Electron-releasing Substituents Research Articles

Enantiodivergent Synthesis of Bis-Spiropyrrolidines via Sequential Interrupted and Completed (3 + 2) Cycloadditions.

Both (5R)- and (5S)-1,7-diazaspiro[4.4]nonan-6-ones are obtained via a sequence of interrupted and completed stepwise (3 + 2) cycloadditions between azomethine ylides and π-deficient alkenes. The only source of chirality along the whole process is an enantiopure ferrocenyl pyrrolidine catalytic ligand. When the starting imine incorporates two aryl groups or one aryl group with one electron-releasing substituent, the reaction between the azomethine ylide and the alkene stops at the first step, leading to the corresponding Michael adduct. When imines derived from p-methoxybenzaldehyde are used, the corresponding syn-α-amino-γ-nitro ester is obtained with almost complete enantiocontrol. In contrast, imines derived from benzophenone lead to the corresponding anti analogue. From this interrupted (3 + 2) cycloaddition, cis- and trans-α-amino-γ-lactams can be obtained via hydrogenation of the nitro group followed by in situ cyclization. Imines derived from these latter compounds are the precursors of N-metalated azomethine ylides from which up to four new chiral centers can be generated via completed (3 + 2) cycloaddition reactions with full regio- and diastereocontrol. Cis- and trans-γ-lactams lead to opposite bis-spiropyrrolidine enantiomers. Therefore, both enantiomeric series of spiro compounds can be obtained by means of the same catalytic system. The potential of these rigid, densely substituted homochiral compounds in medicinal chemistry is briefly described.

Role of substituents on the reactivity and product selectivity in reactions of naphthalene derivatives catalyzed by the orphan thermostable cytochrome P450, CYP175A1

The thermostable nature of CYP175A1 enzyme is of potential interest for the biocatalysis at ambient temperature or at elevated temperature under environmentally benign conditions. Although little is known about the substrate selectivity of this enzyme, the biocatalytic activities of CYP175A1 on different substituted naphthalenes have been studied in oxidative pathway, and the effect of the substituent on the reaction has been determined. The enzyme first acts as a peroxygenase to convert these substituted naphthalenes to the corresponding naphthols, which subsequently undergo in-situ oxidative dimerization to form dyes of different colors possibly by the peroxidase-type activity of CYP175A1. The product analyses and kinetic measurements suggested that the presence of electron releasing substituent (ERS) in the substrate enhanced the substrate conversion, whereas the presence of electron withdrawing substituent (EWS) in the substrate drastically reduced the substrate conversion. The position of the ERS in the substrate was also found to play an important role in the transformation of the substrate. The results further demonstrate that mutation of the Leu80 residue to Phe enhances the reactivity of the enzyme by favoring the substrate association in the active site. The observed rates of the enzymatic oxygenation reaction of the substituted naphthalenes followed the Hammett correlation of substituent effect, supporting aromatic electrophilic substitution mechanism catalyzed by the cytochrome P450 enzyme.

Photoremoval of Protecting Groups: Mechanistic Aspects of 1,3-Dithiane Conversion to a Carbonyl Group

Photodeprotection of 1,3-dithianes in the presence of thiapyrylium was performed to return to the parent carbonyl compound, and the mechanism was studied by steady state photolysis, laser flash photolysis, and theoretical calculations. Electron transfer from dithianes to triplet sensitizers is extremely fast, and the decay of dithiane radical cations was not affected by the presence of water or oxygen as the consequence of a favorable unimolecular fragmentation pathway. Similar behaviors were observed for dithianes bearing electron-releasing or electron-withdrawing substituents on the aryl moiety, evidenced by C-S bond cleavage to form a distonic radical cation species. The lack of reaction under nitrogen atmosphere, requirement of oxygen for good conversion yields, inhibition of the photodeprotection process by the presence of p-benzoquinone, and absence of a labeled carbonyl final product when the reaction is performed in the presence of H2(18)O all suggest that the superoxide anion drives the deprotection reaction. Density functional theory computational studies on the reactions with water, molecular oxygen, and the superoxide radical anion support the experimental findings.

Comparative measure of the electronic influence of highly substituted aryl isocyanides.

To assess the relative electronic influence of highly substituted aryl isocyanides on transition metal centers, a series of C4v-symmetric Cr(CNR)(CO)5 complexes featuring various alkyl, aryl, and m-terphenyl substituents have been prepared. A correlation between carbonyl-ligand (13)C{(1)H} NMR chemical shift (δCO) and calculated Cotton-Kraihanzel (C-K) force constant (kCO) is presented for these complexes to determine the relative changes in isocyanide σ-donor/π-acid ratio as a function of substituent identity and pattern. For nonfluorinated aryl isocyanides possessing alkyl or aryl substitution, minimal variation in effective σ-donor/π-acid ratio is observed over the series. In addition, aryl isocyanides featuring strongly electron-releasing substituents display an electronic influence that nearly matches that of nonfluorinated alkyl isocyanides. Lower σ-donor/π-acid ratios are displayed by polyfluorinated aryl isocyanide ligands. However, the degree of this attenuation relative to nonfluorinated aryl isocyanides is not substantial and significantly higher σ-donor/π-acid ratios than CO are observed in all cases. Substituent patterns for polyfluorinated aryl isocyanides are identified that give rise to low relative σ-donor/π-acid ratios but offer synthetic convenience for coordination chemistry applications. In order to expand the range of available substitution patterns for comparison, the syntheses of the new m-terphenyl isocyanides CNAr(Tripp2), CNp-MeAr(Mes2), CNp-MeAr(DArF2), and CNp-FAr(DArF2) are also reported (Ar(Tripp2) = 2,6-(2,4,6-(i-Pr)3C6H2)2C6H3); p-MeAr(Mes2) = 2,6-(2,4,6-Me3C6H2)2-4-Me-C6H2); p-MeAr(DArF2) = 2,6-(3,5-(CF3)2C6H3)2-4-Me-C6H2); p-FAr(DArF2) = 2,6-(3,5-(CF3)2C6H3)2-4-F-C6H2).

Free radical generation from an aniline derivative in HepG2 cells: A possible captodative effect

Xenobiotic metabolism can induce the generation of protein radicals, which are believed to play an important role in the toxicity of chemicals and drugs. It is therefore important to identify chemical structures capable of inducing macromolecular free radical formation in living cells. In this study, we evaluated the ability of four structurally related environmental chemicals, aniline, nitrosobenzene, N,N-dimethylaniline, and N,N-dimethyl-4-nitrosoaniline (DMNA), to induce free radicals and cellular damage in the hepatoma cell line HepG2. Cytotoxicity was assessed using lactate dehydrogenase assays, and morphological changes were observed using phase contrast microscopy. Protein free radicals were detected by immuno-spin trapping using in-cell western experiments and confocal microscopy to determine the subcellular locale of free radical generation. DMNA induced free radical generation, lactate dehydrogenase release, and morphological changes in HepG2 cells, whereas aniline, nitrosobenzene, N,N-dimethylaniline did not. Confocal microscopy showed that DMNA induced free radical generation mainly in the cytosol. Preincubation of HepG2 cells with N-acetylcysteine and 2,2′-dipyridyl significantly prevented free radical generation on subsequent incubation with DMNA, whereas preincubation with apocynin and dimethyl sulfoxide had no effect. These results suggest that DMNA is metabolized to reactive free radicals capable of generating protein radicals which may play a critical role in DMNA toxicity. We propose that the captodative effect, the combined action of the electron-releasing dimethylamine substituent, and the electron-withdrawing nitroso substituent, leads to a thermodynamically stabilized radical, facilitating enhanced protein radical formation by DMNA.

Ruthenium(III) Catalysis in Perborate Oxidation of 5-Oxoacids

Ruthenium(III) catalyzes perborate oxidation of substituted 5-oxoacids in acidic solution. The catalyzed oxidation is first order with respect to the oxidant and catalyst. The rate of ruthenium(III) catalyzed oxidation displays the Michaelis-Menten kinetics on the reductant and is independent of [H+] of the medium. Hydrogen peroxide is the reactive species of perborate and the kinetic results reveal formation of ruthenium(III) peroxo species-5-oxoacid complex. Electron-releasing substituents accelerate the reaction rate and electron-withdrawing substituents retard it. The order of reactivity among the studied 5-oxoacids is p-methoxy ≫ p-methyl > p-phenyl > −H > p-chloro > p-bromo > m-nitro. Activation parameters are evaluated using Arrhenius and Eyring’s plots. A mechanism consistent with the observed kinetic data is proposed and discussed. A suitable rate law is derived based on the mechanism.

ChemInform Abstract: Highly Regioselective Diels—Alder Reaction of 9‐Substituted Anthracenes with Citraconic Anhydride.

The regioselectivity in the Diels–Alder reaction of 9-substituted anthracenes having electron-releasing substituents with citraconic anhydride has been investigated. The ortho regioisomer is preferred in all the cases with good yield. The reaction proceeded best under conventional heating conditions in toluene.

Computational Modeling of Degradation of Substituted Benzyltrimethyl Ammonium

Interest in alkaline fuel cells has been renewed in recent years with the development of the alkaline membrane fuel cells (AMFCs). Inside AMFCs, an anion exchange membrane (AEM) allows hydroxide (OH-) to transport across the membrane between the electrodes and prevents carbonates from forming precipitation. However, AEMs can degrade over time due to the reactions between OH- and the cations attached to the polymer backbone of the membrane, which remains as a challenge for many potential applications of AMFCs.Benzyltrimethyl ammonium (BTMA+) is the most commonly used cation in AEMs and has been investigated extensively for its application in AMFC. Our experimental measurements had shown that unsubstituted BTMA+ cation degrades ~10% within 29 days in 5M NaOH at 80°C.1 Two major OH- degradation pathways for BTMA+ are benzyl SN2 pathway and methyl SN2 pathway2,3 and their transition state (TS) barriers (ΔG≠) are 23.3 kcal/mol and 25.1 kcal/mol respectively at 160°C and 1 atm.4 Thus, the benzyl SN2 pathway is the dominant degradation pathway for BTMA+. In search for BTMA derivative cations with higher degradation barriers, in this research, we modeled the BTMA+ with different substituent groups at different positions (Fig 1) and calculated their ΔΔG≠ values compared with unsubstituted BTMA+ using the density functional theory (DFT) method as reported in our previous paper.4 Based on our calculations results, for every cation, its ΔG≠ of methyl SN2 reaction is higher than its benzyl ΔG≠, and thus, the benzyl SN2 reaction is always the dominant degradation pathway. For the benzyl SN2 reaction (Fig 2), the largest ΔΔG≠ is 1.6 kcal/mol from the double-meta substituted −NH2 and −N(CH3)2, and the ΔΔG≠ values for all −NO2 substitutions are less than 0. All of the benzyl SN2 ΔG≠ values for the double-meta substitutions with electron-releasing substituents are larger than the unsubstituted BTMA+, indicating that this type of substitutions is a promising candidate for cations with higher stability. Encouraged by the large benzyl SN2 ΔΔG≠ values of double-meta −NH2 and −N(CH3)2, we further investigated substituents in –NRR’ form at double-meta positions. We studied four substituents: −NH(CH2CH2CH2CH3), −NH(CH3), −N(CH2CH3)2, and −N(CH2CH2CH3)2. However, none of them results in a higher benzyl SN2 ΔΔG≠.Besides the benzyl and methyl SN2 pathways, BTMA+ may also take the benzyl SN1 pathway. For the double-meta −N(CH3)2 substitution, the benzyl SN1 ΔG≠ is 27.7 kcal/mol, still larger than its benzyl SN2 ΔG≠ (24.9 kcal/mol). The para- −N(CH3)2 has a benzyl SN1 ΔG≠ as small as 11.3 kcal/mol, much smaller than its benzyl SN2 ΔG≠, 22.0 kcal/mol and the benzyl SN1 pathway becomes the dominant degradation pathway. Therefore, in search for the BTMA+ derivative cations with high stability, meta- substitutions with electron releasing substituents are preferred, not only because meta- substitutions have larger benzyl SN2 ΔG≠, but also because ortho- and para- substitutions may have very small benzyl SN1 ΔG≠.Based on our calculation results, the cations with the largest improvement found in this research only resulted in a ΔΔG≠ of 1.6 kcal/mol at 160°C and 1.5 kcal/mol at 80°C. A ΔΔG≠ of 1.5 kcal/mol will result in a decrease in degradation rate of 8.5 times. While potentially meaningful for some applications, this increase is not as large as would be desired and not experimentally validated. Overall, our calculation results suggest that the improvement of the BTMA+ stability by adding substituent groups on the benzyl ring is relatively limited.

Vanadium(V) catalysis of perborate oxidation of substituted 5-oxo acids: a kinetic and mechanistic study

Vanadium (V) catalyzes perborate oxidation of substituted 5-oxo acid in acidic solution, being 1.6 order with respect to the oxidant, first order in the catalyst, inhibited by H+ and displays Michaelis–Menten kinetics on the reductant. In aqueous acetic acid solution, perborate generates hydrogen peroxide and the kinetic results reveal formation of oxodiperoxovanadium(V)-oxo acid complex. At high acidity, the ionic strength of the medium has little influence on the oxidation rates. But at low acidity, the rate increases with increasing ionic strength. The rate of oxidation increases with decreasing dielectric constant of the medium. Electron-releasing substituents in the aromatic ring accelerate the reaction rate and electron-withdrawing substituents retard the reaction. The order of reactivity among the studied 5-oxo acid is p-methoxy >> p-methyl > p-phenyl > -H > p-chloro > p-bromo > m-nitro. Activation parameters have been evaluated using Arrhenius and Eyring’s plots. A mechanism consistent with the observed kinetic data has been proposed and discussed. A suitable rate law has been derived based on the mechanism.

ChemInform Abstract: General and Practical Carboxyl‐Group‐Directed Remote C—H Oxygenation Reactions of Arenes.

ChemInform Abstract: General and Practical Carboxyl‐Group‐Directed Remote C—H Oxygenation Reactions of Arenes.

Highly Regioselective Diels–Alder Reaction of 9-Substituted Anthracenes with Citraconic Anhydride

The regioselectivity in the Diels–Alder reaction of 9-substituted anthracenes having electron-releasing substituents with citraconic anhydride has been investigated. The <i>ortho </i>regioisomer is preferred in all the cases with good yield. The reaction proceeded best under conventional heating conditions in toluene.

Computational Studies of 1,3-Dipolar [3 + 2]-Cycloaddition Reactions of Fullerene-C60 with Nitrones

Solubility of fullerene-C60 improves with functionalization. 1,3-dipolar [3+2]-cycloaddition reactions of fullerene-C60 with substituted nitrones, a versatile method for fullerene functionalization, were investigated at the MO6/6-31G*//PM3 level of theory to elucidate the effect of electron-releasing (-CH3, -CH2CH3, -CH2CH2CH3, C6H5CH2) substituents and electronwithdrawing substituents (-F, -Cl, -Br, -NC, and -NO2) on the energetics of the reaction; the regio- and stereo-selectivity of the mono- and bis-addition of nitrones; and global reactivity descriptors of the molecular systems to rationalize and predict their chemical reactivity and site selectivity. The results show that electron-withdrawing groups on the nitrones increase the activation barrier of the reaction whereas electron-donating groups decrease the activation barriers. However, electron-withdrawing groups on the nitrones result in more stable products compared to the electron-donating groups. It was found that the reactions with electron-donating substituents on the nitrone are normal electron demand reactions, with C60 as the dipolarophile and the substituted nitrones as the dipoles while the reactions with electron-withdrawing substituents on the nitrones are inverse electron demand reactions. The chemical hardness values show greater positive values for adducts with electron-withdrawing substituents on the nitrone and smaller negative values for adducts with electron-donating substituents on the nitrone, confirming the trend that larger activation barriers accompany reactions with electron-withdrawing substituents on the nitrone while electron-donating substituents lower activation barriers. The activation barriers of the second nitrone addition (bisadduct formation) were found to be lower than the barriers for the first nitrone addition (monoadduct formation). Stereo-chemically, syn-bisaddition was found to be thermodynamically and kinetically stable favoured over anti-bisaddition. Electron donating and electron-withdrawing substituents have a marked effect on the energetics of the reaction.

An efficient regioselective bromination protocol of activated coumarins using 2,4,4,6-tetrabromo-2,5-cyclohexadienone

2,4,4,6-Tetrabromo-2,5-cyclohexadienone mediated bromination of a wide assortment of activated coumarins in acetonitrile has been accomplished with high regioselectivity and good to excellent yields. The selectivity and efficiency of bromination were found to be markedly dependent on electronic factors, particularly degree of electron withdrawal from electron-releasing 7-oxygenated substituents to the C-3 position of the α-pyrone moiety by vinylogous resonance and the presence of nucleophilic additives such as water and tetra-n-butylammonium bromide in the reaction medium. The sole by-product of the reaction was converted back to the reagent by oxidation with KBr−KBrO3, which was recycled three times without significant loss of efficiency.

Mefloquine–Oxazolidine Derivatives: A New Class of Anticancer Agents

A series of 23 racemic mefloquine-oxazolidine derivatives, 4-[3-(aryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinolines, derived from (R*, S*)-(±)-mefloquine and arenealdehydes, have been evaluated for their activity against four cancer cell lines (HCT-8, OVCAR-8, HL-60, and SF-295). Good cytotoxicities have been determined with IC50 values ranging from 0.59 to 4.79μg/mL. In general compounds with aryl groups having strong electron-releasing substituents, such as HO and MeO, or electron-rich heteroaryl groups, for example imidazol-2-y-l, are active. However, other factors such as steric effects may play a role. As both the active and non-active conformations of the mefloquine-oxazolidine derivatives are similar, it is concluded that molecular conformations do not play a significant role either. This study is the first to evaluate mefloquine derivatives as antitumor agents. The mefloquine-oxazolidine derivatives are considered to be useful leads for the rational design of new antitumor agents.

Theoretical studies on the reactivity of mono-substituted imidazole ligands

The global and local quantum chemical reactivity descriptors of a series of imidazole derivatives substituted at 2, 4, and 5 positions with different groups including electron-donating and electron-withdrawing substituents have been calculated using the B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) methods. The substituents have been selected to cover a wide range of electronic effects. Considering the calculated Fukui functions, both imidazole derivatives and their anions are found to be suitable nucleophilic sites in the gas phase. For the most substituents it was observed that the calculated Fukui function \(f_{\text{k}}^{ - }\) values at the N-site are small in case of electron-releasing substituents indicating a preferred N-site for hard reaction. In contrast, large \(f_{\text{k}}^{ - }\) values in case of electron-attracting groups indicate a preferred N-site for soft reaction. These two local descriptors predicted the reactivity of the electron-rich imidazole sequence to be 2-substituted imidazoles > 5-substituted imidazoles > 4-substituted imidazole where reactivity toward electrophilic attack at a pyridine nitrogen atom is enhanced by electron donor substituents elsewhere in the molecule, due to resonance effect.

Impacts of medium, substituents, and specific interactions with water on hydration of carbonyl compounds

Theoretical study on hydration of carbonyl compounds has been done at B3LYP/6-31++G** and MP2/6-31++G** levels. The variations in ΔGhyd and hydration constants are explored in terms of medium effect, substituent effect, and hydrogen bonding abilities of carbonyl compounds and their hydrated products. The dielectric of medium decreases the ΔGhyd values thereby favoring the process. The presence of electron-releasing substituents at the carbonyl carbon disfavors the hydration process, while that of electron-withdrawing substituents favor the process. Hydrogen bonding interactions stabilize the product to a larger extent than the carbonyl molecules, thereby favoring the hydration process. Linear correlation between the calculated log Khyd values and the experimental values is seen in case of specific interactions with water (R = 0.976) than in the case without those interactions (R = 0.955).

The Properties and the Use of Substituted Benzofuroxans in Pharmaceutical and Medicinal Chemistry: A Comprehensive Review

Since the synthesis of 4,6-dinitrobenzofuroxan in 1899 by Drost, benzofuroxans have attracted particular attention. This peculiar series of compounds exhibit a broad spectrum of biological activity including antibacterial, antifungal, antileukemic, acaricide and immunodepressive properties. These works embrace a period of more than 50 years since the pioneering paper of Gosh and Whitehouse and papers in this major field of the heterocyclic chemistry are still published in 2013. The review has been built in two independent parts. The first one is directly dedicated to the structure of substituted benzofuroxans and will show many medicinal applications of these compounds such as nitric oxide-releasing abilities, induction of oxidative stress, potent anti-cancer agents, anti-chagas agent, target for antiamoebic agent, Ca2+ channel blockers or cytotoxic, mutagenic and genotoxic agent… The second part of this review will be in close connection with the use of benzofuroxans as synthetic precursors in the preparation of new biological compounds such as quinoxaline dioxide, benzimidazole and phenazine derivatives. The interaction of substituted benzofuroxans with electron rich heterocycles or carbanions is the key step in the synthesis of these new biological active compounds. These derivatives can be used as cytotoxic drugs, antimycobacterial agent and display anti-malarial, antileishmanial and antituberculosis activity. The nature of the substituent linked to the carbocyclic ring of benzofuroxan is of primary importance to understand the medicinal properties of this family of compounds. For example, when benzofuroxans are substituted by electron-releasing substituents, the chemical reactivity is transferred from the carbocyclic ring to the furoxan ring.

Synthesis of Quinoline Dicarboxylic Esters as Biocompatible Fluorescent Tags

A series of dicarboxylic quinoline derivatives bearing electron-releasing or -withdrawing substituents have been synthesized using mono- or/and biphasic methodologies. By controlling the regioselectivity of addition into our electrophilic intermediate, we also characterized by which mechanism the Doebner-Miller cyclization step occurred. As anticipated, electron-releasing substituents induce a red shift of the low-energy absorption allowing excitation in the visible region. In addition, by playing on the strength and position of the electron-releasing substituents, chromophore having interesting fluorescent properties such as large Stoke shifts, good fluorescent quantum yields, emission in the visible green-yellow region and reasonable two-photon absorption in the NIR region have been obtained. These small-size fluorophores, which can be made water-soluble and have been shown to be non-toxic, can be hetero- and/or polyfunctionalized and thus represent promising key units for fluorescence-based physiological experiments with low background interactions.

Theoretical descriptors response to the calculations of the relative pKa values of some boronic acids in aqueous solution: A DFT study

With the specific target of calculating the pKa values of boronic acids (RB(OH)2) in aqueous solution we inquired the solute–solvent interactions of these acids and their corresponding conjugate base. Relative pKa values were computed for each boronic acid using methylboronic acid (CH3B(OH)2) as a reference. All gas phase computations were performed at (MP2/6-311++G(d,p)//B3LYP/6-31+G(d)) level of theory. Solvation was included in the calculations using the polarized continuum model (PCM) at the HF/6-31G(d,p) level. The geometry optimization of studied structures was performed with DFT computation and the optimized structures were used to carry out Natural Bond Orbital (NBO) analysis. Natural Bond Orbital (NBO) analysis was examined as indicator for the variations observed in the calculated pKa. Natural resonance theory (NRT) was used to calculate the natural bond order and predict bond polarity. The NRT results indicate that the O–H bonds in all studied compounds have an electrovalency character. The results revealed that difference in acid strength is more relevant to the type of substituent. The electron withdrawing substituent will increase the acidic strength. However, the electron releasing substituent will have a reverse effect and decrease the acidic strength. There are good agreement between theoretical values and experimental results for this series of compounds, the average error was found to be less than 1.2 pKa unit.

In silico studies toward the recognition of fluoride ion by substituted borazines

The substituted borazines have been computationally investigated as new type of receptors for the recognition of fluoride ion. Fluorine, methyl and phenyl groups have been selected as electron-withdrawing, electron-releasing and aromatic substituents for the study employing DFT (B3LYP/6-311+G**) and ab initio (MP2/6-311+G**) levels of calculations. N-substituted borazines have shown higher fluoride ion affinity than their corresponding B-substituted borazines. In the case of fluorinated borazines, the binding affinity of fluoride is enhanced with the increasing number of substitutions. The F− and Cl− ions, generally, prefer to bind with the boron atom of substituted borazine rings, whereas, Br− ion prefers to bind with NH hydrogens of the borazine receptor units. Phenyl derivatives of borazine also showed analogous behavior with halide anions. The binding affinities of halides with fluorinated and phenyl derivatives of borazine have been found to be much higher than the simple borazine receptor molecule. The NBO analyses performed for the complexation of F− ion with fluorinated borazines suggest that the Lewis energy contribution in the total SCF energy enhanced with increasing the substitutions. However, in the case of methylated borazines, the delocalization energy is responsible for the stabilization of F− ion complexes. The N-trifluoroborazine showed much higher fluoride ion affinity (30.9kcal/mol) in aqueous phase than the simple borazine.