Acyl- und Alkylidenphosphane. XXXII [1, 2]. Di-cyclo-hexoyl- und Diadamant-1-oylphosphan — Keto-Enol-Tautomerie und Struktur

Acyl- and Alkylidenephosphines. XXXII. Di-cyclohexoyl- and Diadamant-1-oylphosphine – Keto-Enol Tautomerism and Structure Lithium dihydrogenphosphide · DME (¹) [12] and cyclo-hexoyl or adamant-1-oyl chloride react in a molar ratio of 3:2 to give lithium di-cyclo-hexoylphosphide · DME and the corresponding diadamant-1-oylphosphide.2THF (¹) resp. Treatment of these two compounds with 85% tetrafluoroboric acid. diethylether adduct yields di-cyclo-hexoyl- ( 1b ) and diadamant-1-oylphosphine ( 1c ). In nmr spectroscopic studies 1b over a range of 203 to 343 K, a strong temperature dependence of the keto-enol equilibrium is found; thermodynamic data characteristic for the formation of the enol tautomer (ΔH⁰ = ?4.3 kJ. mol^?1; ΔS⁰ = ?9.2 J. mol^?1. K (^?1) are compared of 1,3-diketones. The enol tautomer of diadamant-1-oylphosphine ( E-1c ) as obtained from a benzene solution in thin colourless plates, crystallizes in the monoclinic space group P2₁/c {a = 722.2(2); b = 1085.5(4); c = 2434.8(5) pm; ß = 96.43(2)° at –100 ± 3°C; Z = 4}. An X- ray structure analysis (R_w = 0.033) shows bond lengths and angles to be almost identical within the enolic system (P? C 179/180; C? O 130/129; C? C(adamant-1-yl) 152/153 pm; C? P? C 99°; P? C? O 124°/124°; P? C? C 120°/120°; C? C? O 116°/116°. The geometry of the very strong, but probably asymmetric O‥H‥O bridge is discussed (O? H 120/130, O‥O 245 pm).     

An X‐ray crystallographic and density functional theory study of (3Z)‐4‐(5‐ethylsulfonyl‐2‐hydroxyanilino)pent‐3‐en‐2‐one and (3Z)‐4‐(5‐tert‐butyl‐2‐hydroxyanilino)pent‐3‐en‐2‐one

The Schiff base enaminones (3Z)‐4‐(5‐ethylsulfonyl‐2‐hydroxyanilino)pent‐3‐en‐2‐one, C₁₃H₁₇NO₄S, (I), and (3Z)‐4‐(5‐tert‐butyl‐2‐hydroxyanilino)pent‐3‐en‐2‐one, C₁₅H₂₁NO₂, (II), were studied by X‐ray crystallography and density functional theory (DFT). Although the keto tautomer of these compounds is dominant, the O=C—C=C—N bond lengths are consistent with some electron delocalization and partial enol character. Both (I) and (II) are nonplanar, with the amino–phenol group canted relative to the rest of the molecule; the twist about the N(enamine)—C(aryl) bond leads to dihedral angles of 40.5 (2) and −116.7 (1)° for (I) and (II), respectively. Compound (I) has a bifurcated intramolecular hydrogen bond between the N—H group and the flanking carbonyl and hydroxy O atoms, as well as an intermolecular hydrogen bond, leading to an infinite one‐dimensional hydrogen‐bonded chain. Compound (II) has one intramolecular hydrogen bond and one intermolecular C=O...H—O hydrogen bond, and consequently also forms a one‐dimensional hydrogen‐bonded chain. The DFT‐calculated structures [in vacuo, B3LYP/6‐311G(d,p) level] for the keto tautomers compare favourably with the X‐ray crystal structures of (I) and (II), confirming the dominance of the keto tautomer. The simulations indicate that the keto tautomers are 20.55 and 18.86 kJ mol⁻¹ lower in energy than the enol tautomers for (I) and (II), respectively.     

Bildung und Eigenschaften von Aoylphosphinen. III. Molekül- und KristallStruktur von Dipivaloylphosphin

Syntheses and Properties of Acylphosphines. III. Molecular and Crystal Structure of Dipivaloylphosphine In the reaction of tris(trimethylsilyl)phosphine with pivaloyl chloride two Si? P bonds are cleaved and dipivaloyltrimethylsilylphosphine is formed. Reaction with methanol yields dipivaloylphosphine. N.m.r. investigations show a tautomeric equilibrium between keto and enol form as in β-diketones. The substance crystallizes in the orthorhombic space group Pmmn with molecules in two crystallographically different sites [cell parameters: a = 14.04(1), b = 13.82(1), c = 6.28(2) Å]. An X-ray structure determination (R = 5.0%) proves the existence of the enol form in the solid, in that (1.) the molecular symmetry is mm 2(C_2v), (2.) P? C bonds are shortened and C? O bonds are elongated, and (3.) we find a symmetric hydrogen bridge with a very short O? O distance. Bond lengths and angles are compared with those of other β-diketones. The packing of molecules is studied in detail.     

Reactions of the ionized enol tautomer of acetanilide: elimination of HNCO via a novel rearrangement

The reactions of ionised acetanilide, C(6)H(5)NH(=O)CH(3)(.+), and its enol, C(6)H(5)NH(OH)=CH(2)(.+), have been studied by a combination of tandem mass spectrometric and computational methods. These two isomeric radical cations have distinct chemistries at low internal energies. The keto tautomer eliminates exclusively CH(2)=C=O to give ionised aniline. In contrast, the enol tautomer loses H-N=C=O, via an unusual skeletal rearrangement, to form predominantly ionised methylene cyclohexadiene. Hydrogen atom loss also occurs from the enol tautomer, with the formation of protonated oxindole. The mechanisms for H-N=C=O and hydrogen atom loss both involve cyclisation; the former proceeds via a spiro transition state formed by attachment of the methylene group to the ipso position, whereas the latter entails the formation of a five-membered ring by attachment to the ortho position. The behaviour of labelled analogues reveals that these two processes have different site selectivities. Hydrogen atom loss involves a reverse critical energy and is subject to an isotope effect. Surprisingly, attempts to promote the enolisation of ionised acetanilide by proton-transport catalysis were unsuccessful. In a reversal of the usual situation for ionised carbonyl compounds, ionised acetanilide is actually more stable than its enol tautomer. The enol tautomer was resistant to proton-transport catalysed ketonisation to ionised acetanilide, possibly because the favoured geometry of the encounter complex with the base molecule is inappropriate for facilitating tautomerisation.     

Two tautomeric forms of 2‐amino‐5,6‐dimethylpyrimidin‐4‐one

Derivatives of 4‐hydroxypyrimidine are an important class of biomolecules. These compounds can undergo keto–enol tautomerization in solution, though a search of the Cambridge Structural Database shows a strong bias toward the 3H‐keto tautomer in the solid state. Recrystallization of 2‐amino‐5,6‐dimethyl‐4‐hydroxypyrimidine, C₆H₉N₃O, from aqueous solution yielded triclinic crystals of the 1H‐keto tautomer, denoted form (I). Though not apparent in the X‐ray data, the IR spectrum suggests that small amounts of the 4‐hydroxy tautomer are also present in the crystal. Monoclinic crystals of form (II), comprised of a 1:1 ratio of both the 1H‐keto and the 3H‐keto tautomers, were obtained from aqueous solutions containing uric acid. Forms (I) and (II) exhibit one‐dimensional and three‐dimensional hydrogen‐bonding motifs, respectively.     

Acyl- und Alkylidenphosphane. XVII. Triacetylphosphan aus Tris(trimethylsilyl)phosphan

Acyl- and Alkylidenephosphines. XVII. Triacetylphosphine from Tris(trimethylsilyl)-phosphine Tris(trimethylsilyl)phosphine reacts at 0°C with excess acetyl chloride in cyclopentane to form chlorotrimethylsilane and triacetylphosphine 3a . In contrast to the corresponding 2,2-dimethylpropionyl derivate (Z)- 5b the intermediate compounds (E)- and (Z)-acetyl-[1-(trimethylsiloxy)ethylidene]phosphine 5a are thermally instable. They could not be isolated in a pure state, but were characterized by NMR spectroscopic methods only. The isomers differ scarcely in their chemical shift values, but very much in their coupling constants. If the solution is cooled unsufficiently diacetyl-[1-(trimethylsiloxy)vinyl]phosphine 7 and the keto-enol-tautomers of diacetylphosphine K-/E- 2a are formed to a greater extend. ¹H-{³¹P}-INDOR experiments allowed the correlation between ¹H- and ³¹P-NMR resonances and hence the correct identification of the phosphines formed. Within days the compounds 2a and 7 also react at +20°C with an excess of acyl halide to give triacetylphosphine 3a .     

Desmotropy,Polymorphism, and Solid‐State Proton Transfer: Four Solid Forms of an Aromatic o‐Hydroxy Schiff Base

The Schiff base derived from salicylaldehyde and 2‐amino‐3‐hydroxypyridine affords a diversity of solid forms, two polymorphic pairs of the enol‐imino ( D1 a and D1 b ) and keto‐amino ( D2 a and D2 b ) desmotropes. The isolated phases, identified by IR spectroscopy, X‐ray crystallography, and ¹³C cross‐polarization/magnetic angle spinning (CP/MAS) NMR spectroscopy, display essentially planar molecular conformations characterized by strong intramolecular hydrogen bonds of the O? H???N ( D1 ) or N? H???O ( D2 ) type. A change in the position of the proton within this O???H???N system is accompanied by substantially different molecular conformations and, subsequently, by divergent supramolecular architectures. The appearance and interconversion conditions for each of the four phases have been established on the basis of a number of solution and solvent‐free experiments, and evaluated against the results of computational studies. Solid phases readily convert into the most stable form ( D1 a ) upon exposure to methanol vapor, heating, or by mechanical treatment, and these transformations are accompanied by a change in the color of the sample. The course of thermally induced transformations has been monitored in detail by means of temperature‐resolved powder X‐ray diffraction and infrared spectroscopy. Upon dissolution, all forms equilibrate immediately, as confirmed by NMR and UV/Vis spectroscopy in several solvents, with the equilibrium shifted far towards the enol tautomer. This study reveals the significance of peripheral groups in the stabilization of metastable tautomers in the solid state.     

Differential solvation and tautomer stability of a model base pair within the minor and major grooves of DNA

2-(2'-Hydroxyphenyl)benzoxazole (HBO) may be used as a model base pair to study solvation, duplex environment, and tautomerization within the major and minor groves of DNA duplexes. In its ground state, HBO possesses an enol moiety which may be oriented syn or anti relative to the imino nitrogen of the benzoxazole ring. In the absence of external hydrogen-bond donors and acceptors HBO exists as the internally hydrogen-bonded syn-enol, a mimic of the rare base pair tautomer found in DNA, which may be photoinduced to tautomerize and form the keto tautomer, a mimic of the dominant base pair tautomer. Previously, we demonstrated that when incorporated into DNA such that the enol moiety is positioned in the major groove, HBO is not solvated, exists exclusively as the internally hydrogen-bonded syn-enol which is efficiently photoinduced to tautomerize, and the corresponding keto tautomer is preferentially stabilized. In stark contrast, we now show that when HBO is incorporated in DNA such that the enol moiety is positioned in the minor groove, the enol tautomer is preferentially stabilized. Molecular dynamics simulations suggest that this results from the formation of a stable hydrogen-bond between the HBO enol and the O4' atom of an adjacent nucleotide, an H-bond acceptor that is only available in the minor groove. The differential stabilization of the enol and keto tautomers in the major and minor grooves may reflect the functions for which these environments evolved, including duplex replication, stability, and recognition.     

Hindered rotation about the amido N?C bond and the tautomeric equilibrium in N,N-dimethylacetoacetamide

The molecule N,N-dimethylacetoacetamide, which is subject to a keto–enol equilibrium process in solution, also exhibits hindered rotation about the amido N? C bond. The hindered rotation rates have been studied by lineshape fit methods of the nuclear magnetic resonance spectra. In spite of some overlap of the keto and enol N-methyl proton signals, the simultaneous measurement of the two distinct energy barriers in the two forms is possible as well as a determination of the keto–enol equilibrium. The differences in free energy of activation between keto and enol forms for the rotation barrier can be related to the conjugation energy of the N? C π system with the enolic hydrogen bonded ring. Appeal to the model compound acetylacetone reveals a consistent set of energies for the keto and enol forms in the ground and transition states for internal rotation. The opportunity has been taken to reexamine and compare the keto–enol system ethylacetoacetate. Long range, solvent, concentration and temperature sensitive scalar couplings ⁴J(HH) between the enolic –OH and the adjacent methyl group in acetoacetic ester have not hitherto been reported.     

Tautomerism and microsolvation in 2-hydroxypyridine/2-pyridone

The Fourier transform microwave spectra of the hydrated forms of the tautomeric pair 2-pyridinone/2-hydroxypyridine (2PO/2HP) have been investigated in a supersonic expansion. Three hydrated species, 2PO-H?O, 2HP-H?O, and 2PO-(H?O)?, have been observed in the rotational spectrum. Each molecular complex was confidently identified by the features of the 1?N quadrupole hyperfine structure of the rotational transitions. The presence of water affects the tautomeric equilibrium -N═C(OH)- ? -NH-C(═O)-, which is shifted to the enol form for the bare molecules 2PO/2HP but to the keto tautomer for the hydrated forms.     

Inclusion Complexes of β-Cyclodextrin with Keto/Enol Tautomers of 2-Acetyl-1-tetralone. A Comparative Study

The keto–enol interconversion of 2-acetyl-1-tetralone (ATLO) and of 2-acetyl-cyclohexanone (ACHE) occurs at measurable rates in aqueous acid or neutral medium. This finding allowed us to determine the keto–enol equilibrium constants, K _E, by following two distinct methods. Both methodologies afford results in complete agreement. The first one is a test of the Beer-Lambert law under two different experimental conditions that contain the substrate only in the enol form or in a mixture of both tautomers in equilibrium. The second method analyses the UV-absorption spectrum of each substrate under keto–enol equilibrium in aqueous β-cyclodextrin (β-CD) solutions of variable concentration: the presence of β-CD increases the percentage of the enol due to the formation of 1:1 inclusion complexes between this tautomer and β-CD. Rates of keto–enol tautomerization, in neutral and acid medium, and of nitrosation in acid medium under non equilibrium conditions have also been measured. Throughout the study, the presentation of the results is done by comparing the different behaviour observed between ATLO and ACHE. While the enol of ACHE included into the β-CD cavity shows to be unreactive either in tautomerization or in nitrosation, in the case of ATLO it is observed tautomerization through the complexed enol. In addition, with ACHE only the enol tautomer forms inclusion complexes with β-CD, whereas with ATLO the keto tautomer entries also to the β-CD cavity, however the stability constant with the enol is near 3-fold that of the keto isomer. These main differences can be rationalized on the basis of the molecular structure of these diketones.This revised version was published online in July 2005 with a corrected issue number.     

Ultrafast branching of reaction pathways in 2-(2'-hydroxyphenyl)benzothiazole in polar acetonitrile solution

In a combined study on the photophysics of 2-(2'-hydroxyphenyl)-benzothiazole (HBT) in polar acetonitrile utilizing ultrafast infrared spectroscopy and quantum chemical calculations, we show that a branching of reaction pathways occurs on femtosecond time scales. Apart from the excited-state intramolecular hydrogen transfer (ESIHT) converting electronically excited enol tautomer into the keto tautomer, known to be the dominating mechanism of HBT in nonpolar solvents such as cyclohexane and tetrachloroethene, in acetonitrile solution twisting also occurs around the central C-C bond connecting the hydroxyphenyl and benzothiazole units in both electronically excited enol and keto tautomers. The solvent-induced intramolecular twisting enables efficient internal conversion pathways to both enol and keto tautomers in the electronic ground state. Whereas relaxation to the most stable enol tautomer with twisting angle Θ = 0° implies full ground state recovery, a small fraction of HBT molecules persists as the keto twisting conformer with the twisting angle Θ = 180° for delay times extending beyond 120 ps.     

Solid‐state tautomeric structure and invariom refinement of a novel and potent HIV integrase inhibitor

The conformation and tautomeric structure of (Z)‐4‐[5‐(2,6‐difluorobenzyl)‐1‐(2‐fluorobenzyl)‐2‐oxo‐1,2‐dihydropyridin‐3‐yl]‐4‐hydroxy‐2‐oxo‐N‐(2‐oxopyrrolidin‐1‐yl)but‐3‐enamide, C₂₇H₂₂F₃N₃O₅, in the solid state has been resolved by single‐crystal X‐ray crystallography. The electron distribution in the molecule was evaluated by refinements with invarioms, aspherical scattering factors by the method of Dittrich et al. [Acta Cryst. (2005), A 61 , 314–320] that are based on the Hansen–Coppens multipole model [Hansen & Coppens (1978). Acta Cryst. A 34 , 909–921]. The β‐diketo portion of the molecule exists in the enol form. The enol –OH hydrogen forms a strong asymmetric hydrogen bond with the carbonyl O atom on the β‐C atom of the chain. Weak intramolecular hydrogen bonds exist between the weakly acidic α‐CH hydrogen of the keto–enol group and the pyridinone carbonyl O atom, and also between the hydrazine N—H group and the carbonyl group in the β‐position from the hydrazine N—H group. The electrostatic properties of the molecule were derived from the molecular charge density. The molecule is in a lengthened conformation and the rings of the two benzyl groups are nearly orthogonal. Results from a high‐field ¹H and ¹³C NMR correlation spectroscopy study confirm that the same tautomer exists in solution as in the solid state.     

Cu(OAc)2.H2O与1-苯基-3-甲基-4-苯甲酰基吡唑啉酮-5(HPMBP)的固相配位化学反应

在低加热条件下(<100℃), 研究了Cu(OAc)2.H2O与1-苯基-3-甲基-4-苯甲酰基吡唑啉酮-5-(HPMBP)两种异构体(烯醇式与酮式)的固相配位化学反应, 结果表明两种异构体与Cu(OAc)2.H2O固相化学反应活性并不相同。通过IR, UV测定, 发现酮式异构体在与Cu(OAc)2.H2O的固相反应过程中, 其自身经过了一个由酮式到烯醇式的固相异构化。     

Single‐Crystal X‐ray Diffraction Structure of the Stable Enol Tautomer Polymorph of Barbituric Acid at 224 and 95 K

The thermodynamically stable enol crystal form of barbituric acid, previously prepared as powder by grinding or slurry methods, has been obtained as single crystals by slow cooling from methanol solution. The selection of the enol crystal was facilitated by a density‐gradient method. The structure at 224 and 95 K confirms the enol inferred on the basis of powder data. The enol has bond lengths that are consistent with the expected bond order and with DFT calculations that include treatment of hydrogen bonding. In isolation, the enol is higher in energy than the tri‐keto form by 50 kJ mol^?1 which must be more than compensated by enhanced hydrogen bonding. Both crystal forms have four normal H‐bonds; the enol has two additional H‐bonds with O–O distances of 2.49 Å. Conversion into the enol form occurs spontaneously in the solid state upon prolonged storage of the commercial tri‐keto material. Slurry conversion of tri‐one to enol in ethanol is reversed in direction in ethanol‐D₁.     

Study on the Tautomer Interconversion of 3-Oxo Pentanoate During Gas Chromatography

Enol and keto tautomers of methyl 3-oxo pentanoate could be separated on a HP-5 capillary column. The chromatographic peaks were identified by examining characteristic mass ions arose from the corresponding enol and keto molecular ions. The study showed that the area percentage of enol tautomer is a function of temperature of the column. Treating the column as a reactor, the energy of activation for the on-column tautomerization could be extracted (35.1 kJ mol⁻¹) by monitoring the loss of the enol tautomer, because the reaction is found to obey pseudo first-order kinetics. The enthalpy and the entropy changes (ΔH = −3.98 kJ mol⁻¹, ΔS = −7.89 J K⁻¹mol⁻¹) for the enol-to-keto reaction in the stationary phase were also obtained.     

Synthesis,Structure, and Keto-Enol Tautomerism of 3-R<Superscript>1</Superscript>-5,5-R<Superscript>2</Superscript>,R<Superscript>2</Superscript>-6-R<Superscript>3</Superscript>-2,3,5,6-Tetrahydropyran-2,4-diones

Ethyl esters of 2,4-dibromo-2-R¹-4-R²-3-oxopentanoic and -hexanoic acids react with zinc and aliphatic or aromatic aldehydes under the conditions of the Reformatskii reaction to give 3-R¹-5,5-R², R²-6-R³-2,3,5,6-tetrahydropyran-2,4-diones, which are obtained in three forms: keto, enol with enolization of the keto group, and enol with enolization of the ester group. The keto form is isolated by crystallization from a mixture of CCl₄ and petroleum ether; the first enol form, from MeOH, EtOH, and polar aprotic solvents; and the second enol form, from CHCl₃. The second enol form is oxidized in DMSO to form a keto compound containing a hydroxy group at the 3-position of the heteroring.     

Solid‐State NMR Study of the Tautomerism of Acetylacetone Included in a Host Matrix

The tautomerism of the enol form of acetylacetone (=pentane‐2,4‐dione; 1 ) inside a host cavity has been studied by means of solid‐state ¹³C‐NMR spectroscopy (SSNMR) using the variable‐temperature CPMAS technique. It appears that the enol form, 4‐hydroxypent‐3‐en‐2‐one ( 1a ), exists in an equilibrium with an identical tautomer ( 1c ) trough O H ⋅⋅⋅O proton transfer. The experimental results (energy barrier and chemical shifts) were rationalized by means of MP2 and GIAO calculations.     

Tautomeric properties and gas-phase structure of 3-chloro-2,4-pentanedione

The tautomeric properties of alpha-chlorinated acetylacetone, 3-chloro-2,4-pentanedione CH3C(O)-CHCl-C(O)CH3, have been investigated by gas electron diffraction (GED) and quantum chemical calculations (B3LYP and MP2 approximations with different basis sets up to cc-pVTZ). Analysis of the GED intensities resulted in the presence of 100(2)% enol tautomer at 269(8) K. The following skeletal geometric parameters (rh1 values) of the molecule, which possesses Cs symmetry, were derived: r(C=C) = 1.378(3) A, r(C-C) = 1.450(3) A, r(C=O) = 1.243(3) A, r(C-O) = 1.319(3) A, r(O-H) = 1.001(4) A, r(C-Cl) = 1.752(4) A, angleC-C=C = 121.3(1.0) degrees , angleC=C-O = 119.9(1.2) degrees , angleC-C=O = 119.1(1.2) degrees . Due to very small contributions of the keto tautomer in alpha-chlorinated acetylacetone and its parent species, the effect of alpha-chlorination on tautomeric properties cannot be derived from experimental data. Quantum chemical calculations (B3LYP/6-31G**, B3LYP/cc-pVTZ, and MP2/cc-pVTZ) predict that alpha-chlorination of acetylacetone has no pronounced effect on the tautomeric properties. On the other hand, similar calculations for 1-chloro-1,3-butanedion, ClC(O)-CH2-C(O)CH3, demonstrate that chlorination in one beta position destabilizes the enol tautomer. In both chlorinated species the enol form is strongly preferred.     

N.m.r. studies of the keto–enol tautomerism of acylthioacetamides

Acetylthioacetamides exist as different keto and enol isomers in chloroform solutions. The keto form with intramolecular hydrogen bonding between the NH and the carbonyl group is the dominant keto isomer. On the other hand the enol forms with intramolecular hydrogen bonding between the OH and the thioketo group are the dominant enol isomers in the temperature range 60°C to ?60°C. The thermodynamic data of the keto-enol equilibria were obtained by measuring the intensities of appropriate high resolution proton signals as a function of temperature. At low temperatures all lines characteristic of the enol forms are doubled in the N-phenyl-substituted derivatives because the rotation of the NH? C₆H₅ group around the C? N bond becomes slow and the chemical shifts characteristic of the E and Z isomers are different. We estimated approximate thermodynamic data of the E/Z equilibrium in some of the compounds. The changes of the line shape as well as the chemical shifts as a function of temperature indicate the presence of various additional exchange processes. In order to obtain further information we performed curve fittings of the chemical shifts of one acetylthioacetanilide and of a series of monothio-β-diketones (studied in another paper) assuming a fast two site exchange process. On the basis of the results obtained a reaction scheme for N-substituted acylthioacetanilides in solution is proposed.