Presentation on theme: "Organic Structure Analysis"— Presentation transcript:
1Organic Structure Analysis Professor Marcel Jaspars
2AimThis course aims to extend student’s knowledge and experience with nuclear magnetic resonance (NMR) and mass spectroscopy (MS), by building on the material taught in the 3rd Year Organic Spectroscopy course, and also to develop problem solving skills in this area.
3Learning Outcomes By the end of this course you should be able to: Assign 1H and 13C NMR spectra of organic molecules.Analyse complex first order multiplets.Elucidate the structure of organic molecules using NMR and MS data.Use data from coupling constants and NOE experiments to determine relative stereochemistry.Understand and use data from 2D NMR experiments.
4SynopsisA general strategy for solving structural problems using spectroscopic methods, including dereplication methods.Determination of molecular formulae using NMR & MSAnalysis of multiplet patterns to determine coupling constants. Single irradiation experiments. Spectral simulation.The Karplus equation and its use in the determination of relative stereochemistry in conformationally rigid molecules.Determination of relative stereochemistry using the nuclear Overhauser effect (nOe).Rules to determine whether a nucleus can be studied by NMR & What other factors must be taken into consideration.Multinuclear NMR-commonly studied heteronuclei.Basic 2D NMR experiments and their uses in structure determination.
5BooksOrganic Structure Analysis, Crews, Rodriguez and Jaspars, OUP, 2009Spectroscopic Methods in Organic Chemistry, Williams and Fleming, McGraw-Hill, 2007Organic Structures from Spectra, Field, Sternhell and Kalman, Wiley, 2008Spectrometric Identification of Organic Compounds, Silverstein, Webster and Kiemle, Wiley, 2007Introduction to Spectroscopy, Pavia, Lampman, Kriz and Vyvyan, Brooks/Cole 2009
115 Minute Problem #1MF = C6H12OUnsaturated acyclic ether
12Six Simple Steps for Successful Structure Solution Get molecular formula. Use combustion analysis, mass spectrum and/or 13C NMR spectrum. Calculate double bond equivalents (DBE).Determine functional groups from IR, 1H and 13C NMRCompare 1H integrals to number of H’s in the MF.Determine coupling constants (J’s) for all multiplets.Use information from 3. and 4. to construct spin systems (substructures)Assemble substructures in all possible ways, taking account of DBE and functional groups. Make sure the integrals and coupling patterns agree with the proposed structure.
13Double Bond Equivalents CaHbOcNdXe[(2a+2) – (b-d+e)]DBE =2C2H3O2Cl =
14Tabulate Data Shift (ppm) Int. Mult (J/Hz) Inference 6.48 1H dd, 14, 7 4.17d, 143.97d, 73.692Ht, 71.65quint, 71.42sext, 70.953H
21Determining the Molecular Formula Using NMR and MS Data DEPT-135Organic Structure Analysis, Crews, Rodriguez and Jaspars
22Determining the Molecular Formula Using NMR and MS Data
23Determining the Molecular Formula Using NMR and MS Data
24MS ErrorsExperimental accurate mass measurement (from MS) was suggesting C10H16 is the correct formula.The error between calculated and experimental mass is:= = 0.8 mmuFormuladbeAccurate massC10H163C9H12O4C8H8O25C7H4O36C9H14N3.5C8H12N2
25Molecular Formula Calculators James Deline MFCalc
26Isotope Ratio Patterns: C100H200 For 12Cm13Cn1403.61404.6
27ThermoFinnigan LTQ Orbitrap, Determining molecular formulae by HR-ESI/MSThermoFinnigan LTQ Orbitrap,Xcalibur softwareexamples from MChem group practicals 2009(Rainer Ebel)
36Analysis of isotope patterns experimentalcalculated“monoisotopic peak”(mainly 12C713C1H935Cl14N16O2)
375 Minute Problem #2Al Kaloid, an Honours Chemistry Student at Slug State University has synthesised either A or B below. He is uncertain which one it is but he’s tabulated the 13C NMR shifts and their multiplicities. Can you help Al by determining which one it is?AB
46Coupling in ethanolTo see why the methyl peak is split into a triplet, let’s look at the methylene protons (CH2).There are two of them, and each can have one of two possible orientations- aligned with, or against the applied fieldThis gives rise to a total of four possible states:Hence the methyl peak is split into three,with the ratio of areas 1 : 2 : 1
47Coupling in ethanolSimilarly, the effect of the methyl protons on the methylene protons is such that there are 8 possible spin combinations for the three methyl protons:The methylene peak is split into a quartet.The areas of the peaks have the ratio of 1:3:3:1.
48Pascal’s triangle n relative intensity multiplet 0 1 singlet doublettripletquartetquintetsextetseptet
735 Minute Problem #4Work out which of d 2.1 and d 2.5 is equatorial and which is axial. Also work out the 3 dihedral angles for d 2.1, d 2.5, d 2.8, d 6.8.There are also peaks at: 6.80, 1H, d, J = 0.5 Hz; 1.95, 3H, s; 0.93, 9H, s.30 Hz
136STRATEGY BASED ON C-H CONNECTIVITY – HMBC DATA Organic Structure Analysis, Crews, Rodriguez and Jaspars
137STRATEGY BASED ON C-H CONNECTIVITY – HMBC DATA Organic Structure Analysis, Crews, Rodriguez and Jaspars
138STRATEGY BASED ON C-H CONNECTIVITY – HMBC DATA Organic Structure Analysis, Crews, Rodriguez and Jaspars
139Combinatorial explosion STRATEGY BASED ON C-H CONNECTIVITYRETROSPECTIVE CHECKINGCombinatorialexplosionPieces:Possibilities:Organic Structure Analysis, Crews, Rodriguez and Jaspars
140STRATEGY BASED ON C-H CONNECTIVITY RETROSPECTIVE CHECKING And similarly for COSY dataOrganic Structure Analysis, Crews, Rodriguez and Jaspars
141PROSPECTIVE CHECKING Pieces: Organic Structure Analysis, Crews, Rodriguez and Jaspars
1422D EXERCISE 1. For a simple organic compound the mass spectrum shows a molecular ion at m/z 98. The following data has been obtained from various1D and 2D NMR experiments. Using this information determine the structureof the molecule in question and rationalise the 2D NMR data given.AtomdC (ppm)dH (ppm)1H - 1H COSY(3 bond only)1H 13C Long range(2 - 3 bonds)A218 s-A-b, A-c, A-d, A-eB47 t1.8 ddb-dB-c, B-d, B-e, B-fC38 t2.3 mc-eC-b, C-d, C-eD32 d1.5 md-b, d-e, d-fD-b, D-c, D-e, D-fE31 t2.2 me-c, e-dE-b, E-c, E-d, E-fF20 q1.1 df-dF-b, F-d, F-eOrganic Structure Analysis, Crews, Rodriguez and Jaspars
143An additional peak is present in the 1H NMR at 11.6 ppm (bs). Atom 2D EXERCISE 2. For a simple organic compound the mass spectrum shows a molecular ion at m/z 114. The following data has been obtained from various 1D and 2D NMR experiments. Using this information determine the structure of the molecule in question and rationalise the 2D NMR data given.An additional peak is present in the 1H NMR at 11.6 ppm (bs).AtomdC (ppm)dH (ppm)1H - 1H COSY(3 bond only)1H 13C Long range(2 - 3 bonds)A178 s-A-d, A-bB136 d5.7 mb-c, b-dB-d, B-c, B-eC118 d5.5 mc-b, c-eC-b, C-d, C-e, C-fDt3.0 dd-bD-b, D-cEt2.1 me-c, e-fE-b, E-c, E-fF13 q1.0 tf-eF-c, F-eOrganic Structure Analysis, Crews, Rodriguez and Jaspars