Through‐space 19F–19F spin–spin coupling in ortho‐fluoro Z‐azobenzene

We report through‐space (TS) ¹⁹F–¹⁹F coupling for ortho‐fluoro‐substituted Z ‐azobenzenes. The magnitude of the TS‐coupling constant (^TSJ_FF) ranged from 2.2–5.9 Hz. Using empirical formulas reported in the literature, these coupling constants correspond to non‐bonded F–F distances (d_FF) of 3.0–3.5 Å. These non‐bonded distances are significantly smaller than those determined by X‐ray crystallography or density functional theory, which argues that simple models of ¹⁹F–¹⁹F TS spin–spin coupling solely based d_FF are not applicable. ¹H, ¹³C and ¹⁹F data are reported for both the E and Z isomers of ten fluorinated azobenzenes. Density functional theory [B3YLP/6‐311++G(d,p)] was used to calculate ¹⁹F chemical shifts, and the calculated values deviated 0.3–10.0 ppm compared with experimental values. Copyright © 2015 John Wiley & Sons, Ltd.     

Discrimination of pseudo‐meta and pseudo‐para diamino‐octafluoro[2.2]paracyclophanes by 1H, 19F,and 13C NMR

Pseudo‐meta and pseudo‐para diamino‐octafluoro[2.2]paracyclophanes are challenging to separate either by chromatography or recrystallization, but through the use of a mixture of the two isomers, the ¹H, ¹⁹F, and ¹³C NMR spectra of these compounds have been fully and unambiguously assigned using ¹H COSY, ¹H‐¹⁹F HOESY, ¹H‐¹³C HSQC, ¹H‐¹³C HMBC, and ¹⁹F‐¹³C HSQC techniques. This permits the easy identification of either of the individual isomers. In addition, the ¹³C spectrum of the pseudo‐ortho analogue is reported and assigned for the first time. The gem shift effect in this series of bridge‐fluorinated paracyclophanes serves to deshield ¹H resonances and shield ¹³C. Copyright © 2012 John Wiley & Sons, Ltd.     

Mono‐ and difluorinated 1,1,2,2,9,9,10,10‐octafluoro[2.2]paracyclophanes (AF4s)—A 1H and 19F NMR study

Complete assignment of the ¹H and ¹⁹F chemical shifts in 4‐fluoro‐AF4 (1) were based on the nOes seen in its ¹⁹F‐¹H HOESY spectrum. This allowed for identification of features which can further be applied to the assignment of the regiochemistry of substituted perfluoroparacyclophanes (PCPs) and AF4s: (i) an aromatic fluorine couples with the two fluorines in the closest bridge that are syn to it, with constants of ca. 20 Hz; (ii) an aromatic fluorine couples with the bridge fluorine five bonds away that is anti to it in the same paraphenylene moiety, with a constant of ca. 3.5 Hz; (iii) the geminal coupling of the bridge fluorines is 246 Hz if they have an ortho fluorine and 238 Hz if they do not; (iv) a bridge fluorine couples with those aromatic protons in the same paraphenylene moiety that are four or five bonds away and anti. These features have been used to assign the regiochemistry of the pseudo‐ortho, pseudo‐meta and pseudo‐para‐difluoro AF4s 2–4. It has also been demonstrated that SCS for the bridge fluorines can be used as well for this assignment. Copyright © 2009 John Wiley & Sons, Ltd.     

2D F/F NOESY for the assignment of NMR spectra of fluorochemicals

Two-dimensional (2D) NMR is an invaluable technique for the complete analysis and assignment of chemical structures. Although ¹⁹F/¹⁹F COSY experiments are routinely used for assignments in perfluorochemicals, interpretation can be difficult because four-bond (⁴J_FF) coupling constants are typically 5-10-fold larger than vicinal (³J_FF) coupling constants. Furthermore, the dependence of long range coupling constants on stereochemistry is not always known. Fluorine-fluorine NOESY correlations represent an enhancement in the arsenal of 2D ¹⁹F NMR experiments. The NOESY and COSY spectra of 2,2,3,3,4,4,4-heptafluorobutanol and a telomeric perfluorochemical iodide show that COSY identifies the 1,4-fluorine interactions whereas NOESY identifies the vicinal fluorine atoms. The combined experiments have been used to unambiguously assign all of the fluorines in a mixture of cis- and trans-perfluoro-1,3-dimethylcyclohexane and in a substituted perfluorotetrahydrofuran.     

Comparison of 1H–19F two‐dimensional NMR scalar coupling correlation pulse sequences

The effectiveness of hetero‐COSY, HETCOR, HMQC, and HSQC two‐dimensional NMR pulse sequences for detection of ¹⁹F–¹H correlations by scalar coupling was evaluated on monofluorinated and polyfluorinated test compounds. All four of these sequences were effective in observing ¹H–¹⁹F correlations, using either ¹⁹F or ¹H as the observe nucleus. All four sequences were amenable, to some degree, to adjustment to observe larger or smaller couplings preferentially. A 1/2J echo filter was effectively applied to remove artifacts from ²J_FF strong coupling. The HETCOR experiments afforded the best overall combination of sensitivity, resolution and selectivity for J_HF. Copyright © 2014 John Wiley & Sons, Ltd.     

1H,13C and 19F NMR data of N‐substituted 6‐(4‐methoxyphenyl)‐7H‐pyrrolo[2,3‐d]pyrimidin‐4‐amines in DMSO‐d6

Chemical shift assignment of seven N‐substituted 6‐(4‐methoxyphenyl)‐7H‐pyrrolo[2, 3‐d]pyrimidin‐4‐amines, six of which are fluorinated, have been performed based on ¹H, ¹³C, ¹⁹F, and 2D COSY, HMBC and HSQC experiments. Copyright © 2009 John Wiley & Sons, Ltd.     

Complete assignment of NMR data of 22 phenyl‐1H‐pyrazoles' derivatives

Complete assignment of ¹H and ¹³C NMR chemical shifts and J(¹H/¹H and ¹H/¹⁹F) coupling constants for 22 1‐phenyl‐1H‐pyrazoles' derivates were performed using the concerted application of ¹H 1D and ¹H, ¹³C 2D gs‐HSQC and gs‐HMBC experiments. All 1‐phenyl‐1H‐pyrazoles' derivatives were synthesized as described by Finar and co‐workers. The formylated 1‐phenyl‐1H‐pyrazoles' derivatives were performed under Duff's conditions. Copyright © 2011 John Wiley & Sons, Ltd.     

2D-NMR studies of a model for Krytox® fluoropolymers

Multiple two‐dimensional nuclear magnetic resonance (2D‐NMR) techniques have been used to study the structures of Krytox^® perfluoro(polyalkyl ether) and its mechanism of polymerization. Model compound K₄, containing four Krytox^® fluoropolymer repeat units, was analyzed to interpret the multiplet patterns in the NMR spectra from the polymer model. ¹⁹F {¹³C}‐Heteronuclear single‐quantum correlation experiments, performed with delays optimized for ¹J_CF and ²J_CF, provided spectra that permitted identification of resonances from individual monomer units. Selective, ¹⁹F‐¹⁹F COSY 2D‐NMR experiments were performed with different excitation regions; these experiments were combined with selective inversion pulses to remove ¹⁹F‐¹⁹F J couplings in the f₁ dimension. The resulting COSY spectra were greatly simplified compared with standard ¹⁹F‐¹⁹F COSY spectra, which are too complicated to interpret. They give information regarding the attachments of monomer units and also provide insights into the nature of the stereoisomers that might be present in the polymer. Both infrared and NMR spectra show peaks identifying chain end structures. With the help of these studies, resonances can be assigned, and the average number of repeat units in the polymer chain can be calculated based on the assignments obtained. Copyright © 2011 John Wiley & Sons, Ltd.     

Full multinuclear resonance analysis of 4-amino-1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane

The complete assignment of 19F, 1H and 13C NMR spectra for a monosubstituted octafluoro[2.2]paracyclophane derivative is described for the first time. The unambiguous assignments were achieved through the combination of 19F--1H HOESY, 1H COSY and 19F COSY techniques and then further confirmed employing a complementary approach using a Karplus-dependent 3JCF interaction. Interesting aspects of the coupling patterns for various JHH, JHF, JCF and JFF interactions are also discussed.     

Precise Measurement of Long‐Range Heteronuclear Coupling Constants by a Novel Broadband Proton–Proton‐Decoupled CPMG‐HSQMBC Method

A broadband proton–proton‐decoupled CPMG‐HSQMBC method for the precise and direct measurement of long‐range heteronuclear coupling constants is presented. The Zangger–Sterk‐based homodecoupling scheme reported herein efficiently removes unwanted proton–proton splittings from the heteronuclear multiplets, so that the desired heteronuclear couplings can be determined simply by measuring frequency differences between singlet maxima in the resulting spectra. The proposed pseudo‐1D/2D pulse sequences were tested on nucleotides, a metal complex incorporating P heterocycles, and diglycosyl (di)selenides, as well as on other carbohydrate derivatives, for the extraction of ⁿJ(¹H,³¹P), ⁿJ(¹H,⁷⁷Se), and ⁿJ(¹H,¹³C) values, respectively.     

Transannular Hydrogen Bonding in Planar‐Chiral [2.2]Paracyclophane‐Bisamides

A series of [2.2]paracyclophane‐bisamide regioisomers and alkylated comparators were designed, synthesized, and characterized in order to better understand the transannular hydrogen bonding of [2.2]paracyclophane‐based molecular recognition units. X‐Ray crystallography shows that transannular hydrogen bonding is maintained in the solid‐state, but no stereospecific self‐recognition is observed. The assignment of both transannularly and intermolecularly hydrogen bonded N?H stretches could be made by infrared spectroscopy, and the effect of transannular hydrogen bonding on amide bond rotation dynamics is observed by ¹H‐NMR in nonpolar solvents. The consequences of transannular hydrogen bonding on the optical properties of [2.2]paracyclophane is observed by comparing alkylated and non‐alkylated pseudo‐ortho 4,12‐[2.2]paracyclophane‐bisamides. Finally, optical resolution of 4‐mono‐[2.2]paracyclophane and pseudo‐ortho 4,12‐[2.2]paracyclophane‐bisamides was achieved through the corresponding sulfinyl diastereoisomers for circular dichroism studies. Transannular hydrogen bonding in [2.2]paracyclophane‐amides allows preorganization for self‐complementary intermolecular assembly, but is weak enough to allow rapid rotation of the amides even in nonpolar solvents.     

Synthesis of 1‐silacyclopent‐2‐ene derivatives using 1,2‐hydroboration, 1,1‐organoboration and protodeborylation

The reaction of di(alkyn‐1‐yl)vinylsilanes R¹(H₂C═CH)Si(C≡C―R)₂ (R¹ = Me ( 1 ), Ph ( 2 ); R = Bu (a), Ph (b), Me₂HSi (c)) at 25°C with 1 equiv. of 9‐borabicyclo[3.3.1]nonane (9‐BBN) affords 1‐silacyclopent‐2‐ene derivatives ( 3a , 3b , 3c , 4a , 4b ), bearing one Si―C≡C―R function readily available for further transformations. These compounds are formed by consecutive 1,2‐hydroboration followed by intramolecular 1,1‐carboboration. Treated with a further equivalent of 9‐BBN in benzene they are converted at relatively high temperature (80–100°C) into 1‐alkenyl‐1‐silacyclopent‐2‐ene derivatives ( 5a , 5b 6a , 6b ) as a result of 1,2‐hydroboration of the Si―C≡C―R function. Protodeborylation of the 9‐BBN‐substituted 1‐silacyclopent‐2‐ene derivatives 3 , 4 , 5 , 6 , using acetic acid in excess, proceeds smoothly to give the novel 1‐silacyclopent‐2‐ene ( 7 , 8 , 9 , 10 ). The solution‐state structural assignment of all new compounds, i.e. di(alkyn‐1‐yl)vinylsilanes and 1‐silacyclopent‐2‐ene derivatives, was carried out using multinuclear magnetic resonance techniques (¹H, ¹³C, ¹¹B, ²⁹Si NMR). The gas phase structures of some examples were calculated and optimized by density functional theory methods (B3LYP/6‐311+G/(d,p) level of theory), and ²⁹Si NMR parameters were calculated (chemical shifts δ²⁹Si and coupling constants ⁿJ(²⁹Si,¹³C)). Copyright © 2014 John Wiley & Sons, Ltd.     

m‐Methoxy Substituents in a Tetraphenylethylene‐Based Hole‐Transport Material for Efficient Perovskite Solar Cells

Three tetrapheynlethylene derivatives (N,N‐di(4‐methoxyphenyl)aminophenyl‐substituted tetraphenylethylene; TPE‐4DPA) with different methoxy positions (pp‐, pm‐, and po‐) have been synthesized and characterized. The methoxy groups can control the oxidation potential of the materials, and the electronic properties of the derivatives were affected by the position of the methoxy substituents. These compounds were synthesized in a facile and cost‐effective way, and were applied as hole‐transport materials in perovskite solar cells. The corresponding cell performances were compared with respect to their structure modifications, and it was found that the derivative with m‐OMe substituents showed the highest power conversion efficiency (PCE) of 15.4 %, with a J_sc value of 20.04 mA cm^?2, a V_oc value of 1.07 V, and a fill factor (FF) value of 0.72, which is higher than the p‐OMe and o‐OMe substituents. Moreover, the PCE of pm‐TPE‐4DPA is comparable with that of the state‐of‐the‐art 2,2′,7,7′‐tetrakis(N,N′‐di‐p‐methoxyphenylamine)‐9,9′‐spirobifluorene under identical conditions.     

Structure elucidation of [1,3]oxazolo[4,5‐e][2,1]benzisoxazole and naphtho[1,2‐d][1,3]‐ and phenanthro[9,10‐d]oxazoles using gradient selected gHMBC,gHMQC and gHMQC‐TOCSY NMR techniques

Structure elucidation of compounds in the benzisoxazole series ( 1 – 6 ) and naphtho[1,2‐d][1,3]‐ ( 7 – 10 ) and phenanthro[9,10‐d][1,3]oxazole ( 11 – 14 ) series was accomplished using extensive 2D NMR spectroscopic studies including ¹H–¹H COSY, long‐ range ¹H–¹H COSY, ¹H–¹³C COSY, gHMQC, gHMBC and gHMQC‐TOCSY experiments. The distinction between oxazole and isoxazole rings was made on the basis of the magnitude of heteronuclear one‐bond ¹J_{C2, H2} (or ¹J_{C3, H3}) coupling constants. Complete analysis of the ¹H NMR spectra of 11 – 14 was achieved by iterative calculations. Gradient selected gHMQC‐TOCSY spectra of phenanthro[9,10‐d][1,3]oxazoles 11 – 14 were obtained at different mixing times (12, 24, 36, 48 and 80 ms) to identify the spin system where the protons of phenanthrene ring at H‐5, H‐6 and at H‐9 and H‐7 and H‐8 were highly overlapping. Copyright © 2003 John Wiley & Sons, Ltd.     

Complete assignments of the 1H and 13C NMR spectra of 15 limonoids

Unambiguous and complete assignments of ¹H and ¹³C NMR chemical shifts for 15 limonoids, eight of them found in natural sources and seven other synthetic derivatives, are presented. The assignments are based on 2D shift‐correlated [¹H,¹H‐COSY, ¹H,¹³C‐gHSQC‐¹J(C,H), ¹H,¹³C‐gHMBC‐ⁿJ(C,H) (n = 2 and 3)] and NOE experiments. Copyright © 2003 John Wiley & Sons, Ltd.     

The synthesis,structural characterization and biological evaluation of N‐(ferrocenylmethyl amino acid) fluorinated benzene‐carboxamide derivatives as potential anticancer agents

A series of N‐(ferrocenylmethyl amino acid) fluorinated benzene‐carboxamide derivatives 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i and 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i have been synthesized by coupling ferrocenylmethyl amine 3 with various substituted N‐(fluorobenzoyl) amino acid derivatives using the standard N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride, 1‐hydroxybenzotriazole protocol. The amino acids employed in this study were glycine and L‐alanine. All of the compounds were fully characterized using a combination of ¹H NMR, ¹³C NMR, ¹⁹F NMR, distortionless enhancement by polarization transfer (DEPT)‐135, ¹H–¹H correlation spectroscopy (COSY) and ¹H–¹³C COSY (heteronuclear multiple‐quantum correlation) spectroscopy. The compounds were biologically evaluated on the oestrogen‐positive MCF‐7 breast cancer cell line. Compounds 4g , 4i , 5h and 5i exhibited cytotoxic effects on the MCF‐7 breast cancer cell line. N‐(Ferrocenylmethyl‐L‐alanine)‐3,4,5‐trifluorobenzene‐carboxamide ( 5h ) was the most active compound, with an IC₅₀ value of 2.84 μm . Compounds 4i , 5h and 5i had lower IC₅₀ values than that found for the clinically employed anticancer drug cisplatin (IC₅₀ = 16.3 μm against MCF‐7). Guanine oxidation studies confirmed that 5h was capable of generating oxidative damage via a reactive oxygen species‐mediated mechanism. Copyright © 2013 John Wiley & Sons, Ltd.     

BASHD‐J‐resolved‐COSY: a new method for measuring proton‐proton spin coupling constants of multiplet signals

An effective pulse sequence for measuring H–H coupling constants, named BASHD‐J‐resolved‐COSY, has been developed. In the spin systems such as –CH_A–CH_B(CH₃)–CH_C–, a methine proton H_B splits into a multiplet owing to several vicinal couplings, resulting in attenuation of its cross‐peak intensity. Therefore, the measurements of ³J_H–H with respect to H_B are generally difficult in the E‐COSY‐type experiments. With the aim of accurate measurements of ³J_H‐H in such a spin system, we have developed a new pulse sequence, which selectively decouples the secondary methyl group. The proposed pulse sequence provides the simplified cross‐peak patterns, which are suitable for reliable measurements of ³J_H‐H in a complicated natural product. Copyright © 2012 John Wiley & Sons, Ltd.     

Stereospecific 5JHortho,OMe couplings in methoxyindoles,methoxycoumarins, and methoxyflavones

Long‐range coupling constants ⁵J_Hortho,OMe were measured in series of methoxyindoles, methoxycoumarins, and methoxyflavones by the modified J doubling in the frequency domain method. The COSY and NOESY spectra revealed the coupling of the –OMe group with a specific proton at the ortho position and its preferred conformation. Homonuclear ¹H–¹H couplings were confirmed by irradiation of the –OMe signal. Density functional theory calculations of ⁵J_Hortho,OMe using the modified aug‐cc‐pVTZ basis set evidenced that the Fermi contact term shows good agreement with the experimental J values. Accurate chemical shift and coupling constant values followed after iterative quantum mechanical spectral analysis using the PERCH software. Copyright © 2014 John Wiley & Sons, Ltd.     

Hydrogen Bonding of Fluorinated Saccharides in Solution: F Acting as H‐Bond Acceptor in a Bifurcated H‐Bond of 4‐Fluorinated Levoglucosans

4‐Fluorinated levoglucosans were synthesised to test if OH???F H‐bonds are feasible even when the O???F distance is increased. The fluorinated 1,6‐anhydro‐β‐D ‐glucopyranoses were synthesised from 1,6 : 3,4‐dianhydro‐β‐D ‐galactopyranose ( 8 ). Treatment of 8 with KHF₂ and KF gave 43% of 4‐deoxy‐4‐fluorolevoglucosan ( 9 ), which was transformed into the 3‐O‐protected derivatives 13 by silylation and 15 by silylation, acetylation, and desilylation. 4‐Deoxy‐4‐methyllevoglucosan ( 19 ) and 4‐deoxylevoglucosan ( 21 ) were prepared as reference compounds that can only form a bivalent H‐bond from HO? C(2) to O? C(5). They were synthesised from the ⁱPr₃Si‐protected derivative of 8 . Intramolecular bifurcated H‐bonds from HO? C(2) to F? C(4) and O? C(5) of the 4‐fluorinated levoglucosans in CDCl₃ solution are evidenced by the ¹H‐NMR scalar couplings ^h1J(F,OH) and ³J(H,OH). The OH???F H‐bond over an O???F distance of ca. 3.0 Å is thus formed in apolar solvents, at least when favoured by the simultaneous formation of an OH???O H‐bond.