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Con o ma ional equilib ium in sup amolecula chemis y: Dibu yl iu e case
M oczyńska, Ka ina; Kaczo owska, Małgo za a; Kolehmainen, E kki; G ubecki,
I eneusz; Pie zak, Ma ek; Ośmiałowski, Bo ys
M oczyńska, K., Kaczo owska, M., Kolehmainen, E., G ubecki, I., Pie zak, M., &
Ośmiałowski, B. (2015). Con o ma ional equilib ium in sup amolecula chemis y:
Dibu yl iu e case. Beils ein Jou nal o O ganic Chemis y, 11, 2105-2116.
h ps://doi.o g/10.3762/bjoc.11.227
2015
2105
Con o ma ional equilib ium in sup amolecula chemis y:
Dibu yl iu e case
Ka ina M oczyńska1, Małgo za a Kaczo owska1, E kki Kolehmainen2,
I eneusz G ubecki1, Ma ek Pie zak1 and Bo ys Ośmiałowski*1
Full Resea ch Pape Open Access
Add ess:
1Facul y o Chemical Technology and Enginee ing, UTP Uni e si y o
Science and Technology, Semina yjna 3, PL-85326 Bydgoszcz,
Poland and 2Depa men o Chemis y, Uni e si y o Jy äskylä, P.O.
Box 35, FI-40014, Jy äskylä, Finland
Email:
Bo ys Ośmiałowski* - [email p o ec ed]
* Co esponding au ho
Keywo ds:
associa ion; hyd ogen bonding; NMR; o ame ism; sup amolecula
chemis y
Beils ein J. O g. Chem. 2015, 11, 2105–2116.
doi:10.3762/bjoc.11.227
Recei ed: 13 July 2015
Accep ed: 10 Oc obe 2015
Published: 05 No embe 2015
Associa e Edi o : P. R. Sch eine
© 2015 M oczyńska e al; licensee Beils ein-Ins i u .
License and e ms: see end o documen .
Abs ac
The associa ion o subs i u ed benzoa es and naph hy idine dianions was used o s udy he complexa ion o dibu yl iu e . The i le
molecule is he simples molecule able o o m wo in amolecula hyd ogen bonds. The naph hy idine sal was used o b eak wo
in amolecula hyd ogen bonds a a ime while wi h he use o subs i u ed benzoa es he sys ema ic app oach o s udy associa ion
was achie ed. Bo h, i a ions and a iable empe a u e measu emen s shed he ligh on he impo ance o con o ma ional equilib-
ium and i s in luence on associa ion in solu ion. Mo eo e , he associa es we e obse ed by mass spec ome y. The DFT-based
compu a ions o complexes and single bond o a ional ba ie s suppo s expe imen al da a and helps unde s anding he p ope ies
o mul iply hyd ogen bonded complexes.
2105
In oduc ion
The hyd ogen bond (HB) is one o he mos common non-co a-
len in e ac ions. Since i s abilizes, o example, he double
helix o DNA and in luences pep ide olding i is qui e eason-
able o assume ha HBing is c ucial o exis ence o li e. I is
also p esen in many small molecules ac ing as an in amolec-
ula con igu a ional lock. This is ealized in hyd azones [1],
he e ocyclic u ea de i a i es [2], molecules exhibi ing pho oex-
ci ed p o on ans e [3] and o he compounds [4-6] epo ed
also by us [7-10]. The in amolecula HBing p esen in some
he e ocycles esul s in a molecula geome y sui able o associ-
a ion by mul iple hyd ogen bonding [11-23] making possible
he o ma ion o , in e alia, s able sup amolecula polyme s [24-
30]. Such polyme iza ion needs p ope ly p ea anged mono-
me s wi h in e molecula hyd ogen bonding pa e ns i ing
be ween molecules. In his sense he con o ma ional eedom is
a main limi ing ac o in molecula design. On he o he hand in
o ms s abilized by an in amolecula hyd ogen bond i is
possible o b eak an in amolecula HB and o ma ion o a com-
Beils ein J. O g. Chem. 2015, 11, 2105–2116.
2106
Figu e 1: The compounds used in his s udy and hei a om numbe ing.
plex in al e na i e o ame ic s a e. This obse a ion gi es he
oppo uni y o con ol such p ocesses [2] making con-
o ma ional equilib ium [4,31-35] one o he ac o s, o a ool,
ha should be aken in o accoun in molecula design. To he
bes o ou knowledge he e a e only ew publica ions ocused
on simple molecules capable o o m wo in amolecula HBs
[36,37] ha b eak upon associa ion. This phenomenon is s ill
unde discussion [37-39]. The said HB b eakage and a con-
o ma ional change may only be ealized ia s ong enough
in e ac ion be ween hos (H) and gues (G) molecules. This is
because, as E e 's ules [40] s a e, in amolecula hyd ogen
bonding is s onge han in e molecula one and mo e p obable
due o he en opy easons.
In o de o cons uc a molecule capable o o m in amolecula
hyd ogen bonds one should bea in mind some condi ions:
a) such a molecule mus con ain a hyd ogen bond dono and
accep o in a close p oximi y and his is especially ue when
one assumes ha b) a six-membe ed quasi- ing s abilized by
hyd ogen bonds is p e e ed o e he i e-membe ed one and
ha c) om he sup amolecula /in e molecula in e ac ions
poin o iew he mos e icien associa ion exis s in complexes
in which all hyd ogen bond dono s belong o one molecule and
all hyd ogen bond accep o s o he o he . The las condi ion was
es ed o quad uple hyd ogen bonded associa es [14], while he
basis o his phenomenon a e seconda y in e ac ions [41] ha
ac diagonally be ween neighbou ing hyd ogen bonding si es.
The b eakage o single in amolecula hyd ogen bonding upon
associa ion leading o o ame ism was ou mo i a ion o sea ch
o mo e complex sys ems han p e iously epo ed [2,9,10].
Since he amide g oup is common in biomolecules we ha e
ocused on dibu yl iu e (1) ha con ains NH and CO g oups.
This molecule ul ils he needed p ope ies (a–c abo e). The
pa en iu e o ms wo in amolecula hyd ogen bonds in he
solid s a e [42] and upon cooling [43]. The associa ion o pa en
iu e wi h ca ions has al eady been s udied by MS [44] while
i s in e ac ion p e e ences wi h anions in solu ion a e no
known. On he o he hand he is-u ea de i a i es wi h a space
be ween NHCONH g oups we e used in se e al sup a-
molecula complexes including hose wi h encapsula ed anions
[45,46], sensing ne e agen s [47] o in sel -healing ma e ials
[48]. In iu e de i a i es no such space is p esen yielding a
DDDD (D – hyd ogen bonding dono ) pa e n in i s linea o m.
The syn hesis o dibu yl iu e was p e iously desc ibed [49]
bu we used an al e na e me hod (see expe imen al pa ). I is
wo h men ioning ha iu e is known as a byp oduc o he
u ic acid deg ada ion [44].
The goal o his s udy is o p obe he subjec ed molecule by
anionic coun e pa s in o de o ob ain i s in e ac ion scheme
and o s udy i s in a- s in e molecula HBing. Fo ha pu pose
he anionic coun e pa s chosen a e 4-subs i u ed benzoa es 2–9
and di e abu ylammonium 1,8-naph hy idin-2,7-diola e (10)
(Figu e 1).
The benzoa e anions o ming wo hyd ogen bonds [10] we e
chosen in o de o ob ain a se ies o anions wi h uneable HB
accep o p ope ies, while he naph hy idine de i a i e was used
o es i he dibu yl iu e is able o exis in linea o m wi hou
any in amolecula HBs and s abilized by ou in e molecula
ones.
In gene al he dibu yl iu e molecule ca ying ou hyd ogen
bond dono s (D, ed, Figu e 2) and h ee hyd ogen bond accep-
o s (A, blue) can exis in a ious con o ma ions s abilized by
one o wo in amolecula hyd ogen bonds and des abilized by
elec onic epulsions (black do ) in some o hem [50].
The con o ma ions o 1 co espond o he ollowing hyd ogen-
bonding pa e ns: 1a DDDD, 1b DDA, 1c DDDA, 1d DDA,
and 1e ADDA. This means ha he subjec ed compound may
associa e by quad uple (in 1a, 1c and 1e), iple (in 1b and 1d)
and double (all o ms) hyd ogen bonding wi h sui able coun e -
pa s. Fo example, DDDD pa e n in 1a should be able o
in e ac wi h AAAA o 10. On he o he hand all con o ma ions
can associa e wi h 2–9 by in e ac ion wi h a DD pa o
lis ed pa e ns. The p incipal in e ac ions in 1 (Figu e 2) o i s
Beils ein J. O g. Chem. 2015, 11, 2105–2116.
2107
Figu e 2: Possible con o ma ions o 1.
Figu e 3: D i ing o ces in luencing associa ion exempli ied on wo "ex eme" con o ma ions o 1∙∙∙benzoa e.
complex (Figu e 3) a e: a) mul iple hyd ogen bonding,
b) seconda y a ac i e o epulsi e in e ac ions and c) elec-
onic epulsions.
As epo ed ecen ly by us he in e molecula elec onic epul-
sions [51] can be c ucial because hey in luence on he selec-
i i y o associa ion o he ela i e popula ion o o ame s [50].
In he cu en s udy hese o ces coexis wi h o he ones in he
same molecule.
Resul s and Discussion
S udies by NMR echniques
P ope ies o 1
The dilu ion s udies o 1 p o ided i s sel -associa ion cons an
Ksel = 170 M−1 (CDCl3, , Suppo ing In o ma ion File 1,
Figu e S1). The a iable empe a u e (VT) 1H NMR spec a
e eal ha NH p o ons a e qui e ine o he empe a u e
change. The b oad single obse ed a 8.95 ppm ( ) shi s o
9.12 ppm upon cooling he sample (−40 °C) while he signal
obse ed a 7.89 ppm ( ) shi s o 8.17 ppm (−40 °C) spli ing
in o a sha p iple a −15 °C e ealing he signal o igina es
om H1/H7 wi h 3J(H,H) = 5.42 Hz (–CONH-CH2–). The said
sha pening is ela ed o he loss o he molecule’s lexibili y a
lowe ed empe a u es caused by in amolecula hyd ogen
bonding. A he same ime he in e molecula hyd ogen bonding
is bi u ca ed in he (di)mul ime o 1 (Figu e 4).
Tha de ini ely also in luences i s chemical shi . I is wo h
keeping in mind ha oge he wi h empe a u e lowe ing wo
e en s coexis – limi ed dissocia ion o associa e and enhance-
men o s abiliza ion o o ms locked by in amolecula
hyd ogen bonding making o ms 1e o 1d he majo ones. Since
he spec um eco ded a low empe a u e shows he compound
is symme ic we concluded ha he majo o m is 1e.
On he o he hand 1a is ano he ex eme o m ha should be
aken in o accoun . The sel -associa ed 1a mus ul il wo
p e equisi es o exis : a) b eakage o he in amolecula
hyd ogen bond(s) and b) associa ion o wo (o mo e) mole-
cules o 1a ha a e much less igid s uc u es han o he ones
locked by in amolecula HB. The p obabili y o exis ence o
o m 1a is low a lowe ed empe a u es. The signal b oadening
a oom empe a u e is caused by as in NMR ime-scale equi-
lib ium be ween a ious o ms. The NOE expe imen s o 1
(and associa ed 1) a lowe ed empe a u es did no ga e any
unequi ocal da a ega ding he shi o equilib ium owa ds any
o m. This excludes he exis ence o he dime o mul ime o
1a as he majo o m a low empe a u e.
Beils ein J. O g. Chem. 2015, 11, 2105–2116.
2108
Figu e 4: Two possible, ex eme mul iple hyd ogen bonded mul ime ic s uc u es o 1 and VT 1H NMR spec a ( om +25 o −40 °C, low empe a-
u es a bo om, CDCl3).
Figu e 5: The p oposed s uc u e explaining unusual beha io o he i a ion cu e o 1∙∙∙9 i a ion and aniso opy in luence on me hylene chemical
shi .
The co ela ion o chemical shi o H1/H7 and H3/H5 wi h
empe a u e is high in he ange o −40 °C o ca. +5 °C. The
chemical shi s de ia e om linea unc ion abo e +5 °C
(Suppo ing In o ma ion File 1, Figu e S2). No e ha H3/H5
beha e i egula ly a highe empe a u es while H1/H7 da a i s
well o ano he linea unc ion. This p o es ha a compound
1 exis s as a mix u e o o ms being unde dynamic equilib ium.
P o ons H1/H7 beha e linea ly, mos p obably, due o b eaking
in amolecula hyd ogen bonds and o ma ion o in e molec-
ula ones. I is wo h men ioning ha he nega i e slope o said
unc ion a highe empe a u es is mo e han h ee imes highe
han ha o lowe empe a u es. Lowe slope o lowe
empe a u es is caused by in amolecula hyd ogen bonding
making H1/H7 p o on no so sensi i e in 1e o empe a u e
change.
Associa ion o 1 wi h benzoa es 2–9
Since 1 exis s in a dynamic equilib ium a i was easonable
o associa e 1 wi h anionic coun e pa s wi h hei p ope ies
Table 1: Associa ion cons an s o 1a [M−1] measu ed wi h he use o
H1, H3.
Coun e pa (R) KassocH1 KassocH3
2 (NMe2) 110 170
3 (OMe) 100 160
4 (Me) 200 180
5 (H) 280 270
6 (F) 170 120
7 (Cl) 190 160
8 (CF3) 160 220
9 (NO2) 210 250
a[1] = 18.9 mmol dm−3, [2–9] = 10–12 × [1], T = 293 K, sol en CDCl3.
uned sys ema ically o he subs i uen e ec . The associa ion
cons an s (Kassoc) a e collec ed in Table 1 (see Suppo ing
In o ma ion File 1 o igu es). Usually he NH/OH p o ons a e
used o ind Kassoc bu in some cases CH chemical shi s a e
also use ul [9,52]. He e he p o ons o me hylene a ached

Beils ein J. O g. Chem. 2015, 11, 2105–2116.
2109
di ec ly o ni ogen a om we e obse ed du ing he expe imen s
(Suppo ing In o ma ion File 1, Figu e S13).
Changes in he chemical shi o me hylene a e small bu s ill
no iceable. Small changes may be explained by he ac ha
only one o hese p o ons alls in he aniso opic cone o he
associa ed coun e pa (exempli ied in Figu e 5). S ill i was
possible o ind he complexa ion-induced shi (CIS) eliably
o H11, which is, o example, equal o 0.14 ppm in he 1∙∙∙6
complex. I is wo h men ioning ha o he 1∙∙∙9 i a ion
(Suppo ing In o ma ion File 1, Figu e S10) an unusual beha -
io was no iced. The chemical shi o H11 dec eases (as in
emaining benzoa es) a he beginning o he i a ion and hen
inc eases. This may be explained by he al e na i e binding o 9
wi h 1e o m as shown in Figu e 5.
The ollowing may be concluded based on unna u al beha io
o he i a ion cu e: a) wi hin hyd ogen-bonded o ms p esen
in solu ion o a leas one magne ic aniso opy is impo an o
chemical shi , b) wo al e na e hyd ogen bonded complexes
s abilized by CO−···HN and NO···HN b idges may be p esen in
1∙∙∙9, c) his a angemen is obse ed only o anion ca ying
ano he hyd ogen bonding g oup as NO2. The dual cha ac e o
he NO2 g oup (elec on-accep ing and hyd ogen bonding)
causes unusual H11 beha io e iden (Suppo ing In o ma ion
File 1, Figu e S10). This ype o aniso opic in luence on CH2
chemical shi may only exis in 1e o m (shown in Figu e 5).
Only in his o m wo in e ac ing molecules a e in such an
a angemen as o loca e CH2 p o ons close o he aniso opic
cone o he espec i e moie ies in benzoa e – no such e ec is
possible in o he o m∙∙∙benzoa e complexes. This sugges s ha
said al e na e 1e∙∙∙benzoa e binding may be p esen and ha
NO2 g oup has highe aniso opic in luence on CH2 shi han
-CO2– one.
Associa ion o 1 wi h naph hy idine dianion 10
The Kassoc equal o 300 M−1 o 1∙∙∙10 complex ( ) was ound
based on a oma ic double s in 10. Al hough up o ou hyd ogen
bonds s abilize he 1∙∙∙10 complex his associa ion is no high
due o con o ma ional equilib ia and addi ional s abiliza ion o
compe i i e o ms by in amolecula HBing. I was impossible
o calcula e he associa ion based on NH chemical shi s
because NH p o ons in 1 a e no obse ed a oom empe a u e
du ing i a ion when he [G]:[H] (G – gues , H – hos 1) is
highe han 0.2. This, again, sugges s as in NMR ime-scale
equilib ium. In he 1∙∙∙10 complex he i a ion cu e has also a
non-s anda d shape (sigmoidal, see Suppo ing In o ma ion
File 1, Figu e S11 (inse )).
I is ai o men ion ha he associa ion cons an is loaded wi h
an e o highe han in ou p e ious publica ions and should be
ea ed as an app oxima e alue. This is due o he ac ha he
i a ion cu es we e i ed o ha e he smalles esiduals
s a ing om ca. 0.8 [G]:[H] a io ill in ini e gues concen a-
ion. Due o he sigmoidal beha io o all i a ion cu es he
i ing is no possible o he beginning o he da ase . Also i is
no possible o di ide hese da a in o wo sepa a e se s as be o e
[9] because no saddle poin ha could be used o ha pu poses
is p esen . S ill his p o es ha 1 is in o a ional equilib ium,
which is dependen om in e ac ion wi h o he molecules.
I is also wo h men ioning ha o he i a ion cu es o
[G]:[H] = 0 a he cu e's in lec ion poin , mos p obably, wo
(o mo e) sepa a e cu es o e lap. One o hese exhibi s a
dec ease o he chemical shi in he beginning o i a ion wi h
ela i ely small CIS alue and eaches i s pla eau ela i ely as .
The said dec ease o he chemical shi may only be caused by
he o ame ism and change o in a- o in e molecula hyd ogen
bonding.
Subs i uen e ec on associa ion
Recen ly we ha e obse ed he co ela ion o he Kassoc and
subs i uen cons an in sup amolecula complexes [10]. The lack
o such co ela ion o complex o 1 wi h benzoa es may be
explained by a) mul iple equilib ium ( o ame ism in 1) and
b) opposi e e ec s o he subs i uen on complexes s abili y
( u he discussion in Suppo ing In o ma ion File 1).
The use o subs i u ed benzoa e sal s ga e a se o poin s shown
in Figu e 6.
I is easy o see ha he subs i uen e ec on chemical shi is
no as high as be o e (compa e di e ence in CIS alues in
N-py idin-2-ylu ea de i a i e [10]). I is mainly exp essed as
s eepe cou se o i a ion cu e in case o elec on dona ing
subs i uen s han ha in case o elec on accep ing ones. The
a iable CIS alues a e di ec ly seen in Figu e 6. Fo a di ec
compa ison be ween wo ex eme subs i uen s see Suppo ing
In o ma ion File 1, Figu e S12.
The highe sigmoidal cha ac e is clea ly obse ed o H1/H7,
while o H3/H5 he cu e is linea -like in he [G]:[H] ange
whe e he H1/H7 unc ion changes om con ex o conca e.
This is caused by di e en cha ac e o H1/H7 s H3/H5
p o ons. The s eepes i a ion cu e was ob ained o 2
(R = NMe2, black ma ke s in Figu e 6), while o 9 (NO2 sal )
he cu e's shape esemble s aigh line in he beginning o i a-
ion ( ed ma ke s in Figu e 6). The ac ha he cu e a i s
beginning is no alling down, as be o e [9], sugges s he associ-
a ion akes place be ween o ms/ o ame s in ol ed in in a- and
in e molecula hyd ogen bonding o simila s eng h. P obably
he Kassoc is an o de o magni ude highe o he mo e s able
Beils ein J. O g. Chem. 2015, 11, 2105–2116.
2110
Figu e 6: Collec i e i a ion cu es (H1/H7 and H3/H5 chemical shi s, CDCl3) o complex o 1 wi h subs i u ed benzoa es.
complex and his co esponds o he i a ion da a om ca.
0.6–0.7 [2–9]:[1] a io o in ini y. Tha is unde s andable since
1e may o m doubly hyd ogen-bonded associa e a low [G]:[H]
whe e a compe i ion be ween 1e2 s abilized by in amolecula
hyd ogen bonds and i s he e ocomplex akes place, while a
highe [G]:[H] a ios he p obabili y o o ma ion o in e molec-
ula hyd ogen bond is highe . The o ame ism and mul iple kind
o equilib ium in 1 cause ha he gene al in e ac ion scheme is
non-speci ic yielding a non-linea change o he associa ion
cons an . On he o he hand he egula changes o anion p op-
e ies a e exp essed by some egula endency in he pa ial
i a ion-de i ed da a (discussion in Suppo ing In o ma ion
File 1, page S9). The shapes o cu es show ha he e exis wo
o mo e associa es a a ime especially in he egion close o he
1:1 mola a io. A his poin he cu e passes h ough he
in lec ion poin loca ed a a iable [2–9]:[1] a io. Fo mo e
de ailed discussion on in lec ion poin analysis e e o
Suppo ing In o ma ion File 1. He e i is enough o men ion ha
he posi ion o he in lec ion poin is linea ly dependen om
he subs i uen (Hamme ) cons an aken om he publica ion
by Hansch and Ta [53].
To sum up he subs i uen e ec on associa ion i is wo h o
s ess ha he goal o his wo k was o check how he lexi-
bili y o he molecule in luences he associa ion. In his case a
subs i uen e ec is no obse ed di ec ly (associa ion
cons an s) bu s ill can be seen in he shape o he i a ion
cu e, i s in lec ion poin posi ion and CIS alues.
VT measu emen s o complexes
The VT 1H NMR expe imen s we e conduc ed o ha e a deepe
insigh in o he na u e o he o ame ic equilib ium wi hin he
complexes. The ollowing sal s we e chosen (a a ious
[1]:[benzoa e] a ios [1] = 18.9 mmol dm−3): a) unsubs i u ed 5
(R = H), b) ca ying elec on dono 2 (R = NMe2) and
c) ca ying elec on accep o 8 (R = CF3) and 10. The sal 9 was
no aken in o accoun because, mos p obably, i o ms wo
ypes o complexes as discussed ea lie . Fo sal s 2, 5 and 8 he
ollowing [1]:[benzoa e] a ios we e used: 1:0.5, 1:1 and 1:2,
while o [1]:[10] 1:0.1, 1:0.5 and 1:1. The empe a u e ange
was −40 o +25 °C o benzoa es and −70 o +20 °C o he
naph hy idine de i a i e.
The benzoa e case
The 1:1 [1]:[5] VT 1H NMR da a shows he linea
δ [ppm] = (T) cha ac e in case o pa ial da a ( he da a de ia e
om linea i y a highe empe a u es as be o e o 1 –
Suppo ing In o ma ion File 1, Figu e S2). In Table 2 he co e-
la ion coe icien s, linea i y ange (l. . in °), slope (a) and in e -
cep (b) o he i ed linea unc ions a e collec ed.
Figu e 7 shows he signal labeling. The signals we e assigned as
ollows: a) 1d by in eg a ion ( he mos popula ed o m – see
compu a ional pa in Suppo ing In o ma ion File 1), b) 1c by
signal shape ( he mos b oad due o as “anion shi ” be ween
wo o ms o 1c∙∙∙5 wi hin DDD/AA pa e n), c) 1e emaining
signal. Some signals a e obse ed a empe a u es highe han
−40 °C and wi h a ious a ios (Figu es S17–S25). The com-
pa ison o he VT 1H NMR spec a wi h anions ca ying a ious
subs i uen s is p esen ed in Suppo ing In o ma ion File 1,
Figu e S26a–c.
The spec um in Figu e 7 shows ha a leas h ee o ms o 1∙∙∙5
can be obse ed in solu ion a low empe a u es. The signals
sugges hese o ms a e symme ic bu i is impo an o keep in
mind ha some o a ional equilib ium may s ill be p esen . In
1d associa ed o 5 signals o H1/H7 p o ons a e much sha pe
showing a iple a 8.45 ppm. The signal o H1/H7 in asso-
cia ed 1e o m a 8.21 ppm lies in he simila egion as in 1
(dime o polyme ) a he same empe a u e and has simila
Beils ein J. O g. Chem. 2015, 11, 2105–2116.
2111
Table 2: The linea i ing o he δ [ppm] = (T) unc ion o benzoa es.
Fo m(s) l. .a [°C] a (slope) b (in e cep ) Rbδ ch.c
1c
low ield −40 – +15 −0.0146 11.97 0.999 down
1e −40 – −5d−0.0130 11.61 0.996 —e
1d −40 – −5 −0.0016 11.06 0.996 up
1c
high ield −40 – +5 −0.0118 9.52 0.999 down
1e −40 – −20 −0.0018 8.14 0.995 —
1d −40 – +10 −0.0027 8.34 0.995 up
aLinea i y ange, bco ela ion coe icien , cchanges o he chemical shi a e eaching l. . limi , dsignal no seen abo e −5 °C, esignal disappea a
highe empe a u es, a empe a u e −5 °C he chemical shi suddenly inc eases (Figu e 8) ha was in e p e ed as 1d+5→o he o m∙∙∙5 isome iza-
ion and a e aging o peaks. The simila is ealized o H1/H7 (high ield signal o 1d).
Figu e 7: The signal labelling o [1]:[5] in 1:1 a io exempli ied on he spec a eco ded a −40 °C (CDCl3) and s uc u e o complexes.
shape (b oadened single ending o iple shape), while H3/H5
signals shi om 9.13 (1) o 12.04 ppm due o in e ac ion wi h
an anion. The b oades NH signals come om 1c∙∙∙5 complex
ha , mos p obably, exis in a as equilib ium as shown in
Figu e 7. In he alipha ic pa o he spec um, excep he me h-
ylene o +N(n-Bu)4 ca ion (a 3.09 ppm, ou o he g een box,
Figu e 7), wo cha ac e is ic signals a e isible. I is wo h
poin ing ou ha hei assignmen based on in eg a ion is in
pe ec ag eemen wi h he da a ob ained by in eg a ion o NH
p o ons in he same spec um. The a io o 3.597/3.195 = 1.126
while he espec i e sum o NH (H3/H5) in eg a ion in 1c and
in eg a ion o NH in 1e di ided by in eg a ion o NH in 1d
(H3/H5) is 1.411/1.255 = 1.124. Figu e 8 shows a apid change
o he chemical shi obse ed a empe a u es ca. 0 o +10 °C
o 1d∙∙∙5.
This is caused by as equilib ium be ween o ms in solu ion. In
his case he signal is a e aged and since i was shown in
Figu e 7 ha o he han 1d∙∙∙5 o ms a e ep esen ed by highe
NH chemical shi s he men ioned signal a e aging causes
inc ease o he chemical shi and signal b oadening a highe
empe a u e (Suppo ing In o ma ion File 1, Figu e S21, o
example). This may be especially ue i one ealize ha NH
g oups a e in ol ed in in amolecula hyd ogen bonding a e
dissocia ion o he complex a highe empe a u es. Mo eo e ,
he p oposed o ms ha a e p esen a low empe a u es we e
Beils ein J. O g. Chem. 2015, 11, 2105–2116.
2112
Figu e 8: The a iable empe a u e (+20 o −40 °C, CDCl3) dependence o he main signals ( he highes in eg al alues) in 1d∙∙∙5 complex.
calcula ed and hei ene ge ic ela ions a e in ag eemen wi h
obse ed da a (see da a in Suppo ing In o ma ion File 1 and
Figu e S34 o he ene gy diag am).
The naph hy idine case
The signal obse a ion di icul ies (disappea ance o NH peaks)
in 1∙∙∙10 we e o e come by obse a ion o a oma ic double s o
10. The lack o NH signals in he spec um may be caused by:
a) as equilib ium o b) he p o on ans e be ween 1 and naph-
hy idine dianion 10. While he p o on ans e is mo e p ob-
able a highe empe a u es and lowe ing he empe a u e causes
he inc ease o he popula ion o o m wi h in amolecula
hyd ogen bond we op o a gumen "a". Figu e 9 shows he
changes in he spec a upon cooling ( op spec um ep esen s
+20 °C, spec a we e eco ded in 5° s eps; he las spec um a
bo om ep esen s a empe a u e o −70 °C).
The coalescence empe a u e o complex 1∙∙∙10 is −15 °C. A
empe a u es below −25 °C he equilib ium is slow enough o
obse e an asymme ic complex. I is impo an o keep in mind
ha hese spec a a e eco ded o a 1:0.1 mola a io o 1 and
10 o be su e ha mos o 10 is associa ed. F om VT 1H NMR
measu emen s he Gibb's ee ene gy equal o 66.6 kJ/mol was
ob ained (Ey ing equa ion). Two o ms in 1∙∙∙10 complexes a e,
mos p obably 1a∙∙∙10 (high empe a u e) and 1c∙∙∙10 (low
empe a u e). Be ween hese wo o a ional ansi ion s a es
exis and one o m ep esen ed by a local ene gy minium
(Figu e 10).
These a e ansi ion s a es ela ed o a) con o ma ional change
o 1 and b) shi o he anion 10 along he hyd ogen bonding
pa e n o minimize he elec on epulsion. Along he same con-
Figu e 9: The VT (+20 o −70 °C, CDCl3) 1H NMR s acked spec a
(low emp. a bo om) o 1∙∙∙10 in 1:0.1 mola a io (on he le spec-
um a small sa elli e signal om esidual chlo o o m is seen).
o ma ional pa h ano he o m o 1c∙∙∙10 ( o m 1) is p esen .
This o m is, howe e , less s able han 1c∙∙∙10 ( o m 2) due o
elec onic epulsion be ween basic cen e s in he complex. Fo
de ailed discussion ha suppo s expe imen al indings e e o
he compu a ions sec ion in Suppo ing In o ma ion File 1.
Mass spec ome y
To ha e a mo e comple e iew o p ope ies o 1 we applied he
combina ion o so ioniza ion echnique elec osp ay ioniza-
ion (ESI) wi h high esolu ion mass spec ome y (HRMS) o
he s udy o he associa ion p ocesses o 1 wi h benzoa e 5 and