Efficient Hydroboration of Esters and Nitriles Using a Quinazolinone-Supported Titanium(IV) Multitasking Catalyst

We report catalytic hydroboration of esters as well as nitriles under solvent-free and mild conditions using single titanium(IV) metal complex, [{κ²-C₆H₄C(O)N(ⁱPr)C(N-ⁱPr)=N}{κ³-(ⁱPr)N=C(O)−C₆H₄−NC(NMe₂)N(ⁱPr)}TiNMe₂] 1 as a sustainable, economical, and efficient pre-catalyst. The molecular structure of the Ti^IV complex in the solid state reveals the unique coordination of Ti^IV metal with N, N, and O atoms of one quinazolinone unit via in-situ rearrangement, while another quinazolinone moiety coordinates in bidentate fashion via both N atoms only. The Ti^IV complex demonstrates excellent activity as a pre-catalyst towards the hydroboration of a wide array of esters and nitriles with pinacolborane (HBpin) to afford alkoxyboranes and diboryl amines in high yield (up to 99 %) with greater tolerance to a variety of electron-withdrawing and electron-donating functional groups. A most plausible mechanism of hydroboration of esters is also proposed based on kinetics and NMR studies, which suggests the formation of titanium-hydride species as an active catalyst.     

Mechanistic Insight into Hydroboration of Imines from Combined Computational and Experimental Studies

Boron Lewis acid-catalyzed and catalyst-free hydroboration reactions of imines are attractive due to the mild reaction conditions. In this work, the mechanistic details of the hydroboration reactions of two different kinds of imines with pinacolborane (HBpin) are investigated by combining density functional theory calculations and some experimental studies. For the hydroboration reaction of N-(α-methylbenzylidene)aniline catalyzed by tris[3,5-bis(trifluoromethyl)phenyl]borane (BAr^F₃), our calculations show that the reaction proceeds through a boron Lewis acid-promoted hydride transfer mechanism rather than the classical Lewis acid activation mechanism. For the catalyst- and solvent-free hydroboration reaction of imine, N-benzylideneaniline, our calculations and experimental studies indicate that this reaction is difficult to occur under the reaction conditions reported previously. With a combination of computational and experimental studies, we have established that the commercially available BH₃ ⋅ SMe₂ can serve as an efficient catalyst for the hydroboration reactions of N-benzylideneaniline and similar imines. The hydroboration reactions catalyzed by BH₃ ⋅ SMe₂ are most likely to proceed through a hydroboration/B−H/B−N σ-bond metathesis pathway, which is very different from that of the reaction catalyzed by BAr^F₃.     

Hydroboration of Arynes with N‐Heterocyclic Carbene Boranes

Arynes were generated in situ from ortho‐silyl aryl triflates and fluoride ions in the presence of stable N‐heterocyclic carbene boranes (NHC? BH₃). Spontaneous hydroboration ensued to provide stable B‐aryl‐substituted NHC‐boranes (NHC? BH₂Ar). The reaction shows good scope in terms of both the NHC‐borane and aryne components and provides direct access to mono‐ and disubstituted NHC‐boranes. The formation of unusual ortho regioisomers in the hydroboration of arynes with an electron‐withdrawing group supports a hydroboration process with hydride‐transfer character.     

Spectrophotometric Determination of N-2-Pyridyl(maleic acid monoamide)

The behavior of N-2-pyridyl(maleic acid monoamide) in various hydrolyzing media has been studied. It is found that the substance is instantly hydrolyzed by 6 M CH₃COOH under normal conditions to form 2-aminopyridine. The molar absorptivity of the hydrolyzate is several times higher than that of N-2-pyridyl(maleic acid monoamide) in various media, which can be used for the sensitive determination of the substance. A procedure for the spectrophotometric determination of N-2-pyridyl(maleic acid monoamide) has been developed.     

Toxicity of naturally occurring Bio-fly and chitosan compounds to control the Mediterranean fruit fly Ceratitis capitata (Wiedemann)

The efficacy of five compounds of a biopolymer chitosan and Bio-fly (Beauveria bassiana fungus) as biopesticide was evaluated on Ceratitis capitata under laboratory conditions. The inhibitory effects on acetylcholinesterase (AChE) and adenosinetriphosphatase (ATPase) as biochemical indicators were also determined in vivo. The results indicated that B. bassiana based Bio-fly exhibited significant toxicity against C. capitata (LC₅₀ = 3008 and 3126 mg/L after 48 h in females and males, respectively) followed by the derivatives of chitosan, N-(4-propylbenzyl)chitosan and N-(2-nitrobenzyl)chitosan. Bio-fly displayed remarkable inhibition of AChE activity (IC₅₀ = 2220 mg/L) while N-(2-chloro,6-flourobenzyl)chitosan, N-(4-propylbenzyl)chitosan and N-(3,4-methylenedioxybenzyl) chitosan had no significant difference in inhibitory action. In adult males, N-(2-nitrobenzyl)chitosan exhibited the highest inhibitory action (IC₅₀ = 6569 mg/L). In addition, the toxic effects of the tested compounds on the activity of ATPase indicated that highly significant inhibition was found with N-(4-propylbenzyl)chitosan with an IC₅₀ of 8194 and 8035 mg/L, in females and males, respectively.     

Theoretical insight into the solvent effect on the stoichiometric reduction of carbonyl compounds by ammonia borane and N-methyl amine borane

For the traditional reduction of ketones and aldehydes, NH₃BH₃ ( AB ) and N-methyl amine borane ( M _n AB ) have been effective reducing agents. However, the reaction process is indefinite and different mechanisms have been proposed; also the solvent effect, which is closely related to the mechanism, has not been considered seriously. Here we employ density functional theory to carry out a comprehensive study on the mechanism. The calculated free energy of the concerted double hydrogen transfer process is lower than the hydroboration mechanism by 4.7 kcal/mol, which indicates that reduction of carbonyl by AB is likely due to be the concerted double hydrogen transfer in both aprotic (tetrahydrofuran) and protic (MeOH) solvents. For the reduction by M _n AB , the corresponding free energies of all reactions are higher than those of AB . Meanwhile, the reduction of benzaldehyde by M _n AB (n = 1, 2) also favors a concerted double hydrogen transfer rather than hydroboration.     

N-Heteroaromatic Fluoroalkylation through Ligand Coupling Reaction of Sulfones

Ligand coupling on hypervalent main group elements has emerged as a pivotal methodology for the synthesis of functionalized N-heteroaromatic compounds in recent years due to the avoidance of transition metals and the mildness of the reaction conditions. In this direction, the reaction of N-heteroaryl sulfur(IV) and N-heteroaryl phosphorus(V) compounds has been well studied. However, the ligand coupling of sulfur(VI) is still underdeveloped and the reaction of alkyl N-heteroarylsulfones is still elusive, which does not match the high status of sulfones as the chemical chameleons in organic synthesis. Here we present a ligand coupling-enabled formal SO₂ extrusion of fluoroalkyl 2-azaheteroarylsulfones under the promotion of Grignard reagents, which not only enriches the chemistry of sulfones, but also provides a novel and practical synthetic tool towards N-heteroaromatic fluoroalkylation.     

Oxidation of N-acyl-2-(cycloalk-1-enyl)anilines with ozone and hydrogen peroxide

Treatment of the ozonization products from N-acetyl- or 2-methyl-N-trifluoroacetyl-6-(cyclopent-1-enyl)anilines with NaBH₄ gives 6-methyl-2-tetrahydropyranylaniline. When treated with Me₂S, the ozonization products yield the corresponding oxoaldehyde dimethyl acetals. The oxidation of N-acetyl-2-(cyclopent-1-enyl)- or -(cyclohex-1-enyl)anilines with H₂O₂ in HCOOH affords -(2-acetamidophenyl)-5-oxopentanoic or -6-oxohexanoic acid, respectively. The reaction of N-acetyl-2-(cyclopent-1-enyl)aniline with H₂O₂ in the presence of Na₂WO₄ and H₃PO₄ gives 3,1-benzooxazine in high yield.     

NMR studies on interactions between diperoxovanadate and picolinamide-like ligands

To understand the effects of picolinamide-like ligands on reaction equilibrium, a series of picolinamide derivatives were synthesized and the interactions between the diperoxovanadate complex [OV(O₂)₂L]^? (L = D₂O or HOD, abbr. bpV) and picolinamide ligands in solution were explored using multinuclear (¹H, ¹³C, and ⁵¹V) magnetic resonance, COSY, and HSQC in 0.15 mol L^?1 NaCl ionic medium for mimicking physiological conditions. Formation constants among the picolinamide-like ligands are N-(1-hydroxypropan-2-yl)-picolinamide ≈N-(2-hydroxypropyl)-picolinamide>N-(3-hydroxypropyl)-picolinamide>N-propyl-picolinamide. The substituting group influences the equilibrium by electronic effects. The interactions result in a series of new seven-coordinate diperoxovanadate species [OV(O₂)₂L′]^? (L′ = picolinamide-like ligands).     

Boron Lewis Acid‐Catalyzed Hydroboration of Alkenes with Pinacolborane: BArF3 Does What B(C6F5)3 Cannot Do!

The transition‐metal‐free hydroboration of various alkenes with pinacolborane (HBpin) initiated by tris[3,5‐bis(trifluoromethyl)phenyl]borane (BAr^F₃) is reported. The choice of the boron Lewis acid is crucial as the more prominent boron Lewis acid tris(pentafluorophenyl)borane (B(C₆F₅)₃) is reluctant to react. Unlike B(C₆F₅)₃, BAr^F₃ is found to engage in substituent redistribution with HBpin, resulting in the formation of Ar^FBpin and the electron‐deficient diboranes [H₂BAr^F]₂ and [(Ar^F)(H)B(μ‐H)₂BAr^F₂]. These in situ‐generated hydroboranes undergo regioselective hydroboration of styrene derivatives as well as aliphatic alkenes with cis diastereoselectivity. Another ligand metathesis of these adducts with HBpin subsequently affords the corresponding HBpin‐derived anti‐Markovnikov adducts. The reactive hydroboranes are regenerated in this step, thereby closing the catalytic cycle.     

A Frustrated and Confused Lewis Pair

We report a new class of frustrated Lewis pairs (FLPs) by the hydroboration of bulky isocyanates ^iPr2ArNCO (^iPr2Ar=2,6‐iPr₂C₆H₃) and ^Ph2tBuArNCO (^Ph2tBuAr=2,6‐Ph₂‐4‐tBuC₆H₂) with Piers’ borane (HB(C₆F₅)₂). While hydroboration of smaller isocyanates such as ^iPr2ArNCO leads to isocyanate—N/B FLP adducts, hydroboration of the bulkier ^Ph2tBuArNCO allows isolation of the substrate‐free aminoborane with a short, covalent N?B bond. This confused FLP reversibly binds unsaturated substrates such as isocyanates and isocyanides, suggesting the intermediacy of a “normal” FLP along the reaction pathway, supported by high‐level DFT studies and variable‐temperature NMR spectroscopy. These results underscore the possibility of FLP behavior in systems that possess no obvious frustrated Lewis acid–base interaction.     

Separation and quantification of basic hydroxycinnamic amides and hydroxycinnamic acids by reversed-phase high-performance liquid chromatography

A method for the separation of basic hydroxycinnamic amides and hydroxycinnamic acids by high-performance liquid chromatography is described. N-p-Coumaryl-, N-caffeyl- and N-ferulylpetrescine, N-p-coumryl-, N-caffeyl- and N-ferulylspermidine and p-coumaric, caffeic, ferulic and sinapic acids were chromatographed on a μBondapak C₁₈ reversed-phase column (particle size 9 μm) with different methanol—water gradients as the mobile phase. It is possible with this high-resolution and reproducible method to assay biological samples containing mre that 10⁻⁵ M of hydroxycinnamic amides, using either p-coumaric or ferulic acid as the internal standard: this is demonstrated for tobacco extracts.     

Regioselective Rhodium-Catalyzed 1,2-Hydroboration of Pyridines and Quinolines Enabled by the Tris(8-quinolinyl)phosphite Ligand**

A Rh(I) complex [κ²(P,N)-{P(Oquin)₃}RhCl(PPh₃)] ( 1 ) bearing the P,N ligand tris(8-quinolinyl)phosphite, P(Oquin)₃, has been synthesized and structurally characterized. The molecular structure of complex 1 shows that P(Oquin)₃ acts as a bidentate P,N chelate ligand. Reactivity studies of 1 reveal that the triphenylphosphine ligand can be replaced by Pcy₃ or removed upon oxidation with concomitant coordination of a second 8-quinolyl unit of P(Oquin)₃. In addition, the Rh(III) complex [RhCl₂{OP(Oquin)₂}] ( 3 ), resulting from treating 1 with either wet CDCl₃ or, sequentially, with HCl and water, was identified by X-ray diffraction analysis. Complex 1 catalyzes the 1,2-regioselective hydroboration of pyridines and quinolines, affording N-boryl-1,2-dihydropyridines (1,2-BDHP) and N-boryl-1,2-hydroquinolines (1,2-BDHQ) in high yield (up to >95 %) with turnover numbers (TONs) of up to 130. The system tolerates a variety of substrates of different electronic and steric nature. In comparison with other transition-metal-based hydroboration catalysts, this system is efficient at a low catalyst loading without the requirement of base or other additives.     

Method for trace determination of N-nitrosamines impurities in metronidazole benzoate using high-performance liquid chromatography coupled with atmospheric-pressure chemical ionization tandem mass spectrometry

Genotoxic impurity control has been a great concern in the pharmaceutical industry since the recall of the large round of sartans worldwide in 2018. In these sartans, N-nitrosamines were the main contaminants in active pharmaceutical ingredients and formulations. Numerous analytical methods have been developed to detect N-nitrosamines in food, drugs, and environmental samples. In this study, a sensitive method is developed for the trace determination of N-nitrosamine impurities in metronidazole benzoate pharmaceuticals using high-performance liquid chromatography/atmospheric-pressure chemical ionization tandem mass spectrometry in the multiple reaction monitoring mode. The method was validated regarding system suitability, selectivity, linearity, accuracy, precision, sensitivity, solution stability, and robustness. The method showed good linearity with R² ≥ 0.999 and F_Mandel < F_tab(95%) ranging from 0.33 to 8.00 ng/ml. The low limits of detection of N-nitrosamines were in the range of 0.22–0.80 ng/ml (0.0014–0.0050 ppm). The low limits of quantification were in the range of 0.33–1.20 ng/ml (0.0021–0.0075 ppm), which were lower than the acceptable limits in metronidazole benzoate pharmaceuticals and indicated the high sensitivity of the method. The recoveries of N-nitrosamines ranged from 84% to 97%. Thus, this method exhibits good selectivity, sensitivity, and accuracy. Moreover, it is a simple, convenient, and scientific strategy for detecting N-nitrosamine impurities in pharmaceuticals to support the development of the pharmaceutical industry.     

Hydroboration as an Efficient Tool for the Preparation of Electronically and Structurally Diverse N→B‐Heterocycles

Ladder‐type organoboranes featuring intramolecular N→B coordination have been prepared through hydroboration of a 2‐(ortho‐styryl)pyridine ( PhPy ) with a series of hydroboranes, including 9H‐9‐borabicyclo[3.3.1]nonyl (9H‐BBN), BH₃ ? THF, HBCl₂ ? SMe₂, HB(C₆F₅)₂, and a 9H‐9‐borafluorene derivative. The hydroboration reaction results in highly regioselective borylation under mild conditions and gives the products in good to excellent yields. The molecular structure and electronic properties of the obtained boranes have been experimentally investigated in detail, and complemented with DFT calculations to further elucidate the origin of differences in optical and electronic properties. The electron affinity of the conjugated system can be controlled through variation of the borane, while the optical properties are likewise directly linked to the type and molecular structure of the substituents on boron. The broad substrate range shows that this preparative approach is widely applicable to introduce chemically diverse boryl groups into conjugated systems.     

Synthesis of various boron-containing disilanes

The stepwise reaction of the Si-Cl functions of 1,1,2,2-tetrachlorodimethyldisilane with RMgBr using the diethylamino unit as protecting group enables the synthesis of disilanes Si₂Me₂R_xCl_4–x, bearing one to four olefinic substituents (R = vinyl, -allyl and ethynyl). The catalyst free hydroboration of such molecules represents a convenient way to prepare boron containing chlorodisilanes. 9-BBN exhibits a very high regioselectivity in the hydroboration of vinyl-, allyl-or ethynyldisilanes. In case of the ethynyl group, the hydroboration of 1,1,2-trichloro-2-ethynyldimethyldisilane and 1,2-dichloro-1,2-diethynyldimethyldisilane by the twofold addition of the 9-BBN in two separate steps was confirmed by NMR spectroscopy.     

Synthesis and Structures of cis- and trans-[Os(Bcat)(aryl)(CO)2(PPh3)2]: Compounds of Relevance to the Metal-Catalyzed Hydroboration Reaction and the Metal-Mediated Borylation of Arenes

Support for key steps of the mechanism for the transition metal catalyzed hydroboration reaction is provided by the characterization and reactions of 1 , a cis-(boryl)(aryl) complex of osmium(II ). This compound readily eliminates o-tolylBcat to give the osmium(0) intermediate 2 , which in the presence of HBcat reestablishes the osmium–boron bond by forming 3 . R=o-tolyl, H₂cat=catechol=1,2-(HO)₂C₆H₄.     

Molecular structure of N-chlorosuccinimide studied by gas-phase electron diffraction and quantum-chemical methods

The molecular structure of N-chlorosuccinimide has been studied by GED method at the nozzle temperature of 116 °C. Vibrational corrections to the r _a parameters, Δ(r _a − r _e), have been calculated using the scaled quadratic and cubic force constants from B3LYP/6-31G(df,p) calculations. The force field scaling has been carried out using the IR and Raman spectra of the solid N-chlorosuccinimide. The molecular skeleton and the bond conformation around nitrogen were found to be planar within large experimental errors. The equilibrium geometrical parameters derived from the experimental data assuming C _2v molecular symmetry and those from MP2(fc)/6-311G(3df,2pd) calculations are in a good agreement.     

Stereodivergent Hydroboration of Allenes

Full details of a stereodivergent hydroboration of allenes are reported. While hydroboration of an allene with 9‐BBN provided a thermodynamically stable (E)‐allylic alcohol after oxidative work‐up, the reaction of an identical allene with HB(Sia)₂ (disiamylborane) formed a (Z)‐allylic alcohol as the kinetic product. The developed conditions allowed for the synthesis of trisubstituted olefins in a highly stereoselective fashion, which is known to be challenging. The method was also applied to the stereodivergent synthesis of structural motifs such as skipped dienes and allylbenzenes, which are often embedded in biologically active natural products.     

Mass spectrometric analysis of N-substituted cyclohexene-1,2-dicarboximides

Both low and high resolution mass spectra of cis-4-cyclohexene-1,2-dicarboximide, its N-methyl, N-ethyl, N-n-propyl and N-n-butyl derivatives, and cyclohexane-1,2-dicarboximide were obtained at 70 eV. Each of the spectra exhibited characteristic nominal ions at masses 151, 136, 123 and a group of ions at masses 77, 78, 79, 80 and 81 of which m/e 80 was always the base peak except for the unsubstituted cyclohexane compound. The m/e 77 to 81 fragments are composed of carbon and hydrogen and derived from the cyclohexene ring. The ions possessing higher masses are heterocyclic and certain of them show doublets and triplets. Evidence for a 1,3 hydrogen migration was supplied by studies with the N-(ethyl-2-d₃) derivative and evidence for a 1,4 migration by the N-(n-propyl-3-d₃) derivative.