Enthalpy of phase transitions of lactams

The transpiration method is used to measure the temperature dependences of the vapors pressures of azacyclobutan-2-one (I, CAS 930-21-2) azacyclohexan-2-one (II, CAS 675-20-7); azacyclooctan-2-one (III, CAS 673-66-5); azacyclononan-2-one (IV, CAS 935-30-8) and azacyclotridecan-2-one (V, CAS 947-04-6). Enthalpies of sublimation and vaporisation are determined. The temperatures and enthalpies of fusion of compounds (I, III-V) are found by means of differential scanning calorimetry. The dependences of the enthalpies of vaporisation of lactones, lactams, cycloalkanes, cycloalkanones on the size of a cycle are analyzed.     

The enthalpies of formation of two dibenzocyclooctadienones

The standard molar enthalpies of formation (Δ_fH_m⁰(s)/kJmol⁻¹) for 2,3:6,7-dibenzocycloocta-2,6-dien-1-one and 2,3:7,8-dibenzocycloocta-2,7-dien-1-one [6H-11,12-dihydro-dibenzo[a,e]cycloocten-5-one (ketone 1) and 10H-11,12-dihydrodibenzo[a,d]-cycloocten-5-one (ketone 2), respectively] were derived from enthalpies of combustion, measured by means of a microbomb calorimeter. The fusion and vaporization enthalpies of these compounds were obtained from DSC and correlation gas chromatography measurements. The standard molar enthalpies of formation in the gas phase were calculated by combining the condensed phase standard molar enthalpies of formation with the fusion and vaporization enthalpies adjusted to 298.15 K. Values for Δ_fH_m⁰(g) of (−39.9±5.5) and (−14.8±5.3) kJ mol⁻¹ were obtained for 2,3:6,7-dibenzocycloocta-2,6-dien-1-one and 2,3:7,8-dibenzocycloocta-2,7-dien-1-one, respectively. Quantum chemical calculations are reported for the compounds investigated experimentally and an additional four isomers. Isomerization enthalpies are derived from computed energies. The enthalpies of formation are also calculated by group additivity, compared with the experimental values and then correlated with the structure of the molecules investigated. The X-ray analysis of ketone 1 is also reported.     

The thermochemistry of 2,4-pentanedione revisited: observance of a nonzero enthalpy of mixing between tautomers and its effects on enthalpies of formation

The enthalpies of formation of pure liquid and gas-phase (Z)-4-hydroxy-3-penten-2-one and 2,4-pentanedione are examined in the light of some more recent NMR studies on the enthalpy differences between gas-phase enthalpies of the two tautomers. Correlation gas chromatography experiments are used to evaluate the vaporization enthalpies of the pure tautomers. Values of (51.2 +/- 2.2) and (50.8 +/- 0.6) kJ.mol(-1) are measured for pure 2,4-pentanedione and (Z)-4-hydroxy-3-penten-2-one, respectively. The value of (50.8 +/- 0.6) kJ.mol(-1) can be contrasted to a value of (43.2 +/- 0.2) kJ.mol(-1) calculated for pure (Z)-4-hydroxy-3-penten-2-one when the vaporization enthalpy is measured in a mixture of tautomers. The difference is attributed to an endothermic enthalpy of mixing that destabilizes the mixture relative to the pure components. Calculation of new enthalpies of formation for (Z)-4-hydroxy-3-penten-2-one and 2,4-pentanedione in both the gas, Delta(f)H degrees (m)(g) = (-378.2 +/- 1.2) and (-358.9 +/- 2.5) kJ.mol(-1), respectively, and liquid phases, Delta(f)H degrees (m)(l) = (-429.0 +/- 1.0) and (-410.1 +/- 1.2) kJ.mol(-1), respectively, results in enthalpy differences between the two tautomers both in the liquid and gas phases that are identical within experimental error, and in excellent agreement with recent gas-phase NMR studies.     

Total synthesis of aristolactams via a one-pot suzuki-miyaura coupling/aldol condensation cascade reaction

A direct one-pot synthesis of phenanthrene lactams, which employs a Suzuki-Miyaura coupling/aldol condensation cascade reaction of isoindolin-1-one with 2-formylphenylboronic acid, has been developed. The approach is used to efficiently produce a number of natural aristolactams, such as aristolactam BII (cepharanone B), aristolactam BIII, aristolactam FI (piperolactam A), N-methyl piperolactam A, and sauristolactam.     

Synthesis of [1]benzothienonaphthyridines

3-Chlorobenzo[b]thiophene-2-carbonyl chloride reacted readily with 2-amino-, 3-amino-, or 4-aminopyridine to give the corresponding amides. Photocyclization of the amides afforded the following lactams: [1]ben-zothieno[2,3-c][1,5]naphthyridin-6(5H)-one ( 14 ), [1]benzothieno[2,3-c][1,6]naphthyridin-6(5H)-one ( 7 ), [1]benzo-thieno[2,3-c][1,7]naphthyridin-6(5H)-one ( 11 ), and [1]benzothieno[2,3-c][1,8]naphthyridin-6(5H)-one ( 3 ). These lactams have been converted to other derivatives including in two instances the unsubstituted ring system.     

Melting,volatilisation and crystal lattice enthalpies of acridin-9(10H)-ones

The enthalpies and temperatures of melting and sublimation of acridin-9(10H)-one, 10-methylacridin-9(10H)-one, 2,10-dimethylacridin-9(10H)-one, 10-methyl-2-nitroacridin-9(10H)-one, 10-ethylacridin-9(10H)-one and 10-phenylacridin-9(10H)-one were measured by DSC. Enthalpies and temperatures of volatilisation were also obtained by fitting TG curves to the Clausius-Clapeyron relationship. Complementary investigations for anthracene showed the extent to which the thermodynamic characteristics thus obtained compare with those determined by means of other techniques. For compounds whose crystal structures are known, experimental enthalpies of sublimation correspond reasonably well to crystal lattice enthalpies predicted theoretically as the sum of electrostatic, dispersive and repulsive interactions. Analysis of crystal lattice enthalpy contributions indicates that dispersive interactions always predominate. Interactions are enhanced in acridin-9(10H)-one where intermolecular hydrogen bonds occur: this is reflected in the relatively high enthalpy of sublimation. This revised version was published online in July 2006 with corrections to the Cover Date.     

Thermochemistry of aromatic ketones. Experimental enthalpies of formation and structural effects

The standard enthalpies of formation Δ_fH^o (liq. or cr.) at the temperature T = 298.15 K were measured using combustion calorimetry for benzophenone (A), 1-indanone (B), -tetralone (C), 9-fluorenone (D), anthrone (E) and dibenzosuberone (F). The standard enthalpies of vaporization Δ_vH^o or sublimation Δ_sH^o of A-F and 5,7-dihydro-6H-dibenzo[a,c]cyclohepten-6-one (G) were obtained from the temperature function of the vapor pressure measured in a flow system. Enthalpies of fusion Δ_mH of solid compounds were measured by DSC. From the enthalpies of formation of the gaseous compounds of A-G the values of their strain enthalpies were derived and structural effects discussed.

     

A novel synthesis of the isoxazolo[5,4,3-kl]acridine ring system

The Schmidt reaction of 6,7-dihydro-3-phenyl-1,2-benzisoxazol-4(5H)-one ( 1 ) is described. In addition to the expected isomeric lactams, 3-phenyl-5,6,7,8-tetrahydro-4H-isoxazolo[4,5-c]azepin-4-one ( 3 ) and 7,8-dihydro-3-phenyl-4H-isoxazolo[4,5-b]azepin-5(6H)-one ( 4 ), 4-amino-3-phenyl 1,2-benzisoxazole (5) was isolated, along with 4,5-dihydro-3H-isoxazolo[5,4,3-kl]acridine ( 6 ). Possible mechanisms for the formation of these products are discussed and some chemistry of the little-known ring system represented by 6 is also described.     

Indolizidine synthesis by transannular cyclization

Beckmann rearrangement of alkylcyclooctenone oximes VIa and VIb gave corresponding nine-membered lactams 1,3,4,5,8,9-hexahydro-3-methyl-2H-azonin-2-one (VIIIa) and 1,3,4,5,8,9-hexahydro-3-butyl-2H-azonin-2-one (VIIIb), respectively. A stereospecific transannular cyclization was induced by mercuric acetate leading to alkyl indolizinones Xa and Xb. Temperature and solvent dependent nmr spectra of the medium ring lactams indicates the stereochemical control is caused by steric interactions of the alkyl side chain. Lithium aluminum hydride reduced Xa/Xb to cis-octahydro-6-methylindolizidine (XIa) and cis-octahydro-3-n-butylindolizidine (XIb).     

Thermodynamic properties of quinoxaline-1,4-dioxide derivatives: a combined experimental and computational study

The mean (N-O) bond dissociation enthalpies were derived for three 2-methyl-3-(R)-quinoxaline 1,4-dioxide (1) derivatives, with R = methyl (1a), ethoxycarbonyl (1b), and benzyl (1c). The standard molar enthalpies of formation in the gaseous state at T = 298.15 K for the three 1 derivatives were determined from the enthalpies of combustion of the crystalline solids and their enthalpies of sublimation. In parallel, accurate density functional theory-based calculations were carried out in order to estimate the gas-phase enthalpies of formation for the corresponding quinoxaline derivatives. Also, theoretical calculations were used to obtain the first and second N-O dissociation enthalpies. These dissociation enthalpies are in excellent agreement with the experimental results herewith reported.     

Thermodynamic functions of lactones in the gaseous state

The temperature dependences of the vapor pressures of oxacyclobutan-2-one and oxacyclopentan-2-one were measured by the transpiration method. The entropies of gaseous oxacycloalkan-2-ones (lactones) were determined based on the experimental values of entropy in the condensed state, vapor pressure, and enthalpy of vaporization. Thermodynamic functions of lactones with a ring size of n = 4—8 (number of atoms in the ring) were determined by quantum chemistry and statistical physics methods in the ideal gas approximation taking into account the molar fractions of all conformers and optical isomers in the temperature range from 298.15 to 1500 K. The enthalpies of ring strain were calculated based on the enthalpies of formation.     

Intramolecular hydrogen abstraction promoted by amidyl radicals. Evidence for electronic factors in the nucleophilic cyclization of ambident amides to oxocarbenium ions

A tandem 1,5-hydrogen atom transfer/radical oxidation/nucleophilic cyclization mechanism is proposed for the intramolecular hydrogen abstraction reaction promoted for primary carboxamidyl radicals. The electron-withdrawing capacity of the C-5 substituent can switch the reaction to give exclusively bicyclic spirolactams (6-oxa-1-azaspiro[4.5]decan-2-one) when R(1) = H or spirolactones (1,6-dioxaspiro[4.5]decan-2-one) when R(1) = OAc. With a substituent of medium polarity (R(1) = OMe), a mixture of lactones and lactams is formed.     

Isofagomine lactams,synthesis and enzyme inhibition

The synthesis of isofagomine lactams (2-oxoisofagomines) corresponding to the biologically important hexoses is presented. The D-glucose/D-mannose analogue (3S,4R,5R)-3,4-dihydroxy-5-hydroxymethylpiperidin-2-one (9) was synthesised in 9 steps from D-arabinose, the D-galactose analogue (3S,4S,5R)-3,4-dihydroxy-5-hydroxymethylpiperidin-2-one (10) was synthesised in 11 steps from D-arabinose and the L-fucose analogue (3R,4R,5R)-3,4-dihydroxy-5-methylpiperidin-2-one (11) was synthesised in 12 steps from L-arabinose. The three lactams 9-11 were found to be glycosidase inhibitors with micro- to nanomolar inhibition constants. The lactam 10 showed slow onset inhibition of beta-galactosidase from A. Oryzae. The rate constants for this process were determined to be k(on) = 2.55 x 10(4) M-1 s-1 and k(off) = 1.7 x 10(-3) s-1. The activation energies and standard thermodynamic functions were also determined.     

Enthalpy of the gas-phase CO2 + Mg reaction from ab initio total energies

Various highly accurate ab initio composite methods of Gaussian-n (G1, G2, G3), their variations (G2(MP2), G3(MP2), G3//B3LYP, G3(MP2)//B3LYP), and complete basis set (CBS-Q, CBS-Q//B3LYP) series of models were applied to compute reaction enthalpies of the ground-state reaction of CO2 with Mg. All model chemistries predict highly endothermic reactions, with DeltaH(298) = 63.6-69.7 kcal x mol(-1). The difference between the calculated reaction enthalpies and the experimental value, evaluated with recommended experimental standard enthalpies of formation for products and reactants, is more than 20 kcal x mol(-1) for all methods. This difference originates in the incorrect experimental enthalpy of formation of gaseous MgO given in thermochemical databases. When the theoretical formation enthalpy for MgO calculated by a particular method is used, the deviation is reduced to 1.3 kcal x mol(-1). The performance of the methodologies used to calculate the heat of this particular reaction and the enthalpy of formation of MgO are discussed.     

A new chemoenzymatic approach to the synthesis of chiral 4-aryl-1,4-dihydro-2H-isoquinolines via the enzymatic resolution of 2-acetyl-4-phenyl-1,4-dihydro-2H-isoquinolin-3-one

A new chemoenzymatic method is proposed for the synthesis of enantiomerically pure 4-phenyl-1,4-dihydro-2H-isoquinolines based on the enzymatic kinetic resolution of 2-acetyl-4-phenyl-1,4-dihydro-2H-isoquinolin-3-one. For the enzymatic resolution of the racemic substrate, readily available ‘home made’ animal liver acetone powders (LAPs) were used. Excellent enantioselectivity, exceeding 500, was achieved in a short reaction time upon application of turkey liver acetone powder as the biocatalyst. Reduction of obtained product led to the formation of amine (R)-1, which is hardly available using standard procedures. These results show that N-acetyl lactams are a new type of substrate for enzymatic biotransformations.     

The synthesis of medium-sized cyclic lactams by the intramolecular friedel-crafts cyclization of isocyanates. Formation of novel pyrazolo[3,4-c]benzolactams

A series of 4-ω-phenylalkyl substituted-1H-pyrazol-5-amines has been synthesized from the corresponding α-acetylphenylalkanenitriles and methylhydrazine. They were converted into the corresponding 5-isocyanates and cyclized under Friedel-Crafts conditions to medium-sized cyclic lactams. The reaction was shown to give the 7-, 8-, 9-, and 10-membered lactams but failed to yield the 11-membered lactam. Rings synthesized were: pyrazolo[3,4-c][2]benzazepin-2(1H)-one; 10H-pyrazolo[3,4-c][2]benzazocin-10-one; pyrazolo[3,4-c][2]benzazonin-11(1H)-one; 12H-pyrazolo[3,4-c][2]benzazocin-12-one.     

NMR study of cis3̄trans isomerism in N-methylated lactams with 11- and 13-membered rings

From ¹H-NMR spectra of 1-methyl-azacyclo-undeca-2-one and 1-methyl-azacyclo-trideca-2-one, the bands corresponding to the cis and trans forms have been assigned and analyzed; based on this analysis, conformational structures about the C-C bond next to nitrogen are proposed. By analysis of the relative areas and shapes of the N-methyl bands measured for the two lactams in 1,1,2,2-tetrachloroethane-d₂, over a broad temperature range, the equilibrium and thermodynamic parameters characterizing the cis—trans isomerism of the amide bond in these lactams have been determined. Peaks corresponding to the cis and trans forms in the ¹³C-NMR spectra of these lactams have also been assigned.     

Straightforward asymmetric entry to highly functionalized 3-substituted 3-hydroxy-beta-lactams via Baylis-Hillman or bromoallylation reactions

The reaction of various activated vinyl systems, including 2-cyclopenten-1-one, with enantiopure azetidine-2,3-diones 1 was promoted by DABCO to afford the corresponding optically pure Baylis-Hillman adducts 2 without detectable epimerization. However, the reaction of alpha-keto lactams 1 with but-3-yn-2-one was not as successful, giving the corresponding beta-halo Baylis-Hillman adduct in low yield. Metal-mediated bromoallylation reaction between 2,3-dibromopropene and azetidine-2,3-diones 1 was investigated in aqueous media. Surprisingly, indium was unable to promote the bromoallylation reaction of alpha-keto lactams 1, but the Sn-Hf(4)Cl-promoted bromoallylation of ketones 1 proceeded efficiently to achieve bromohomoallyl alcohols 5 as single diastereomers. On this basis, simple and fast protocols for the asymmetric synthesis of the potentially bioactive 3-substituted 3-hydroxy-beta-lactam moiety were developed.     

Insights into regioselective oxy (-O-) and imino (-NH-) group insertions of 3-nortricyclanone.

Lactam 4-azatricyclo[3.2.1.0(2,7)]octan-3-one (16a) was proven to be formed in a previously reported reaction that claimed production of lactam 3-azatricyclo[3.2.1.0(2,7)]octan-4-one (17a). In a related reaction, bicyclo[3.1.0]hex-2-ene-endo-6-carbonitrile (15), lactam (16a), and novel hydroxycarbonitriles 19-21 were selectively formed when 3-nortricyclanone (1) was treated with aqueous hydroxylamine-O-sulfonic acid (HOSA). Since nitrile 15 neither hydrolyzed nor underwent intramolecular Ritter reaction under these conditions, mechanisms involving Beckmann rearrangement of 3 to nitrilium ion 9 (normal) and Beckmann fragmentation of 3 to cation 8 (abnormal) were investigated using semiempirical calculations. When alkaline HOSA was employed, lactams 16a and 17a were formed in a 1:2 ratio, perhaps via oxaziridine 6a. A similar selectivity was observed using an NH(3)/NaOCl reagent solution, which afforded lactone 4-oxatricyclo[3.2.1.0(2,7)]octan-3-one (16b) in addition to both lactams. Consequently, the Baeyer-Villiger oxidation of 1 with NaOCl gave 16b exclusively. Finally, the Schmidt reaction of ketone 1 gave only the lactam 17a, via cyclopropyl migration, and the same fragmentation products obtained from the acidic HOSA reaction. Migration selectivities are rationalized in terms of nucleofugacity, electronic effects, cyclopropyl regulation, and MO theory.     

Computational study of the thermochemistry of organophosphorus(III) compounds

The enthalpies of formation of organophosphorus(III) compounds have been calculated at the G3X, G3X(MP2), and B3LYP/6-311+G(3df,2p)//B3LYP/6-31G(d,p) levels of theory using the atomization energy procedure and the method of isodesmic reactions. The Delta f H298 degree values for 50 relatively large molecules with up to 10 non-hydrogen atoms, such as P(CH3)3, P(C2H5)3, P(OCH3)3, n-C4H9OPCl2, [(CH3)2N]2PCl, (C2H5)2NPCl2, and [(CH3)2N]2PCN, have been calculated directly from the G3X atomization energies. A good agreement between the known experimental values and G3X results for 14 compounds provides support to our predictions for remaining species whose experimental enthalpies of formation are unknown or known with relatively large uncertainties. On the basis of our calculations and sometimes conflicting experimental data a set of internally consistent enthalpies of formation has been recommended for organophosphorus(III) compounds. Our computational results call into question the experimental enthalpies of formation of P(C2H5)3 and P(n-C4H9)3. From comparison with most reliable experimental data, the accuracy of the theoretical enthalpies of formation is estimated as ranging from 5 to 10 kJ/mol. The recommended Delta f H298 degree values were used to derive the group additivity values (GAVs) for 45 groups involving the phosphorus(III) atom. These GAVs significantly extend the applicability of Benson's group additivity method and may be used to estimate the enthalpies of formation of larger organophosphorus(III) compounds, where high level quantum chemical calculations are impracticable.