Imino Form Research Articles

Crystal structure of 2-aminobenzothiazolinium nitrate and theoretical study of the amino-imino tautomerism of 2-aminobenzothiazole

Abstract 2-Aminobenzothiazolinium nitrate (1) was characterized by elemental analysis, melting point, IR, 1H NMR, and X-ray crystallography. The driving force for the 2-aminobenzothiazole tautomerism in methanol solution was studied using theoretical calculations. It is suggested that the 2-aminobenzothiazolinium cation is an intermediate product between the amino form (2) and imino form (3) of 2-aminobenzothiazole. The tautomerization reaction can proceed in two steps through protonation and deprotonation between the two forms 2 and 3.

Effect of α- and β-cyclodextrins on S-triazine derivatives: spectral and molecular modelling studies

Cyclodextrins (CDs, α-CD and β-CD) effects on three S-triazine derivatives (1A, 1B and 1C) were investigated by absorption, fluorescence and molecular modelling studies. A regular red and blue shift observed in acidic buffer medium suggests intramolecular proton transfer (IPT) present in these molecules. The longer wavelength emission intensity dramatically increased with the β-CD concentrations while in α-CD solution, the shorter wavelength emission intensity is increased. Considering size and shape of the CDs and guest molecules, S-triazine molecules are partially encapsulated within the CD cavity. Semiempirical quantum mechanical calculations have also been carried out to ascertain the mode of inclusion process. These results indicate that amino form is energetically favourable than imino form, which is consistent with experimental results.

Effects of positive and negative ionization for 2-aminopyrimidine in the gas phase and in water solution

Quantum-chemical calculations were performed for neutral 2-aminopyrimidine (2APM) and for its ionized forms (2APM−e→2APM+ and 2APM+e→2APM−) in the gas phase {DFT(B3LYP)/6-311+G(d,p)} and in water solution {PCM(water)//DFT(B3LYP)/6-311+G(d,p)}. For calculations, the complete tautomeric mixture containing the amino and imino forms was considered. Geometric isomerism of the exoNH group for the imino forms was also taken into account. There is a good correlation between prototropy and electron delocalization for the neutral isomers of 2APM. The aromatic amine NH2 tautomer is favored for neutral and ionized 2APM in the gas phase and in water solution. Positive and negative ionization increase the stability of the imine NH isomers containing the labile proton at the endo N-aza atom that their contribution cannot be neglected in the positively and negatively ionized tautomeric mixture. Ionization influences also electron delocalization. For the major and minor forms of 2APM, the exo N atom may lose preferentially one of the non-bonding electrons, and the pyrimidine ring may gain one excess electron. The adiabatic ionization potential and the adiabatic electron affinity change when going from the gas phase to water solution by ca. 2eV.

Design and Synthesis of Cyclic ADP‐4‐Thioribose as a Stable Equivalent of Cyclic ADP‐Ribose, a Calcium Ion‐Mobilizing Second Messenger

Design and Synthesis of Cyclic ADP‐4‐Thioribose as a Stable Equivalent of Cyclic ADP‐Ribose, a Calcium Ion‐Mobilizing Second Messenger

Synthesis and spectroscopic analysis of substituted 2-aminothiazolines

2-Aminothiazolines can exist in two tautomeric species, amino and imino forms, which can theoretically exist as two stereoisomers. Several methods and techniques have been used to evaluate tautomeric process, but in this case 15N NMR spectroscopy was used due to tautomeric process involves two nitrogen atoms. In this paper, we present the synthesis and a HMBC 1H-15N study of four 2-substituted aminothiazolines. It was observed from HMBC contour plot correlation between five membered ring CH2 groups with sp2 nitrogen around 250ppm, while aliphatic hydrogen correlates with sp3 nitrogen around 90ppm, suggesting that amino form is the major or the unique tautomer present in solution. Theoretical calculations at the M06-2X/cc-pVDZ level were performed and indicated that amino tautomer is slightly more stable (∼1kcalmol−1) than imino one.

Synthesis, spectroscopic, structural and conformational study of some tri-substituted ureas derived from N-methylpiperazine containing phenyl and N-heterocyclic substituents

A series of tri-substituted ureas containing an N-methylpiperazine moiety as well as phenyl and N-heterocyclic substituents were synthesized and studied by 1H, 13C NMR and IR spectroscopies. From 1H and 13C NMR data, in CDCl3 solution at room temperature, a fast inter-conversion of the piperazine ring with the N-CH3 group in equatorial position can be proposed. Amino–imino tautomerism is observed for both thiazole and benzothiazole derivatives. Moreover, with the exception of the imino form of the thiazole derivative, the aryl substituted N-carbamoyl group rotates freely. IR data show that the compounds adopt a planar trans conformation of the CONH moiety.

Photophysics of cytosine tautomers: new insights into the nonradiative decay mechanisms from MS-CASPT2 potential energy calculations and excited-state molecular dynamics simulations

A comprehensive picture of the ultrafast nonradiative decay mechanisms of three cytosine tautomers (amino-keto, imino-keto, and amino-enol forms) is revealed by high-level ab initio potential energy calculations using the multistate (MS) CASPT2 method and also by on-the-fly excited-state molecular dynamics simulations employing the CASSCF method. To obtain a reliable potential energy profile along the deactivation pathways, the MS-CASPT2 method is employed even for the optimization of minimum energy structures in the excited state and conical intersection (CI) structures between the ground and excited states. In the imino (imino-keto) form, we locate a new CI structure involving the twisting of the imino group, and the decay pathway leading to this CI is found to be barrierless, suggesting a remarkably efficient deactivation of imino cytosine. In the keto (amino-keto) form, the MS-CASPT2 calculations exhibit an efficient decay path to the ethylene-like CI involving the twisting of the C-C double bond in the six-membered ring, with a barrier of ∼0.08 eV from the minimum of the (1)ππ* state. In the enol (amino-enol) form, three types of CIs are identified for the first time. Among them, the ethylene-like CI with a similar molecular structure to the keto form provides the most preferred deactivation pathway in enol cytosine. This pathway exhibits a higher barrier of ∼0.22 eV and a higher energy of CI than those of keto cytosine. Nonadiabatic molecular dynamics simulations provide a time-dependent picture of the deactivation processes, including the excited-state lifetime of each tautomer. In particular, the decay time of the imino tautomer is predicted to be only ∼100 fs. Our computational results are in remarkably good agreement with the experimental findings of recent femtosecond pump-probe photoionization spectroscopy [J. Am. Chem. Soc., 2009, 131, 16939; J. Phys. Chem. A, 2011, 115, 8406], supporting the coexistence of more than one tautomer in the photophysics of isolated cytosine and that each tautomer exhibits a different excited-state lifetime.

Amino–Imino Adenine Tautomerism Induced by the Cooperative Effect between Metal Ion and H2O/NH3

Tautomerization processes of amino-imino adenine isomer (A → A1) in five different environments are studied by the density functional theory (B3LYP) method. The five environments are metal ion (M, M = K(+), Na(+), Cu(+), Zn(+), Ca(2+), Mg(2+), Cu(2+), Zn(2+)) coordinated bidentate system, either monowater (W) or monoammonia (N) attached system, both metal ion and monowater cooperative system (M-W), and both metal ion and monoammonia cooperative system (M-N). Results show that the complexes formed by noncanonical rare imino form A1 are more stable than those formed by the canonical amino one in most of these environments. The tautomerization of A → A1 becomes quite easy in either M-W or M-N system. It is noteworthy that under divalent M-N environment the A → A1 process meets with particularly lower and even free energy barrier, indicating the instability of the amino adenine isomer and probable existence of more stable imino adenine isomer. Expanding studies for the microhydration at the metal ion of the M-N system predict the required number (n) of water molecules to remain the amino adenine isomer A (AMNnW) stable. The number of n is 2, 3, 3, and 4 for M = Ca(2+), Zn(2+), Cu(2+), and Mg(2+), respectively. The present study provides further understanding for the amino-imino tautomerization behavior of the most stable adenine under the influence of several related closely factors, and is useful for rational design of these different environments for the purposes of prevention and control of pyrimidines mispairing, which is responsible for the mutagenic properties of the nucleic acid bases.

N-[(2Z,4Z)-4-Benzyl-idene-6-chloro-1,4-dihydro-pyrido[2,3-d][1,3]thia-zin-2-yl-idene]benzamide.

In the crystal structure of the title compound, C21H14ClN3OS, mol­ecules assemble into inversion dimers via pairs of N—H⋯N hydrogen bonds involving the N—H hydrogen of the thia­zine ring and the N atom of the pyridine ring. There is a close intra­molecular contact [2.570 (2) Å] between the carbonyl O atom of the benzamide and the S atom of the puckered thia­zine ring. The title compound can exist in two tautomeric forms, viz. amino or imino. The observed structure is compatible with the imino form on the basis of observed residual electron density and the two C—N bond lengths of 1.308 (2) and 1.353 (2) Å.

Theoretical study of the deamination of 1-(2-hydroxy-1-phenylethyl)adenine

In this paper the deamination mechanism of 1-(2-hydroxyl-1-phenylethyl)adenine (HPA) was studied using density functional method. As is known adenine has two possible forms under different pH values. One is the protonated amino form and the other is the neutral imino form. Through our calculations there exist four different mechanisms for the two form HPAs. Among them, pathway d from neutral imino form HPA involving an intramolecular cyclization of 2-hydroxyl-1-phenylethyl side chain is the preferred pathway with lowest energy barriers. In this pathway the hydroxyl group attacks the C6 atom of adenine to produce an oxazolinium intermediate, which is different from the mechanism of adenine deamination. Our calculations demonstrate that unlike other simple 1-alkyladenines, HPA are readily deaminated through intramolecular cyclization due to low energy barrier. In addition HPA occur deamination more easily under neutral condition than under acid condition.

2-[N-(4-{4-[(2-Hydroxy-5-methoxybenzylidene)amino]benzyl}phenyl)carboximidoyl]-4-methoxyphenol

In the title Schiff base, C29H26N2O4, the complete molecule is generated by a crystallographic twofold axis and is V-shaped. The planes of the benzene rings of the central diphenyl­methane unit make a dihedral angle of 78.11 (4)° while adjacent benzene and 5-meth­oxy­salicyl­idene rings are twisted with respect to each other by a dihedral angle of 11.84 (8)°. The Schiff base is in the enol–imino form and an intra­molecular O—H⋯N hydrogen bond is observed.

Crystal structures of hydrazones, 2-(1,3-benzothiazolyl)-NH—N=CH—Ar, prepared from arenealdehydes and 2-hydrazinyl-1,3-benzothiazole

Abstract Structures of hydrazones, [1: 2-(1,3-benzothiazolyl)-NH—N=CH—C6H3—XY], prepared from arenecarbäaldehydes and 2-hydrazinyl-1,3-benzothiazole, are reported. Compounds include unsolvated species, (1: X = 4-Cl, 4-Br, 4-NMe2; Y = H), [1: X,Y = 2,4-Me2, 2,4-(OMe)2], and solvated ones, [(1: X = 4-OH; Y = H) · H2O], [(1: X = 3-OMe; Y = 4-OH) · H2O], and [(1: X = 2-OH; Y = 5-NO2) · DMSO]. The solvated compound, [(1: X = 2-OH; Y = 5-NO2) · DMSO], exists in the imino form in contrast to the (E)-2-(1,3-benzothiazolyl)-NH—N=CH—Ar form exhibited by the other compounds. Common intermolecular interactions in the non-solvated compounds, (1: X = 4-Cl, 4-Br, 4-NMe2; Y = H) and [1: X,Y = 2,4-Me2, 2,4-(OMe)2], are strong dimer forming N—H · · · N hyädrogen bonds and weaker π · · · π interactions. The latter involve the benzothazole rings, except in [1: X,Y = 2,4-(OMe)2], where the π · · · π interactions involve thiazole and C6H3(OMe)2 rings. The dimer forming N—H · · · N intermolecular hydrogen bonds and π · · · π stacking interactions persist in the hydrate, [(1: X = 3-OMe; Y = 4-OH) · H2O], but not in the other solvates, [(1: X = 4-OH; Y = H) · H2O] and [(1: X = 2-OH; Y = 5-NO2) · DMSO]. For [(1: X = 4-OH; Y = H) · H2O], the important direct links between [(1: X = 4-OH; Y = H) are chain forming O—H · · · N hydrogen bonds, supplemented by π · · · π interactions. For all solvated compounds, the solvate molecules are involved in indirect links between the hydrazone molecules. In the case of [(1: X = 2-OH; Y = 5-NO2) · DMSO], present in the imino form, a network of rings is generated from the hydrogen bonding interactions of the DMSO solvate with the N—H and N—O(nitro) moieties of (1: X = 2-OH; Y = 5-NO2).

Methylation Stabilizes the Imino Tautomer of dAMP and Amino Tautomer of dCMP in Solution

Alkylating agents cause methylation of adenosine and cytidine in DNA to generate 1-methyladenosine and 3-methylcytidine. These modified nucleosides can serve as regulators of cells or can act as agents of mutagenesis depending on the context and the partner enzymes. Solution structures and the chemical interactions with enzymes that lead to their recognition are of inherent interest. At physiological pH, 1-methyladenosine and 3-methylcytidine are presumed to be in the protonated amino forms in the literature. We report the structures, ionization states, and UV resonance Raman spectra of both substrates over a range of pH (2.5-11.0). The Raman excitation wavelength was tuned to selectively enhance Raman scattering from the nucleobase (260 nm) and further specifically from the imino form (210 nm) of 1-me-dAMP. We find that contrary to the general assumption, 1-me-dAMP is present in its neutral imino form at physiological pH and 3-me-dCMP is in the amino form.

Tautomers of cytosine and their excited electronic states: a matrix isolation spectroscopic and quantum chemical study

We have measured the IR and UV spectra of cytosine in a low-temperature argon matrix. An attempt was made to determine the tautomeric ratios existing in the matrix, making use of the matrix-isolation IR spectrum and computed IR intensities of the tautomers in a least squares fitting procedure. The mole fractions are about 0.22 for oxo(-amino) form, 0.26 and 0.44 for the two rotamers, respectively, of the hydroxy(-amino) form and 0.08 for the (oxo-)imino tautomer. These ratios were then used to simulate the matrix-isolation UV spectrum as a composite of the individual spectra, the latter calculated ab initio at high levels of electron correlation theory. The agreement between simulated and experimental UV spectra seems satisfactory. This indicates that, in contrast to the solid state and solution spectra described up to now by the oxo(-amino) form alone, the reproduction of the matrix-isolation UV spectrum needs at least the hydroxy(-amino) and oxo(-amino) forms, and probably also the (oxo-)imino form.

Metal-promoted synthesis of amidines containing the model nucleobases 1-methylcytosine and 9-methyladenine

The amidine complexes cis-[L(2)PtNH==C(R){1-MeCy(-2H)}]NO(3) (R = Me, 1a; Ph, 1b, Me(3)C, 1c; Ph(2)(H)C, 1d) and cis-[L(2)PtNH==C(R){9-MeAd(-2H)}]NO(3) (R = Me, 2a; Ph, 2b; Me(3)C, 2c; Ph(2)(H)C, 2d), are formed when cis-[L(2)Pt(μ-OH)](2)(NO(3))(2) (L = PPh(3)) reacts with 1-methylcytosine (1-MeCy) and 9-methyladenine (9-MeAd) in solution of MeCN, PhCN, Me(3)CCN and Ph(2)(H)CCN. Reaction of 1a,b and 2a,b with HCl affords the protonated amidines [NH(2)==C(R){1-MeCy(-H)}]NO(3) (R = Me, 3a; Ph, 3b) and [NH(2)==C(R){9-MeAd(-H)}]NO(3) (R = Me, 4a; Ph, 4b) and cis-(PPh(3))(2)PtCl(2) in quantitative yield. Treatment of 3b and 4b with NaOH allows the isolation of the neutral benzimidamides NH(2)-C(Ph){1-MeCy(-2H)} (5b) and NH(2)-C(Ph){9-MeAd(-2H)} (6b). In the solid state 3b shows a planar structure with the hydrogen atom on N(4) cytosine position involved in a strong H-bond with the NO(3)(-) ion. Intermolecular H-bonds between the oxygen of the cytosine ring and one of the H atoms of the amidine-NH(2) group allow the dimerization of the molecule. A detailed analysis of the spectra of 3b in DMF-d(7) at -55 °C indicates the presence of an equilibrium between the species [NH(2)==C(R){1-MeCy(-H)}]NO(3) and [NH(2)==C(R){1-MeCy(-H)}](2)(NO(3))(2), exchanging with trace amounts of water at 25 °C. [(15)N,(1)H]-HMBC experiments for 5b and 6b indicate that the amino tautomer H(2)N-C(Ph){nucleobase(-2H)}, is the only detectable in solution and such structure has been confirmed in the solid state. The reaction of 5b and 6b with cis-L(2)Pt(ONO(2))(2) (L = PPh(3)), in chlorinated solvents, determines the immediate appearance of a pale yellow colour due to the coordination of the neutral amidine, likely in its imino form HN==C(Ph){nucleobase(-H)}, to give the adducts cis-[L(2)PtNH==C(Ph){nucleobase(-H)}](2+). In fact, addition of "proton sponge" leads to the immediate deprotonation of the amidine ligand with formation of the starting complexes 1b and 2b.

Theoretical study of tautomerization and isomerization of methylamino- and phenylamino-substituted cyclic azaphospholines, oxaphospholines and thiaphospholines in gas and aqueous phases

Results of B3LYP/6-31+G(d,p) calculations are reported. Special emphasis is put on the effect of the environment on relative stability and structures of different isomers and tautomers of methylamino- and phenylamino-substituted cyclic azaphospholine, oxaphospholine and thiaphospholine in gas and aqueous phases. In the gas phase, the imino forms are found to be the most stable species for the cyclic azaphospholines and thiaphospholines, whereas for oxaphospholines, the amino species are predicted to be more stable. The calculations in the aqueous media were done by considering two different models, i.e., the PCM–SCRF and the Microsolvated/SCRF model. It is found that solvation shifts the stability towards the amino forms, except for the phenyl-substituted cyclic azaphospholine and thiaphospholine, for which the imino forms are more stable in solution. The molecular geometries change only little when going from the gas phase to the aqueous phase. The stability in gas phase and in PCM–SCRF is attributed to the presence of intramolecular hydrogen bonding. In the Microsolvated/SCRF model, the presence of intermolecular hydrogen bonds affects the relative stability of tautomers and isomers.

Keto–enol tautomerism in asymmetric Schiff bases derived from p-phenylenediamine

Reaction of dehydroacetic acid and p-phenylenediamine afforded a monosubstituted Schiff base, I, with the other amino group free. In further reactions with various salicylaldehyde derivatives, I served as a precursor for synthesis of asymmetric bis-Schiff bases. The synthesized compounds are thus comprised of two subunits, dehydroacetic ( dha) and salicylidene ( sal), which are bridged by the phenylene linker. All products were investigated by means of elemental analysis, FT-IR and NMR spectroscopy, thermal methods, powder X-ray diffraction and, when possible, by single crystal X-ray crystallography. Structural and spectroscopic studies revealed that in the bis-products, the dha subunit adopts the keto–amino tautomeric form, while the sal subunit adopts the enol–imino form. Tautomeric forms were not affected if a methoxo group was introduced on the salicylidene ring. Both tautomeric subunits are stabilized by strong resonance-assisted hydrogen bonds, RAHB. The two subunits of the prepared bis-Schiff bases predominantly retain in solution the same tautomeric forms as found in the solid state.

ChemInform Abstract: Two Practical and Efficient Approaches to Fluorinated and Nonfluorinated Chiral β-Imino Sulfoxides.

Reaction of fluorinated and nonfluorinated N-substituted imidoyl chlorides 1 with lithium derivatives of enantiopure methyl p-tolyl sulfoxide 2a (or racemic methyl phenyl sulfoxide 2b) gave a wide variety of chiral N-substituted β-imino sulfoxides 4 in good to excellent yields. The title compounds (R)-4 were also prepared by aza-Wittig reaction of γ-fluoro-β-keto sulfoxides (R)-5 and N-aryl iminophosphoranes 6. The imino−enamino equilibrium was studied, showing, in all instances, the imino form as the predominant tautomer independent of the nature of the N-substituent. The configuration of the CN double bond was found to be Z for both N-alkyl and N-aryl derivatives on the basis of 1H NMR NOE difference experiments performed over several compounds. Ab initio calculations (HF/6-31G*) carried out on several representative examples of 1 and 4 are, in general, consistent with the experimental results.

Theoretical Study of the 5-Aminotetrazole Thermal Decomposition

The thermal decomposition of 5-aminotetrazole was studied theoretically using the G3 multilevel procedure and DFT B3LYP technique. The unimolecular primary decomposition reactions of the three most stable isomers of 5-ATZ were studied in the gas phase and in the melt using a simplified model of the latter. The influence of the melt on the elementary reaction barrier was taken into account by the calculation of the solvation free energies using the PCM model. In contrast to all previous publications, we considered the bimolecular reactions of 5-ATZ and demonstrated that they are very important especially in the condensed phase. It was found that the imino form undergoes fast isomerization to the amino form in the H-bonded dimers and does not participate in the 5-ATZ thermolysis. On the contrary, amino and, probably, the 2H isomer are the main isomers of 5-ATZ in the melt and gas phase. The N(2) elimination reaction was found to be the dominant unimolecular channel of the amino and 2H isomer decomposition in both the gas phase and melt. The significant lowering of the activation barriers of decomposition reactions in H-bonded dimers was found. In agreement with the existing experimental data, HN(3) elimination dominates for some of the considered complexes. It was concluded that the initial stages of thermolysis of 5-ATZ cannot be satisfactory described by the simple unimolecular reactions proposed in the literature.

Tautomerism of anthraquinones: VIII. Tautomerism and conformations of 1,4-diamino-9,10-anthraquinone

The compound widely known as 1,4-diamino-9,10-anthraquinone is in fact an equilibrium mixture of 4,9-diamino-1,10-anthraquinone and tautomeric imino forms, 10-amino-9-hydroxy-1,4-anthraquinone 1-imine and its conformer, and 4-amino-1-hydroxy-9,10-anthraquinone 9-imine or 4,9-dihydroxy-1,10-anthraquinone diimine. Amino-imino tautomerism and rotational isomerism are responsible for fine structure of the πl,π*-absorption of the title compound.