X-ray structure and conformational study of tris(2-(dimethylamino)phenyl)methanol: Roles of hydrogen bond in conformational conversions of molecules

Article abstract of DOI:10.1016/j.molstruc.2015.03.009

Tris(2-(dimethylamino)phenyl)methanol, (2-(Me)₂N-C₆H₄)₃COH, was synthesized and characterized by using NMR, EA and ESI-MS. Single crystal of the 2-syn/1-anti conformer of the tertiary alcohol was obtained and an

Full text of DOI:10.1016/j.molstruc.2015.03.009

Journal of Molecular Structure 1092 (2015) 72–80
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
X-ray structure and conformational study
of tris(2-(dimethylamino)phenyl)methanol: Roles of hydrogen
bond in conformational conversions of molecules
Yong-Ping Niu a, , Jun-Kai Zhang a,b, Xiao-Wei Wang a, Xiao-Fei Ma a, Jun-Qing Cai a, Na Zhou a,
⇑
Zhi-Wu Zheng a, Rui-Mao Hua b,
⇑
a School of Chemical Engineering and Pharmaceutics, Henan University of Science & Technology, Luoyang 471023, China
b Department of Chemistry, Tsinghua University, Beijing 100084, China
h i g h l i g h t s
g r a p h i c a l a b s t r a c t
Roles of hydrogen bond in conformational conversions of tris(2-(dimethylamino)phenyl)methanol: syn-
thesis, X-ray structure and conformational study by variable-temperature 1H NMR spectroscopy.
ꢀ
Tris(2-(dimethylamino)
phenyl)methanol was synthesized
and characterized.
ꢀ
ꢀ
The X-ray crystal structure of the 2-
syn/1-anti conformer is reported.
Variable-temperature 1H NMR
studies indicate four conformers in
solution.
ꢀ
ꢀ
Intra-molecular hydrogen bond
affects inter-conversions between
conformers.
Mechanisms of intra- and inter-
conformational conversions are
proposed.
a r t i c l e i n f o
a b s t r a c t
Article history:
Tris(2-(dimethylamino)phenyl)methanol, (2-(Me)2N-C6H4)3COH, was synthesized and characterized by
using NMR, EA and ESI-MS. Single crystal of the 2-syn/1-anti conformer of the tertiary alcohol was
obtained and analyzed by X-ray diffraction. The variable-temperature 1H NMR experiments reveal that,
in solution, the tertiary alcohol is an equilibrium mixture of four conformers, all-syn, 2-syn/1-anti, 1-syn/
2-anti and all-anti. The results show that hydrogen bond plays an important role in both intra- and
inter-conformational conversions of molecules. The intra-conformational conversions within specific
conformers are just helical changes. The inter-conformational conversions between conformers occurred
via one-ring flip process.
Received 5 January 2015
Received in revised form 5 March 2015
Accepted 6 March 2015
Available online 13 March 2015
Keywords:
Tris(2-(dimethylamino)phenyl)methanol
Triarylmethanol derivatives
Hydrogen bond
Ó 2015 Elsevier B.V. All rights reserved.
Ring flip mechanism
Conformational analysis
Introduction
⇑
Corresponding authors. Tel.: +86 0379 64231914; fax: +86 0379 64232193
(Y.-P. Niu). Tel.: +86 10 62792596; fax: +86 10 62771149 (R.-M. Hua).
E-mail addresses: yongpingniu@gmail.com (Y.-P. Niu), ruimao@mail.tsinghua.
edu.cn (R.-M. Hua).
The stereochemistry of triarylmethanes (TAMs) and structurally
related compounds have attracted much attention since the
publications by Kurkland et al. in the middle 1970’s. [1–3]. In the
http://dx.doi.org/10.1016/j.molstruc.2015.03.009
0022-2860/Ó 2015 Elsevier B.V. All rights reserved.

Y.-P. Niu et al. / Journal of Molecular Structure 1092 (2015) 72–80
73
early 1980’s, Mislow and co-workers had demonstrated that TAMs
molecules undergo conformational changes through restricted and
correlated rotations of their attached aryl groups [4–7]. It was now
generally accepted that the enantiomerization of TAMs molecules
can principally involve eight pathways (Fig. 1), one zero-ring, three
one-ring, three two-ring and one three-ring flip paths [3,4,8]. For
these multi-blade propeller molecules, the lowest energy (thresh-
old) rotating mechanism can be one-ring flip [9,10], two-ring flip
[5,11,12] or n-ring flip [13]. The choice of rotating mechanism
should depend on the contributions of the steric effect of the
attached aryl groups [14].
before use. Ethyl carbonochloridate and n-butyllithium were pur-
chased from Aldrich. Other commercially available reagents were
purchased and used as received. 1H NMR and 13C NMR spectra
were recorded on Bruker Avance III 400 and 600 MHz NMR spec-
trometers. Element Analysis was determined with Thermo
Scientific Flash 2000 Organic Elemental Analyzer. Infrared (IR)
spectrum was measured on a Bruker’s VERTEX 70 Series Fourier
transform infrared (FTIR) spectrometer.
Tris(2-(dimethylamino)phenyl)methanol
Recently, Hey-Hawkins’ group have described the synthesis and
properties of ortho-amino substituted arylmethanol derivatives
(2-(R1)2N-C6H4-C(R2)2OH, R1 = Me, Et, R2 = Ph, Cy;). The common
feature of these tertiary alcohols is that they form the intramole-
cular hydrogen bond (OAHÁ Á ÁN(alkyl)2) [15]. Pozharskii’s group
has reported the synthesis and properties of triarylmethanol
derivatives (TAMols) bearing one or two 1,8-bis(dimethylamino)-
naphthalen-2-yl arms [16]. 1H NMR studies of these TAMols shown
the proton of their hydroxyl groups would induce the temperature-
driven tandem configuration inversion of the both nitrogen atoms
via intermolecular hydrogen bond [17].
Under ice-water bath cooling, 4.7 mL (42.5 mmol) ethyl car-
bonochloridate was added drop-wise into the stirring solution of
(2-(dimethylamino)phenyl)lithium, which was used as prepared
by the reaction of 16.2 mL (128 mmol) N,N-dimethylaniline with
45 mL n-butyllithium (2.89 M, dissolved in TMEDA/n-hexane
(21.5 mL/120 mL)) [20–22]. The mixture was gradually warmed
to room temperature, stirred overnight and then terminated with
ethanol (95%, 5 mL). After solvents evaporated under reduced pres-
sure, the residues were dissolved in 50 mL dichloromethane. The
obtained dichloromethane solution was washed times with water,
dried with anhydrous MgSO4, and then filtered. After evaporating
dichloromethane under reduced pressure, the crude product was
finally obtained as a colorless viscous liquid which crystallize
slowly to form centimeter crystals in a few months later. The
uncrystallized liquid fraction was poured out and the remaining
crystals were washed times with cold n-hexane (yield: 5.48 g,
ꢁ33%). EA for C25H31N3O: Calculated: C, 77.08, H, 8.02, N,
10.79; Flash EA: C, 77.08, H, 8.05, N, 10.77; 1H NMR (CDCl3,
25 °C) dppm (m, J(Hz), xH, assignment): a). SSS conformer: 2.79
(s, 18H, Methyl), 6.66 (d, 3H, 15.7, Ar-3-H), 7.15 (t, 3H, 15.5, Ar-
5-H), 7.44 (t, 3H, 14.8, Ar-4-H), 7.66 (d, 3H, 15.9, Ar-6-H), 14.82
(s, 1H, OH, À50 °C); b). SSA and SAA conformers: 2.26(18H, s),
7.01(dt, 12.3, 2.9, 3H, Ar-5-H), 7.22 (dd, 3H, 18.8, 2.9 Ar-3-H),
7.22 (dt, 22.6, 2.8, 3H, Ar-4-H), 7.27 (dd, 8.1, 1.6, 3H, Ar-6-H),
9.709 (s, 1H, OH); c.) AAA conformer: 1.97 (Methyl, s, À50 °C).
13C NMR d(ppm, CDCl3, 25 °C): SSA and SAA conformers:
45.93(CMe), 83.46(COH), 123.48(C3), 123.71(C4), 127.69(C5),
131.21(C6), 143.61(C1), 153.13(C2); Other conformers: not
detected; m/e (ESI-MS):389.9(389.2 + H), 372.2(389.9 AOH); IR
These recent researches imply that TAMols bearing three
ortho-dialkylamino substituted aryl arms would have interesting
stereochemistry.
A
simple example is tris(2-(dimethy-
lamino)phenyl)methanol, which had been prepared and reported
by Bayer a century ago [18]. Comparing with tris(4-(dimethy-
lamino)phenyl)methanol (crystal violet base) [18,19], studies on
this compound is rare, despite a long history of discovery. In this
work, this tertiary alcohol was synthesized and studied as a model
of this kind of compounds.
Experimental
General remarks
All necessary manipulations involving air- and moisture-
sensitive compounds were performed by standard Schlenk tech-
niques under nitrogen atmosphere in vacuum-line. n-Hexane and
N, N-dimethylaniline were thoroughly dried over phosphorus pen-
toxide and CaH2, respectively. N1,N1,N2,N2-tetramethylethane-1,2-
diamine (TMEDA) was dried with molecular sieve 4 Å and distilled
data (KBr pellets,
CAH, Ar), 2968/2936 and 2816/2777 (s., CAH, asy. and sy., Me),
m
/cmÀ1): 3380(s., OAH), 3053 and 3014 (s.,
Zero-Ring
One-Ring
Fli
p
X
X
Flip
X
X
Two-Ring
Flip
Flip
X
X
Three-Ring
Fig. 1. The rotational (flip) mechanisms for the Ar3ZX systems [4].

74
Y.-P. Niu et al. / Journal of Molecular Structure 1092 (2015) 72–80
Table 1
1593,1572,1483 and 1443 (s., CAC, ring), overlapped (deform.,
CAH, asy. and sy., Me), 1358 (deform., OAH), overlapped (s., CAN,
Ar and Me), 1094 (s., CAO), 762 (wag., CAH, Ar and deform., ring).
Crystal data and structure refinement for tris(2-(dimethylamino)phenyl)methanol.
Empirical formula
Formula weight
Temperature (K)
Wavelength (Å)
Crystal size (mm3)
Crystal system
Space group
a (Å)
C25H31N3O
389.53
296(2)
X-ray diffraction measurements
0.71073
0.32 Â 0.21 Â 0.18
Monoclinic
P21/c
8.8799(9)
24.205(2)
11.0329(11)
90
106.5150(10)
90
2273.5(4)
4
The crystal data were collected on a Bruker SMART APEX II CCD
diffractometer. The crystal structure was solved using direct meth-
ods and refined by full-matrix least-squares procedures on F2 with
SHELXL-2014/7 [23]. Crystal data and structure refinement details
are summarized in Table 1. Relevant data of the selected bond
length (Å) and angles (°) were summarized in Table 2.
b (Å)
c (Å)
a
(°)
b (°)
c
(°)
Volume (Å3)
Z
Results and discussion
Calculated density (Mg/m3)
Absorption coefficient (mmÀ1
F(000)
1.138
0.070
840
)
TAMols were usually prepared by using aryl magnesium com-
pounds through multi-step reactions [18]. The synthetic routes of
the present work were shown in Scheme 1. It can be conveniently
prepared through the reaction of ethyl carbonochloridate with
(2-(dimethylamino)phenyl)lithium, which was previously prepared
by the reaction of N,N-dimethylaniline with n-butyllithium/
TMEDA in n-hexane [20–22]. The crude product was finally
obtained as a viscous liquid, which crystallize slowly to centimeter
crystals in a few months later. Single crystals, suitable for X-ray
diffraction studies, were obtained by layering methanol solution
of the tertiary alcohol onto deionized water (4:1).
According to the orientations of the three dimethy-
laminophenyl arms with respective to a reference plane (defined
by the three carbon atoms attached to the central carbon), the
tertiary alcohol can have four possible conformers, including
all-syn(SSS), 2-syn/1-anti(SSA), 1-syn/2-anti(SAA) and all-anti(AAA).
However, despite efforts made to obtain that of the other
conformers, only the single crystals of the SSA conformer were
obtained (Fig. 2).
X-ray analysis reveals that the structural motif of the obtained
SSA crystal is an intermolecular hydrogen bonded dimer of two
enantiomeric molecules. The basic geometry (distances and angles)
around the central carbon atom and the attached hydroxyl group is
within the range of typical values recorded for analogous TAMols
[15–17]. The interatomic distance (Å) of C(1)AC(2) (1.558(2)) is
slightly larger than that of C(1)AC(8) (1.544(2)) and C(1)AC(14)
(1.540(2)), indicating that there are steric repulsion between the
dimethylamino group of anti-arm and the inner edges of benzene
rings of two syn-arms. Structural features of SSA conformer can
still be classified as a helical arrangement, despite a smaller dihe-
dral angle of 11.84° between the O(1)AC(1)AC(2) plane and the
benzene ring plane of anti-arm. The corresponding dihedral angles
observed for the two syn-arms are respectively 43.89° (OAH---N
binding syn-arm) and 68.47°. These two angles are slightly larger
than the dihedral angles of 37.46° and 65.42° recorded for analo-
gous TAMols bearing two 1,8-di(dimethylamino)-2-naphthyl
(syn-)arms [17]. The dihedral angle between the two benzene ring
planes of the syn-arms is 66.48°. Correspondingly, the two dihedral
angles between the benzene ring plane of anti-arm and that of two
syn-arms are respectively 85.64° and 86.35° (OAH---N binding
syn-arm), approximately perpendicular. The dihedral angle
between the C(20)AN(1)AC(21) plane and the benzene ring plane
of anti-arm is 89.41°, nearly perpendicular. The corresponding
dihedral angles observed in the two syn-arms are respectively
76.58° and 83.89° (OAH---N binding syn-arm). These dihedral
angles indicate the three aryl arms and their attached dimethy-
lamino groups have some flexibility to fit the molecular
conformation.
h range for data collection (°)
Limiting indices
2.39–25.50
À10 6 h 6 10
À29 6 k 6 29
À12 6 l 6 13
15,190/4223 [R(int) = 0.0348]
99.6%
Reflections collected/unique
Completeness to h = 25.50
Absorption correction
Max. and min. transmission
Refinement method
None
0.9875 and 0.9779
Full-matrix least-squares on F2
4223/0/269
1.019
R1 = 0.0461
wR2 = 0.1083
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2
r
(I)]
R indices (all data)
R
1 = 0.0797
wR2 = 0.1266
0.116 and À0.144
Largest diff. peak and hole (e ÅÀ3
)
show that in chloroform-d, the tertiary alcohol is an equilibrium
mixture, which are mainly composed of one conformer (Fig. S2.).
The 2d NMR spectra, HSQC, HMBC, COSY and NOESY, had been
done to analysis these conformers (Fig. S3–S6). However, except
the main conformer, the other minor conformers are difficult to
be identified because of their low populations. The NMR observa-
tions indicate that in addition to temperature, hydrogen bond
should play a role in the inter-conversions between conformers.
To clarify the roles of the hydrogen bond, models of four possi-
ble conformers were established and calculated by using CS
ChemBio3D software (Ver., 14.0) and the attached programs. The
MM94 calculations suggest that the trigonal pyramidal config-
uration is more favorable for the nitrogen atoms of dimethylamino
groups (Fig. 3. first row). The minimized conformational energy of
SSA1 model is 125.945 kcal/mol, which is lower than that of the
other conformers, 129.812 (SSS1), 130.852 (SAA1) and 145.076
(AAA1) kcal/mol. For the models with syn-arms (SSS1, SSA1 and
SAA1), the inward lone-pair elections of the nitrogen atoms on
their syn-arms were also suggested to form hydrogen bonds with
the central hydroxyl group. However, the MM2 force field calcula-
tions indicate that the lone-pair electrons of their nitrogen atoms
would like to conjugate with the attached benzene rings (Fig. 3.
second row). This conjugating status would increase the steric
hindrance between aromatic arms, and therefore to some extent
hinder the ring-flips of them. Therefore, the decisive factor stabiliz-
ing the different conformers was thought to be the dimethylamino
groups. The minimized conformational energies of models calcu-
lated by the MM2 method are respectively 90.1697 (SSS2),
95.9137 (SSA2), 100.7246 (SAA2) and 105.4372 (AAA2) kcal/mol.
Each of them is correspondingly smaller than that calculated by
MM94 method.
Comparing MM94 models with the corresponding MM2 mod-
els, it was found that the formation of the intramolecular hydrogen
Conformational studies of the tertiary alcohol in solution were
carried out by using the variable-temperature 1H NMR. Results

Y.-P. Niu et al. / Journal of Molecular Structure 1092 (2015) 72–80
75
Table 2
of lower conformational energies. Despite the similarity of MM94
SSA1 model to its solid structure, the realtime configuration of
specific conformers in solution should be similar but different with
the calculated static models (MM94 and MM2). Molecules of each
specific conformers were thought to equilibrium between their
MM94 and MM2 models, along with the configuration changes of
its three nitrogen atoms (induced by the formation of an
intramolecular hydrogen bond). However, driven by the formation
of the intromolecular hydrogen bond and the steric hindrance
among the substituents, it is difficult to clarify to the direction of
these intra-conformational equilibria (Fig. 3, green colored).
The above calculations indicate that the strong signals in spec-
tra can be assigned to the SSA conformer. However, the influences
of hydrogen bond formation on the chemical shifts of methyl and
aromatic protons should not to be neglected, because hydrogen
binding was generally regarded to be dominant over that of the
geometric differences [16,17]. If the constant states of SSA con-
former in solution are the molecules with the MM94 model char-
acter, the protons of the binding syn-arm and the protons of the
other two arms should give different chemical shift values.
Therefore, there must have exchanges meet the requirements of
protons’ chemical equivalence.
To interpret the considerations, the possible equilibria of the
intra-conformational changes of SSA conformer were examined
with the consideration of the hydrogen bond influences and on
the basis of the ring flip mechanism (Scheme 2). The results of
the conformational analysis reveal that to satisfy the equal proba-
bility requirement, SSA conformer should have twelve states. It is
self-evident that the interconversions between the enantiomeric
pair need to break the specific conformational states. Therefore,
the twelve states of SSA conformer should separately belong to
two equilibrium cycles of six each [24].
The both equilibrium cycles of SSA conformers include basically
two intra-conformational change process (Scheme 2), proton-
bonded (PB) helical changes (also to be arm exchanges) and pro-
ton-induced (PI) helical changes (also to be donor exchanges).
The PB helical changes of SSA conformer are virtually two-ring flip
conversions, which need the other two non-binding arms syn-
chronously rotating through the reference plane. Therefore, the
PB helical changes of SSA conformer were thought to be high bar-
rier conversions, which are less possible to occur. While, the PI
helical changes of the SSA conformer are low barrier conversions
following zero-ring flip pathway, which did not need any ring
rotating through the reference plane. The intra-conformational
analysis of SSA conformer shows that the nitrogen atoms of its’
two syn-arms have more opportunities to form hydrogen bond
with the hydroxyl proton than that of anti-arms. The above analy-
sis also indicates that the intra-conformational changes of SSA con-
former itself cannot meet the requirements of protons’ chemical
equivalence. This prompts us to examine conformational states
of the other conformers and the conversions among all the
conformers.
Selected bond length (Å) and angles (°) for tris(2-(dimethylamino)phenyl)methanol.
C(1)AO(1)
C(1)AC(8)
C(2)AC(7)
C(3)AC(4)
C(4)AC(5)
C(6)AC(7)
C(8)AC(9)
C(9)AN(2)
C(11)AC(12)
C(14)AC(15)
C(15)AC(16)
C(16)AC(17)
C(18)AC(19)
C(21)AN(1)
C(23)AN(2)
C(25)AN(3)
O(1)AC(1)AC(8)
O(1)AC(1)AC(2)
C(8)AC(1)AC(2)
C(7)AC(2)AC(1)
C(4)AC(3)AC(2)
C(2)AC(3)AN(1)
C(4)AC(5)AC(6)
C(6)AC(7)AC(2)
C(13)AC(8)AC(1)
C(10)AC(9)AC(8)
C(8)AC(9)AN(2)
C(10)AC(11)AC(12)
C(12)AC(13)AC(8)
C(15)AC(14)AC(1)
C(14)AC(15)AC(16)
C(16)AC(15)AN(3)
C(16)AC(17)AC(18)
C(18)AC(19)AC(14)
C(3)AN(1)AC(20)
C(23)AN(2)AC(22)
C(9)AN(2)AC(23)
C(15)AN(3)AC(24)
1.431(2)
1.544(2)
1.392(2)
1.391(3)
1.369(3)
1.384(3)
1.407(3)
1.434(2)
1.374(3)
1.391(2)
1.395(3)
1.368(3)
1.369(3)
1.454(2)
1.452(3)
1.468(3)
102.6(1)
108.7(1)
110.8(1)
118.2(2)
119.6(2)
120.9(2)
119.0(2)
121.9(2)
120.5(2)
118.9(2)
120.7(2)
119.3(2)
122.8(2)
121.1(2)
120.1(2)
119.9(2)
119.8(2)
122.0(2)
112.4(2)
110.9(2)
114.2(2)
112.4(2)
C(1)AC(14)
C(1)AC(2)
C(2)AC(3)
C(3)AN(1)
C(5)AC(6)
C(8)AC(13)
C(9)AC(10)
C(10)AC(11)
C(12)AC(13)
C(14)AC(19)
C(15)AN(3)
C(17)AC(18)
C(20)AN(1)
C(22)AN(2)
C(24)AN(3)
O(1)AC(1)AC(14)
C(14)AC(1)AC(8)
C(14)AC(1)AC(2)
C(7)AC(2)AC(3)
C(3)AC(2)AC(1)
C(4)AC(3)AN(1)
C(5)AC(4)AC(3)
C(5)AC(6)AC(7)
C(13)AC(8)AC(9)
C(9)AC(8)AC(1)
C(10)AC(9)AN(2)
C(11)AC(10)AC(9)
C(11)AC(12)AC(13)
C(15)AC(14)AC(19)
C(19)AC(14)AC(1)
C(14)AC(15)AN(3)
C(17)AC(16)AC(15)
C(19)AC(18)AC(17)
C(3)AN(1)AC(21)
C(21)AN(1)AC(20)
C(15)AN(3)AC(25)
C(9)AN(2)AC(22)
C(25)AN(3)AC(24)
1.540(2)
1.558(2)
1.399(2)
1.439(2)
1.369(3)
1.390(2)
1.394(3)
1.367(3)
1.386(3)
1.395(2)
1.453(2)
1.376(3)
1.459(2)
1.462(3)
1.468(3)
109.7(1)
115.0(1)
109.7(1)
117.5(2)
124.3(2)
119.5(2)
121.9(2)
120.1(2)
117.4(2)
121.9(2)
120.4(2)
122.5(2)
119.1(2)
117.5(2)
121.3(2)
120.0(2)
120.8(2)
119.8(2)
114.3(2)
111.3(2)
112.5(2)
114.9(2)
111.9(2)
bond can hold up one syn-arm to a specific orientation (Fig. 3, first
row). And as a result, one benzene ring of three aromatic arms
could take a more perpendicular status with respect to the
reference plane. This perpendicular status of one benzene ring
can empty space for the other two benzene rings, especially for
the one with a smaller dihedral angle to the reference plane, to
accomplish the ring-flip process (Fig. 3, first row). Therefore, the
formation of intro-molecular hydrogen bond was thought to be
critically necessary for the inter-conversions between conformers.
In the dissolving process, the MM94 (crystal) molecules of SSA con-
former can change to the MM94 molecules of the other conformers
via inter-conformational conversions through one-ring flip pro-
cess. However, they would be also likely change to the correspond-
ing molecules of themselves with MM2 model character, because
In spectra (Figs. S2 and 4), the signal at around 2.79 ppm was
assigned to methyl protons of the SSS conformer. Although weak,
the four aromatic signals of the SSS conformer can be clearly iden-
tified in the spectra (Figs. S2 and 4). According to the chemical shift
values and the splitting patterns, these four 1H proton signals can
be respectively assigned to the Ar-x-H protons of this specific con-
former. The hydroxyl proton signal of this conformer can be
observed at around 14.7–14.9 ppm, only in low temperature spec-
tra obtained at around below À50 °C (Fig. 4). The integral ratios of
this set of signals (Methyl/Ar-x-H/OH) is very close to 18/3/1, indi-
cating the correlation of them.
N
N
Li
n
-Butyllithium/TMEDA (1:1.2)
in -Hexane
n
O
N
N
OH
1/3
1.)
O
Cl
2.) 95% Ehanol
N
Therefore, the SSS conformer should also be composed of the
two propeller enantiomers (Scheme 3). Taking SSS conformation,
the hydroxyl proton would induce the lone-pair electrons of all
Scheme 1. Synthesis of Tris(2-(dimethylamino)phenyl)methanol.

76
Y.-P. Niu et al. / Journal of Molecular Structure 1092 (2015) 72–80
Fig. 2. Crystal structure of SSA conformer with thermal ellipsoids at 30% probability level. Selected (bond) distances (Å) and (torsion) angles (deg): O(1)AH(1) 0.820(1),
N(3)AH(1) 1.978(2), C(23)AH(23c) 0.960(2), H(23c)AO(1) 2.397(1), O(1)AH(1)AN(3) 143.3(1), O(1)AH(23c)AC(23) 127.7(1), O(1)AC(1)AC(2)AC(7) 12.5(2),
O(1)AC(1)AC(8)AC(9) 65.4(2), O(1)AC(1)AC(14)AC(15) 45.4(2).
Fig. 3. Conformational models of tris(2-(dimethylamino)phenyl)methanol and assumed equilibria among conformers (models).
the nitrogen atoms orienting inward to facilitate the formation of
the intramolecular hydrogen bond [15–17]. The binding com-
petition of the three dimethylamino groups to hydroxyl proton,
the so called ‘‘proton sponge’’ effect [16,17,25,26], would result
in the formation of ‘‘dynamic’’ hydrogen bond. The formed
dynamic hydrogen bond, as well as the steric hindrance among
substituents, would to some extend, restrict the rotational freedom
of the aniline moieties and maintain the stability of the SSS

Y.-P. Niu et al. / Journal of Molecular Structure 1092 (2015) 72–80
77
Scheme 2. Two assumed equilibria cycles of SSA conformer (For clarity, N-methyl groups were omitted, and hydrogen bonds (OAH---N) were expressed as O---N).
conformation. As observed, the signals of this conformer can still
be recognized in high temperature spectra, according to their vary-
ing trends with temperature (Fig. S2.).
The helical change between propellers of SSS conformer can
follow the zero-ring flip pathway, which did not need any benzene
ring rotating through the reference plane. It can be accomplished
by synchronizing the switching of the hydroxyl proton, the adjust-
ments of the dimethylamino groups and the unidirectional rota-
tions of aryl arms (Scheme 3.). The derivative time-averaged
conformation of C3 symmetry was thought to be consistent with
the 1H NMR observations. With the temperature increasing, the
gradually broadening of the methyl resonance should be caused
by the increase of molecular thermal motion ability. With the tem-
perature decreasing, the gradually broadening of the methyl reso-
nance should indicate the slowdown of proton switching (helical
change). Similarly, the gradual emergence of the hydroxyl proton
resonance should be an evidence that the hydroxyl proton
becomes stuck to a specific nitrogen atom at low temperature.
The separated distribution of its aryl signals was thought to be
the time-averaged influence of switching hydroxyl proton on the
chemical shifts of aromatic protons. The SSS conformer reaches
its highest proportion at around À10 °C with a ratio of 8.88/100,
Fig. 4. Full spectra of tris(2-(dimethylamino)phenyl)methanol at low temperature
and aromatic region of SSS conformer at 25 °C (Chloroform-d).
calculated by the integrated area of its methyl signals with respec-
tive to that of the strong methyl signals at around 2.26 ppm. As
indicated by the sharp methyl signals, the helical change of SSS
conformer was regarded to be a fast low barrier process at around
room temperature. The above considerations and observations
indicate that SSS conformer itself can meet the requirement of pro-
tons’ chemical equivalence.
Due to the fast helical change, the three syn-arms of SSS con-
former were thought to have the equal opportunities of flipping,
which results in the easy formation of SSA conformer. As a compar-
ison, the generation of SSS conformer from SSA conformer was
thought to be a slow process, which needs the benzene ring flip
of the only anti-arm of SSA conformer (Fig. 3 red1 colored). To
accomplish the conversion, the PI helical change of SSA conformer
is necessary, because of the large steric hindrance between the bind-
ing sys-arm and the only anti-arm. A competition to the ring flip of
the only anti-arm is the ring flip of the newborn non-binding syn-
arm (after PI helical change of SSA conformer). The latter ring flip,
generating SAA conformer, was thought to be more liable to occur
than the former, because of a smaller steric hindrance.
The presence of SAA comfomer remains an enigma, since it was
not directly observed. Similar to SSA conformer, conformational
analysis show that SAA conformer should also have twelve states,
which separately belong to two equilibrium cycles of six each
(Scheme 4). The two equilibrium cycles of SAA conformers also
include two intra-conformational change process, proton-bonded
(PB) helical changes (just helical conversions) and hydrogen-
bond-blocked (HBB) helical changes (including both donor and
1
For interpretation of color in Fig. 3, the reader is referred to the web version of
this article.

78
Y.-P. Niu et al. / Journal of Molecular Structure 1092 (2015) 72–80
can be accomplished through one-ring flip of one of two anti-arms.
The PB helical changes of SAA conformer would also promise the
two anti-arms equal opportunities to flip. Therefore, it was
regarded that the inter-conformational conversions between the
SSA and SAA conformers, a one-ring flip process, would control
the overall arm exchanges rates of them both. And as a result, these
would ultimately surpass or flatten the difference in donor
exchange rates between them, indicating that they will behave like
one conformer. The strong resonances in the spectra were once
thought to be correlated only with SSA conformer. However, this
easy assignment is obviously inconsistent with the above analysis
that the arm exchanges rates of inter-conformational process
(one-ring flip, SSA M SAA) are faster than that of the intra-con-
formational process (two-ring flip, the PB process of SSA and the
HBB process of SAA). That is to say, on the basis of combined con-
siderations of both intra- and inter-conformational changes, we
would like to believe that protons of SAA conformer should also
have contributions to these strong signals.
N
N
Helical Change
N
N
OH
N
OH
N
M-propeller
P-propeller
H
O
time-averaged conformation
Proton Sponge
H
O
O
H
The internal steric hindrance between the three anti-arms were
thought to be the only factor which stabilizes AAA conformer and
distinguishes itself from the other conformers. AAA conformer was
thought to be thermodynamically unstable because of a high inter-
nal energy. Logically, this conformer can only be generated from
SSA conformer. The conversion needs firstly the breaking of
intra-molecular hydrogen bond of SAA conformer, then following
the ring flip of the only syn-arm (Fig. 3. blue colored). And
therefore, it should be a minor conformer. The resonances of the
hydroxyl and aryl protons of the AAA conformer might be too weak
to be visible or be overlapped by the resonances of the other con-
formers (Fig. 4 and S1.). However, in the high field region of spectra
(Fig. S2a), the emerging signal, which presents firstly as a sharp
shoulder peak, then grows up gradually to a separate peak and
finally vanished with temperature increasing, can be assigned to
the methyl protons of this specific conformer. The variation trend
of the methyl resonance was thought to be consistent with the
opposing effects of the increased temperature on the thermal sta-
bility and the dynamic generation of this specific conformer. The
broadened methyl signals in high temperature spectra should indi-
cate the configuration changes of nitrogen atoms (between trigonal
pyramidal and planar), which is caused by the increase of the
molecular thermal motion ability. With the temperature decreas-
ing, the sharp trend of its methyl signal should indicate a frozen
conformation of C3 symmetry. The helical conversions of AAA con-
former were thought, at least in low temperature condition, to be
difficult because of the large steric hindrance and the low thermal
motion ability. With temperature increasing, AAA conformer
reaches its highest proportion at around À30 °C with a ratio of
3.80/100, calculated by the integrated area of its methyl signals
with respective to that of the strong methyl signals at around
2.26 ppm.
Scheme 3. Assumed conformational changes and time-averaged conformation of
SSS conformer It was generally agreed that TAMs exist as racemic mixtures of M-
and P-propeller structures [8].
arm exchanges). The PB helical changes of SAA conformer are low-
barrier intra-conformational conversions following zero-ring flip
pathway. However, the HBB helical changes of SAA conformer
could occur only if the hydrogen-bond barrier and the two-ring flip
barrier are crossed simultaneously.
The intra-conformational analysis shows that in SAA con-
formational states, the nitrogen atom of the only syn-arm has more
opportunities to form hydrogen bond with the hydroxyl proton
than that of the other two anti-arms. The intra-conformational
analysis also shows that the PI process of SSA conformer should
be more fast than the HBB process of SAA conformer. The two con-
siderations reveal a significant difference between the overall
donor (N) exchange rates between SSA and SAA conformers,
indicating that the time-averaged chemical shifts of their attached
protons should also be different. The above analysis show that only
intra-conformational changes cannot meet the requirement of
chemical equivalence and, the inter-conversions between the both
conformers should be considered as factors.
The inter-conformational conversions via two-ring flip process,
SSS M SAA and SSA M AAA, were thought to be unlikely to occur,
because of a relatively high transition state barrier. As already
mentioned, the interconversions between the enantiomeric pair
of SSA and SAA conformers all need to break the specific con-
formational states of individual conformer. If not considering these
inter-conformational conversions between SSA conformer and SAA
conformer, there should be a big difference in probabilities that
their nitrogen atoms of syn-arms and anti-arms to form hydrogen
bonds with the hydroxyl proton. The interconversions of the enan-
tiomeric pair of the SSA and SAA conformers can be accomplished
via two one-ring flip process, respectively through SSS and AAA
conformational states. While, the conversions between twelve con-
formational states of SSA conformer and that of SAA conformer
(Scheme 2 and 4), each to each, only need one one-ring flip process
(Fig. 3, equilibrium black colored). The conversion from SSA con-
former to SAA conformer can be easily accomplished through the
one-ring flip of the non-binding syn-arm. Or else, this conversion
can also be accomplished through a PI helical change of SSA con-
former, and then a subsequent ring flip of the newborn non-bind-
ing syn-arm. That indicates that PI helical changes would afford
equal opportunities for the two syn-arms of SSA conformer to flip.
Similarly, the conversion from SAA conformer to SSA conformer
Additional variable-temperature 1H NMR experiments, from
À60 to 60 °C, were carried out in methanol-d4 (Fig. S7). The
variation trends of conformers in methanol are similar to that in
chloroform (Fig. S2), except the absence of AAA conformer.
Calculation results show that the steric hindrance among the
groups, as well as thus produced the inward orientation of the
lonely pair of nitrogen atoms, counts against the tertiary alcohol
to form the NÁ Á ÁHAOCH3 inter-molecular hydrogen bonds with
methanol (solvent). Instead, methanol would like to form inter-
molecular hydrogen bonds with the hydroxyl group of the tertiary
alcohol (Fig. 5). Comparing with the calculation results of the pre-
ceding models (Fig. 3, first row), the relative smaller energies of the
present models in Fig. 5, 119.746 (SSS3), 116.128 (SSA3), 122.119
(SAA3) and 137.472 (AAA3) kcal/mol, should indicate more stable
conformations. At the same temperature, the line width of the
methyl signal of SSS conformer in methanol is broader than that

Y.-P. Niu et al. / Journal of Molecular Structure 1092 (2015) 72–80
79
Scheme 4. Two assumed equilibria cycles of SAA conformer (For clarity, N-methyl groups were omitted and hydrogen bonds (OAH---N) were expressed as O---N).
Fig. 5. Conformational models of tris(2-(dimethylamino)phenyl)methanol in methanol.
in chloroform. The binding solvent molecule was thought to
increase the steric hindrance. And therefore, the broadened methyl
signal at low temperature (À50–60 °C) should indicate the
slowdown of the helical changes of SSS conformer (Fig. S7a).
With temperature increasing, the broadened and weakened methyl
signal of SSS conformer should indicate the increase of the molecu-
lar thermal motion ability and the strength reduction of the inter-
molecular hydrogen bond. The above observations should indicate
that the formation of inter-molecular hydrogen bond, as a dis-
turbing factor, might to some extent hinder the helical changes
of SSS conformer and, as well as that of the other conformers
(Fig. 5). According to the calculation results, the stronger signals
can still be assigned to the SSA and SAA conformers. However,
due to the same reasons in chloroform, it is difficult to clarify the
contributions of SAA conformer to the strong signals. The variation
trend of their methyl signal is similar to that of the SSS conformer.
With the variation of temperature, it was also found that the vary-
ing intensity of their methyl signal in methanol is larger than that
in chloroform (Fig. S2). Their four aromatic signals showed a more
separate distribution in low temperature spectra (Fig. S7b), differ-
ent with the crowded distribution in chloroform (Fig. S2b). These
observations should indicate that the formation of inter-molecular
hydrogen bond increase the interface of the intra-molecular hydro-
gen bond to methyl groups and benzene rings. With temperature
decreasing, the shifting trend of the Ar-3-H signal to low field is
nearly stopped (with respect to that of the other aromatic protons
and comparing with that observed in chloroform, Fig. S7b). From
the conjugate relations, Ar-3-H protons are more close to the nitro-
gen atoms than the other aromatic protons. Therefore, the observa-
tion should indicate that the influence of intra-molecular hydrogen
bonds to the Ar-3-H protons is stronger than to the other aromatic
protons. This observation should also indicate that in addition to
the decrease of thermal motion ability, the strength of intra-
molecular hydrogen bond can also be increased by the formation
of inter-molecular hydrogen bond. Moreover, with temperature
decreasing to À50 °C (Fig. S7b), the signal of Ar-3-H protons was
found to become broadened with respect to that of the other aro-
matic protons, indicating the slowdown of the conversion between
SSA and SAA conformers. The above observations and considera-
tions suggest that in methanol, both the steric hindrance between
groups and the strength of intra-molecular hydrogen bond
increased with temperature decreasing, due to the formation of
inter-molecular hydrogen bond. Considering the conversion from
SAA conformer to AAA conformer is the only one which needs
the breaking of intra-molecular hydrogen bond, it is reasonable
to accept the absence of AAA conformer in methanol.
Conclusion
In summary, tris(2-(dimethylamino)phenyl)methanol has been
synthesized and characterized. X-ray structure of SSA conformer
reveals that the 2-dimethylaminophenyl arms and their attached

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Y.-P. Niu et al. / Journal of Molecular Structure 1092 (2015) 72–80
dimethylamino groups have some flexibility to fit the molecular
conformation. Variable-temperature 1H NMR experiments
confirmed that, in solution, the tertiary alcohol is an equilibrium
mixture of the four conformers, SSS, SSA, SAA and AAA.
Calculation results show that SSA conformer is the one with small-
est conformational energy. And in solution, the tertiary alcohol
mainly exists as SSA conformer. Calculation results indicate that
the intro-molecular hydrogen bond can hold up one aromatic
arm in a perpendicular orientation with respect to the reference
plane. This perpendicular status facilitates the benzene ring flip
of the non-binding aromatic arms, especially the one with a smal-
ler dihedral angle with respect to the reference plane. The inter-
conversions between conformers were regarded mainly though
the one-ring flip pathway, instead of two-ring flip pathway.
While, the intra-conformational conversions for individual
conformers are just helical conversions, which occurred by follow-
ing a zero-ring flip pathway. The SSS conformer undergoes a fast
helical change, which derived a time-averaged conformation of
C3 symmetry at around room temperature. The steric hindrance
is the only factor stabilizing the AAA conformer, which exhibits a
frozen conformation of C3 symmetry at low temperature. The
overall arm and donor (N) exchanges of both SSA and SAA
conformers were found to be controlled by the one-ring flip con-
versions between them. And as a result, the both conformers
behave like one conformer, which gives same chemical shifts.
ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk). The following ZIP
file contains the MOL files of models of conformers and the spectra
files referred to in this article.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.molstruc.2015.03.
009.
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Acknowledgment
The authors would like to acknowledge the financial supports
from NSFC (Projects 51175149 and 21002023) and from Henan
University of Science and Technology (Projects 09001304 and
13090074).
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Crystallographic data for the structure reported in this paper
has been deposited with the Cambridge Crystallographic Center,
CCDC No 1002962. (Copies of the data can be obtained free of
charge on application to The Director, CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK, fax: +44 1223 336 033, e-mail: deposit@