Solvent Hydrogen Bond Donor Research Articles

Tert‐Butyl as a Functional Group: Non‐Directed Catalytic Hydroxylation of Sterically Congested Primary C−H Bonds

AbstractThe tert‐butyl group is a common aliphatic motif extensively employed to implement steric congestion and conformational rigidity in organic and organometallic molecules. Because of the combination of a high bond dissociation energy (~100 kcal mol−1) and limited accessibility, in the absence of directing groups, neither radical nor organometallic approaches are effective for the chemical modification of tert‐butyl C−H bonds. Herein we overcome these limits by employing a highly electrophilic manganese catalyst, [Mn(CF3bpeb)(OTf)2], that operates in the strong hydrogen bond donor solvent nonafluoro‐tert‐butyl alcohol (NFTBA) and catalytically activates hydrogen peroxide to generate a powerful manganese‐oxo species that effectively oxidizes tert‐butyl C−H bonds. Leveraging on the interplay of steric, electronic, medium and torsional effects, site‐selective and product chemoselective hydroxylation of the tert‐butyl group is accomplished with broad reaction scope, delivering primary alcohols as largely dominant products in preparative yields. Late‐stage hydroxylation at tert‐butyl sites is demonstrated on 6 densely functionalized molecules of pharmaceutical interest. This work uncovers a novel disconnection approach, harnessing tert‐butyl as a potential functional group in strategic synthetic planning for complex molecular architectures.

Tert-Butyl as a Functional Group: Non-Directed Catalytic Hydroxylation of Sterically Congested Primary C-H Bonds.

The tert-butyl group is a common aliphatic motif extensively employed to implement steric congestion and conformational rigidity in organic and organometallic molecules. Because of the combination of a high bond dissociation energy (~ 100 kcal mol-1) and limited accessibility, in the absence of directing groups, neither radical nor organometallic approaches are effective for the chemical modification of tert-butyl C-H bonds. Herein we overcome these limits by employing a highly electrophilic manganese catalyst, [Mn(CF3bpeb)(OTf)2], that operates in the strong hydrogen bond donor solvent nonafluoro-tert-butyl alcohol (NFTBA) and catalytically activates hydrogen peroxide to generate a powerful manganese-oxo species that effectively oxidizes tert-butyl C-H bonds. Leveraging on the interplay of steric, electronic, medium and torsional effects, site-selective and product chemoselective hydroxylation of the tert-butyl group is accomplished with broad reaction scope, delivering primary alcohols as largely dominant products in preparative yields. Late-stage hydroxylation at tert-butyl sites is demonstrated on 6 densely functionalized molecules of pharmaceutical interest. This work uncovers a novel disconnection approach, harnessing tert-butyl as a potential functional group in strategic synthetic planning for complex molecular architectures.

(Radio)Fluoro-iodination of Alkenes Enabled by a Hydrogen Bonding Donor Solvent.

We have developed a widely applicable (radio)fluoro-iodination of alkenes using readily available and easily handled KF (18F). The reactions exhibited high functional group tolerance and needed only an ambient atmosphere. Furthermore, the resulting product could be further functionalized with various nucleophiles.

Solvent Replacement Strategies for Processing Pharmaceuticals and Bio-Related Compounds—A Review

An overview of solvent replacement strategies shows that there is great progress in green chemistry for replacing hazardous di-polar aprotic solvents, such as N,N-dimethylformamide (DMF), 1-methyl-2-pyrrolidinone (NMP), and 1,4-dioxane (DI), used in processing active industrial ingredients (APIs). In synthetic chemistry, alcohols, carbonates, ethers, eucalyptol, glycols, furans, ketones, cycloalkanones, lactones, pyrrolidinone or solvent mixtures, 2-methyl tetrahydrofuran in methanol, HCl in cyclopentyl methyl ether, or trifluoroacetic acid in propylene carbonate or surfactant water (no organic solvents) are suggested replacement solvents. For the replacement of dichloromethane (DCM) used in chromatography, ethyl acetate ethanol or 2-propanol in heptanes, with or without acetic acid or ammonium hydroxide additives, are suggested, along with methanol acetic acid in ethyl acetate or methyl tert-butyl ether, ethyl acetate in ethanol in cyclohexane, CO2-ethyl acetate, CO2-methanol, CO2-acetone, and CO2-isopropanol. Supercritical CO2 (scCO2) can be used to replace many organic solvents used in processing materials from natural sources. Vegetable, drupe, legume, and seed oils used as co-extractants (mixed with substrate before extraction) can be used to replace the typical organic co-solvents (ethanol, acetone) used in scCO2 extraction. Mixed solvents consisting of a hydrogen bond donor (HBD) solvent and a hydrogen bond acceptor (HBA) are not addressed in GSK or CHEM21 solvent replacement guides. Published data for 100 water-soluble and water-insoluble APIs in mono-solvents show polarity ranges appropriate for the processing of APIs with mixed solvents. When water is used, possible HBA candidate solvents are acetone, acetic acid, acetonitrile, ethanol, methanol, 2-methyl tetrahydrofuran, 2,2,5,5-tetramethyloxolane, dimethylisosorbide, Cyrene, Cygnet 0.0, or diformylxylose. When alcohol is used, possible HBA candidates are cyclopentanone, esters, lactone, eucalytol, MeSesamol, or diformylxylose. HBA—HBA mixed solvents, such as Cyrene—Cygnet 0.0, could provide interesting new combinations. Solubility parameters, Reichardt polarity, Kamlet—Taft parameters, and linear solvation energy relationships provide practical ways for identifying mixed solvents applicable to API systems.

Synthesizing Hypercrosslinked Polymers with Deep Eutectic Solvents to Enhance CO2 /N2 Selectivity.

Hypercrosslinked polymers (HCPs) are widely used in ion exchange, water purification, and gas separation. However, HCP synthesis typically requires hazardous halogenated solvents e. g., dichloroethane, dichloromethane and chloroform which are toxic to human health and environment. Herein we hypothesize that the use of halogenated solvents in HCP synthesis can be overcome with deep eutectic solvents (DES) comprising metal halides-FeCl3 , ZnCl2 that can act as both the solvent hydrogen bond donor and catalyst for polymer crosslinking via Friedel Crafts alkylation. We validated our hypothesis by synthesizing HCPs in DESs via internal and external crosslinking strategies. [ChCl][ZnCl2 ]2 and [ChCl][FeCl3 ]2 was more suitable for internal and external hypercrosslinking, respectively. The specific surface areas of HCPs synthesized in DES were 20-60 % lower than those from halogenated solvents, but their CO2 /N2 selectivities were up to 453 % higher (CO2 /N2 selectivity of poly-α,α'-dichloro-p-xylene synthesized in [ChCl][ZnCl2 ]2 via internal crosslinking reached a value of 105). This was attributed to the narrower pore size distributions of HCPs synthesized in DESs.

Semi-empirical design and synthesis of novel 4-hydroxy-6-sulphonaphthyl azohydroxynaphthalenes with predominant hydrazone form

Due to their enhanced photochromic effects, hydrazone forms of tautomeric azo compounds are commercially preferred as photoreceptors and binary switches. While ortho-hydroxyazo compounds readily exhibit an intramolecular hydrazone re-arrangement, the predominance of hydrazone tautomers of para-hydroxyazo compounds is less frequently observed. The objective of this study was to design and synthesize sulphonated 4-naphthylazo naphth-1-ols with preferential hydrazone shift.PM6 calculations were used to quantify contributions of selected structural features to hydrazone stability in a set of model compounds. Synthesis of five computationally-optimized compounds (3a-e) was subsequently carried out via diazo coupling of 5‑hydroxy-7-sulphonaphthalene-2-diazonium ion with naphthol derivatives. The azo-hydrazone equilibria of 3a-e were further characterized using spectroscopic techniques and density functional theory (DFT).Computational design revealed that sulphonic acid substitution on the coupling components of the dyes and, solvation effect of the substituents were the highest contributors to hydrazone shift of the compounds. The ring position and electron withdrawing resonance effect of substituents were less contributory. Increasing substitution with sulphonic acid or another hydrophilic group (amino) also resulted in higher hydrazone stability. Mass spectral, IR and NMR data confirmed computational results with mono sulphonated 3a and poly substituted 3c-e existing predominantly as azo and hydrazone forms respectively. UV–Visible spectral analysis revealed that azo and hydrazone forms of 3a predominated in hydrogen bond acceptor and donor solvents respectively. In contrast, absorption spectra of 3b-e showed lone hydrazone bands in all solvents investigated. The DFT/M06-2X/6-31G(dp) characterization of the azo-hydrazone equilibrium of the compounds confirmed experimental results and showed that hydrazone tautomers of 3b, 3c and 3d were more stable than corresponding azo forms by 1.536, 0.289 and 1.359 kcal/mol respectively. DFT also confirmed involvement of sulphonic acid and imino groups in the transition of the dyes’ structures to the keto form.Three novel p-hydroxyazo dyes with increased hydrazone stability have been synthesized.

Spectroscopic study of solvent effects on the electronic absorption spectra of morpholine and its complexes

The electronic absorption spectra of morpholine and its five morpholine complexes have been studied in different solvents of various polarities. The regression and correlation coefficients have been calculated with the SPSS program. Solvation energy relationships were deduced from spectral shifts and correlated with solvent parameters α (solvent hydrogen bond donor acidity), β (solvent hydrogen bond acceptor basicity), and π* (dipolarity/polarizability). The percentage contributions of the calculated solvatochromic parameters show that classic solvation effects play a major role in explaining the spectral shifts in all investigated complexes. The blue shift of [Fe(MOR)3Cl3]·4H2O, [Ni(MOR)4Cl2]·4H2O, and [Cu(MOR)4Cl2]·6H2O complexes is due to the formation of hydrogen bonds, which suggests the stabilization of the ground electronic state compared with the excited state. [CuNi(MOR)2Cl4]·4H2O and [CuZn(MOR)3Cl4]·2H2O are mixed metal complexes that suffer a red shift due to the solute-solvent interactions, which causes stabilization of the excited solute state with increasing solvent polarity. The bands are affected by specific solute-solvent interactions including hydrogen bond donor ability (acidity) and hydrogen bond acceptor ability (basicity) and nonspecific solute-solvent interactions including electromagnetic interaction between the dipole moments of solute and polar solvents.

Hydrogen Bonding-Assisted and Nonheme Manganese-Catalyzed Remote Hydroxylation of C-H Bonds in Nitrogen-Containing Molecules.

The development of catalytic systems capable of oxygenating unactivated C-H bonds with excellent site-selectivity and functional group tolerance under mild conditions remains a challenge. Inspired by the secondary coordination sphere (SCS) hydrogen bonding in metallooxygenases, reported herein is an SCS solvent hydrogen bonding strategy that employs 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a strong hydrogen bond donor solvent to enable remote C-H hydroxylation in the presence of basic aza-heteroaromatic rings with a low loading of a readily available and inexpensive manganese complex as a catalyst and hydrogen peroxide as a terminal oxidant. We demonstrate that this strategy represents a promising compliment to the current state-of-the-art protection approaches that rely on precomplexation with strong Lewis and/or Brønsted acids. Mechanistic studies with experimental and theoretical approaches reveal the existence of a strong hydrogen bonding between the nitrogen-containing substrate and HFIP, which prevents the catalyst deactivation by nitrogen binding and deactivates the basic nitrogen atom toward oxygen atom transfer and the α-C-H bonds adjacent to the nitrogen center toward H-atom abstraction. Moreover, the hydrogen bonding exerted by HFIP has also been demonstrated not only to facilitate the O-O bond heterolytic cleavage of a putative MnIII-OOH precursor to generate MnV(O)(OC(O)CH2Br) as an active oxidant but also to affect the stability and the activity of MnV(O)(OC(O)CH2Br).

Hydrogen Bond Donor and Unbalanced Ion Pair Promoter-Assisted Gold-Catalyzed Carbon–Oxygen Cross-Coupling of (Hetero)aryl Iodides with Alcohols

We have developed an efficient gold-catalyzed C–O cross-coupling reaction of (hetero)aryl iodides with primary and secondary alcohols via an AuI–AuIII catalytic cycle. This protocol featured moisture/air insensitivity, simple operation, and excellent functional group tolerance. Good yields were obtained regardless of steric hindrance and electronic factor (electron-rich or poor) of substrates, and the chirality of chiral alcohol starting materials could be preserved. Our protocol worked well for both intermolecular and intramolecular couplings. In addition, the RuPhos ligand was applied to gold-catalyzed cross-couplings. An unbalanced ion pair promoter and hydrogen bond donor solvent might be crucial in this transformation.

Rationalizing hydrogen bond solvation with Kamlet-Taft LSER and molecular torsion balances.

The strength of a weak intramolecular hydrogen bond was quantified using molecular torsion balances and found to vary between -0.99 kcal mol-1 and +1.00 kcal mol-1 due to solvation. Analyzing the results using Kamlet-Taft's Linear Solvation Energy Relationship enabled partitioning of the hydrogen-bond strength into physically meaningful solvent parameters through a linear equation: ΔGH-Bond = -1.37 - 0.14α + 2.10β + 0.74(π* - 0.38δ) kcal mol-1 (R2 = 0.99, n = 14), where α and β represent the solvent hydrogen-bond acceptor and donor parameters, respectively, and π* associates with the solvent nonspecific polarity/dipolarity parameter. Based on the coefficient of each solvent parameter (derived by linear regression), the β electrostatic term emerged as the dominant contributor to solvent effects on hydrogen bonding. This finding aligns with the natural attributes of hydrogen bonds as electrostatic interactions, but the contributions from the nonspecific interactions of the solvent (e.g., dispersion) are also important. Hydrogen bond solvation affects molecular properties and functions, and this study provides a predictive tool to harness the efficiency of hydrogen bonds.

Sustainable extraction of antioxidants from out-of-caliber kiwifruits

Valorisation of discarded kiwifruits is proposed by extracting bioactive compounds using sustainable solvents namely deep eutectic solvents (DES). A screening of fifteen DES and several hydrogen bonding donor solvents was carried out. Extraction efficiency was measured in terms of antioxidant activity using DPPH and FRAP tests. The influence of solvents characteristics in particular DES structure, presence of ethanol or water, and pH of DES/water mixture on the antioxidant properties of the extracts was studied. Results show that kiwi peels extracts obtained with DES based on carboxylic acids exhibit enhanced antioxidant activity compared to conventional solvents and alcohol-based DES with a maximum DPPH scavenging activity of 42.0 mg TE/g DW. Glycerol or ethylene glycol are also efficient at extracting antioxidant compounds with DPPH scavenging activity of 33.1 and 36.7 mg TE/g DW. Finally, a chemical analysis of extracts using HPTLC revealed that most active compounds extracted are polyphenolic compounds, presumably tannins.

Synthesis of (tricyanofuran-3-ylmethylene)hydrazinyl thiazole-containing chromophore: A study of its photophysical properties, solvatochromism, and TD-DFT computations.

The chromophore 2-2-(3-cyano-5,5-dimethyl-4-((2-[thiazol-2-yl]hydrazono)methyl)-furan-2(5H)-ylidene)malononitrile (TzHTCF) was prepared by diazo-coupling of diazotized 2-aminothiazole with 3-cyano-2-(dicyanomethylene)-4,5,5-trimethylfuran (TCF). The TzHTCF absorption solvatochromism, in different polarity solvents, demonstrated a ΔEmax = +4.74 in which the positive sign implied the occurrence of a red shift and the TzHTCF lowest excited state was more polar than its ground state. In addition, the TzHTCF fluorescence spectrum produced a λem in the 416-670 nm range and was more dependent on the solvent polarity than the absorption λmax , despite both exhibiting a red shift of 24 and 254 nm, respectively. To discover the Stokes shift ( behaviour of the TzHTCF derivative, Lippert-Mataga and linear solvation-energy relationship (LSER) formulations were utilized in which the LSER approach displayed better results than the Lippert-Mataga method (R2 = 0.9931). Furthermore, the LSER showed that the absorption and fluorescence solvatochromic behaviours were dependent on the solvent's hydrogen-bond donor (α) and acceptor (β), along with the solvent's polarizability (π*). Moreover, DFT calculations showed that TzHTCF has a planar configuration and its simulated absorption and emission spectra in dimethyl sulphoxide revealed that λmax primarily originated from the HOMO→LUMO and HOMO-1→LUMO transitions, respectively.

Synthesis, solvatochromism and DFT study of pyridine substituted benzanthrone with ICT characteristics

We have explored the relation between the substituent and optical nonlinearity of pyridinepiperazine substituted benzanthrone dye. We report the synthesis of 3-(4-(pyridine-2-yl)piperazin-1-yl)-7H-benzo[de]anthracen-7-one (Pyridine-PBA). The molecular structure of the title dye was further confirmed by using FT-IR, 1H NMR, 13C NMR, and X-ray crystallographic techniques. The 3-substituted benzanthrone dye was examined for solvent dependent photophysical properties. The polarity plots indicate that hydrogen bonding interactions are influential in most of the solvents. Further analysis of Stokes’ shift data with multi parameter solvent polarity scale signifies that with an increase in solvent hydrogen bond donor ability a bathochromic shift is observed resulting in an increment in the dipole moment of the Pyridine-PBA dye on excitation. Computational results indicate that the electron excitation has some charge transfer characteristics. Furthermore, the calculated first static hyperpolarizability (β) and second hyperpolarizability (γ) values using range separated DFT methods fare better than the estimates for urea.

Rationalization of the effects of hydrogen bond donor solvent and nucleofugicity of fluoride ion on nucleophilic aromatic substitution reactions in non-polar aprotic solvent: reaction of 2,4-dinitrofluorobenzene with cyclohexylamine in toluene and toluene

The kinetics of the reaction of 2,4-dinitrofluorobenzene with cyclohexylamine were studied at different concentrations in toluene and toluene-alkanol mixtures. The reaction was not base-catalysed in toluene. Addition of small amounts of hydrogen-bond donor solvent, alkanol (ranging from methanol to hexanol) to the toluene medium of the reactions produced a different effect in comparison to uncatalysed reactions — slight increase in rate of reaction. The results are rationalized in terms of the effect of amine-solvent interaction on the nucleophilicity of the amine in addition to some other factors operating through cyclic transition states leading to products. It is also attributed to the peculiar nature of fluoride ion as a leaving group.

Disclosure of the solvatochromism and the reversal switch in some tailor-made electron push-push anils

The impacts of a series of organic solvents, having diverse polarities on the electronic absorption spectra of some selected anils, N-benzylideneaniline, and its five derivatives with hydroxy and methoxy substituents were investigated. The absorption spectra of each of the anils displayed a cluster of absorption bands within 200–500 nm. The electronic transitions and the effect of substituents on the solvatochromism of these anils were successfully deciphered. The reversal in solvatochromism was observed in moving from the hydrogen bond acceptor to hydrogen bond donor solvents. This fact was attributed to the structural transition of the anils due to the interaction with solvents of differential polarity or due to the obscurity of anils within the solvent cage. The ET(30) values at which the reversal solvatochromic switch due to the anils appeared was controlled by the position and nature of the substituents. The early accomplishment of the reversal solvatochromism in o-OH substituted anils connoted the non-polar characteristics of these anils. By subjecting the electronic transition energies to multiple regression analysis with fourteen different solvent parameters, the multi-parametric regression models were optimized following the successive exclusion of variable technique. The linearity of the plot of the calculated electronic transition energy against corresponding observed values validated the regression models. The induced solvatochromism observed in the case of o/p-hydroxy-substituted anils in ethylene glycol medium was attributed to the formation of the corresponding conjugate acids of the anils. The solvent-solute interaction models were proposed to probe the localization site of anils in the solvents. The intramolecular H-bonding and the twisted structure of the anils due to the substituent effects were found to play the predominant role in deciding the localization sites of the anils.

Preferential solvation index as a tool in the analysis of the behavior of solvatochromic probes in binary solvent mixtures

The analysis of the solvation of a given solute is a puzzling phenomenon if the solute is placed in binary solvent mixtures. This is due to the preferential solvation (PS) of the solute by one of the solvents of the mixture. Solvatochromic dyes are used to describe binary solvent mixtures with different proportions of the components, from plots of molar transition energy (ET) values of a solvatochromic dye as a function of the mole fraction of the most polar solvent (X2) in the mixture. The quantitative analysis of these plots is commonly made by fitting the data using a quantitative solvent exchange model, with considerable success. However, although the fits are generally good, the results obtained are of difficult interpretation. Recently, a PS (or non–ideality) index (PSI) was introduced in an attempt to develop a simple tool for the qualitative and quantitative analysis of deviations from linearity verified in ET (dye) with X2 in mixtures of water with alcohols. Thus, it is necessary to extend the study related to the PSI to different probes and other solvent mixtures, to verify the advantages and limitations regarding the applications of this tool. Herein the solvatochromic behavior of five solvatochromic dyes in sixty–two binary solvent mixtures of a hydrogen–bond acceptor solvent (DMSO or acetonitrile) and a hydrogen–bond donor solvent (water and alcohols) was investigated. The PSI values were calculated and interpreted for each binary mixture. The comparison of PSIs for structurally different dyes in the binary mixtures provided interesting information about the solvation of the dyes. Thus, the analysis of the PSI values for the mixtures allow to interpret the phenomenon of PS not only in terms of a commitment of solute–solvent and solvent–solvent interactions, but also in terms of the intrinsic properties of the probe.

Hydrogen-Bond-Donor Solvents Enable Catalyst-Free (Radio)-Halogenation and Deuteration of Organoborons.

A hydrogen bond donor solvent assisted (radio)halogenation and deuteration of organoborons has been developed. The reactions exhibited high functional group tolerance and needed only an ambient atmosphere. Most importantly, compared to literature methods, our conditions are more consistent with the principals of green chemistry (e.g., metal-free, strong oxidant-free, more straightforward conditions).

Prediction of solvatochromic parameters of electronic transition energy for characterizing dipolarity/polarizability and hydrogen bonding donor interactions in binary solvent systems of liquid nonpolar-polar mixtures, CO2-expanded liquids and supercritical carbon dioxide with cosolvent

Solvatochromic parameter of electronic transition energy (ET) provides information on dipolarity/polarizability and hydrogen bonding donor interactions in the solvation shell. In this work, a predictive framework is proposed for estimating ET values of phenol blue indicator in three mixed-solvent systems as (i) liquid nonpolar-polar mixtures, (ii) CO2-expanded liquid solvent and (iii) supercritical carbon dioxide (scCO2)-polar cosolvent mixtures. The equations of the ET framework for binary mixtures of nonpolar solvent with polar hydrogen bond acceptor (HBA) solvent can be directly adopted from the previous framework for Kamlet-Taft dipolarity/polarizability (KT-π*) [Ind. Eng. Chem. Res. 2020, 59, 12319–12330] because of the linearity of the homomorphism line between ET and KT-π* for pure nonpolar solvents and pure polar HBA solvents. However, due to specific hydrogen bonding interactions of the phenol blue with polar hydrogen bond donor (HBD) solvents, the ET framework for binary mixtures of nonpolar solvent with polar HBD solvent was the modification by the addition of HBD contribution factor. The HBD contribution factor can be simply estimated by a deviation of an actual ET value of pure HBD solvents from the homomorphism line. To validate the framework, the ET values of seventeen liquid nonpolar-polar mixtures, (ii) three CO2-expanded solvent mixtures and (iii) five scCO2-polar cosolvent mixtures collected from the literature were used. The framework was found to give a reliable ET value with an overall deviation of 0.26% and was also applicable to ET values of Reichardt, Nile red and HxQMBu2 indicators with an overall deviation of 1.73%, 0.36% and 0.40%, respectively. Only four properties of pure components are required for predictions as: (i) gas-phase dipole moment of polar component, (ii) CO2 density, (iii) ET and KT-π* values and (iv) homomorphism relationship between ET and KT-π* values.

A Study of the Reichardt $$E_{{\text{T}}}^{{\text{N}}} \left( {30} \right)$$ Parameter using Solvent Molecular Properties Derived from Computation Chemistry and Consideration of the Kamlet and Taft α Scale of Solvent Hydrogen Bond Donor Acidities

Reichardt’s normalized $$E_{{\text{T}}}^{{\text{N}}} \left( {30} \right)$$ parameter for solvent polarity has been analyzed in terms of properties of solvent molecules estimated from quantum–mechanical calculations of isolated solvent molecules. The analyses show that $$E_{{\text{T}}}^{{\text{N}}} \left( {30} \right)$$ has a strong dependence on the partial charge on the most positive hydrogen atom in the solvent molecule, reflecting hydrogen bonding at the pendant oxygen atom of the betaine dye used to define the ET(30) scale. There are smaller, and roughly equal, dependences on the dipole moments and quadrupolar amplitudes of the solvent molecules and an inverse dependence on the solvent polarizability. These three dependences reflect the solvent polarity, that is, the ability to stabilize charge through longer-range interactions. The reason for the inverse dependence on the solvent polarizability is unclear, but a similar dependence was found previously in the analysis of the Kamlet, Abboud and Taft π* scale. The resulting equation for $$E_{{\text{T}}}^{{\text{N}}} \left( {30} \right)$$ reproduces the experimental values for around 160 solvents, representing most classes of organic solvents, with a standard deviation of around 0.07 { $$E_{{\text{T}}}^{{\text{N}}} \left( {30} \right)$$ values range from 0 to 1}. The Kamlet and Taft α scale of hydrogen bond donor acidities, which is, in effect, derived from the differences between the $$E_{{\text{T}}}^{{\text{N}}} \left( {30} \right)$$ and π* values for a solvent, is discussed. The results of the present analyses of $$E_{{\text{T}}}^{{\text{N}}} \left( {30} \right)$$ and earlier analyses of π* indicate that, while the α values capture the effect of solvent hydrogen bond donor acidity, it also contains residual dependences on other molecular properties. These residual dependences result from the differences in the dependences of the $$E_{{\text{T}}}^{{\text{N}}} \left({30} \right)$$ and π* on solvent properties.

Regio- and Stereoselective Synthesis of 1,2-Dihaloalkenes Using In-Situ-Generated ICl, IBr, BrCl, I2, and Br2

We describe a catalyst-free 1,2-trans-dihalogenation of alkynes with an unprecedented substrate scope and exclusive regio- and stereoselectivity. This versatile dihalogenation system-a combination of NX1S electrophile and alkali metal halide (MX2) in acetic acid-is applicable for diverse categories of alkynes (electron-rich or poor alkynes, internal and terminal alkynes, or heteroatoms such as O-, N-, S-substituted alkynes). The hydrogen bonding donor solvent acetic acid is essential for the in-situ generation of X1X2 electrophile, including ICl, IBr, BrCl, I2, and Br2.