Crystal Growth & Design
Article
to be observed in the previously studied tertiary Mannich bases.
In the work presented here, we broaden the studies on inter-
action between secondary Mannich bases in the solid state,
when the zwitterionic species are formed, on the example of
two compounds: 4-bromo-2-[(aminopropyl)methyl]-phenol
(1) and 4-nitro-2-[(aminopropyl)methyl]-phenol (2). These
compounds, differing only by substituents at the para- position
in the phenyl ring were synthesized, their crystal structures
were determined, and careful IR studies in polarized light of
isotopically neat as well as deuterated species at room and
liquid nitrogen temperatures were performed. Experimental
data and quantum chemical calculations demonstrate consid-
erable influence of substituents on molecular interactions in the
solid state.
Chart 1. The Investigated Compounds
methanol (15 mL) was prepared at room temperature and stirred. On
addition of n-propylamine (0.82 g, 0.0138 mol, 1.14 mL) heating
evolved and the reaction mixture became intensely yellow. Stirring was
continued overnight. Then NaBH4 (0.18 g, 0.0047 mol) was added
portion-wise resulting in the discoloration of the solution. TLC of the
mixture (CHCl3:CH3OH, 95:5, v/v) revealed no traces of the starting
material or the corresponding Schiff base. The desired product
separated as a white powder after evaporation of about one-third of the
volume of the mixture. The solid was filtered off and dried in air.
4-Bromo-2-[(aminopropyl)methyl]-phenol (1.48 g, 56%), mp 93−
95 °C (from hexane). Found: C, 49.1; H, 5.7; N, 5.7. Calc. for
C10H14BrNO: C, 49.2; H, 5.7; N, 5.7. δH (400 MHz; CDCl3) 0.94
(3H, t, J1,2 7, Me), 1.55 (2H, m, CH2), 2.62 (2H, t, J1,2 7, CH2), 3.95
(2H, s, Ar−CH2−N), 6.70 (1H, d, J1,2 8, Ar), 7.09 (1H, m, Ar), 7.22−
7.25 (1H, m, Ar). δC (100 MHz; CDCl3) 11.5, 22.6, 50.3, 52.1,110.5,
118.1, 124.5, 130.6, 131.2, 157.6.
Synthesis of 4-Nitro-2-[(aminopropyl)methyl]-phenol (2).
Suspension of 3-nitro-6-hydroxybenzaldehyde (2.50 g, 0.015 mol) in
methanol (30 mL) was prepared at room temperature and stirred. On
addition of n-propylamine (0.89 g, 0.015 mol, 1.23 mL) additional
portion of the solid separated and another 20 mL of methanol was
added. Stirring of the suspension was continued for 5 h at room
temperature, and then about half of the volume of the mixture was
evaporated under reduced pressure. Yellow solid of the Schiff base
contaminated with traces of the starting aldehyde was filtered off and
was purified by crystallization from hexane (2 g, 49% yield). The Schiff
base (1.5 g, 0.0071 mol) was dissolved in MeOH, and NaBH4 (0.12 g,
0.0032 mol) was added portion-wise, with intense stirring resulting in
a yellowish suspension. The desired product separated as a white
powder after evaporation of about half of the mixture’s volume. The
solid was filtered off and dried in air.
4-Nitro-2-[(aminopropyl)methyl]-phenol (1.0 g, 66%), mp 190−
192 °C (from hexane). Found: C, 57.1; H, 6.6; N, 13.2. Calc. for
C10H14N2O3: C, 57.1; H, 6.6; N, 13.3. δH (400 MHz; CDCl3) 0.95
(3H, t, J1,2 7.2, Me), 1.55−1.64 (2H, m, CH2), 2.66 (2H, t, J1,2 7.2,
CH2), 4.09 (2H, s, Ar−CH2−N), 6.84 (1H, d, J1,2 9, Ar), 7.95 (1H, m,
Ar), 8.09 (1H, m, Ar). δC (100 MHz; CDCl3) 11.5, 22.3, 50.4, 52.0,
116.7, 122.1, 124.3, 125.1, 139.9, 165.2.
Crystal Structure Determination. Crystal structure was
evaluated at the Crystallographic Laboratory of the Faculty of
Chemistry of Wrocław University. CCDC-804823 for 1 and CCDC-
804824 for 2 contain the supplementary crystallographic data for this
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK: fax:
It was found that intramolecular hydrogen bonds in 1 and 2
+
are completely broken. The NH2 groups are double proton
donors to different PhO− groups in neighboring molecules
forming cyclic tetramers, which is probably the main factor
stabilizing the proton transfer (PT) forms of these molecules.
A similar pattern of hydrogen bonds was described previously
in the crystal of an intermolecular complex between 2,4-dinitro-
phenol and morpholine.14
The pattern of hydrogen bonded net in both crystals can be
15,16
2
2
described as R2 (12) and differently oriented R4 (8) units
in basic tetramers. Additionally, the stability of the crystal is
enhanced due to weak C−H···π and C−H···O interactions.
Stacking contacts between aromatic rings were not found.
In the case of previously studied tertiary para-NO2 Mannich
bases, the zwitterionic forms were observed,17 but for para-Br
similarly to para-Cl derivatives the acidity of phenols was too
low to form the zwittterionic structures in the solid state.1
In extension of our previous study, it was interesting to learn
to what extent the interaction between particular hydrogen
bonds takes place. a very efficient method to study such tasks
was developed by Flakus et al.18−22 They have revealed that
dynamic coupling in hydrogen bond systems, involving proton
(or deuteron) stretching vibrations in the hydrogen bonds, and
the electronic motions in the associated molecules stabilize
crystal lattices. In such circumstances, a nonrandom distribu-
tion of proton and deuterons takes place for the vast majority of
hydrogen bonded crystalline systems. The consequence of
these results in the IR spectra attributed to the “residual”
hydrogen bonds in not entirely deuterated crystals, which
remain unchanged, despite the growing concentration of
deuterons in their lattices (the H/D isotopic “self-organization”
effects). Identical hydrogen isotope atoms, proton or
deuterons, are grouped together in fragments of a lattice
(domains). A particular way of occurring of the H/D isotopic
“self-organization” for an individual crystal depends on the
electronic properties of the associating molecules. Study of the
IR crystalline spectra, measured in polarized light, gives the
possibility to identify the hydrogen bonds which are active in
these interactions. Quantum mechanical calculations were
performed to explain the differences in coupling in crystals 1
and 2, as well as the influence of surrounding polarity.
Crystal Data of 1. C10H13BrNO, M = 243.12, monoclinic, a =
10.935(2), b = 5.6281(3), c = 16.630(3) Å, β = 102.98(2)°, U =
997.4(3) Å3, T = 100(2) K, space group P21/c (No. 14), Z = 4, 11696
reflections measured, 2304 unique (Rint = 0.0285) which were used in
all calculations. The final wR(F2) was 0.0458 (all data).
Crystal Data of 2. C10H14N2O3, M = 210.23, triclinic, a =
5.391(3), b = 9.633(3), c = 10.258(3) Å, α = 73.51(3), β = 87.74(3),
γ = 82.89(3)°, U = 506.9(3) Å3, T = 100(2) K, space group P1
(No. 2), Z = 2, 3401 reflections measured, 1752 unique (Rint = 0.0117)
which were used in all calculations. The final wR(F2) was 0.0955
(all data).
EXPERIMENTAL SECTION
■
̅
Synthesis and Purification. Synthesis of compounds 1 and 2 was
performed by the amination−reduction of the corresponding aldehyde
and n-propylamine. Analytical samples and single crystals for X-ray
measurements have been obtained by crystallization from hexane.
Synthesis of 4-Bromo-2-[(aminopropyl)methyl]-phenol (1).
Solution of 3-bromo-6-hydroxybenzaldehyde (2.50 g, 0.0123 mol) in
The structures of 1 and 2 were solved and refined using SHELXS-
97 and SHELXL-97 software.23
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dx.doi.org/10.1021/cg201179x | Cryst. Growth Des. 2012, 12, 589−598