One- and two-dimensional NMR studies of methyl acrylate/vinyl acetate/N-vinyl carbazole terpolymers

Terpolymers of methyl acrylate/vinyl acetate/N-vinyl carbazole (M/A/C) with different compositions were synthesized by solution polymerization using AIBN as an initiator. Composition of terpolymers was determined from quantitative ¹³C{¹H} NMR spectrum. Two-dimensional heteronuclear single quantum correlation (HSQC) and total correlated spectroscopy (TOCSY) were used to assign the methylene and methine carbon resonances by analyzing two and three bond order couplings. Various resonance signals were assigned to different compositional and configurational sequences with the help of one- and two-dimensional NMR spectra. Three and four bond order coupling between carbonyl carbon and other neighboring protons have been investigated with the help of 2D heteronuclear multiple bond correlation (HMBC) spectra. The complex and overlapped ¹H NMR spectrum of terpolymer was analyzed completely with the help of 2D HSQC and TOCSY spectra.     

2D NMR studies of acrylonitrile-methyl acrylate copolymers

The microstructure of acrylonitrile-methyl acrylate copolymers prepared by the solution polymerization using 2,2′-azobisisobutyronitrile (AIBN) as free radical initiator was investigated by two-dimensional NMR techniques. 2D-heteronuclear single quantum correlation (HSQC) and the total correlation spectroscopy (TOCSY) have been utilized to resolve the complex ¹H NMR spectrum and to establish the compositional and configurational sequences of acrylonitrile-methyl acrylate copolymers. 2D HSQC and TOCSY showed compositional and configurational sensitivity of methine protons of A and M units upto the triad level. Heteronuclear multiple-bond correlation (HMBC) spectroscopy has been used to study carbon (carbonyl/nitrile)-proton coupling. The carbonyl and nitrile carbons showed compositional sensitivity upto the triad level. The values of reactivity ratios were determined by Kelen-Tudos (KT) and non-linear error in variable method (RREVM).     

Structure elucidation from 2D NMR spectra using the StrucEluc expert system: detection and removal of contradictions in the data

The elucidation of chemical structures from 2D NMR data commonly utilizes a combination of COSY, HMQC/HSQC, and HMBC data. Generally COSY connectivities are assumed to mostly describe the separation of protons that are separated by 1 skeletal bond (3JHH), while HMBC connectivities represent protons separated from carbon atoms by 1 to 2 skeletal bonds (2JCH and 3JCH). Obviously COSY and HMBC connectivities of lengths greater than those described have been detected. Though experimental techniques have recently been described to aid in the identification of the nature of the couplings the detection of whether a coupling is 2-bond or greater still remains a challenge in most laboratories. In the StrucEluc software system the common lengths of the connectivities, 1-bond for COSY and 1- or 2-bond for HMBC, derived from 2D NMR data are set as the default. Therefore, in the presence of any extended connectivities contradictions can appear in the 2D NMR data. In this article, algorithmic methods for the detection and removal of contradictions in 2D NMR data that have been developed in support of StrucEluc are described. The methods are based on the analysis of molecular connectivity diagrams, MCDs. These methods have been implemented in the StrucEluc system and tested by solving 50 structural problems with 2D NMR spectral data containing contradictions. The presence of contradictions was detected by the algorithm in 90% of the cases, and the contradictions were automatically removed in approximately 50% of the problems. A method of "fuzzy" structure generation in the presence of contradictions has been suggested and successfully tested in this work. This work will demonstrate examples of the application of developed methods to a number of structural problems.     

Reactive processing of polymers: Structural characterisation of products by H and C NMR spectroscopy for glycidyl methacrylate grafting onto EPR in the absence and presence of a reactive comonomer

Grafted GMA on EPR samples were prepared in a Thermo-Haake internal mixer by free radical melt grafting reactions in the absence (conventional system; EPR-g-GMA_CONV) and presence of the reactive comonomer divinyl benzene, DVB (EPR-g-GMA_DVB). The GMA-homopolymer (poly-GMA), a major side reaction product in the conventional system, was almost completely absent in the DVB-containing system, the latter also resulted in a much higher level of GMA grafting. A comprehensive microstructure analysis of the formed poly-GMA was performed based on one-dimensional ¹H and ¹³C NMR spectroscopy and the complete spectral assignments were supported by two-dimensional NMR techniques based on long range two and three bond order carbon-proton couplings from HMBC (Heteronuclear Multiple Bond Coherence) and that of one bond carbon-proton couplings from HSQC (Heteronuclear Single Quantum Coherence), as well as the use of Distortionless Enhancement by Polarization Transfer (DEPT) NMR spectroscopy. The unambiguous analysis of the stereochemical configuration of poly-GMA was further used to help understand the microstructures of the GMA-grafts obtained in the two different free radical melt grafting reactions, the conventional and comonomer-containing systems. In the grafted GMA, in the conventional system (EPR-g-GMA_CONV), the methylene protons of the GMA were found to be sensitive to tetrad configurational sequences and the results showed that 56% of the GMA sequence in the graft is in atactic configuration and 42% is in syndiotactic configuration whereas the poly-GMA was predominantly syndiotactic. The differences in the microstructures of the graft in the conventional EPR-g-GMA_CONV and the DVB-containing (EPR-g-GMA_DVB) systems is also reported     

Determination of the stereochemistry of gamma-butyrolactones by DPFGSE-NOE experiments

The stereochemistry of gamma-butyrolactons tetrahydro-6a-phenylfuro[3,4-b]furan-2(3H)-one (1), 1,4,5,9b-tetrahydro-3a-methylnaphtho[2,1-b]furan-2(3aH)-one (2), 1,4,5,9 b-tetrahydro-3a-methylfuro[2,3-c]quinolin-2(3aH)-one (3) and hexahydro-furo[3,2-c]benzofuran-2-one (4) was studied using DPFGSE-NOE experiments. Compounds 1-3 contain two stereocenters, while 4 contains three. Both (1)H and (13)C spectra showed a single diastereomer of all the compounds. Routine 2D experiments (DQF)-COSY, HMQC/HSQC, and HMBC were used to assign (1)H and (13)C spectra completely. Diastereotopic methylene protons with resolved (1)H NMR signals as well as protons of cyclohexane served as references for the construction of the spatial arrangement in the molecules. NOE contacts between protons attached to the stereocenter and the diastereotopic protons were thus used to determine the configuration of the molecules. Vicinal coupling constants (3)J assisted the assignment of the conformational arrangement of the cyclohexane ring of 4.     

Syntheses of Cyclopropylcarbonyl Compounds

There are three important direct routes to cyclopropylcarbonyl compounds: 1. Cyclization of chains of three carbon atoms, the first or third of which is adjacent to a carbonyl or potential carbonyl carbon atom (this type includes syntheses by intramolecular alkylation of γ-halogeno ketones or related compounds in alkaline media); 2. insertion of a methylene group or substituted methylene group into the olefinic double bond of an α,β-unsaturated carbonyl compound; and 3. introduction of an acetonyl group into the double bond of an olefin. However, cyclopropylcarbonyl compounds can also be obtained from 1,2-epoxycyclobutane and 2-bromocyclobutanone derivatives by ring contraction. Another possibility is the dehalogenation of α,α-bis(bromomethyl) cycloalkanones. This review concludes with a discussion of these little known routes and of a particularly suitable method which involves the reaction of methylene iodide, a Zn? Cu couple, and α,β-unsaturated ketones.     

Synthesis and dynamic NMR studies of Pt(eta(5)-C(5)Me(5))(CO){C(O)NR(2)} complexes

The formation of Pt(eta(5)-C(5)Me(5))(CO){C(O)NR(2)} (R=Me, Et) complexes was established by spectroscopic analysis. The infrared spectra of these complexes showed a sharp absorption due to the presence of coordinated carbonyl group in the region 2017-2013cm(-1). The N,N-dialkylcarbamoyl ligands showed a characteristic CO stretching absorption in the range 1609-1616cm(-1). The proton NMR spectra of these complexes revealed the expected singlet arising from five equivalent methyl groups on the cyclopentadienyl ring with satellites due to coupling to (195)Pt. The N-methyl and N-ethyl protons exhibited very broad resonances due to restricted rotation about the N-C bond at room temperature. On cooling to -30 degrees C, the N,N-dimethyl protons for complex Pt(eta(5)-C(5)Me(5))(CO){C(O)NMe(2)} showed two sharp singlets at delta 2.86 and 3.09ppm as expected for the static structure. For the N,N-diethyl derivative, Pt(eta(5)-C(5)Me(5))(CO){C(O)NEt(2)}, the methyl protons exhibited only a single triplet at delta 1.06ppm at -10 degrees C due to coupling with the methylene protons. This single resonance arises through accidental overlap as the methylene protons of the ethyl groups are inequivalent at this temperature and each exhibited a quartet at delta 3.33 and 3.70ppm due to coupling with the methyl protons. The singlet resonances for the methyl and ring carbons of the eta(5)-C(5)Me(5) group found in (13)C{(1)H} NMR spectra are illustrative of the chemical equivalence of all the carbon atoms caused by free rotation of the ring in these complexes. The signals attributable to the carbonyl and carbamoyl carbon atom resonances are found downfield as two singlets each with a large coupling constant to platinum. The platinum coupling constants of the downfield resonances could not be identified for Pt(eta(5)-C(5)Me(5))(CO){C(O)NMe(2)} due to presence of impurities.     

Automated structure verification based on a combination of 1D (1)H NMR and 2D (1)H - (13)C HSQC spectra

A method for structure validation based on the simultaneous analysis of a 1D (1)H NMR and 2D (1)H - (13)C single-bond correlation spectrum such as HSQC or HMQC is presented here. When compared with the validation of a structure by a 1D (1)H NMR spectrum alone, the advantage of including a 2D HSQC spectrum in structure validation is that it adds not only the information of (13)C shifts, but also which proton shifts they are directly coupled to, and an indication of which methylene protons are diastereotopic. The lack of corresponding peaks in the 2D spectrum that appear in the 1D (1)H spectrum, also gives a clear picture of which protons are attached to heteroatoms. For all these benefits, combined NMR verification was expected and found by all metrics to be superior to validation by 1D (1)H NMR alone. Using multiple real-life data sets of chemical structures and the corresponding 1D and 2D data, it was possible to unambiguously identify at least 90% of the correct structures. As part of this test, challenging incorrect structures, mostly regioisomers, were also matched with each spectrum set. For these incorrect structures, the false positive rate was observed as low as 6%.     

NMR assignments and X-ray diffraction spectra for two unusual kaurene diterpenes from Erythroxylum barbatum

The structural characterization of two new, unusual kaurene diterpenes isolated from roots of Erythroxylum barbatum is described. 1D NMR and several 2D shift-correlated NMR pulse sequences (1H,1H-COSY, HMQC, HMBC and NOESY) were used for structure elucidation and the unambiguous 1H and 13C chemical shifts assignments. Single crystal X-ray diffraction analysis was also used to confirm the final relative configuration of the compounds possessing the C-20 methyl and the CH2-15 methylene groups in cis-orientation.     

Structure elucidation of a pyrazolo[3,4]pyran derivative by NMR spectroscopy

The structure of a representative pyrazolo[3,4]pyran derivative was determined by 1D and 2D NMR techniques. Complete 1H and 13C chemical shifts for this compound are reported. Careful analysis of the HMBC (Heteronuclear Multi-Bond Correlation) spectrum helped to elucidate the configuration of the derivative around C7 and C8. The results showed that the characteristic double-strong and double-weak cross peak pattern in the HMBC spectrum for C7 and C8 might be useful for establishing the structures of other pyrazolo[3,4]pyran derivatives.     

Interactions of aziridines with nickel complexes: oxidative-addition and reductive-elimination reactions that break and make C-N bonds

Reaction of the N-tosylaziridines (p-CH(3)C(6)H(4)SO(2))NCH(2)CHR (1a, R = H; 1b, R = Me; 1c, R = n-Bu; 1d, R = i-Pr) with (bpy)Ni(cod) (2; bpy = 2,2'-bipyridine; cod = 1,5-cyclooctadiene) or (bpy)NiEt(2) (3) results in elimination of cod or butane from 2 and 3, respectively, and oxidative addition of an aziridine C-N bond to give the azametallacyclobutane complexes (bpy)Ni(NTosCHRCH(2)) (4a, R = H; 4b, R = Me; 4c, R = n-Bu; 4d, R = i-Pr) as maroon solids in 50-70% isolated yields. The structure of 4b exhibits a puckered four-membered azametallacycle containing a pyramidal nitrogen and with Ni-N(1) = 1.911(5) A; the tosyl group on N and the methyl substituent on the adjacent C are disposed in an anti conformation. The monodeuterated aziridine syn-(p-CH(3)C(6)H(4)SO(2))NCHDCH-n-Bu (1e) reacts with either 2 or 3 to give (bpy)Ni[NTosCH(n-Bu)CHD] (4e) in 60-65% yield, having an anti arrangement of the methine and methylene protons in the azametallacycle, and indicates that >95% inversion of stereochemistry has occurred at the methylene carbon during the oxidative-addition reaction. When the azametallacyclobutane complexes 4a-e are exposed to oxygen, oxidatively induced reductive elimination ensues, giving the free aziridines in 30-60% isolated yields. In the oxidation of 4e, the product aziridine is spectroscopically identical to its parent, 1e, indicating the elimination that forms the C-N bond also proceeds with inversion of stereochemistry (approximately 92% by (1)H NMR) at the methylene carbon.     

Atranes

The PMR spectra of acidified solutions of metalloatrane-3,7,10-trione dihydrates containing a group-IIIB metal atom (M=Al, Ga, In, Tl) in D₂O were studied. The equivalence of the three atrane half-rings in all of the investigated molecules and of the methylene protons in each half-ring was proved. Spin-spin coupling of²⁰³Tl and²⁰⁵Tl with protons, which is apparently realized through a TlN transannular coordinate bond, is observed in the PMR spectrum of thallatrane-3,7,10-trione (M=Tl). The factors that determine the magnitudes of the chemical shifts of the methylene protons are discussed.See [1] for communication XXXII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 312–314, March, 1973.     

A Structural Study of Epoxidized Natural Rubber (ENR-50) and Its Cyclic Dithiocarbonate Derivative Using NMR Spectroscopy Techniques

A structural study of epoxidized natural rubber (ENR-50) and its cyclic dithiocarbonate derivative was carried out using NMR spectroscopy techniques. The overlapping ¹H-NMR signals of ENR-50 at δ 1.56, 1.68-1.70, 2.06, 2.15-2.17 ppm were successfully assigned. In this work, the ¹³C-NMR chemical shift assignments of ENR-50 were consistent to the previously reported work. A cyclic dithiocarbonate derivative of ENR-50 was synthesized from the reaction of purified ENR-50 with carbon disulfide (CS₂), in the presence of 4-dimethylaminopyridine (DMAP) as catalyst at reflux temperature. The cyclic dithiocarbonate formation involved the epoxide ring opening of the ENR-50. This was followed by insertion of the C-S moiety of CS₂ at the oxygen attached to the quaternary carbon and methine carbon of epoxidized isoprene unit, respectively. The bands due to the C=S and C-O were clearly observed in the FTIR spectrum while the ¹H-NMR spectrum of the derivative revealed the peak attributed to the methylene protons had split. The ¹³C-NMR spectrum of the derivative further indicates two new carbon peaks arising from the >C=S and quaternary carbon of cyclic dithiocarbonate. All other ¹H- and ¹³C-NMR chemical shifts of the derivative remain unchanged with respect to the ENR-50.     

1,6-六亚甲基二异氰酸酯自聚产物的结构表征

用IR与NMR表征了用醋酸钾为催化剂时 1,6 六亚甲基二异氰酸酯 (HDI)自聚产物的结构 .结果表明 ,自聚主产物是三聚体异氰脲酸酯 ,主要含有三聚体异氰脲基、异氰酸根 ,同时含有由杂质带来的微量氨基甲酸酯、脲基甲酸酯基、取代脲基、缩二脲基 .一维核磁谱及二维化学位移相关谱分辨出 7种羰基 ,一种NCO基 ,确定了氮上 8种不同取代结构的分子链连接情况 .通过建立理论模型 ,定量地描述了自聚产物的结构 .     

Piperidone derivative from Dalbergia sympathetica

An alcoholic extract of Dalbergia sympathetica, on column chromatography, yielded a compound which analyzed for C(6)H(11)NO(3) (M(+) 145). The IR spectrum of the compound showed the presence of carbonyl and hydroxyl groups. PMR, (13)C and DEPT NMR spectral studies of the compound showed the presence of one N-methyl, two methine and two methylene groups. A quaternary carbon signal at delta 172.88 ppm was assigned to C-2 carbonyl of the compound. From all the above observations and also from the HMQC 2D NMR spectrum, the compound was identified as 3, 6-dihydroxy-N-methyl-2-piperidone. This is the first report of the natural occurrence of this compound from plant sources.     

Stereochemical and compositional assignment of acrylonitrile/methyl methacrylate copolymers by DEPT and inverse HECTOR NMR spectroscopy

The acrylonitrile/methyl methacrylate copolymers of different monomer concentration were prepared by photo polymerization using uranyl ion as initiator. The carbon 13 and proton spectra of these copolymers are overlapping and complex. The complete spectral assignment of the ¹³C- and ¹H-NMR spectra were done with the help of Distortionless Enhancement by Polarization Transfer (DEPT) and two dimensional ¹³C–¹H Heteronuclear Single Quantum Correlation (HSQC) experiments. The methylene, methine and the methyl carbon resonances show both stereochemical (triad level) and compositional (dyad, triad, tetrad, pentad and hexad level) sensitivity. 2D Double Quantum Filtered Correlated Spectroscopy (DQFCOSY) experiment was used to ascertain the various geminal couplings between the methylene protons. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1081–1092, 1998     

1H and 13C NMR spectral study of some 3,5-bis[(E)-thienylmethylene]piperidin-4-ones

(1)H and (13)C NMR spectra have been recorded for 3,5-bis[(E)-thienylmethylene]piperidin-4-one (1a), 3',3″-dimethyl-3,5-bis[(E)-thienylmethylene]piperidin-4-one (1b), 5',5″-dibromo-3,5-bis[(E)-thienylmethylene]piperidin-4-one (1c), their 1-methyl derivatives 2a-c and 3,5-bis[(E)-thienylmethylene]-2r,6c-diphenylpiperidin-4-one (3a). For selected compounds 2D spectra have been recorded. The spectral data are used to study the configuration and conformation of these molecules. The chemical shifts are discussed in light of steric, electronic and magnetic anisotropic effects. The magnetic anisotropic effects of thiophene ring and phenyl group are noteworthy. (1)H-(1)H COSY spectrum of 2b suggests that long-range (1)H-(1)H coupling, up to seven bonds, is possible in it. HMBC spectrum of 2b displays the magnetic nonequivalence of C-2 and C-6 and protons at these carbons.     

Total assignment of the 1H and 13C NMR spectra of benzo[f][1]benzothieno[2,3-c]quinoline by inverse-detected two-dimensional NMR techniques

The proton and carbon nmr spectra of benzo[f][1]benzothieno[2,3-c]quinoline have been totally assigned using a combination of 2D nmr methods including concerted use of HMQC (heteronuclear multiple quantum correlation) and HMBC (heteronuclear multiple bond correlation) experiments.     

Selective detection and assignment of the solution NMR signals of bacteriochlorophyll a in a reconstituted subunit of a light-harvesting complex

High-resolution solution NMR spectra have been obtained for bacteriochlorophyll (BChl) a molecules in a biologically functional subunit of a bacterial core light-harvesting complex based on a modified reconstitution method. The reconstituted subunit of pigment-integral membrane polypeptides is stable and homogeneous at high concentrations at room temperature and exhibits a Q(y) absorption peak at 818 nm. (1)H and (13)C chemical shifts have been specifically assigned for BChl a using the fully and selectively (13)C-labeled pigments incorporated with natural abundance polypeptides in deuterated detergent solution. Remarkable signal broadening has been observed upon reconstitution, where the bacteriochlorin macrocycle is shown in a highly restricted molecular motion while the phytol side chain remains relatively mobile. Two sets of resonances are revealed for 3(2), 8(1), 10, 12(1), and 13(4) protons, and 8(2) methyl protons exhibit four resonances with large upfield complexation shifts. The result indicates a nonequivalent state for the two BChl a molecules in the subunit and can be best interpreted in terms of a parallel face-to-face configuration with partial overlap over the pyrrolic rings II, III, and V. In comparison with BChl a in acetone, 8(2), 13(2), and 13(4) protons are largely perturbed, and the propionic and phytol side chain may adopt a different conformation in the reconstituted subunit. The (13)C chemical shift of 3(1) carbonyl carbon shows a large change downfield, indicating strong hydrogen bonding for all the acetyl carbonyls. Carbonyl carbons at 13(1) give rise to two (13)C resonances with equal intensities, suggesting that the keto carbonyl in one BChl a molecule within a subunit forms a stronger hydrogen bond than that in another BChl a molecule.     

Application of two‐dimensional selective‐TOCSY HMBC for structure elucidation of impurities in mixture without separation

In the pharmaceutical industry, regulatory expectations driven by patient safety considerations make structure elucidation of impurities at levels greater than 0.1% in the active pharmaceutical ingredient (API) of primary interest. Impurities can be generated from isomers in starting materials, or produced from different process steps toward the final API. Proton peaks belonging to different impurities could be potentially identified in the one‐dimensional ¹H NMR spectrum, when evaluated in combination with two‐dimensional (2‐D) COSY and HSQC data. However, in 2‐D HMBC data, correlation responses from different impurities may overlap with those from the major component, causing uncertainty of long‐range proton to carbon correlations and quaternary carbon assignments. This observation prompts us to design the 2‐D selective‐TOCSY HMBC experiment to distinguish responses from different impurities in mixtures to obtain 2‐D NMR data for each impurity, thus eliminating the use of a chromatographic isolation step to obtain material for NMR analysis. This methodology is demonstrated for structure elucidation of impurities ranging from 8.2% in the raw material to 0.4% in the API in this study, and would be particularly useful for industrial samples in which the solubility and availability of material are not an issue. Copyright © 2012 John Wiley & Sons, Ltd.