Novel ring-cleaving reaction of 4-nitro-1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane with nucleophiles

When 4-nitro-AF4 is treated with nucleophiles such as alkoxides and cyanide, a novel ring opening, cyclophane destroying reaction is observed whereby, via an S_NAr mechanism, the nucleophile attacks the bridgehead aryl carbon vicinal to the nitro group with subsequent aryl-CF₂ bond cleavage.     

Synthetic studies on 3-arylquinazolin-4-ones: intramolecular nucleophilic aromatic substitution reaction of 2-carboxamido-3-arylquinazolin-4-ones and its application to the synthesis of secondary aryl amines

The general synthesis and a novel intramolecular nucleophilic aromatic substitution (S_NAr) reaction of 2-carboxamido-3-arylquinazolin-4-ones, a potentially useful scaffold in the field of medicinal chemistry, are described. The synthetic utility of the S_NAr reaction as a tool for the synthesis of secondary aryl amines, including diaryl amines, is also demonstrated.     

NMR studies of 4(3H)-quinazolinones and 4(3H)-quinazolinethiones

Summary Unambiguous¹H and¹³C NMR assignments for 4(3H)-quinazolinones1–6 and their corresponding 4-thiones7–12 have been made. This resulted in the revision of the previous assignments for the two benzenoid carbons (C-5 and C-8) of quinazolinones1,2,4, and5. Thionation of the nucleophilic amides1–6 has been found to cause a distinct change in the¹³C chemical shift of particularly C-4, but also of those of C-4a, C-5, and C-8a. One-bond and several long range heteronuclear coupling constants for the compounds have also been measured.

---

Kernresonanzspektroskopie von 4(3H)-Chinazolinonen und 4(3H)-Chinazolinthionen

Zusammenfassung Die¹H- und¹³C-NMR-Spektren der 4(3H)-Chinazolinone1–6 und ihrer entsprechenden 4-Thione7–12 wurden zugeordnet. Dabei zeigte sich, daß eine frühere Zuordnung der beiden benzoiden Kohlenstoffe (C-5 und C-8) der Chinazolinone1,2,4 und5 falsch war. Ersatz des Sauerstoffs durch Schwefel in den nukleophilen Amiden1–6 führt insbesondere für C-4, aber auch für C-4a, C-5 und C-8a zu einer deutlichen Änderung der chemischen Verschiebung. Heteronukleare Kopplungskonstanten über eine und über mehrere Bindungen wurden bestimmt.

     

1H NMR spectra and ring shapes of the 4,5,8-trimethyl and 4-methyl derivatives of 1-tetralone

The 220 MHz spectra of the title compounds are reported and values for the internal ring dihedral angle, Ψ, formed between the C-2? C-1 and C-3? C-4 bonds, calculated using the R-value method. The trimethyltetralone exists in a conformer having Ψ = 51° and the 4-methyl group in the axial position. 4-Methyl-1-tetralone exists in a conformational equilibrium where the mean value of Ψ for the conformers adopted is 56°.     

1, 3-双磷(膦)酰基丙烯类化合物的^1H、^3^1P NMR研究

本文报道了标题类化合物中十个化合物的^1H和^3^1PNMR的研究结果。其中分别运用了2DJ分解谱以及异核COSY谱等多种技术,解析了它们的^1H和^3^1P图谱,从而证实了合成反应的区域选择性和立体选择性。文章中,讨论了手性中心或其它因素而表现出的不等性;讨论了影响δ~P和J~p~H数值的各种因素:还报道了比较少见的^3^1P-^3^1P之间的远程偶合。其中,顺式产物的^4J~P~P数值(约9Hz)大于反式产物的^4J~P~P(约7Hz)。     

Regioselective, nucleophilic carbon-carbon bond formation at the C4-position of indoles initiated by the aromatic Pummerer-type reaction

The treatment of the 5-(phenylsulfinyl)indoles with trifluoroacetic anhydride in the presence of carbon nucleophiles achieved the title reactions with complete regioselectivity.     

Mechanism and kinetics of the reaction NO3 + C2H4

The reaction of NO(3) radical with C(2)H(4) was characterized using the B3LYP, MP2, B97-1, CCSD(T), and CBS-QB3 methods in combination with various basis sets, followed by statistical kinetic analyses and direct dynamics trajectory calculations to predict product distributions and thermal rate constants. The results show that the first step of the reaction is electrophilic addition of an O atom from NO(3) to an olefinic C atom from C(2)H(4) to form an open-chain adduct. A concerted addition reaction mechanism forming a five-membered ring intermediate was investigated, but is not supported by the highly accurate CCSD(T) level of theory. Master-equation calculations for tropospheric conditions predict that the collisionally stabilized NO(3)-C(2)H(4) free-radical adduct constitutes 80-90% of the reaction yield and the remaining products consist mostly of NO(2) and oxirane; the other products are produced in very minor yields. By empirically reducing the barrier height for the initial addition step by 1 kcal mol(-1) from that predicted at the CBS-QB3 level of theory and treating the torsional modes explicitly as one-dimensional hindered internal rotations (instead of harmonic oscillators), the computed thermal rate constants (including quantum tunneling) can be brought into very good agreement with the experimental data for the overall reaction rate constant.     

1H and 13C NMR studies on 3-aryl-2-thioxo-4-oxazolidinones and 3-arylrhodanines

3-Aryl-2-thioxo-4-oxazolidinones and 3-arylrhodanines have been studied for magnetic non-equivalence of diastereotopically related proton and ¹³C nuclei in rotational isomers, and for steric interactions between the aryl and heterocyclic moieties of these compounds. For the majority of rotational isomers the barriers to internal rotation about the aryl C? N bond were >100 kJ mol^?1, due to the steric bulk of the thiocarbonyl group. Chemical isolation of several of the diastereomers was achieved. The enhanced steric effect and the difference in the electronic effect of the sulphur atom in relation to the oxygen atom appeared to have no influence on the small chemical shift differences of the rotational isomers, detected for some ¹H and some ¹³C nuclei.     

Vibrational spectrum of 3-methyl and 4-methylpyridine

The assignments of the vibrational spectra of the 3-methyl and 4-methylpyridine molecules have been carried out following the SQMFF methodology (scaled quantum mechanical force field). The theoretical frequencies have been obtained by calculating the RHF/3-21G force field, using the scale factors for pyridine and 2-methylpyridine and are correlated in a satisfactory manner with the frequencies recorded in the IR and Raman of these methyl derivatives.     

H NMR studies on the reductively triggered release of heterocyclic and steroid drugs from 4,7-dioxoindole-3-methyl prodrugs

Hypoxia is a feature of several disease states, including cancer and rheumatoid arthritis. Prodrug systems which, after bioreduction, selectively release active drugs in these tissues may be important in therapy. An improved preparation of 1,2-dimethyl-3-hydroxymethyl-5-methoxyindole-4,7-dione was developed. Mitsunobu coupling with (5-substituted) isoquinolin-1-ones (potent inhibitors of poly(ADP-ribose)polymerase) gave 1-(1,2-dimethyl-4,7-dioxo-5-methoxyindol-3-ylmethoxy)isoquinolines and N-(1,2-dimethyl-4,7-dioxo-5-methoxyindol-3-ylmethyl)isoquinolin-1-ones. Similar coupling with the anticancer drug pentamethylmelamine gave its potential prodrug 1,2-dimethyl-3-(N-(4,6-bis(dimethylamino)-1,3,5-triazin-2-yl)-N-methylaminomethyl)-5-methoxyindole-4,7-dione. Treatment of sodium prednisolone hemisuccinate with 3-chloromethyl-1,2-dimethyl-5-methoxyindole-4,7-dione gave an analogous candidate prodrug of the anti-inflammatory drug prednisolone. In a chemical model system for bioreduction, SnCl₂ in CDCl₃/CD₃OD triggered rapid stoichiometric release of isoquinolin-1-ones from the O-linked prodrugs but not from the N-linked analogues. Use of this system allowed the release process to be monitored in situ by ¹H NMR spectroscopy. Diethyl hydrazine-1,2-dicarboxylate was found to reduce Sn^IV to Sn^II, making the overall reductive release catalytic in tin. The reduced (hydroquinone) prodrug may have a short lifetime under these reductive conditions, meaning that only good leaving groups are expelled. Thus 1-(1,2-dimethyl-4,7-dioxo-5-methoxyindol-3-ylmethoxy)isoquinolines and analogues may be useful as reductively triggered prodrugs.     

A shock-tube study of the kinetics of reaction of hydroxyl radicals with H2, CO,CH4, CF3H,C2H4, and C2H6

Concentration-time profiles have been measured for hydroxyl radicals generated by the shock-tube decomposition of hydrogen peroxide in the presence of a variety of additives. At temperatures close to 1300°K the rate constants for the reaction are found to be in the ratio 0.18:0.19:0.59:1.00:2.33:2.88 for the additives CO:CF₃H:H₂:CH₄:C₂H₄:C₂H₆, respectively.     

自然轨道福井函数和成键活性描述符应用于解释苯硫醌和1, 3-二烯的[2+4]和[4+2]环加成反应中的成键机理

苯硫醌与脂肪族烯烃可以发生[2+4]和[4+2]环加成反应。为了解释这些环加成反应中的成键过程,本文使用了自然轨道福井函数(NOFF)与成键活性描述符。自然轨道福井函数揭示了苯硫醌和脂肪族烯烃的键或轨道的亲电性,表明电子供体的成键轨道和电子受体的反键/成键轨道之间发生了电子转移,然后成环,在这一过程中有两个共价键形成,得到了环状产物。成键活性描述符表明共价键比较容易在一个分子中具有较大f_k1⁺值的k1原子与另一个分子中具有较大f_k2^-值的k2原子之间形成。自然轨道福井函数与成键活性描述符都可以有效解释苯硫醌与1, 3-二烯之间的[2+4]与[4+2]环加成反应的机理。     

Unambiguous structure elucidation of the reaction products of 3-acyl-4-methoxy-1-methylquinolinones with hydroxylamine via NMR spectroscopy

Reaction of 3-acyl-4-methoxy-1-methylquinolinones 2a,b with hydroxylamine has been investigated under different experimental conditions. Whereas compound 2a gives rise selectively and exclusively to the regioisomeric isoxazolo[4,5-c]- or isoxazolo[4,3-c]quinolin-4(5H)one (compound 3a or 4a, respectively), reaction of 2b always led to a mixture of the required isoxazole together with the oxazole derivative. Structural elucidation of all products has been independently achieved by multinuclear (¹³C and ¹⁵N) magnetic resonance spectroscopy.     

1H and 13C NMR studies of some aromatic dilactones (precursors of paracyclophanes)

Carbon-13 and proton NMR data of macrocyclic diaromatic dilactones are presented. The observed behaviour of the spectra as a function of temperature shows that the energy barrier for the re-orientation of the side chains is lower than 49 kJ mol^?1 (12 kcal mol^?1) and that the energy barrier for the rotation of the aromatic rings is larger than 99 kJ mol^?1 (24 kcal mol^?1). Hence, chiral substituted dilactones of this type will be resolvable, and the enantiomers can be easily handled at room temperature.     

1H NMR Study on the Isomerization of 2,4,6-Triphenyl-4H-Seleno(Thio)Pyrans

It is shown using ¹H NMR spectroscopy that 2,4,6-triphenyl-4H-seleno(thio)pyrans can be isomerized into 2H-isomers by the action of lithium perchlorate or lithium chloride in DMF or only by DMF. The reaction time is found to depend on the Lewis acidity of used salt. It is supposed that isomerization in presence of Lewis acids proceeds as endocyclic 1,3-proton transfer or as a series of two 1,2-hydride shifts.     

Vibrational and electronic absorption spectra of 4-chloro 2-methyl, 4-chloro 3-methyl and 6-chloro 3-methyl phenols

The infrared spectra of 4-Cl 2-Me, 4-Cl 3-Me and 6-Cl 3-Me phenols have been recorded. The vibrational spectrum has been analysed assuming that the molecules belong toC _s point group and a tentative assignment of the observed frequencies to various modes of vibration has been proposed. The near ultraviolet absorption spectrum of these compounds has also been recorded. Assuming the transition to be electronically allowed the strongest band on the longer wavelength side has been assigned as the (0, 0) band in each case. The spectrum has been analysed in terms of several excited state frequencies which have been correlated with the ground state frequencies observed in the infrared spectrum.     

2－氯／2－甲磺酰基－5－（2－苯基－4－喹啉基）－1，3，4－噁二唑化合物的合成及其亲核取代的研究

借处理２－羟基－５－（２－苯基－４－喹啉基）－１，３，二唑同ＰＣｌ＿５／ＰＯＣｌ＿３之间的反应合成了２－氯－５－（２－苯基－４－喹啉基）－１，３，４－二唑（３）和通过２－基－５－（２－苯基－４－喹啉基）－１，３，４－二唑的甲基化，然后氧化制得２－甲磺酰基－５－（２－苯基－４－喹啉基）－１，３，４－二唑（６）．并分别研究了３和６同胺、叠氮及肼的反应，得到２，５－二取代的二唑新衍生物．初步观察了部分化合物的抗菌活性．     

1H, 13C NMR, X-ray and conformational studies of new 1-alkyl-3-benzoyl-pyrazole and 1-alkyl-3-benzoyl-pyrazoline derivatives

The (1)H and (13)C NMR resonances of 22 1-alkyl-pyrazole and 25 1-alkyl-pyrazoline derivatives were assigned completely using the concerted application of one- and two-dimensional experiments (DEPT, gs-HMQC and gs-HMBC). Nuclear Overhauser enhancement (NOE) effects, conformational analysis and X-ray crystallography confirm the preferred conformation of those compounds.     

The preparation and cycloaddition reaction of 1-sulfonyl-1-trifluoromethyl allenes

A series of 1-sulfonyl-1-trifluoromethyl allenes were prepared for the first time from commercial available 2-bromo-3,3,3-trifluoropropene. Cycloaddition reaction of these trifluoromethylated allenes with nitrones occured readily under mild conditions, giving the corresponding trifluoromethylated isoxazolidines in high yields.