Dialkylamino Substituents Research Articles

A Physical Organic Chemistry Approach to Developing Cyclopropenium-Based Energy Storage Materials for Redox Flow Batteries

ConspectusRedox flow batteries (RFBs) represent a promising modality for electrical energy storage. In these systems, energy is stored via paired redox reactions of molecules on opposite sides of an electrochemical cell. Thus, a central objective for the field is to design molecules with the optimal combination of properties to serve as energy storage materials in RFBs. The ideal molecules should undergo reversible redox reactions at relatively high potentials (for the molecule that is oxidized during battery charging, called the catholyte) or low potentials (for the species that is reduced during battery charging, called the anolyte). Furthermore, anolytes and catholytes must be highly soluble in the electrolyte solution and stable to extended electrochemical cycling in all battery-relevant redox states. The ideal candidates would undergo more than one reversible electron transfer event. Finally, the optimal structures should be resistant to crossover through a selective separator in order to maintain isolation of the two sides of the cell. This Account describes our design and optimization of organic molecules for this application. We first provide background for the metrics and experiments used to characterize anolytes/catholytes and to progress them toward deployment in flow batteries. We then use our studies of aminocyclopropenium-based catholytes to illustrate this workflow and approach.We identified tris(dimethylamino) cyclopropenium hexafluorophosphate as a first-generation catholyte for nonaqueous RFBs based on literature reports from the 1970s describing its reversible chemical and electrochemical oxidation. Cyclic voltammetry and electrochemical cycling experiments in acetonitrile/LiPF6 confirmed that this molecule undergoes oxidation at relatively high potential (0.86 V versus ferrocene/ferrocenium) and exhibits moderate stability toward charge-discharge cycling. Replacing the methyl groups with isopropyl substituents led to enhanced cycling stability but poor solubility of the radical dication (<0.1 M in acetonitrile). Solubility was optimized using quantitative structure-property relationship modeling, which predicted derivatives with ≥10-fold enhanced solubility. Cyclopropeniums with 300-500 mV higher redox potentials were identified by replacing one of the dialkylamino substituents with a less electron-donating thioalkyl or aryl group. Multielectron catholytes were developed by creating hybrid structures that contain a di(amino) cyclopropenium conjugated with a phenothiazine moeity. Finally, oligomeric tris(amino) cyclopropeniums were designed as crossover resistant catholytes. Optimization of their solubility enabled the deployment of these oligomers in high concentration asymmetric redox flow batteries with energy densities that are comparable to the state-of-the-art commercial aqueous inorganic systems.

Strongly emitting, centrosymmetric, ladder-type bis-coumarins with crankshaft architecture.

Quadrupolar bis-coumarins bearing dialkylamino groups, prepared by a double Pechmann reaction and subsequent oxidation, strongly emit yellow-orange light. Comparison with non-substituted analogs reveals that, the photophysical properties of the conjugated bis-coumarins are controlled both by the dialkylamino substituents and by the π-system. Analogous but non-conjugated bis-coumarins emit blue light both in solution and in crystalline state. Unusually fast oxidation process in the crystalline state is responsible for the presence of two bands in their solid-state emission. Two-center, charge-transfer transition from an orbital delocalized on the entire molecule to the central benzene ring is responsible for photophysical properties.

Synthesis and Fluorescence Mechanism of the Aminoimidazolone Analogues of the Green Fluorescent Protein: Towards Advanced Dyes with Enhanced Stokes Shift, Quantum Yield and Two‐Photon Absorption

AbstractNovel small‐molecular analogues the green fluorescence protein (GFP) chromophore were synthesised to expand and improve this fluorophore family and to deepen the understanding of their fluorescence mechanism. The introduction of an aminophenyl substituent and the repositioning of the hydroxyl group, to enable strong intramolecular hydrogen bonding, not only enhanced fluorescence emission but also resulted in an increased Stokes shift and a considerable redshift. Experimental and computational results described dual fluorescence involving both excited‐state intramolecular proton transfer and internal charge transfer (ESIPT‐ICT) mechanisms. Screening of the pH and the solvent medium revealed a complicated equilibrium involving hydrogen bonding, protonation and deprotonation that influences the absorption and emission spectra. Further improvement of the photophysical properties via the systematic variation of dialkylamino substituents at a single position of the chromophore led to a two‐orders of magnitude enhancement in the quantum yields. In addition, the novel compounds also have significant two‐photon absorption, which widens the possibilities for applications in the field of bioimaging.

Research on the controllable degradation of N-methylamido and dialkylamino substituted at the 5th position of the benzene ring in chlorsulfuron in acidic soil.

Owing to the lengthy residual problems associated with chlorsulfuron, metsulfuron-methyl, and ethametsulfuron, which prevents them from being used in the “annual multi-crop planting system”, the application of these sulfonylurea herbicides (SU) has regrettably been terminated in China since 2014. In this field, we were the first to discover that the 5th position of the benzene ring in chlorsulfuron is a key point for influencing its degradation rate and the amino moiety at this position showed faster degradation rates and maintained their original potent bioactivity. In this study, we further elaborated on N-methylamido and dialkylamino substituents at the same position in chlorsulfuron to obtain 18 novel structures as M and N series. Their half-life degradation (DT50) values were faster, to varying degrees, than chlorsulfuron in acidic soil. It was found that most of the titled structures also retained their potent herbicidal activity and the crop safety of the M series towards corn greatly increased. Based on these data, a comprehensive graph describing the structure/degradation relationship was established first. Relating to the new molecules, their herbicidal activity (A), degradation rates (D), and crop safety (S) relationship were correlated and we used this approach to predict and explore the most preferable molecule, which coincided to the corresponding experimental data. The new concept of controllable degradation will provide us with more insight when searching for new ecological bioactive molecules in the future.

N-Arylphenothiazines as strong donors for photoredox catalysis - pushing the frontiers of nucleophilic addition of alcohols to alkenes.

A new range of N-phenylphenothiazine derivatives was synthesized as potential photoredox catalysts to broaden the substrate scope for the nucleophilic addition of methanol to styrenes through photoredox catalysis. These N-phenylphenothiazines differ by their electron-donating and electron-withdrawing substituents at the phenyl group, covering both, σ and π-type groups, in order to modulate their absorbance and electrochemical characteristics. Among the synthesized compounds, alkylaminylated N-phenylphenothiazines were identified to be highly suitable for photoredox catalysis. The dialkylamino substituents of these N-phenylphenothiazines shift the estimated excited state reduction potential up to −3.0 V (vs SCE). These highly reducing properties allow the addition of methanol to α-methylstyrene as less-activated substrate for this type of reaction. Without the help of an additive, the reaction conditions were optimized to achieve a quantitative yield for the Markovnivkov-type addition product after 20 h of irradiation.

Novel fluconazole derivatives with promising antifungal activity

The fungistatic nature and toxicity concern associated with the azole drugs currently on the market have resulted in an increased demand for new azole antifungal agents for which these problematic characteristics do not exist. The extensive use of azoles has resulted in fungal strains capable of resisting the action of these drugs. Herein, we report the synthesis and antifungal activity of novel fluconazole (FLC) analogues with alkyl-, aryl-, cycloalkyl-, and dialkyl-amino substituents. We evaluated their antifungal activity by MIC determination and time-kill assay as well as their safety profile by hemolytic activity against murine erythrocytes as well as cytotoxicity against mammalian cells. The best compounds from our study exhibited broad-spectrum activity against most of the fungal strains tested, with excellent MIC values against a number of clinical isolates. The most promising compounds were found to be less hemolytic than the least hemolytic FDA-approved azole antifungal agent voriconazole (VOR). Finally, we demonstrated that the synthetic alkyl-amino FLC analogues displayed chain-dependent fungal membrane disruption as well as inhibition of ergosterol biosynthesis as possible mechanisms of action.

Aziridinyl Fluorophores Demonstrate Bright Fluorescence and Superior Photostability by Effectively Inhibiting Twisted Intramolecular Charge Transfer.

Replacing conventional dialkylamino substituents with a three-membered aziridine ring in naphthalimide leads to significantly enhanced brightness and photostability by effectively suppressing twisted intramolecular charge transfer formation. This replacement is generalizable in other chemical families of fluorophores, such as coumarin, phthalimide, and nitrobenzoxadiazole dyes. In highly polar fluorophores, we show that aziridinyl dyes even outperform their azetidinyl analogues in aqueous solution. We also proposed one simple mechanism that can explain the vulnerability of quantum yield to hydrogen bond interactions in protonic solvents in various fluorophore families. Such knowledge is a critical step toward developing high-performance fluorophores for advanced fluorescence imaging.

Synthesis and photophysical properties of fluorescent arylstyrylimidazo[1,2-a]pyridine-based donor-acceptor chromophores

A series of novel fluorescent arylstyrylimidazo[1,2-a]pyridines was synthesized and fully characterized. All styryl derivatives have an E-configuration of the vinyl double bond as unequivocally shown by 1H NMR spectroscopy. It was observed that the E isomers are stable in the solid state; however, the derivatives with strong electron donating dialkylamino substituents underwent partial E-Z isomerization in solution at room temperature. The styryl derivatives absorb in the UV or visible region and emit light with moderate Stokes shifts. These compounds exhibit fluorosolvatochromism, namely the emission band is red shifted with increasing solvent polarity. Moreover, the absorption and emission properties of the styryl derivatives change drastically upon acidification, as the protonation of the nitrogen atoms of the imidazo[1,2-a]pyridine ring increases the donor-acceptor interplay of the π system.

Magnesium Azaphthalocyanines: An Emerging Family of Excellent Red-Emitting Fluorophores

Magnesium(II), zinc(II), and metal-free phthalocyanines (Pcs) and azaphthalocyanines (AzaPcs) containing alkylsulfanyl, aryloxy, and dialkylamino peripheral substituents have been synthesized. The complexation of magnesium(II) by metal-free Pcs and AzaPcs has been studied in detail to determine the optimal reaction conditions necessary to ensure a complete conversion. Photophysical and photochemical measurements in tetrahydrofuran showed that magnesium(II) AzaPcs with aryloxy and alkylsulfanyl substituents have excellent fluorescent properties (Φ(F) up to 0.73) and that the corresponding zinc(II) Pcs are efficient singlet oxygen producers (Φ(Δ) up to 0.68). The presence of dialkylamino substituents causes intramolecular charge transfer within the molecule that competes with fluorescence and singlet oxygen formation. Alkylsulfanyl MgAzaPc and ZnAzaPc were the most photostable compounds among the series of studied derivatives. In addition, high molar absorption coefficients (ε ∼ 300,000 M(-1) cm(-1)), absorption (λ(max) ∼ 650 nm), and emission (λ(em) ∼ 660 nm, high Φ(F)) in the red region suggest that these molecules are potential fluorescent probes that are superior to the commercial red cyanine dye Cy5. MgAzaPc, when incorporated into lipidic bilayers of liposomes, maintains excellent fluorescence properties (Φ(F) = 0.64). Water-soluble MgAzaPc with quaternary ammonium peripheral substituents retained a high fluorescence quantum yield even in water (Φ(F) = 0.25). The described properties show that magnesium(II) AzaPcs are excellent red-emitting fluorophores with potential applications as fluorescent probes in sensing or in vitro imaging applications.

Effect of intramolecular charge transfer on fluorescence and singlet oxygen production of phthalocyanine analogues

Intramolecular charge transfer (ICT) was studied on a series of magnesium, metal-free and zinc complexes of unsymmetrical tetrapyrazinoporphyrazines and tribenzopyrazinoporphyrazines bearing two dialkylamino substituents (donors) and six alkylsulfanyl or aryloxy substituents (non-donors). The dialkylamino substituents were responsible for ICT that deactivated excited states and led to considerable decrease of fluorescence and singlet oxygen quantum yields. Photophysical and photochemical properties were compared to corresponding macrocycles that do not bear any donor centers. The data showed high feasibility of ICT in the tetrapyrazinoporphyrazine macrocycle and significantly lower efficiency of this deactivation process in the tribenzopyrazinoporphyrazine type molecules. Considerable effect of non-donor peripheral substituents on ICT was also described. The results imply that tetrapyrazinoporphyrazines may be more suitable for development of new molecules investigated in applications based on ICT.

Photoactive azoimine dyes: 4-(2-Pyridylazo)- N, N-diethylaniline and 4-(2-pyridylazo)- N, N-dimethylaniline: Computational and experimental investigation

4-(2-Pyridylazo)- N, N-dimethylaniline and 4-(2-pyridylazo)- N, N-diethylaniline, two photoactive azoimine dyes, were prepared from the reaction of 2-aminopyridine with N, N-dialkyl-1,4-nitrosoaniline at room temperature. Structural characterizations of these dyes using single crystal X-ray diffraction, 1H NMR, elemental analysis, mass spectroscopy and IR spectroscopy have been carried out. The X-ray structure indicates a trans configuration around the azo group. The photochemical behavior of these compounds differs from that of 2-phenylazopyridine, the non-dialkylamino substituent compound. The synthesized compounds show emission spectra at room temperature while 2-phenylazopyridine does not. The excitation spectra of these compounds differ from their absorption spectra which can be explained on the basis of the trans to cis photoisomerization which is supported by the TD-PBE0/6-31G(d,p) calculations. Both oxidation of the dialkylamino substituents (–NR 2; R = –CH 3 and –C 2H 5) and reduction of –N N–/–N N– − and –N N– −/–N N– 2− were observed in the cyclic voltammogram indicating a π-acidity of both dyes.

The ‘t‐Amino Effect’ of ortho‐Nitroso Amines. Synthesis of 2,6‐Diaminoadenine Derivatives from 6‐(Dialkylamino)‐5‐nitrosopyrimidines

AbstractThe ‘t‐amino effect’ of amino‐nitroso compounds was documented by preparing the (dialkylamino)‐nitroso pyrimidines 4–18, and cyclising them under thermal conditions in high yields to the purine derivatives 19–32. The reactivity of the amino‐nitroso‐pyrimidines, particularly of 17 derived from diethyl iminodiacetate, and of 19, derived from 1‐phenylimidazolidine, correlates with the stability of the intermediate azomethine ylide. Thermolysis of the amino‐nitroso‐pyrimidines 34–37, possessing dialkylamino substituents at C(4) and C(6), proceeded by protiodenitrosation, leading to 38–41.

Orthoamide, LXIX [1]. Beiträge zur Synthese N,N,N´,N´,N´´-peralkylierter Guanidine und N,N,N´,N´,N´´䞲,N´´-persubstituierter Guanidiniumsalze / Orthoamides, LXIX [1]. Contributions to the Synthesis of N, N, N´, N´, N´-peralkylated Guanidines and N, N, N´, N´, N´´, N´´-persubstituted Guanidinium Salts

N, N, N´, N´-Tetraalkyl-chloroformamidinium chlorides 6 are prepared from N, N, N´, N´-tetraalkylureas 5 and phosgene in acetonitrile. The iminium salts 6 react with primary and secondary amines in the presence of triethylamine to give N, N, N´, N´, N´´-pentasubstituted and N, N, N´, N´, N´´, N´´- hexasubstituted guanidinium salts 7 and 8, respectively, Treatment of the guanidinium salts 7 with sodium hydroxide in excess affords the N, N, N´N´, N´´-pentasubstituted guanidines 9a - 9aa. Additionally, the N, N, N´, N´, N´´-pentasubstituted and N, N, N´, N´, N´´, N´´-hexasubstituted guanidinium salts 7l´, 7p´ and 8a - c can be obtained from the reaction mixtures by addition of stoichiometric amounts of sodium hydroxide. A modified method is described for the preparation of guanidinium salts possessing dialkylamino substituents consisting of two long-chain alkyl groups (&gt;C14). Some guanidines 9 were alkylated with allyl chloride and bromide, ethyl bromide, butyl bromide, benzyl bromide and chloride, dimethyl sulfate, diethyl sulfate, and methyl methansulfonate to give the corresponding guanidinium salts 11 - 15. By alkylation of the N, N, N´, N´, N´´-pentasubstituted guanidine 9v with triethyloxonium tetrafluoroborate the guandinium tetrafluoroborate 16a is accessible. N-Functionalized guanidinium salts 17 - 18a - c result from the reaction of N, N, N´, N´, N´´-pentasubstituted guanidines with ethyl bromoacetate and bromoacetonitrile, respectively, and subsequent anion exchange with sodium tetraphenylborate. N, N, N´, N´-Tetramethylguanidine (21) adds to ethyl acrylate to give the labile guanidine 22, which forms the guanidinium salt 23a on treatment with methyl iodide. Zwitterionic guanidinium salts 25 result, when N, N, N´, N´, N´´-pentasubstituted guanidines are treated with sultones 24.

Establishing the Chelating α‐Azocarbonyl Function in π‐Acceptor Ligands

Strong acceptor, weak coordination: The heterodinuclear complex ion [LCu(dppf)]+ (see formula) contains the as yet unrecognized strong π-acceptor system NNCO, which is involved in a charge-transfer interaction with the copper center but is not reduced through full electron transfer. This situation is likely caused by steric hindrance and the donor function of the dialkylamino substituents on the CO carbon atom.

Amino Alcohols in Organocatalysed Acylation and Deacylation: The Effect of Dialkylamino Substituents on the Rate

AbstractIn alcohols and esters, a neighbouring dialkylamino group can enhance the reactivity towards acylation and deacylation, respectively, that is, such amino alcohols can act as transacylation catalysts like DMAP. This effect is dependent on the number of (carbon) spacer atoms, flexibility of the molecule and the presence and position of further heteroatoms. Based on this effect, the site selective acylation and deacylation of desmycosin, a macrocycle antibiotic possessing an amino sugar moiety, is described.

Small boranes, carboranes, and heterocarboranes

Abstract Dehalogenation of 1,2-dichloro-diborane(4) derivatives with Na/K alloy does not lead to planar cyclo-tetraboranes but to the blue puckered diisopropylamino compound and to the yellow 2,2,6,6-tetramethylpiperidino-tetraboratetrahedrane derivative, respectively. With smaller dialkylamino substituents, the formation of orange-red cyclo-hexaborane (BNMe2)6 and the green closo -hexaborane (BNEt2)6 is observed. When a 1:1 mixture of Me2NBCl2 and [Me2N(Cl)B]2 is dehalogenated, a small amount of colorless crystals of the planar diamond-shaped tetrabora-bicyclo-butane [(Me2N)2BB -BNMe2]2 is obtained. Its MO analysis reveals that eight framework electrons are used to form two 3c,2e sigma bonds, one 4c,2e pi bond, and one 4c,2e sigma bond along the edges. A new approach to reactive closo-dicarbapentaboranes involves the hydroboration of dichloroboryl-tbutylacetylene with HBCl2 leading to Me3CCH2C(BCl2)3. On heating, it is transformed into the closo-dicarbapentaborane (Me3CCH2C)2(BCl)3, in which the chlorine atoms may be substituted to give new derivatives. By reacting B2Cl4 with C5Me5-SiMe3 the nido-1-borane-2,3,4,5,6-pentacarbahexa- borane(6)is stabilized by the Lewis acid BCl3 to give (MeC)5B-BCl3. Hydroboration of 3,4-bis(isopropylidene)-1,3-diborolanes leads to the formation of nido-2,3,5-tricarbahexaboranes(7),which may be deprotonated to give the corresponding anions isolobal with C5H5 -. Heterotricarbahexaboranes are obtained when a 3,4-bis(dichloroboryl)-2,5-hexadiene derivative is reacted with heptamethyldisilazane and hexamethyl-disilthiane to give the corresponding 1,2,5-azadiborolane and thiadiborolane. Their hydroboration leads to the aza-and thia-nido-dicarbahexaboranes, respectively.

Synthesis of light-emitting π-conjugated poly(pyrimido[5,4- d]-pyrimidine-2,6-diyl) with bulky side chains and high molecular weight

New poly(pyrimido[5,4- d]pyrimidine-2,6-diyl) (PPympym) with bulky dialkylamino substituents (–NR 2, R=hexyl, decyl) was prepared by organometallic dehalogenative polycondensation using a zerovalent Ni complex. The obtained PPympym was soluble in common organic solvents such as CHCl 3 and THF, and GPC analysis (in CHCl 3; vs. polystyrene standards) indicated that new Ppympyms had high number-average molecular weights M n of 19,100–34,000; they also gave a high [ η] value of about 2.1 dl g −1. PPympym showed strong photoluminescence both in CHCl 3 and in film, and greenish-blue electroluminescence from PPympym-based double-layer light-emitting devices (ITO/PEDOTh/PPympym/Ca–Al; PEDOTh, poly(ethylenedioxythiophene)) was observed.

Pyridazine based inhibitors of p38 MAPK

Trisubstituted pyridazines were synthesized and evaluated as in vitro inhibitors of p38 MAPK. The most active isomers were those possessing an aryl group α and a heteroaryl group β relative to the nitrogen atom in the 2-position of the central pyridazine. Additionally, substitution in the 6-position of the central pyridazine with a variety of dialkylamino substituents afforded a set of inhibitors having good (p38 IC 50 1–20 nM) in vitro activity.

Crystallographic Investigation of Substituted Allyl and Titanacyclobutane Complexes of Bis(2-N,N-dialkylaminoindenyl)titanium. Structure and Reactivity as a Function of the Dialkylamino Substituents

Substituted allyl complexes of bis(2-N,N-dialkylaminoindenyl)titanium(III) undergo highly regioselective central carbon alkylation upon treatment with organic free radicals, providing a general synthesis of 2,3-disubstituted titanacyclobutane complexes. This reactivity contrasts that of the corresponding bis(pentamethylcyclopentadienyl)titanium(III) series, for which titanacyclobutane formation is observed only in reactions of the unsubstituted allyl complex. Unexpectedly, the radical alkylation is more general for complexes of bis(2-N,N-dimethylaminoindenyl)titanium than complexes of the closely analogous bis(2-piperidinoindenyl)titanium, despite only subtle differences between the two ancillary ligands. In addition, the 2-methyl-3-alkyltitanacyclobutane complexes derived from alkylation of bis(2-N,N-dimethylaminoindenyl)titanium(η3-crotyl) are more thermally robust than those derived from the 2-piperidinoindenyl ligand system, resisting decomposition via β-hydride elimination from the α-methyl substituent. To gain insight into the function of the dialkylaminoindenyl ligands and to probe the differences between 2-N,N-dimethylaminoindenyl and 2-piperidinoindenyl complexes, crystal structures of bis(2-N,N-dimethylaminoindenyl)titanium(η3-1-phenylallyl) (4a) and bis(2-N,N-dimethylaminoindenyl)titanium(η3-crotyl) (4b) have been determined and compared to the crystal structure of bis(2-piperidinoindenyl)titanium(η3-1-phenylallyl), 3a. The effects of allyl coordination on the disposition of the dialkylaminoindenyl ligands are revealed by a comparison with the crystal structure of the corresponding chloride complex, bis(2-N,N-dimethylaminoindenyl)titanium(III)chloride·lithium chloride·(THF)2, a rare Ti(III)halide/lithium halide adduct. Although it is difficult to control for the effects of crystal packing forces, substantial changes in ancillary ligand structure and orientation are observed as a function of the amino substituent and the coordination environment. The difference in titanacyclobutane stability and the response of the dialkylaminoindenyl ligands to the change in oxidation state have been investigated by comparing the crystal structures of two disubstituted titanacyclobutane complexes, 3-isopropyl-2-phenylbis(2-piperidinoindenyl)titanacyclobutane (7) and 3-isopropyl-2-phenylbis(2-N,N-dimethylaminoindenyl)titanacyclobutane (8), each prepared by free radical alkylation.

THERMAL OLIGOMERIZATION OF UNSYMMETRICALLY B-TRISUBSTITUTED BORAZINES

The B-alkylaminosubstituted borazines (NEt 2) 3 B 3 N 3 H 3 (1), (ΝE1 2) 2 (ΝΗΡ0Β 3 Ν 3 Η 3 (2), (NEt 2)(NHPr') 2 B 3 N 3 H 3 (3) and (NMe 2)(NHMe) 2 B 3 N 3 l-l3 (4) have been prepared and characterized by spectroscopic techniques. Their thermolyses at moderate temperature have been investigated in order to elucidate the effects of the nature of the B-alkylamino substituents on the resulting polyborazines backbone. Early stages of the degradations were accompanied by the elimination of primary and secondary amines for (2), (3) and (4). On the basis of 13 C NMR data, oligomerizations have been shown to occur mainly via the formation of direct interring B-N bonds rather than classical deamination with formation of-N(R)-bridges between borazine rings. This phenomenon should be related to the presence of dialkylamino substituents on the boron atoms.