Pinacolone

Pinacolone

Name	Pinacolone
Synonyms	3,3-Dimethylbutanone
Name in Chemical Abstracts	3,3-Dimethyl-2-butanon
CAS No	75-97-8
EINECS No	200-920-4
Molecular formula	C6H12O
Molecular mass	100.16
SMILES code	CC(C)(C)C(=O)C

1H-NMR

1H-NMR: Pinacolone 250 MHz, CDCl3 delta [ppm] mult. atoms assignment 1.12 s 9 H CH3 tert-butyl 2.12 s 3 H CH3-C(=O)- Pinacol pinacolone rearrangement Reaction type: pinacol rearrangement, Wagner-Meerwein rearrangement Substance classes: alcohol, ketone Techniques: simultaneous distillation / extraction (SDE), column distillation, stirring with magnetic stir bar, heating with oil bath Degree of difficulty: Easy H2SO4 ; Side reactions       13C-NMR 13C-NMR: crude product 62.5 MHz, CDCl3 delta [ppm] assignment 14.1 CH3 ethyl 24.6 C1 26.3 C4, tert-butyl-CH3 44.3 C3 214.3 C2 76.5-77.5 CDCl3 3C-NMR: Pinacolone 62.5 MHz, CDCl3 delta [ppm] assignment 14.1 CH3 ethyl 24.6 C1 26.3 C4, tert-butyl-CH3 44.3 C3 214.3 C2 76.5-77.5 CDCl3 //////////////////////////////////////////// IR: Pinacolone [ATR, T%, cm-1] [cm-1] assignment 2969, 2874 aliph. C-H valence 1705 C=O valence, ketone 1355, 1365 char. for tert-butyl Substances required Batch scale: 0.01 mol 0.1 mol Pinacol Educts Amount Risk Safety Pinacol Xi 11.8 g R 38 S 37 Reagents Amount Risk Safety Sulfuric acid 24 percent C 50 mL R 35 S 1/2-26-30-45 Solvents Amount Risk Safety tert-Butyl methyl ether F Xi 40 mL R 11-38 S 2-9-16-24 Solvents for analysis Amount Risk Safety tert-Butyl methyl ether F Xi R 11-38 S 2-9-16-24 Substances produced Batch scale: 0.01 mol 0.1 mol Pinacol Products Amount Risk Safety Pinacolone F Xn 7.3 g R 11-22 S 16-20/21 Byproducts Amount Risk Safety 2,3-Dimethylbut-3-en-2-ol R no data S no data Waste Disposal acid aqueous phase (neutralize) solvent water mixtures, halogen free distillation residues organic solvents, halogen free distilled tert-butyl methyl ether solvents for rectification sulfuric acid can be reused for this reaction about five times Equipment Batch scale: 0.01 mol 0.1 mol Pinacol round bottom flask 100 mL round bottom flask 50 mL simultaneous distillation extraction (SDE) apparatus heatable magnetic stirrer with magnetic stir bar heatable magnetic stirrer with magnetic stir bar Vigreux column distillation apparatus oil bath oil bath procedure http://kriemhild.uft.uni-bremen.de/nop/en/instructions/pdf/3028_en.pdf   LiteratureC. J. Collins,Quart. Rev.1960,14, 357 ////////

Tetratopic pyrimidine–hydrazone ligands

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The first tetratopic pyrimidine–hydrazone (pym–hyz) molecular strands containing terminal hydroxymethyl (L1) and acryloyl (L2) functional groups have been synthesised. L1 was produced by step-wise imine condensation reactions, starting with 6-hydroxymethyl-2-pyridinecarboxaldehyde. L2 was then synthesised through the treatment of L1 with acryloyl chloride. NMR spectroscopy and X-ray crystallography showed that the ligands adopted a helical shape, comprised of 1 and 1/3 helical turns. Both L1 and L2 uncoiled upon reaction with an excess amount of Pb(II), Zn(II) and Cu(II) ions, resulting in linear M₄LA₈ complexes (where M = Pb(II), Zn(II), or Cu(II); L = L1 or L2; and A = ClO₄⁻, SO₃CF₃⁻ or BF₄⁻). Horse-shoe shaped Pb₂LA₄ complexes were also formed by reacting Pb(II) ions with either L1 or L2 in a 2:1 metal to ligand ratio. The addition of Ag(I) ions to either L1 or L2 resulted in Ag₂L₂A₂ double helicates, which were stable in the presence of excess Ag(I). The Pb(II), Zn(II) and Ag(I) complexes were characterised by NMR spectroscopy, while UV-Vis spectroscopy was used to probe the Cu(II) complexes. In addition, X-ray crystallography was used to analyse the linear Pb₄L1A₈, horse-shoe shaped Pb₂L1(ClO₄)₄, twisted Cu₃L2(SO₃CF₃)₆, and double helicate Ag₂L1₂(SO₃CF₃)₂ complexes yielding the structures [Pb₄L1(ClO₄)₇(H₂O)]ClO₄·4CH₃NO₂ (1), [Pb₄L1(SO₃CF₃)₈]₂·6CH₃CN·H₂O (2), [Pb₂L1(ClO₄)₂(CH₃CN)(H₂O)](ClO₄)₂·2CH₃CN·C₄H₁₀O·H₂O (3), [Cu₃L2(SO₃CF₃)₃(CH₃CN)₂(H₂O)](SO₃CF₃)₃·2CH₃CN·H₂O (4) and [Ag₂L1₂](SO₃CF₃)₂·CH₃CN·H₂O (5), respectively.

 

 

 

Tetratopic pyrimidine–hydrazone ligands modified with terminal hydroxymethyl and acryloyl arms and their Pb(II), Zn(II), Cu(II) and Ag(I) complexes

Daniel J. Hutchinson,^a   Lyall R. Hanton*^a and   Stephen C. Moratti^a  

*Corresponding authors

^aDepartment of Chemistry, University of Otago, PO Box 56, Dunedin, New Zealand
E-mail: lhanton@chemistry.otago.ac.nz

Dalton Trans., 2014,43, 8205-8218

DOI: 10.1039/C3DT53559B

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// http://pubs.rsc.org/en/content/articlelanding/2014/dt/c3dt53559b#!divAbstract

Two new ent-kaurane diterpenoids from Albizia mollis (Wall.) Boiv

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Mollisside A (1) was isolated as white powder. Its molecular formula was determined to be C₂₆H₄₄O₈ with five unsaturation degrees by HRFABMS (m/z 483.2959 [M-1]^-) and ¹³C NMR spectra. The ¹H NMR spectrum of compound 1 clearly showed signals to three methyls at δ 0.83 (3H, s), 1.03 (3H, s), 1.07 (3H, s), and one anomeric hydrogen of β-type sugar at δ 4.30 (1H, d, J 7.8 Hz). The ¹³C NMR ({¹H} and DEPT) spectroscopic data (Table 1) revealed the presence of 3 methyls, 10 methylenes, 9 methines and 4 quaternary carbons. Carbon signals at δ 106.8 (d), 75.6 (d), 77.7 (d), 71.6 (d), 78.2 (d), 62.8 (t) suggested the presence of one glucose, which were further confirmed by its MS fragmentation peaks at m/z 323 [M-1-160 = C₆H₈O₅ formed by fragmentation involving glc moiety C₆H₁₀O₅]^- and the acid hydrolysis of 1. Comparison of these NMR data with those similar data reported in the literature¹³ showed that compound 1 had the same ent-kaurane skeleton. The linkage of glucose moiety to C-3 was determined by the HMBC correlations from H-1' (δ 4.30), H-18 (δ 1.03) and H-19 (δ 0.83) to C-3 (δ 90.9) (Figure 2). The attachment of one hydroxyl at C-17 in 1 was established by HMQC and HMBC spectra revealing correlations of H-17 (δ 3.27) with C-16 (δ 80.7), C-13 (δ 42.3) and C-15 (δ 53.1). Besides, the relative configuration of 1 was elucidated by a ROESY experiment and by comparison of the NMR data with those reported in the literature.¹⁴ The key ROESY correlations of H-3/H-18, H-3/H-5 and H-9/H-5 (Figure 3), indicated α-orientation of C-3 glycoside and β-orientations of H-5 and H-9. The α-orientation of CH₂OH-17 (δc 70.6) in 1 was elucidated by comparison of the ¹³C NMR data with those reported δc 69.8 for α-orientation and δc 66.2 for β-orientation at C-17.¹⁴ Based on the above evidences, compound 1 was identified as 3α, 16β, 17-trihydroxy-ent-kaurane 3-O-β-D- glucopyranoside, named Mollisside A.
 

Mollisside B (2) was determined to have a molecular formula C₂₆H₄₀O₉ on the basis of the positive HRFABMS (m/z 519.2565 [M+Na]⁺) and ¹³C NMR (DEPT) spectra, which possessed seven unsaturation degrees. Its IR spectrum showed a broad band (3518-2930 cm^-1) and absorption 1691 cm^-1 for a carboxyl and 1607 cm^-1 for a double bond. The ¹H NMR spectrum of compound 2 exhibited three methyls at δ 0.88 (3H, s), 1.12 (3H, s), 1.16 (3H, s), one anomeric proton of β-type sugar at δ 4.32 (1H, d, J 7.8 Hz) and one olefinic proton at δ 6.48 (1H, s). The ¹³C NMR spectroscopic data (Table 1) revealed 26 carbon atoms, including one carboxyl (C-17 at δ 164.1) and two olefinic carbons (C-16 at δ 139.9, C-15 at δ 154.7). Comparison of these NMR data with mollisside A showed that compound 2 had the similar skeleton of compound 1 except for the distinct differences of chemical shift of C-2 (δ 68.1) adjacent one oxygenated group and C-17, C-15 and C-16 conforming the α,β-unsaturation ketone system. The linkage of the glucose moietiy to C-3 (δ 96.1) was determined by the HMBC correlations from H-1' (δ 4.32), H-18 (δ 1.12) and H-19 (δ 0.88) to C-3 (Figure 2). Besides, the relative configuration of 2 was elucidated by a ROESY experiment and by comparison of the NMR data with 1. The α-orientation of H-2 was established by key ROESY correlations of H-2/H-1α, H-2/H-19 and H-2/H-20 (Figure 3) and the coupling constant J 9.3 Hz observed in the signal corresponding to H-3 (interaction axial- axial with H-2). Moreover, the β-orientations of H-3, H-5 and H-9 were confirmed by ROESY between H-3/H-5, H-3/H-18 and H-5/H-9. Based on the above evidences, the structure of 2 was elucidated as 2β,3α-dihydroxy-ent-kaur-15-en-17-oic acid 3-O-β-D-glucopyranoside, named Mollisside B.


Mollisside A
White powder, mp 292-294 ºC; [α]_D²¹ +6.3116 (c 0.101, CH₃OH); UV (CH₃OH) λ_max/nm (log ε): 193(3.587), 205 (3.829), 277 (3.250); IR (KBr) ν_max/cm^-1: 3420, 2937, 1166, 1074, 1020; ¹H NMR (400 MHz, CD₃OD) and ¹³C NMR (100 MHz, CD₃OD) see Table 1; HRESIMS (negative ion) m/z 483.2959 [M-1]^- (Calc. for C₂₆H₄₄O₈, 483.2957); FABMS (negative ion) m/z(%) 483[M-1]^- (100), 391 (5), 323 (15), 282 (5), 159 (6), 113 (5).
Mollisside B
White powder, mp 270-271 ºC; [α]_D²¹ -1.5989 (c 0.246, CH₃OH); UV (CH₃OH) λ_max/nm (log ε): 196 (3.393), 203 (4.108), 276 (2.890); IR (KBr) ν_max/cm^-1: 3518, 3380, 3190, 2980, 2930, 1691, 1607, 1073, 1037; ¹H NMR (500 MHz, CD₃OD) and ¹³C NMR (125 MHz, CD₃OD) see Table 1; HRESIMS (positive ion) m/z 519.2565 [M+Na]⁺ (Calc. for C₂₆H₄₀O₉Na, 519.2570); FABMS (negative ion) m/z(%): 495[M-1]^- (100), 400 (5), 335 (5), 281(6), 123 (4).

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ABSTRACT
Two new kaurane diterpenoids, 3α, 16β, 17-trihydroxy-ent-kaurane 3-O-β-D-glucopyranoside and 2β,3α-dihydroxy-ent-kaur-15-en-17-oic acid 3-O-β-D-glucopyranoside, were isolated from the bark of Albizia mollis (Wall.) Boiv. The structures of two new compounds were elucidated by extensive 1D- and 2D-NMR spectroscopic methods in combination with MS experiments.

Journal of the Brazilian Chemical Society

Print version ISSN 0103-5053

J. Braz. Chem. Soc. vol.21 no.9 São Paulo  2010

http://dx.doi.org/10.1590/S0103-50532010000900025 

Two new ent-kaurane diterpenoids from Albizia mollis (Wall.) Boiv


Zhong-Quan Cheng^I,II; Dan Yang^I; Yu-Qing Liu^I; Jiang-Miao Hu^I; He-Zhong Jiang^I; Peng-Cheng Wang^I; Ning Li^III; Jun Zhou^I; You-Xing Zhao^I,*
IState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, the Chinese Academy of Sciences, Kunming 650204, P. R. China
^IIGraduate School of the Chinese Academy of Sciences, Beijing 100049, P. R. China
^IIISchool of Life Sciences, Anhui University, Hefei 230039, P. R. China



Keywords: Albizia mollis, kaurane diterpenoids, mollisside A, mollisside B

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Rapid structure determination of microgram-level drug metabolites using HPLC-MS, fraction collection and NMR spectroscopy

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A robust method for in vitro metabolite generation and facile sample preparation on analytical HPLC was established for rapid structure determination of microgram-level drug metabolites by using high-field NMR equipped with a cryoprobe. A single 1–5 mL incubation of drug candidate (10–30 μM) in microsomes, hepatocytes, or recombinant drug-metabolising enzymes, typically cytochrome P450s and UDP-glucuronosyltransferases, was used for metabolite formation. Following precipitation of proteins and solvent removal, metabolite mixtures were chromatographed with 5–10 injections onto an HPLC-MS system. Metabolites were collected into a 96-well plate, dried, and reconstituted in deuterated NMR solvents. NMR spectra of isolated metabolites were acquired on a 500 MHz spectrometer equipped with a 5 mm cryogenic probe. The methodology has been successfully employed as an extension of HPLC-MS/MS-based metabolite identification and applied frequently to 0.5–10 μg quantities of metabolite. Most structure determinations were achieved rapidly by 1D ¹H NMR with satisfactory signal-to-noise ratios, whereas some required 2D NMR data analysis. This report describes the method development and metabolite structure determination using the model compound trazodone. In addition to trazodone, a large number of examples from our laboratories have proven that the microgram-level NMR method avoids time-consuming preparative-scale metabolite generation and purification and circumvents technical complications associated with online LC-NMR. Most importantly, the turnaround time of metabolite structure determination for metabolically unstable compounds using the present methodology is more in sync with the cycle time during which medicinal chemists modify metabolic softspots while performing other iterative lead optimisation activities, demonstrating a real impact on the drug-discovery process.

Rapid structure determination of microgram-level drug metabolites using HPLC-MS, fraction collection and NMR spectroscopy

Kim A. Johnson,^a   Xiaohong Liu,^a   Stella Huang,^a   Vikram Roongta,^a   W. Griffith Humphreys^a and   Yue-Zhong Shu*^a  

*Corresponding authors

^aPharmaceutical Candidate Optimization, Bristol-Myers Squibb Research & Development, 5 Research Parkway, Wallingford, USA
E-mail: yuezhong.shu@bms.com

Anal. Methods, 2010,2, 1542-1549

DOI: 10.1039/C0AY00290A
 http://pubs.rsc.org/en/content/articlelanding/2010/ay/c0ay00290a/unauth#!divAbstract






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