Coupling Constants (J)Coupling constants are a very important and useful feature of an NMR spectrumImportantly, coupling constants identifies pairs of nuclei that are chemically bonded to each other

Multiplicity identifies the number of protons (or other nuclei) that are chemical bonded to the other nuclei

The magnitude of the coupling constants identifies the coupling partner, and provides information on dihedral angles, hydrogen bonds, the number of intervening bonds, and the type of coupled nuclei (1H, 13C, 15N, 19F, etc.)

Coupling Constants (J)- spin-spin coupling, scalar coupling or J-couplingRandom tumbling of molecules averages through-space effect of nuclear magnets to zero Borandom tumbling leads to no interaction between the spin-states despite the small magnetic fields

Coupling Constants (J)- spin-spin coupling, scalar coupling or J-couplingInstead, nuclear spin state is communicated through bonding electrons Energy of electron spin states are degenerate in absence of nuclear spin With a nuclear spin, the electron spin opposite to nuclear spin is lower energy Number of possible energy states of nuclear-electron spin pairs increases with the number of nuclear spins Spin state is sensed through bonds resulting in higher or lower energy- aligned or anti-aligned with magnetic field

aaabbabbaabbaabbCoupling ConstantsEnergy level of a nuclei are affected by covalently-bonded neighbors spin-statesSpin System OneSpin System TwoMixing of Spin Systems One and Two

Coupling ConstantsMixing of energy levels results in additional transitions peaks are splitI SJ (Hz)Spin-States of covalently-bonded nuclei want to be alignedThe magnitude of the separation is called coupling constant (J) and has units of HzJ (Hz)

Through-bond interaction that results in the splitting of a single peak into multiple peaks of various intensities Spacing in hertz (hz) between the peaks is a constantIndependent of magnetic field strength Multiple coupling interactions may existIncrease complexity of splitting patternCoupling can range from one-bond to five-bondOne, two and three bond coupling are most commonLonger range coupling usually occur through aromatic systemsCoupling can be between heteronuclear and homonuclear spin pairsBoth nuclei need to be NMR active i.e. 12C does not cause splittingCoupling Constantsone-bondthree-bondfour-bondfive-bond

Coupling ConstantsSplitting pattern depends on the number of equivalent atoms bonded to the nucleiDetermines the number of possible spin-pair combinations and energy levelsEach peak intensity in the splitting pattern is determined by the number of spin pairs of equivalent energy

Coupling ConstantsPascals triangleSplitting pattern follows Pascals triangleNumber of peaks and relative peak intensity determined by the number of attached nucleiPeak separation determined by coupling constant (J)Negative coupling reverse relative energy levels 3 attached nucleiQuartet1133Relative IntensityJJJ

Common NMR Splitting PatternsCoupling Rules:equivalent nuclei do not interactcoupling constants decreases with separation ( typically # 3 bonds)multiplicity given by number of attached equivalent protons (n+1)multiple spin systems multiplicity (na+1)(nb+1) Relative peak heights/area follows Pascals triangleCoupling constant are independent of applied field strengthCoupling constants can be negativeIMPORTANT: Coupling constant pattern allow for the identification of bonded nuclei.Coupling Constants

Coupling ConstantsCommon NMR Splitting Patterns

Coupling ConstantsCoupling only occurs between non-equivalent nucleiChemical shift equivalenceMagnetic equivalenceFor no coupling to occur, nuclei has to be BOTH chemical shift and magnetic equivalentThe CH3 protons (H1, H2, H3) are in identical environments, are equivalent, and are not coupled to one another The Ha and Hb protons are in different environments (proximity to Cl), are not equivalent, and are coupled

Coupling ConstantsRules for Chemical Shift Equivalence:Nuclei are interchangeable by symmetry operationRotation about symmetric axis (Cn)Inversion at a center of symmetry (i)reflection at a plane of symmetry (s)Higher orders of rotation about an axis followed by reflection in a plane normal to this axis (Sn)Symmetry element (axis, center or plane) must be symmetry element for entire moleculeSymmetry planesExamples of Chemical Shift Equivalent Nuclei

Coupling ConstantsRules for Chemical Shift Equivalence:Nuclei are interchangeable by a rapid process > once in about 10-3 secondsRotation about a bond, interconversion of ring pucker, etc.Rapid exchange Rapid exchange Examples of Chemical Shift Equivalent Nuclei

Coupling ConstantsMagnetic Equivalence:Nuclei must first be chemical shift equivalentMust couple equally to each nucleus in every other set of chemically equivalent nucleineed to examine geometrical relationshipsthe bond distance and angles from each nucleus to another chemical set must be identicalNuclei can be interchanged through a reflection plane passing through the nuclei from the other chemical set and a perpendicular to a line joining the chemical shift equivalent nuclei Examples of Non-magnetically equivalent nucleiChemical shift equivalent, but not magnetic equivalent3Jab 3Jab3Jab 3Jab3JHaFa 3JHaFa3JHaFa 3JHaFa3JHaHc 3JHaHc3JHbHc 3JHbHc3JHaHc 3JHbHc3JHaHc 3JHbHc

Coupling ConstantsMagnetic Equivalence:Non-magnetically equivalent nuclei may lead to second order effects and very complex splitting patternsSecond order effects will be discussed laterDue to small chemical shift differences between coupled nuclei (Dn ~ J)http://www.chem.wisc.edu/areas/reich/chem605/index.htm

Coupling ConstantsMultiple Spin Systemsmultiplicity (na+1)(nb+1) What is the splitting pattern for CH2?3JHb = 6 Hz3JHa = 7 HzCoupling to Hb splits the CH2 resonance into a doublet separated by 6 Hz3JHb = 6 HzCoupling to Ha splits each doublet into a quartet separated by 7 HzDown-field resonance split into quartetup-field resonance split into quartet

Coupling ConstantsWhat Happens to Splitting Pattern if J changes?3JHb = 7 Hz3JHa = 7 HzLooks like a pentet!3JHb = 6 Hz3JHa = 3 HzLooks like a sextet!Occurs because of overlap of peaks within the splitting patternIntensities dont follow Pascals triangle (1 4 6 4 1)Intensities dont follow Pascals triangle (1 5 10 10 5 1)

Coupling ConstantsCoupling Constants Provide Connectivity Information chemical shifts identify what functional groups are presentNMR Peaks for coupled nuclei share the same coupling constants CH2CH3CH6 Hz6 Hz6 Hz7 Hz7 Hz7 Hz6 Hz7 HzIntegral:123

Coupling ConstantsDeconvoluting a spin system determining the J-values determining the multiplicities presentJ coupling analysis:Is the pattern symmetric about the center?Assign integral intensity to each line, outer lines assigned to 1Are the intensities symmetric about the center?Add up the assigned intensitiesSum must be 2n, n = number of nucleiEx: sum = 16, n = 4Separation of outer most lines is a coupling constantRelative intensity determines the number of coupled nucleiEx: intensity ratio: 1:2, 2 coupled nuclei1st splitting pattern is a triplet (1:2:1)Draw the first coupling patternAccount for all the peaks in the spin pattern by repeatedly matching the 1st splitting patternSmallest coupling constant has been assigned

Coupling ConstantsDeconvoluting a spin system determining the J-values determining the multiplicities presentJ coupling analysis:ix.Coupling pattern is reduced to the center lines of the 1st splitting pattern.x.Repeat processEx: sum = 8, n = 3Ex: intensity ratio: 1:1, 1 coupled nuclei2nd splitting pattern is a doublet (1:1)xi.Repeat until singlet is generated

Coupling ConstantsDemo ACD C+H NMR Viewer software first order coupling constants

CH3CH2FCH3CH2RCoupling ConstantsDescription of Spin System each unique set of spins is assigned a letter from the alphabet the total number of nuclei in the set are indicated as a subscript the relative chemical shift difference is represented by separation in the alphabet sequence Large chemical shift differences are represented by AX or AMX (nAX >> JAX) Small chemical shift differences are represented by AB (nAB < 5JAB) Can also have mixed systems: ABX magnetically in-equivalent nuclei are differentiated by a single quote: AAXX or brackets [AX]2 A2X systemA2M2X systemA3X2 system[AX]2 or AAXX systemAB system

A M XA M XTMSA M XJ(AM)J(AX)J(AX)J(MX)J(AM)J(AM)J(MX)J(AX)J(AX)J(AM) = 4 HzJ(AX) = 2.5 HzJ(MX) = 6 Hz

Observed splitting is a result of this electron-nucleus hyperfine interactionCoupling is measured in hertz (Hz)Range from 0.05 Hz to thousands of HzCan be positive or negative1JC-H and many other one-bond coupling are positive1JA-X is negative if g are opposite sign 2JH-H in sp3 CH2 groups are commonly negative3JH-H is always positiveCoupling Constants (J)For an AX system, JAX is negative if the energy of the A state is lower when X has the same spin as A (aa or bb)

The spin states and transitions are swapped reversedreversedreversed

Coupling Constants (J)Measure the Relative Sign of Coupling ConstantsMultiple experimental approaches (different NMR pulse sequences) or simulationsE. COSY two-dimensional NMR experiment

cross peaks identify which chemical shifts are coupled

Coupling Constants (J)Measure the Relative Sign of Coupling ConstantsThe cross-peak patterns identifies the coupling constant sign and magnitude Yellow-highlighted regions are expandedBased on the slopes of the diagonal line drawn through coupling pattern

3JAX and 3JBX have the same sign3JAB opposite sign of 3JAX and 3JBX

Coupling Constants (J)Magnitude of the splitting is dependent on: Number of bonds

Bond order (single, double triple)

Angles between bonds

3JHH 8 Hz3JHH 11.6 & 19.1 Hztrans 3JHH ~ 17 Hzcis 3JHH ~10 Hz3JHH 9.1 Hzgeminal 2JHH ~2.5 Hz3JAB 9.4 Hz4JAC 1.1 Hz5JAB 0.9 Hz

Coupling Constants (J)Magnitude of the splitting is dependent on: dihedral angleFixed or average conformation

Coupling Constants (J)Magnitude of the splitting is dependent on: Cyclohexanes dihedral anglesFixed or average conformation3Jaa 9-12 Hz3Jee or 3Jea 3-4 Hz

3Jaa >> 3Jee,3Jea Dual Karplus curves for the axial and equatorial protons

Magnitude of the splitting is dependent on: Cyclohexanes dihedral anglesexamplesCoupling Constants (J)

Coupling Constants (J)Magnitude of the splitting is dependent on: Cyclopentanes dihedral anglesFixed or average conformation

Coupling Constants (J)Magnitude of the splitting is dependent on: Comparison between Cyclohexanes and Cyclopentanes

Because of range of cyclopentane conformations, vicinal couplings are variable: Jcis > Jtrans and Jcis > Jtrans

Only in rigid cyclopentanes can a stereochemistry be defined: Jcis > JtransIn chair cyclohexane, only one vicinal coupling can be large (>7 Hz)In cyclopentane, two or three vicinal coupling can be large (>7 Hz)

Coupling Constants (J)Magnitude of the splitting is dependent on: Cyclobutanes are flatter than cyclopentanes, so: Jcis > Jtrans unless structure features induce strong puckering of the ring or electronegative substituents are present

Cyclopropanes are rigidly fixed, so Jcis > Jtrans is always true

Coupling Constants (J)Magnitude of the splitting is dependent on: Orientation unless structure features induce strong puckering of the ring or electronegative substituents are present

Internal hydrogen bonds may lead to constrained conformations and distinct different coupling constantsSince methyl groups can freely rotate, the observed coupling is the average of the three individual coupling constants

Coupling Constants (J)Magnitude of the splitting is dependent on: Electronegativity of Substituents3JH-H coupling constant decreases as electronegativity increases3JH-H decreases even more with two electronegative substituents

Coupling Constants (J)3JH-H coupling constant decreases as electronegativity of substituents increases for cycloalkenes3JH-H coupling constant decreases as electronegativity of substituents increases for alkenesMagnitude of the splitting is dependent on: Electronegativity of Substituents

Coupling Constants (J)Magnitude of the splitting is dependent on: Ring SizeCoupling constants decrease as ring size gets smaller

Coupling constants also decrease as ring is formed and gets smaller

Coupling Constants (J)Magnitude of the splitting is dependent on: Bond orderCoupling constant decreases as bond order decreases

HeterocyclesHeterocycles have smaller coupling constants compared to hydrocarbons systems

3JH-H = 8.65 x (n bond order) + 1.66

Magnitude of the splitting is dependent on: Proportional to gagb

s character of bonding orbitalIncreases with increasing s-character in C-H bondCoupling Constants (J)1JC-H 125 Hz1JN-H 95 Hz2JF-H 48.2 Hz

Magnitude of the splitting is dependent on: Attenuated as the number of bonds increaseUsually requires conjugated systems (aromatic, allylic, propargylic, allenic) or favorable geometric alignment (W-coupling)Not usually seen over more than 4 to 5 bonds (acetylenes and allenes)Coupling Constants (J)

Coupling Constants (J)Magnitude of the splitting is dependent on: Geminal protons (H-C-H) fall into two major groupsUnstrained sp3 CH2 protons: 2JH-H -12 Hz

Vinyl sp2 CH protons: 2JH-H 2 Hz

Coupling Constants (J)Magnitude of the splitting is dependent on: Geminal protons coupling constants are effected by the electronic effects of substituentsBased on the interaction between the filled and empty orbitals of the CH2 fragmentNote: opposite trend

Coupling Constants (J)Magnitude of the splitting is dependent on electronic effects: In acyclic and unstrained ring systems: 2JH-H ~ -10 to -13 HzWhen CH2 is substituted with a p-acceptor, like carbonyl or cyano coupling becomes more negative: 2JH-H ~ -16 to -25 Hz Reliable and can help with structure assignments

Conjugated aryl, alkene and alkyne substituents also makes coupling becomes more negative

Coupling Constants (J)Magnitude of the splitting is dependent on electronic effects: In unsaturated carbons: 2JH-H ~ 2.5 HzElectronegative substituents (F,O) behave as p-acceptors with a negative effect with 2JH-H close to zeroElectropositive substituents (Si, Li) behave as p-donors with a negative effect with 2JH-H

Oxygen substituents can behave as a strong s-acceptor and strong p-donor (lone pair), both positive effects leading to a large 2JH-H or as a strong p-acceptor leading to large negative coupling

Coupling Constants (J)Magnitude of the splitting is dependent on electronic effects: Summary of effects, s and p acceptors have opposite effects on coupling, as do s and p donors

Coupling Constants (J)

Coupling Constants (J)

Coupling Constants (J)

Coupling ConstantsWeak coupling or first-order approximationUp to now, we have assumed the frequency difference (chemical shift) between the coupled nuclei is large Dn >> JSecond order effects come into play when this assumption is no longer valid Dn < 5JSecond order effects lead to very complex splitting patterns that are difficult, if not impossible to interpret manually and leads to incorrect chemical shifts and coupling constantsInterpreting NMR spectra with second-order effects usually requires software

Coupling Constants (J)Second-Order Effects (Strong Coupling) occurs when chemical shift differences is similar in magnitude to coupling constants (Dn/J < 5) chemical shifts and coupling constants have similar energy and intermingle results from mixing of the equivalent ab and ba spin states none of the transitions are purely one nuclei described by quantum mechanical wave functions AB spin system

Coupling Constants (J)Second-Order Effects (Strong Coupling) perturbs peak intensity and position

as chemical shift differences decrease, intensity of outer lines become weaker and internal lines become stronger the multiplet leans towards each other (roof effect) which increases as chemical shift difference decreasesAB spin system

Second-Order Effects (Strong Coupling) becomes easier to interpret at higher magnetic field strengthsCoupling Constants (J)Higher field increases Dn/J

Coupling Constants (J)Second-Order Effects (Strong Coupling) hierarchy of coupling constants with increasing second-order effectsAX and all other first order systems (AX2, AMX, A3X2, etc.)AB Line intensities start to lean J can be measured, d can be calculatedAB2Extra linesBoth J and d have to be calculatedABX, ABX2, ABX3 JAB can be measured, everything else requires calculationABCBoth J and d have to be determined from computer simulationAAXXDo not become first order even at high magnetic fieldsBoth J and d have to be determined from computer simulationAABBAABBXEtc.

Coupling Constants (J)Second-Order Effects (Strong Coupling) general effect of strong couplings on NMR spectraLine intensities are no longer integral ratios, no longer follow Pascals triangleLine positions are no longer symmetrically related to chemical shift position Multiplet center may no longer be chemical shift (AB and higher)Some or all coupling constants can no longer be obtained from the line separations (ABX and higher)The signs of coupling constants affect the line positions and intensities (ABX and higher)Additional lines over the number predicted by simple coupling rules appearPeaks with intensities of 2 or more are split into individual componentsMore lines then the expected triplet for the boxed CH2 pair

Coupling Constants (J)Second-Order Effects (Strong Coupling) general effect of strong couplings on NMR spectraCoupling between equivalent nuclei (JAA or JXX) affects line count and positionSecond order effects appear even if Dn/J is large for groups of magnetically non-equivalent protons with identical chemical shifts which are coupled

Do not get simpler at higher fieldsComputer analysis becomes mandatory to extract accurate J and d values (ABC and higher)Ultimately spectra become so complex that the only useful information is integration, chemical shift and general appearance.

Coupling Constants (J)Second-Order Effects as the chemical shifts coalesce intensity of outer lines decrease inner peaks eventually collapse to singlet nuclei become chemically and magnetically equivalentAB spin systemMay be misinterpreted as a quartetWeaker outer lines may be overlooked and interpreted as a doublet

Coupling Constants (J)Second-Order Effects (AB) analysis of second-order splitting patterns remember: resonance positions are also perturbed separation between outer lines and inner lines (a-b, c-d) yields coupling constantJAB = (na-nb) = (nc-nd) true chemical shift is not the doublet centers ncenter = (nb+nc) DnAB = (na-nd) (nb-nc) nA = ncenter + DnAB nB = ncenter - DnABdAdB

Coupling Constants (J)

Coupling Constants (J)Second-Order Effects (AB2) as the chemical shifts coalesce line intensities no longer follow simple rules arithmetic average of the line positions no longer give true chemical shifts JAB can still be measured directly from spectrum none of the line separation correspond to JAB additional lines appearAB2 spin systemNote: splitting of intense lines

Coupling Constants (J)Second-Order Effects (AB2) four A lines n1 n4 and four B lines n5 n8 and the very weak combination line n9 calculation of nA, nB, and JAB is simple:

how to report an AB2 spin system in a journal manuscript:report the two chemical shifts as an AB2 multiplete (m): 2.63, 2.69 (AB2m, 3H, JAB = 12.2 Hz)

Coupling Constants (J)Second-Order Effects (AB2) unique features of second-order splitting pattern for AB2 system Spectrum depends only on the ratio Dn/J lines 1 to 4 correspond to the one proton part (A) lines 5 to 8 correspond to the two-proton part (B2) line 5 (n5) is the most intense line lines 5 and 6 often do not split up when Dn/J

Second-Order Effects (ABX) most complex spin-system that can still be manually analyzed ABX has a common appearance AB unsymmetrical 8-line pattern that integrates to 2 protons AB 4 doublets with the same separation JAB with strong leaning X symmetric 6-line pattern that integrates to 1 proton X 5th and 6th lines are small and not often seen, apparent doublet of doublet JAB and nX are directly measurable from spectrum

JAX, JBX, nA and nB need to be calculatedCoupling Constants (J)

Second-Order Effects (ABX) Many ABX patterns are sufficiently close to AMX (nAB >> JAB)first-order solution has an excellent chance of being correct

First, identify the distorted doublet of doublets for both A and B Remove the splitting (identify the center of each doublet), which leaves an AB pattern Solve AB pattern as before to get JAB, nA, and nB large errors when JAX and JBX are very different or nAB small compared to JABCoupling Constants (J)A & B doublet of doubletseparation is JAX & JBXCenter doublets and get AB pattern

Second-Order Effects (ABX) Correct analysis of ABX patternsReverse the order of extracting coupling constants to approximate solution

First, identify the two AB quartets separation between the four pairs of lines are identicaltall inner line associated with shorter outer line (leaning)Coupling Constants (J)Identify the two AB quartetsJab+ = Jab-

Second-Order Effects (ABX) Correct choice of ab quartet

Incorrect choice of ab quartetCoupling Constants (J)

Second-Order Effects (ABX) Solve the two ab quartetsTreat as normal AB patterns and obtain four chemical shifts (na+,nb+,na-,nb-)Dont know which half is a and which is b - two possible solutions

Coupling Constants (J)

Second-Order Effects (ABX) Solution 1 and Solution 2 depends on the relative sign of JAX and JBXSolution 1: JAX and JBX same signSolution 2: JAX and JBX different sign

Coupling Constants (J)Swap the a & b labels

Second-Order Effects (ABX) Which solution is the correct one? Several criteria can be used:Magnitude of the couplings one solution may give dubious (very large or very small) couplingsSigns of coupling constants the signs can sometimes be predicted and rule out a solution all vicinal 3J couplings are positive, geminal 2J couplings at sp3 carbons are usually negative CHXCHAHB JAX and JBX have the same signCHACHBHX JAX and JBX have different signsAnalysis of the X-part the intensities of the lines in the X-part are always different most reliable way to identify the correct solution

Coupling Constants (J)Two different X patterns depending on relative sign of JAX and JBX

Second-Order Effects (ABX) Effective of relative sign of JAX and JBX on AB pattern

Coupling Constants (J)Solution 1JAX and JBX same signSolution 2JAX and JBX different sign

Second-Order Effects (ABX) AB pattern from ABX spin system as a function of changing nAB

Coupling Constants (J)

Second-Order Effects (ABX) AB pattern from ABX spin system as a function of the relative sign and Magnitude of JAX and JBX

Coupling Constants (J)JAX and JBX same signJAX and JBX different sign

Coupling Constants (J)Demo ACD C+H NMR Viewer software second order coupling constants

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