Retardation effect of jojoba chain length on the chemical reactivity of the liquid wax

Jojoba wax and its derivatives are slow-reacting compounds. To elucidate the reasons for this phenomenon, we reacted jojoba mono- and bis-epoxide and trans-jojoba bis-epoxide (C₃₈–C₄₄ long-chain esters), as well as side chain esters of three steroid skeleton mono-epoxide derivatives with NaI under acidic conditions to yield the corresponding iodohydrins, which then formed the respective bis-keto (or mono-ketone) derivatives. The kinetics, activation energies, and thermodynamic parameters of activation of nucleophilic epoxide opening and pinacol rearrangement were determined for all these compounds. The reaction rates of the jojoba derivatives were similar to those of two of the epoxides derived from the steroid skeleton compounds, and in the third case the steroid derivative reacted somewhat faster than all the rest. This pattern of rate retardation could stem either from folding of the long jojoba chain, resulting in steric hindrance around the reaction centers, or from repeated unproductive collisions along the long hydrocarbon chain of the jojoba wax (statistical effect). Our results appear to suggest that the multiple unsuccessful collisions were the dominant factor, although steric hindrance cannot be ruled out.     

Understanding the interplay of weak forces in [3,3]-sigmatropic rearrangement for stereospecific synthesis of diamines

Chiral diamines are important building blocks for constructing stereoselective catalysts, including transition metal based catalysts and organocatalysts that facilitate oxidation, reduction, hydrolysis, and C-C bond forming reactions. These molecules are also critical components in the synthesis of drugs, including antiviral agents such as Tamiflu and Relenza and anticancer agents such as oxaliplatin and nutlin-3. The diaza-Cope rearrangement reaction provides one of the most versatile methods for rapidly generating a wide variety of chiral diamines stereospecifically and under mild conditions. Weak forces such as hydrogen bonding, electronic, steric, oxyanionic, and conjugation effects can drive this equilibrium process to completion. In this Account, we examine the effect of these individual weak forces on the value of the equilibrium constant for the diaza-Cope rearrangement reaction using both computational and experimental methods. The availability of a wide variety of aldehydes and diamines allows for the facile synthesis of the diimines needed to study the weak forces. Furthermore, because the reaction generally takes place cleanly at ambient temperature, we can easily measure equilibrium constants for rearrangement of the diimines. We use the Hammett equation to further examine the electronic and oxyanionic effects. In addition, computations and experiments provide us with new insights into the origin and extent of stereospecificity for this rearrangement reaction. The diaza-Cope rearrangement, with its unusual interplay between weak forces and the equilibrium constant of the reaction, provides a rare opportunity to study the effects of the fundamental weak forces on a chemical reaction. Among these many weak forces that affect the diaza-Cope rearrangement, the anion effect is the strongest (10.9 kcal/mol) followed by the resonance-assisted hydrogen-bond effect (7.1 kcal/mol), the steric effect (5.7 kcal/mol), the conjugation effect (5.5 kcal/mol), and the electronic effect (3.2 kcal/mol). Based on both computation and experimental data, the effects of these weak forces are additive. Understanding the interplay of the weak forces in the [3,3]-sigmatropic reaction is interesting in its own right and also provides valuable insights for the synthesis of chiral diamine based drugs and catalysts in excellent yield and enantiopurity.     

The First Anionic Thia‐Fries Rearrangements at Ferrocene: Ready Access to Trifluoromethylsulfonyl‐Substituted Hydroxyferrocenes and an Extremely High Interannular Stereoinduction between Cyclopentadienyl Ligands

Attempts originally directed towards the generation of ferrocyne (1,2‐dehydroferrocene, 4 ) and ferrocenediyne (1,2,1′,2′‐tetradehydroferrocene, 5 ) by triflate elimination from the respective ferrocenyl triflates led to the discovery of the first anionic thia‐Fries rearrangements at a five‐membered ring. These reactions take place with remarkable efficiency under very mild reaction conditions and yield the respective trifluoromethylsulfonyl‐substituted ferrocenols. Most remarkably, the reaction starting from 1,1′‐ferrocenediyl ditriflate ( 9 ) adopts an extremely high interannular stereoinduction in that exclusively the meso rearrangement product, meso‐2,2′‐bis(trifluoromethylsulfonyl)‐1,1′‐ferrocenediol ( 16 ), is formed, the corresponding racemic product 17 is not observed. It is shown that the second anionic thia‐Fries rearrangement proceeds at a much larger rate than the first one. The stereochemistry and the high rate of this reaction are explained on the basis of electronic as well as steric considerations. The redox behavior of some of the unprecedented ferrocene derivatives has been characterized by cyclovoltammetry.     

Vinyloge Acylverbindungen. XIX. Vinyloge Acylgruppenwanderung am 2-Aminophenol. Ein Beitrag zum Isomerisierungsmechanismus gemischter Diacylderivate des 2-Aminophenols

Vinylogous Acyl Compounds. XIX. Vinylogous Acyl Group Migration in 2-Aminophenol. A Contribution to the Isomerization Mechanism of Mixed Diacyl Derivatives of 2-Aminophenol Starting with 2-acylaminophenols 5 and 2-(2-acylvinylamino)-phenols 6 the N-acyl O-acylvinyl derivatives 7 of 2-aminophenol and their N-acylvinyl O-acyl isomers 8 were prepared and characterized. These vinylogous acyl compounds are able to isomerize in the same manner as simple O,N-diacylated 2-aminophenols 3 and 4 , which under suitable conditions easily rearrange to give a dynamic equilibrium 3 ⇌ 4 . Contrary to 3 and 4 , however, the isomerization of 7 and 8 can be followed directly by spectroscopic methods, so that vinylogs of this type are useful model systems for studying acyl group migrations in 2-aminophenol. Kinetic measurements show that the mutual rearrangement of 7 and 8 is a reversible general based catalyzed reaction, being first order with respect to substrate and catalyst. The isomerization of the N-acetyl derivatives 7a – h as well as the N-benzoyl derivatives 7i – p results in strictly linear HAMMETT correlations with positive reaction constants ϱ. In the case of 7a – h the equilibrium constant K and the forward and reverse velocity constants k₁ and k₂ (including activation parameters) could be determined. The kinetic investigations and additional nonkinetic experiments indicate that the catalyst acts as proton acceptor and not — as hitherto supposed — as acyl group transferring nucleophile. Based on the findings an isomerization mechanism for mixed diacyl derivatives of 2-aminophenol is suggested.     

Stabilizer reactions in cast double base rocket propellants. Part II: Formation and subsequent reactions of N-nitroso derivatives of para-nitro-N-methylaniline and 2-nitrodiphenylamine in mixed-stabilizer propellants aged at 80°C and 90°C

The HPLC determination of the stabilizers para-Nitro-N-methylaniline (pNMA) and 2-Nitrodiphenylamine (2NDPA) and their derivatives in two mixed-stabilizer cast double base rocket propellants undergoing accelerated aging at 80°C and 90°C has led to the conclusion that N-nitroso derivatives play a critical role in the stabilizer depletion processes in this type of propellant. In order to account for the principal stabilizer products in the aged propellants it is suggested that pNMA enters into an equilibrium with its N-nitroso derivative (formed during the initial stages of aging) and that this reacts with 2NDPA in a transnitrosation reaction, to give mainly N-nitroso-2NDPA from which the observed C-nitro derivatives of 2NDPA are in part generated by rearrangement and subsequent oxidation.     

Stereochemical and steric control of the UDP-glucuronosyltransferase-catalyzed conjugation reaction: a rational approach for the design of inhibitors for the human UGT2B7

A set of 76 derivatives of the epimeric tricyclic sesquiterpenols longifolol and isolongifolol was subjected to inhibition and glucuronidation assays employing the human UDP-glucuronosyltransferase (UGT) 2B7. Detailed structure-activity relationships (SARs) with respect to functionality, stereochemical properties, and steric features were derived. To gain further insight into the SARs of UGT2B7 ligands herein, we have developed a 3D-quantitative structure-activity relationship (3D-QSAR) using Comparative Molecular Similarity Analysis (CoMSIA). The formation of the enzyme-inhibitor complex was predominantly controlled by spatially directed hydrophobic interactions. The glucuronidation rate was significantly influenced by the steric demand of substituents in proximity of the nucleophilic hydroxy group. The glucuronidation of the compounds was prevented by the introduction of bulky substituents such as isopropyl, tert-butyl, and phenyl groups. The epimeric longifolol derivatives of series D were the best inhibitors displaying IC(50) values as low as 4.6 nM. This study shows that high-potency substrates can be turned into potent inhibitors by addressing functional, stereochemical, and steric properties.     

Synthese und Reaktionen von β-Campholenverbindungen

Synthesis and Reactions of β-Campholene Compounds In contrast to the well known α-campholenic ( B ) and fencholenic compounds ( C ) little is known about β-campholenic derivatives ( A ) because of their difficult accessibilitiy. β-Campholenic compounds ( A ) can be obtained: (1) by Baeyer-Villiger oxidation of camphor via lactone 7 and β-dihydrocampholenic lactone ( 5 ); (2) by Beckmann fragmentation of camphor oxime via α-( 2 ) and β-campholenic nitril ( 3 ) and the lactone 5 ; and ( 3 ) by acid catalysed rearrangement of α-campholenic derivatives ( B , 17a , b ). The β-analogous brahmanol ( 14 ) can be synthesized by the reaction of the β-campholenic bromide ( 11 ) with methyl diethyl malonate or by rearrangement of brahmanol.     

Factors contributing to the stability of alkoxysilanes in aqueous solution

Parameters controlling intrinsic stability and reactivity of organosilanols generated from alkoxysilanes in aqueous environments have been elucidated in several experiments. Data involving kinetics, equilibrium, phase separation, and bonding studies of alkyl and organofunctional alkoxysilanes are presented. The studies indicate that the rates of hydrolysis of alkoxysilanes are generally related to their steric bulk, but demonstrate that after rate-limiting hydrolysis of the first alkoxy group steric effects are much less important. Aqueous hydrolysis of alkylalkoxysilanes was studied to determine equilibrium constants and the extent of oligomerization up to phase separation. In the case of propyltrialkoxysilane, phase separation is coincident with the formation of tetramer. The equilibrium constant for esterification of silanols is Also, the performance properties of new water-borne silanes were evaluated and in most cases, their performance equalled or exceeded their traditional silane counterparts.     

Analysis of steric mass-action model for protein adsorption equilibrium onto porous anion-exchange adsorbent

The ion-exchange equilibrium of bovine serum albumin (BSA) to an anion exchanger, DEAE Spherodex M, has been studied by batch adsorption experiments at pH values ranging from 5.26 to 7.6 and ionic strengths from 10 to 117.1 mmol/l. Using the unadjustable adsorption equilibrium parameters obtained from batch experiments, the applicability of the steric mass-action (SMA) model was analyzed for describing protein ion-exchange equilibrium in different buffer systems. The parametric sensitivity analysis was performed by perturbing each of the model parameters, while holding the rest constant. The simulation results showed that, at high salt concentrations or low pHs close to the isoelectric point of the protein, the precision of the model prediction decreased. Parametric sensitivity analysis showed that the characteristic charge and protein steric factor had the largest effects on ion-exchange equilibrium, while the effect of equilibrium constant was about 70%-95% smaller than those of characteristic charge and steric factor under all conditions investigated. The SMA model with the relationship between the adjusted characteristic charge and the salt concentration can well predict the protein adsorption isotherms in a wide pH range from 5.84 to 7.6. It is considered that the SMA model could be further improved by taking into account the effect of salt concentration on the intermolecular interactions of proteins.     

Heat deterioration of phospholipids. V. A new rearrangement reaction of sugars and phosphatidylethanolamine

Novel four 2,3-dihydro-1H-imidazo[1,2-a]pyridine-4-ylium derivatives were obtained with increase of UV absorption at 350 nm and browning of the solution by heating paste lecithin from soybean (SL) in octane. These four derivatives were formed by reaction of one molar of any sugar except 2-deoxysugars with two molar of phosphatidylethanolamines (PE) in SL. To confirm the reaction mechanism, several (13)C-labeled-sugars were reacted with 1,2-di-O-stearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE), respectively. These reactants clearly showed that five carbons of the pyridinium ring and one carbon of the substituted group were based on those of a sugar and that the formation of the pyridinium derivatives was accompanied with cleaving between the carbons of 1- and 2-positions in the sugar and rearrangement. This reaction is a new rearrangement reaction and we named it "new pseudo Maillard rearrangement reaction".     

2-嘧啶氧基-N-芳基苄胺类化合物的合成及其重排副反应

2-嘧啶氧基苄基溴与芳胺反应合成2-嘧啶氧基-N-芳基苄胺类化合物,反应过程中会发生生成2-羟基-N-芳基-N-嘧啶基苄胺副反应,即重排反应。芳胺空间位阻越小,亲核性越强,副反应越容易发生,产物除草活性越低。     

Phosphine‐Catalyzed [3+2] and [4+3] Annulation Reactions of C,N‐Cyclic Azomethine Imines with Allenoates

Phosphine‐catalyzed [3+2] and [4+3] annulation reactions of C,N‐cyclic azomethine imines with allenoates have been developed to give a variety of pharmaceutically attractive tetrahydroisoquinoline derivatives in moderate to excellent yields. The two distinct reaction pathways, [3+2] and [4+3] cyclization, depend on the nature of the nucleophilic phosphine and the allenoate. Generally, for α‐alkylallenoates, the reactions always proceed with [3+2] cyclization as the major pathway no matter what phosphine was used; for α‐ArCH₂‐substituted allenoates, the reaction pathway was controlled by the phosphine catalyst used.     

N,O-Diarylation of N-Hydroxycarbamates. Rearrangement and Cleavage Reactions of the Intermediate N,O-Diarylhydroxylamines

The reactions of benzyl N-hydroxycarbamate with 2- and 4-nitrofluorobenzene yielded the corresponding benzyl N-(nitrophenoxy)carbamates. Their reaction with nitrofluorobenzenes yielded derivatives of biphenyl and of diphenyl ether. The formation of these products has been rationalized by assuming the existence of N,O-diphenylhydroxylamines as intermediates which undergo rearrangement analogous to the benzidine rearrangement.     

Design of a rigid side chain for poly(N-vinylamide) derivatives bearing an alkenyl group and evaluation of their ability to inhibit tetrahydrofuran hydrate crystal growth

Kinetic hydrate inhibitors (KHIs) are water-soluble polymers that are used to prevent gas hydrate formation in flow lines during upstream oil and gas production. All commercial polymers have pendant hydrophobic moieties with saturated carbon–carbon bonds. In our previous studies, poly(N-vinylamide) derivatives bearing alkyl groups and ethylene glycol groups were synthesized and investigated as KHIs. For comparison, we have now synthesized poly(N-vinylamide) derivatives in which an alkenyl group has been introduced at the N-position to improve the rigidity and steric hindrance of the side chain. The KHI performances of synthesized polymers were evaluated by the method of tetrahydrofuran (THF) hydrate crystal growth. The molecular weight of the synthesized polymers affected their ability to inhibit THF hydrate crystal growth. Higher molecular weight polymers, above 4,000 g/mol, tended to show higher inhibition efficiencies compared with lower molecular weight polymers of around 1,000 g/mol. However, the KHI performance of poly(N-vinylamide) derivatives bearing alkenyl groups was generally lower than the polymers in the previous studies. This indicates that the side chain rigidity and/or steric hindrance do not significantly influence the KHI performance.     

Synthesis and Antimicrobial Activity of Albicidin Derivatives with Variations of the Central Cyanoalanine Building Block

To investigate the pharmacophore regions of the antibiotic albicidin, derivatives with variations on the central amino acid were synthesized. Charged as well as uncharged residues were chosen to explore the influence of charge, chirality, and steric bulk. The bioactivity of the newly synthesized derivatives was determined by a microdilution technique to obtain minimum inhibitory concentrations (MIC) values. The compounds were also tested in a cell‐free system to obtain information about their ability to inhibit their primary target, DNA gyrase. It was then shown that derivatives with uncharged side chains retain antibacterial activity, whereas incorporation of charged amino acid residues decreases the antibacterial activity dramatically, possibly due to restricted cell penetration of these derivatives. From the newly synthesized derivatives, the threonine derivative shows the most promising results in both tests. The information will help to develop the features of albicidin toward more drug‐like structures.     

Reusable Gold(I) Catalysts with Unique Regioselectivity for Intermolecular Hydroamination of Alkynes

Two gold(I) phosphine complexes bearing the low‐coordinating bis(trifluoromethanesulfonyl)imidate ligand, namely AuSPhosNTf₂ and AuPPh₃NTf₂, are active catalysts for the regioselective intermolecular hydroamination of both internal and terminal alkynes under mild reaction conditions. The catalysts show a regioselectivity based on electronic rather than steric factors, which allow the preferential synthesis of regioisomers opposite to those described previously. This subtle chemo‐ and regioselectivity depends on the catalyst, substrates and reaction conditions employed, and allows one to perform new tandem reactions. These gold(I) complexes operate under free‐solvent conditions, without exclusion of air, without addition of acidic promoters and can be quantitatively recovered and reused by simple precipitation in hexane.     

Biosynthetic Plasticity Enables Production of Fluorinated Aurachins

Enzyme promiscuity has important implications in the field of biocatalysis. In some cases, structural analogues of simple metabolic building blocks can be processed through entire pathways to give natural product derivatives that are not readily accessible by chemical means. In this study, we explored the plasticity of the aurachin biosynthesis pathway with regard to using fluoro- and chloroanthranilic acids, which are not abundant in the bacterial producers of these quinolone antibiotics. The incorporation rates of the tested precursor molecules disclosed a regiopreference for halogen substitution as well as steric limitations of enzymatic substrate tolerance. Three previously undescribed fluorinated aurachin derivatives were produced in preparative amounts by fermentation and structurally characterized. Furthermore, their antibacterial activities were evaluated in comparison to their natural congener aurachin D.     

Synthese von 6-Acetyl-3-alkyl-2-phenyl-chromen-4-onen in phasentransfer-katalysierter Baker-Venkataraman-Reaktion

Synthesis of 6-Acetyl-3-alkyl-2-phenyl-chromen-4-ones by Phasetransfer Catalysed Baker-Venkataraman Reaction Three of the five partial steps of the Baker-Venkataraman xssynthesis of flavones (scheme 1) can be favoured by PTC conditions. In the intermolecular O-acylations of the 4-hydroxyacetophenone 1 (A) and the 5-acetyl-2-hydroxy-acylophenones 3 (C), respectively, the nucleophilicity of the phenolat anions is increased by the PT catalysator. The steric and electronic effects of the substituents in the 5-acetyl-2-benzoyloxy-acylophenones 4 cause the formation of the 6-acetyl-flavones 6 in the phasetransfer catalysed Baker-Venkataraman rearrangement (D) in one step and in good yields. The over-all yields of the 1 → 6 reactions are not higher than 30% because of the limiting step (B). This Fries rearrangement of 4-acyloxy-acetophenones 2 affords only 32–62% of 3 under drastically enhanced conditions.     

Steric and Electronic Effects in Basic Dyes

Absorption spectra of several derivatives of Malachite Green containing more than one substituent in the phenyl ring have been examined. In most cases where steric effects are unimportant an additive relationship is found between the electronic effects of the substituents and the position of the first-frequency absorption band. The presence of a second unsaturated electron-withdrawing group in the phenyl ring leads to a further reduction in the intensity of the first band. In certain cases, the overall electron-withdrawal is such that the equilibrium between dye-base and univalent dye cation in acid solution is shifted in favour of the former species.