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This enhancement of a classic laboratory experiment investigates the kinetic and thermodynamic control of a reaction utilizing ¹H NMR spectroscopy instead of melting point analysis to determine the product distribution. In this experiment, semicarbazide is reacted with cyclohexanone and 2-furaldehyde under varying buffer and temperature conditions to yield semicarbazone derivative products. After ¹H NMR analysis of the products, students compile the class data in a cooperative setting facilitated by graduate teaching assistants. As a result, students are able to analyze a larger data set in this cooperative learning environment in order to describe the product distribution of the reaction on the basis of trends as opposed to using a single data set. The application of 1H NMR spectroscopy to determine the product distribution of the reaction introduces a modern approach to study a well-established example of the kinetic and thermodynamic control of a reaction. [ABSTRACT FROM AUTHOR]

Solution characterizations and ligand binding constants were determined for n-butyllithium in hydrocarbon and ethereal solvents using diffusion-ordered NMR. In hydrocarbon solvents, n-butyllithium exists primarily as an octamer at -40 °C and deaggregates to a hexamer when the temperature is increased. In the presence of THF or diethyl ether, n-butyllithium exists predominantly as a tetra-solvated tetramer and deaggregates to a tetra-solvated dimer in the presence of a large excess or neat THF. The ligand binding constants for the tetra-solvated tetramers were measured using ¹H NMR/DOSY titration. [ABSTRACT FROM AUTHOR]

We report the direct measurement of ligand-binding constants of organolithium complexes using a ¹H NMR/diffusion-ordered NMR spectroscopy (DOSY) titration technique. Lithium hexamethyldisilazide complexes with ethereal and ester donor ligands (THF, diethyl ether, MTBE, THP, tert-butyl acetate) are characterized using ¹H NMR and X-ray crystallography. Their aggregation and solvation states are confirmed using diffusion coefficient-formula weight correlation analysis, and the ¹H NMR/DOSY titration technique is applied to obtain their binding constants. Our work suggests that steric hindrance of ethereal ligands plays an important role in the aggregation, solvation, and reactivity of these complexes. It is noteworthy that diffusion methodology is utilized to obtain binding constants. [ABSTRACT FROM AUTHOR]

We report on the generation of a perfluoroalkyl Grignard reagent (FRMgX) by exchange reaction between a perfluoroalkyl iodide (FR-I) and a Grignard reagent (RMgX). 19F NMR was applied to monitor the generation of n-C3F7MgCl. Additional NMR techniques, including 19F COSY, NOESY, and pulsed gradient spin-echo (PGSE) diffusion NMR, were invoked to assign peaks observed in 19F spectrum. Schlenk equilibrium was observed and was significantly influenced by solvent, diethyl ether, or THF. [ABSTRACT FROM AUTHOR]

We report extension of the D-FW analysis using referenced ²H DOSY. This technique was developed in response to limitations due to peak overlay in ¹H DOSY spectra. We find a corresponding linear relationship (R² > 0.99) between log D and log FW as the basis of the D-FW analysis. The solution-state structure of THF solvated lithium diisopropyl amide (LDA) in hydrocarbon solvent was chosen to demonstrate the reliability of the methodology. We observe an equilibrium between monosolvated and disolvated dimeric LDA complexes at room temperature. Additionally we demonstrate the application of the ²H D-FW analysis using a compound with an exchangeable proton that is readily labeled with ²H. Hence, the ²H DOSY D-FW analysis is shown to provide results consistent with the ¹H DOSY method, thereby greatly extending the applicability of the D-FW analysis. [ABSTRACT FROM AUTHOR]

The solution structures of three mixed aggregates dissolved in toluene-d8 consisting of the lithiated amides derived from (S)-N-isopropyl-1-((triisopropylsilyl)oxy)propan-2-amine, (R)-N-(1-phenyl-2-((triisopropylsilyl)oxy)ethyl)propan-2-amine, or (S)-N-isobutyl-3-methyl-1-((triisopropylsilyl)oxy)butan-2-amine and n-butyllithium are characterized by various NMR experiments including diffusion-ordered NMR spectroscopy with diffusion coefficient-formula weight correlation analyses (D-FW) and other one- and two-dimensional NMR techniques. We report that steric hindrance of R1 and R2 groups of the chiral lithium amide controls the aggregation state of the mixed aggregates. With a less hindered R2 group, lithium (S)-N-isopropyl-1-((triisopropylsilyl)oxy)propan-2-amide forms mostly a 2:2 ladder-type mixed aggregate with n-butyllithium. Increase of steric hindrance of the R1 and R2 groups suppresses the formation of the 2:2 mixed aggregate and promotes formation of a 2:1 mixed aggregate. We observe that lithium (S)-N-isobutyl-3-methyl-1-((triisopropylsilyl)oxy)butan-2-amide forms both a 2:2 mixed aggregate and a 2:1 mixed trimer with n-butyllithium. Further increase in the steric hindrance of R1 and R2 groups results in the formation of only 2:1 mixed aggregate as observed with lithium (R)-N-(1-phenyl-2-((triisopropylsilyl)oxy)ethyl)propan-2-amide. [ABSTRACT FROM AUTHOR]

We report the development of isotopic-labeled 13C diffusion-ordered NMR spectroscopy (DOSY) NMR with diffusion coefficient-formula weight (D-FW) analysis and its application in characterizing the aggregation state of methyllithium aggregates and complexes with several widely used diamines. Commercially available 13c-labeled benzene and several easily synthesized 13C-labeled compounds using 13C-labeled iodomethane as the isotopic source are developed as internal references for diflusion-formula weight analysis (D-FW). The technique greatly expands die applicability of DOSY D-FW analysis to a much wider variety of compounds because of isotopic labeling. These results reveal that methyllithium exists as a tetrasolvated tetramer in diethyl ether and exclusively as bis-solvated dirners with chelating diamines [ABSTRACT FROM AUTHOR]

The crystal structure of a mixed aggregate containing lithiated (S)-N-ethyl-3-methyl-1-(triisopropylsilyloxy)- butan-2-amine derived from (S)-valinol and cyclopentyllithium is determined by X-ray diffraction. The mixed aggregate adopts a ladder structure in the solid state. The ladder-type mixed aggregate is also the major species in a toluene-d8 solution containing an approximately 1:1 molar ratio of the lithiated chiral amide to cyclopentyllithium. A variety of NMR experiments including diffusion-ordered NMR spectroscopy (DOSY) with diffusion coefficient-formula (D-FW) weight correlation analyses and other one- and two-dimensional NMR techniques allowed us to characterize the complex in solution. Solution state structures of the mixed aggregates of n-butyl, sec-butyllithium, isopropyllithium with lithiated (S)-N-ethyl-3-methyl-1-(triisopropylsilyloxy)butan-2-amine are also reported. Identical dimeric, laddertype, mixed aggregates are the major species at a stoichiometric ratio of 1:1 lithium chiral amide to alkyllithium in toluene-d8 solution for all of the different alkyllithium reagents. [ABSTRACT FROM AUTHOR]

The solid-state structures of unsolvated, hexameric cyclopentyllithium and tetrameric cyclopentyllithium tetrahydrofuran solvate were determined by single-crystal X-ray diffraction. Cyclopentyllithium easily crystallized in hydrocarbon solvents. Solution-state structural analyses of cyclopentyllithium and cyclopentyllithium-tetrahydrofuran complexes in toluene-d8 were also carried out by diffusion-ordered NMR spectroscopy with diffusion coefficient-formula weight correlation analyses and other one- and two-dimensional NMR techniques. The solution-state studies suggest that unsolvated cyclopentyllithium exists as hexamer and tetramer equilibrating with each other. Upon solvation with tetrahydrofuran, cyclopentyllithium exists mostly as a tetrahydrofuran tetrasolvated tetramer. [ABSTRACT FROM AUTHOR]

Solution-state characterization of sec-butyllithium in [D8]toluene was conducted by utilizing a variety of NMR spectroscopic experiments including diffusion-ordered NMR spectroscopy (DOSY) with diffusion-coefficient-formula-weight correlation analyses and other one- and two-dimensional NMR spectroscopic techniques. These results suggest that sec-butyllithium exists primarily as a tetramer/hexamer mixture in hydrocarbon solvents. However, the presence of roughly 2-5 % (by mol ratio) lithium sec-butoxide in both commercially available and laboratory-synthesized sec-butyllithium solutions due to the reaction with adventitious dioxygen will lead to the formation of a 1:5 sec-butoxide/ sec-butyllithium mixed hexamer. A sec-butoxide/ sec-butyllithium mixed octamer will emerge when the proportion of butoxide to butyllithium increases. [ABSTRACT FROM AUTHOR]

The solid state structure of lithiated (S)-N¹,N¹-bis(2-methoxyethyl)-N²,3-dimethylbutane-1,2-diamine, which is a chiral amide base synthesized from (S)-valine was determined by single-crystal X-ray diffraction. The complex in solution state is also characterized by a variety of NMR experiments including diffusion-ordered NMR spectroscopy (DOSY) with diffusion coefficient-formula weight correlation analyses and other one- and two-dimensional NMR techniques by dissolving the crystal in toluene-d8. The crystallography and NMR results suggest that the chiral amide is dimeric in both solid and solution states. [ABSTRACT FROM AUTHOR]

The article discusses the biosynthesis of sesquiterpene phytotoxin botrydial, a causal agent of gray mold disease secreted by Botrytis cinerea fungus. It analyses the BcBOT2 gene, a clustered gene of B. cinerea, whose biochemical function can be observed in the conversion of farsesyl diphosphate (FPP) to presilphiperfolan-8&x03B2;-ol (PSP). It cites that various quantum chemical calculations were carried out on PSP formation, and the isomerization of FPP to nerolidyl diphosphate (NPP).

Article A metastable, polymorphic hexameric crystal structure of lithium pinacolone enolate (LiOPin) is reported along with three preparation methods. NMR-based structural characterization implies that the lithium pinacolate hexamer deaggregates to a tetramer in toluene but retains mainly the hexameric structure in nonaromatic hydrocarbon solvents such as cyclohexane. Moreover, the presence of a small amount of lithium aldolate (LiOA) dramatically influences the aggregation state of LiOPin by forming a mixed aggregate with a 3:1 ratio (LiOPin3⋅LiOA). [ABSTRACT FROM AUTHOR]

We report the crystal structure of a substoichiometric, HMPA-trisolvated lithium pinacolone enolate tetramer (LiOPin)4-HMPA3 abbreviated as T3. In this tetramer one HMPA binds to lithium more strongly than the other two causing a reduction in spatial symmetry with corresponding loss of C3 symmetry. A variety of NMR experiments, including HMPA titration, diffusion coefficient-formula weight (D-FW) analysis, and other multinuclear one- and two-dimensional NMR techniques reveal that T3 is the major species in hydrocarbon solution when more than 0.6 equiv of HMPA is present. Due to a small amount of moisture from HMPA or air leaking into the solution, a minor complex was identified and confirmed by X-ray diffraction analysis as a mixed aggregate containing enolate, lithium hydroxide, and HMPA in a 4:2:4 ratio, [(LiOPin)4-(LiOH)2-HMPA4], that we refer to as pseudo-T4. A tetra-HMPA-solvated lithium cyclopentanone enolate tetramer was also prepared and characterized by X-ray diffraction, leading to the conclusion that steric effects dominate the formation and solvation of the pinacolone aggregates. An unusual mixed aggregate consisting of pinacolone enolate, lithium diisopropyl amide, lithium oxide, and HMPA in the ratio 5:1:1:2 is also described. [ABSTRACT FROM AUTHOR]

Abstract: Attempted two-step postsynthetic modifications (Click reaction and recrystallization) of a dinuclear Zn(II) coordination compound Zn2(OOC–C6H4–N3)4(quinoline)2 lead to the formation of a mononuclear Zn(II) compound – Zn(OOC–C6H4–C2HN3–COOCH3)2(quinoline)·DMSO. In this feasibility study, the relatively low stability of the coordination chromophore around Zn(II) in the starting material is evidenced by Hirshfeld surface analysis and results in the transformation of coordination chromophore during the postsynthetic reaction. Diffusion Ordered Spectroscopy NMR experiments confirmed that the intermediate complex Zn(OOC–C6H4–C2HN3–COOCH3)2 formed by Click reaction exists in the coordinated form in the solution phase despite the loss of the neutral ligand-quinoline. The final product Zn(OOC–C6H4–C2HN3–COOCH3)2·(quinoline)·DMSO with a mononuclear crystal structure was formed by recrystallizing the intermediate with presence of quinoline. [Copyright &y& Elsevier]

Abstract: Postsynthetic strategy based on organic coupling reactions has been explored for the synthesis of novel coordination complexes with larger dimensions. A discrete coordination species with a paddlewheel motif, dicopper(II) tetracarboxylate Cu2(OOC-C6H4-N3)4(quinoline)2 (SBU1), was covalently modified with methyl propiolate via “Click” reaction to generate a new coordination compound Cu2(OOC-C6H4-C2N3H-COOCH3)4·(quinoline)2 (1). The combination of single-crystal X-ray diffraction, diffusion NMR and ESR has confirmed the success of covalently modifying SBU1 and the retention of the structural integrity after the postsynthetic modification. [Copyright &y& Elsevier]

The article presents a science experiment to help college students measure the solution viscosity via diffusion-ordered nuclear magnetic resonance (NMR) spectroscopy. In this experiment, students explore the intermolecular forces including viscosity through numerous methods. Emphasis is on the investigation of the viscosity, a physical property based on molecular structure, using advanced NMR techniques.

Summary: Two presumptive terpene synthases of unknown biochemical function encoded by the sscg_02150 and sscg_03688 genes of Streptomyces clavuligerus ATCC 27074 were individually expressed in Escherichia coli as N-terminal-His6-tag proteins, using codon-optimized synthetic genes. Incubation of recombinant SSCG_02150 with farnesyl diphosphate (1, FPP) gave (-)-δ-cadinene (2) while recombinant SSCG_03688 converted FPP to (+)-T-muurolol (3). Individual incubations of (-)-δ-cadinene synthase with [1,1-2H2]FPP (1a), (1S)-[1-2H]-FPP (1b), and (1R)-[1-2H]-FPP (1c) and NMR analysis of the resulting samples of deuterated (-)-δ-cadinene supported a cyclization mechanism involving the intermediacy of nerolidyl diphosphate (4) leading to a helminthogermacradienyl cation 5. Following a 1,3-hydride shift of the original H-1 si of FPP, cyclization and deprotonation will give (-)-δ-cadinene. Similar incubations with recombinant SSCG_03688 supported an analogous mechanism for the formation of (+)-T-muurolol (3), also involving a 1,3-hydride shift of the original H-1 si of FPP. [ABSTRACT FROM AUTHOR]

The utility of recently introduced 6Li diffusion-ordered NMR spectroscopy (DOSY) is demonstrated. 6Li DOSY results can be correlated to 1H data through 2-D 6Li{1H} heteronuclear Overhauser effect NMR spectroscopy (HOESY) experiments. 6Li DOSY quickly confirms 1H DOSY results and allows unambiguous assignment of resonances to specific aggregates. Well known aggregates of lithium-6 n-butyllithium (n-Bu6Li) are examined in deuterated tetrahydrofuran (THF-d8) solution as an example, and to reaffirm the previous literature conclusions about these complexes. [ABSTRACT FROM AUTHOR]

Formula weight (FW) information is important to characterize the composition, aggregation number, and solvation state of reactive intermediates and organometallic complexes. We describe an internal reference correlated DOSY method for calculating the FW of unknown species in different solvents with different concentrations. Examples for both the small molecule (DIPA) and the organometallic complex (aggregate 1) yield excellent correlations. We also found the relative diffusion rate is inversely proportional to the viscosity change of the solution, which is consistent with the theoretical Stokes-Einstein equation. The accuracy of the least-squares linear prediction r2 and the percentage difference of FW prediction are directly related to the density change; greater accuracy was observed with decreasing density. We also discuss the guidelines and other factors for successful application of this internal reference correlated DOSY method. This practical method can be conveniently modified and applied to the characterization of other unknown molecules or complexes. [ABSTRACT FROM AUTHOR]

Four different chiral diamino diethers synthesized from N-isopropyl valinol or N-isopropyl alaninol were lithiated with n-butyllithium in tetrahydrofuran or diethyl ether. Crystal structures of the dilithiated diamino diethers were determined by X-ray diffraction. Three dilithiated diamino diethers including (2S,2'S)-1,1'-(butane-1,4-diylbis- (oxy))bis(N-isopropylpropan-2-amine) 7, (2S,2'S)-1,1'-(pentane- 1,5-diylbis(oxy))bis(N-isopropylpropan-2-amine) 8, and (2S,2 'S)-l,l'-(heptane -l,7 -diylbis (oxy ))b is (N -isopropyl-3 - methylbutan-2-amine) 9 are dimers, whereas dilithiated (2S, 2'S ) - 1,1 '-(pentane -1,5 -diylbis (oxy ) )bis(N-isopropyl-3- methylbutan-2-amine) 10 is a monomer. The lithium atoms in all crystal structures adopt a nonequivalent coordination protocol and exist in two different environments in which one of the lithium atoms is tetra-coordinated while the other one is tri-coordinated. The solution structures o f the dilithiated diamino diethers are also characterized by a variety of NMR experiments including diffusion-ordered NMR spectroscopy (DOSY) with diffusion coefficient-formula (D-FW) weight correlation analyses and other one- and two-dimensional NMR techniques. [ABSTRACT FROM AUTHOR]

The dimeric structure is characterized for a chiral amide base complex consisting of an (S)-N-isopropyl-O-triisopropylsilyl valinol ligand and lithium. The complex is characterized by a variety of NMR techniques, including multinuclear one- and two-dimensional NMR experiments and diffusion ordered NMR spectroscopy (DOSY) as well as diffusion coefficient-formula weight (D-fw) correlation analyses. Spartan calculations are presented which support the structural assignment. This structural characterization leads to an explanation of the behavior and the reactivity of these complexes in solution. [ABSTRACT FROM AUTHOR]

The tetrahydrofuran tetrasolvated dimeric lithium dienolate derived from 2,2,7,7-tetramethyloctan-3,6-dione is characterized in the solid state by X-ray diffraction analysis and in solution by diffusion NMR. This dienolate was reacted with tropanone to yield two new products that are also described. [ABSTRACT FROM AUTHOR]

A system consisting of a chiral lithium amide and n-BuLi in tol-d8 solution was investigated with 1H and 13C INEPT DOSY, 6Li and 15N NMR, and other 2D NMR techniques. A mixed 2:1 trimeric complex was identified as the major species as the stoichiometry approached 1.5 equiv of n-BuLi to 1 equiv of amine compound. 1H and 13C INEPT DOSY spectra confirmed this lithium aggregate in the solution. The formula weight of the aggregate, correlated with diffusion coefficients of internal references, indicated the aggregation number of this complex. Plots of log Drel vs log FW are linear (r > 0.9900). 6Li and 15N NMR titration experiments also corroborated these results. These NMR experiments indicate that this mixed aggregate is the species that is responsible for asymmetric addition of n-BuLi to aldehydes. [ABSTRACT FROM AUTHOR]