A Method for Easily Determining Coupling Constant Values: An

Addendumto A Practical Guide to First-Order Multiplet Analysis

in
1
H NMR Spectroscopy
Thomas R. Hoye* and Hongyu Zhao
Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455
hoye@chem.umn.edu
Received J uly 26, 2000 (Revised Manuscript Received March 28, 2002)
A systemati c procedure to deci pher fi rst-order
1
H NMR mul ti pl ets i s descri bed. Thi s method i s a
very practi cal tool for extracti ng coupl i ng constant val ues. I t requi res onl y that one (a) l earn to
i denti fy each of the 2
n
(n ) number of spi n
1
/
2
nucl ei to whi ch the proton i s coupl ed) uni ts of
i ntensi ty of a mul ti pl et and (b) then appl y a cl earl y del i neated sequence of i terati ve steps that
al l ows the J s to be assi gned i n order (from smal l est to l argest). The approach i s even easi er to use
than one descri bed previ ousl y (J . Org. Chem. 1994, 59, 4096-4103).
Introduction
Several years ago, we descri bed a method for deci pher-
i ng the i ndi vi dual coupl i ng constants from a compl ex,
fi rst-order mul ti pl et i n a
1
H NMR spectrum.
1
Anecdotal
evi dence makes i t cl ear that many have found thi s
di scussi on to be very hel pful . We now present an al terna-
ti ve, compl ementary protocol for obtai ni ng the same
i nformati on. The method we descri be here makes the
task of extracti ng the i ndi vi dual J val ues from compl ex
mul ti pl ets even easi er.
I n general ,
2
a fi rst-order mul ti pl et wi th chemi cal shi ft
, havi ng coupl i ng constants ari si ng from i nteracti on
wi th n spi n
1
/
2
nucl ei , wi l l contai n a maxi mum of 2
n
peaks
that are symmetri cal l y arrayed about the mi dpoi nt ().
The actual number of i ndi vi dual peaks i s usual l y reduced
by degeneraci es ari si ng from certai n rel ati onshi ps among
two or more J s (e.g., two i denti cal J val ues or cases
where a thi rd J i s the sum or di fference of two other J
val ues). Nonethel ess, the total uni ts of i ntensi ty, here-
after cal l ed components, wi l l al ways sum to 2
n
regardl ess
of the presence or absence of l i ne degeneracy. A tri vi al
exampl e makes the poi nt: a 1:1:1:1 doubl et of doubl ets
(dd) and a 1:2:1 tri pl et (i .e., a dd wi th i denti cal J s i n
whi ch components number 2 and 3 are superi mposed)
both contai n a total of four (2
2
) components.
3
The i ncreas-
i ngl y compl ex set of mul ti pl ets shown i n Fi gure 1
rei nforce thi s i mportant poi nt. Recogni ze that each of the
2
n
i ndi vi dual components coi nci des wi th one of the
fol l owi ng l i ne posi ti ons i n the mul ti pl et: (Hz) +
1
/
2
((J
1
( J
2
( J
3
... (J
n
). The furthest downfi el d and upfi el d
l i nes i n the mul ti pl et are (Hz) +
1
/
2
(+J
1
+ J
2
+ J
3
... +
J
n
) and (Hz) +
1
/
2
(-J
1
- J
2
- J
3
... -J
n
), respecti vel y.
I t fol l ows that the separati on between the outermost
peaks of a mul ti pl et i s the sum of the i ndi vi dual coupl i ng
constants.
4,2
I n what fol l ows and for the sake of general i ty, we
consi der any mul ti pl et ari si ng from i nteracti on wi th n
protons to be a seri es of n doubl ets (e.g., dddd for n ) 4)
regardl ess of whether any of the protons are chemi cal l y
and magneti cal l y equi val ent. I n the case of equi val ency,
(1) Hoye, T. R.; Hanson, P. R.; Vyvyan, J. R. J . Org. Chem. 1994,
59, 4096-4103.
(2) Most of the concepts noted i n thi s i ntroductory paragraph are
wel l establ i shed and accepted truths, the ori gi nal statements of whi ch
are di ffi cul t to l ocate but the exi stences of whi ch are evi denced i n many
of the earl y treati ses i n the fi el d: e.g., (a) Jackman, L. M.; Sternhel l ,
S. Applicationsof Nuclear MagneticResonanceSpectroscopyin Organic
Chemistry; Pergamon: Oxford, 1959. (b) Bovey, F. A. Nuclear Magnetic
ResonanceSpectroscopy; Academi c Press: New York, 1969. (c) Becker,
E. D. High-Resolution NMR.; Theory and Chemical Applications;
Academi c Press: New York, 1969.
(3) The outermost peaks i n the mul ti pl et are al ways the smal l est
and shoul d be assi gned a rel ati ve i ntensi ty val ue of 1.
(4) I .e., the total wi dth of the mul ti pl et ) (Hz) +
1
/2(+J 1 + J 2 + J 3
... + J n) - [ (Hz) +
1
/2(-J 1 - J 2 - J 3 ... -J n)] ) (J 1 + J 2 + J 3 ... + J n).
Figure1. Four exampl es of assi gnment of al l 2
n
components
to the i ndi vi dual l i nes i n a fi rst-order mul ti pl et.
4014 J . Org. Chem. 2002, 67, 4014-4016
10.1021/jo001139v CCC: $22.00 2002 Ameri can Chemi cal Soci ety
Publ i shed on Web 05/14/2002
the mul ti pl ets are more commonl y referred to, of course,
as tri pl ets, quartets, pentets, etc. (i .e., dd, ddd, dddd, etc.
wi th i denti cal J s). Recogni ze then, that the method
presented bel ow for deduci ng the val ues of al l J s i n, e.g.,
a dddd i s appl i cabl e to all mul ti pl ets wi th 16 compo-
nents: i .e., a pentet (p), a doubl et of quartets (dq), a
tri pl et of tri pl ets (tt), or a doubl et of doubl et of tri pl ets
(ddt) i n addi ti on to a true doubl et of doubl et of doubl et
of doubl ets (dddd).
The method we now descri be for deduci ng the i ndi -
vi dual J val ues from any fi rst-order mul ti pl et requi res
two pri nci pal operati ons: (i ) assi gnment of each of the
i ndi vi dual 2
n
components (cf. Fi gure 1) and (i i ) systemati c
i denti fi cati on of the i ndi vi dual J s (cf. Chart 1 and the
exampl e i n Fi gure 2).
5
For the fi rst operati on, assi gn every peak i n the
mul ti pl et one or more component numbers from 1 to 2
n
from l eft to ri ght (arbi trari l y) by anal ogy to the exampl es
shown i n Fi gure 1. Thi s i nvol ves assi gni ng the rel ati ve
i ntensi ti es among al l peaks of the mul ti pl et, an operati on
that for some compl ex resonances (cf., Fi gure 1d) mi ght
requi re an i terati ve approach but that i s usual l y strai ght-
forward for mul ti pl ets havi ng 4, 8, 16, and even 32
components.
The second operati on requi res systemati c i denti fi cati on
of the J s by the seri es of steps outl i ned i n Chart 1. Adopt
the conventi on that J
1
e J
2
e J
3
e J
4
e ... J
n
. Appreci ate
that for J
3
and beyond i t i s necessary to have fi rst
determi ned the previ ous coupl i ng constants (e.g., both
J
1
and J
2
must be known before J
3
can be determi ned).
I n other words, one must deduce the J s i n order, from
smal l est to l argest. Assi gn i ndi vi dual coupl i ng constant
val ues starti ng wi th step i (Chart 1), where {1 to x} i s
the di stance i n Hz between component 1 (whi ch, neces-
sari l y, corresponds to the l efthandmost peak) and com-
ponent x. The task i s compl ete (al l J s i denti fi ed) fol l owi ng
step i v for a ddd, vi for a dddd, and vi i i for a ddddd. I n
practi ce, for some compl ex, sl i ghtl y non-fi rst-order (l ean-
i ng/di storted), and/or parti al l y overl apped mul ti pl ets, i t
i s advantageous to work synergi sti cal l y from both ex-
tremi ti es of the mul ti pl et.
Consi der the dddd, whose component numbers were
assi gned i n Fi gure 1c. I n Fi gure 2, the determi nati on of
(5) The process requi res practi ce at the outset, but i t i s wel l worth
l earni ng. Once fami l i ar wi th the techni que, peopl e have deduced the
si x i ndi vi dual J val ues i n the mul ti pl et shown i n Fi gure 3e (a dddddd)
i n 1-2 mi n.
Chart 1. Steps for Identifying J Values in Sequence fromSmallest to Largest (J
1
to J
n
) ({1 to x}
Represents the Distance between the Peak Corresponding to Component 1 to the Peak Corresponding to
Component x)
a
{1 to 2} ) (Hz) +
1
/2(+J 1 + J 2 + J 3 ... + J n) - [ (Hz) +
1
/2(-J 1 + J 2 + J 3 ... + J n)] ) J 1.
b
{1 to 3} ) (Hz) +
1
/2(+J 1 + J 2 + J 3 ...
+ J n) - [ (Hz) +
1
/2(+J 1 - J 2 + J 3 ... + J n)] ) J 2.
c
Each peak i n the mul ti pl et may (and often wi l l ) contai n more than one component;
each component shoul d be i ndi vi dual l y removed from consi derati on or associ ated wi th a J val ue.
d
For a ddd: {1 to 4} (or {1 to 5}) )
(Hz) +
1
/2(+J 1 + J 2 + J 3 ... + J n) - [ (Hz) +
1
/2(-J 1 - J 2 + J 3 ... + J n)] ) J 1 + J 2 and {1 to 5} (or {1 to 4}) ) (Hz) +
1
/2(+J 1 + J 2 +
J 3 ... + J n) - [ (Hz) +
1
/2(+J 1 + J 2 - J 3 ... + J n)] ) J 3.
Figure2. Assi gnment of J 1-J 4 for a dddd by appl yi ng steps
i -vi from Chart 1.
Determi nati on of Coupl i ng Constant Val ues J . Org. Chem., Vol. 67, No. 12, 2002 4015
the J s, arri ved at by sequenti al appl i cati on of steps i -vi ,
i s shown.
Thi s method has proven to be very practi cal . Com-
monl y encountered fi rst-order mul ti pl ets can be qui ckl y
anal yzed.
6
Some sel ected mul ti pl ets from actual spec-
tra are presented i n Fi gure 3 to further demonstrate
the power of thi s method. Noti ce that resol uti on en-
hancement/l i ne broadeni ng (verti cal arrow i n Fi gure
3e) can someti mes make the assi gnment of the 2
n
component numbers more strai ghtforward. Fi nal l y, i t
shoul d not be overl ooked that coupl i ng constant val ues
are val uabl e because they convey i nformati on about
geometry.
7,8
Acknowledgment. Thi s study was supported by a
grant awarded by the DHHS (CA-76497). We thank Mr.
B. M. Ekl ov for hel p wi th renderi ng the graphi cs.
JO001139V
(6) Note Added in Proof. For a very recentl y descri bed, compl e-
mentary approach to automated fi rst-order mul ti pl et anal ysi s, see:
Gol otvi n, S.; Vodopi anov, E.; Wi l l i ams, A. Magn. Reson. Chem. 2002,
40, 331-336.
(7) Karpl us, M. J . Chem. Phys. 1959 30, 11-15.
(8) For exampl e, the vicinal coupl i ng constants for the two protons
shown i n Fi gure 3d,e suggest that the hydrogen-bonded conformati on
1(wi th two gauche rel ati onshi ps between Ha and i ts methi ne nei ghbors
and one gauche and two anti arrangements between Hb and i ts three
nei ghbors) i s a major contri butor i n CDCl 3 to the fami l y of conformers
that defi ne the sol uti on structure of thi s pol yol fragment. Thi s i s not
necessari l y to be expected because of the steri c congesti on fl anki ng
the C(4)-C(5) bond and woul d be a very di ffi cul t i ssue to assess by
any method other than the magnitudes of coupl i ng constants.
Figure 3. Exampl es of experi mental mul ti pl ets for whi ch the compl ete set of J val ues has been determi ned.
4016 J . Org. Chem., Vol. 67, No. 12, 2002 Hoye and Zhao