good selectivity. Moreover, asymmetric desymmetrization of meso-1,X-diols (X = 2-6) are achieved in the presence of 0.5-5 mol % catalyst 1a. A working model for the reaction mechanism is proposed on the basis of the (1)H NMR measurements, X-ray structural analyses, and AM1 and DFT calculations, where the conformation switch system governed by an intramolecular cation-pi interaction between a pyridinium ring and a thiocarbonyl group would play a key role to attain both good selectivity and high catalytic activity.

The Synthesis of Bicyclo[2.2.2]octan-2,6-dione Revisited

The cyclisation conditions for the formation of bicyclo[2.2.2]octan-2,6-di one (1) from 3-substituted cyclohexanones 2 and 3 have been re-investigated. Use of a medium consisting of isobutyric anhydride and trifluoroacetic acid resulted in a simplified and reproducible method for large-scale synthesis of this compound.

New reliable Raman collection system using the wide area illumination (WAI) scheme combined with the synchronous intensity correction standard for the analysis of pharmaceutical tablets

A novel and reliable Raman collection system for the non-destructive analysis of pharmaceutical tablets has been proposed. The main idea was to develop and utilize the wide area illumination (WAI) scheme for Raman collection to cover a large surface area (coverage area: 28.3 mm 2) of solid tablet to dramatically improve the reliability in sample representation and the reproducibility of sampling due to less sensitivity of sample placement with regard to the focal plane. Simultaneously, the effective and synchronous standard configuration using isobutyric anhydride was harmonized with the WAI scheme to correct the problematic variation of Raman intensity from the change of laser power. To verify the quantitative performance of the proposed scheme, the compositional analysis of active ingredient in naproxen tablet has been performed. The average sample composition was successfully represented by using the WAI scheme compared to the conventional scheme with a much smaller illumination area. After the intensity correction using the non-overlapping peak of isobutyric anhydride standard and area normalization, a partial least squares (PLS) model was developed using an optimized spectral range and the concentrations of naproxen in tablets were accurately predicted. The prediction accuracy was not sensitive to changes in laser power or tablet position within ±2 mm. Additionally, the prediction accuracy was repeatable without systematic drift or need for re-calibration.

Steric Effects in the Uncatalyzed and DMAP‐Catalyzed Acylation of Alcohols—Quantifying the Window of Opportunity in Kinetic Resolution Experiments

The kinetics of the reaction of several alcohols (benzyl alcohol, ethanol, 1-phenylethanol, cyclohexanol, and 1-methyl-1-phenylethanol) with a selection of anhydrides (acetic anyhydride, propionic anhydride, isobutyric anhydride, isovaleric anhydride, and pivalic anhydride) as catalyzed by 4-(N,N-dimethylamino)pyridine (DMAP)/triethyl amine have been studied in CH(2)Cl(2) at 20 degrees C. In all cases the reaction kinetics can be described by rate laws containing a DMAP-catalyzed term and an uncatalyzed (background) term. The rate constants for the background reaction respond sensitively to changes in the steric demand of the alcohol and the anhydride substrates, making the reaction of cyclohexanol with acetic anhydride 526 times faster than the reaction with pivalic anhydride. Steric effects are even larger for the catalyzed reaction and the reactivity difference between acetic and pivalic anhydride exceeds a factor of 8000 for the reaction of cyclohexanol. There is, however, no linear correlation between the steric effects on the catalyzed and the uncatalyzed part. As a consequence there are substrate combinations with dominating catalytic terms (such as the reaction of benzyl alcohol with isobutyric anhydride), while other substrate combinations (such as the reaction of cyclohexanol with pivalic anhydride) are characterized through a dominating background process. The implications of these findings for the kinetic resolution of alcohols are discussed.