Synthesis and structural study of 2-arylbenzotriazoles related to Tinuvins

Article abstract of DOI:10.1016/j.tet.2013.01.096

A total number of nineteen 2-arylbenzotriazoles related to the UV absorber Tinuvin P have been studied. Moreover, besides those bearing a 2′-hydroxy substituent, known to experience ESIPT (Excited-State Intramolecular Proton Transfer), we have also prepared three compounds having another ortho-hydroxy group at position 6′. The X-ray molecular structures of five key representatives have been determined and some important features related to their behavior discussed on the basis of solution and solid-state NMR, as well as B3LYP/6-311++G(d,p) computational results.

Full text of DOI:10.1016/j.tet.2013.01.096

Tetrahedron xxx (2013) 1e12
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis and structural study of 2-arylbenzotriazoles related
to Tinuvins
,
b
c
Dolores Santa María a, Rosa M. Claramunt a , Vladimir Bobosik , M. Carmen Torralba ,
*
M. Rosario Torres c , Ibon Alkorta , Jose Elguero
Departamento de Química Organica y Bio-Organica, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia (UNED), Senda del Rey 9,
,
d
d
*
ꢀ
a
ꢀ
ꢀ
ꢀ
E-28040 Madrid, Spain
b
ꢀ
ꢀ
Synkola, Mlynska dolina, Areal PvF UK, SK-84215 Bratislava, Slovak Republic
c
ꢀ
ꢀ
Departamento de Química Inorganica I and CAI de Difraccion de Rayos-X, Facultad de Ciencias Químicas, Universidad Complutense de Madrid (UCM),
E-28040 Madrid, Spain
d
ꢀ
ꢀ
Instituto de Química Medica, Centro de Química Organica “Manuel Lora-Tamayo”, CSIC, Juan de la Cierva 3, E-28006 Madrid, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
A total number of nineteen 2-arylbenzotriazoles related to the UV absorber Tinuvin P have been studied.
Moreover, besides those bearing a 20-hydroxy substituent, known to experience ESIPT (Excited-State
Intramolecular Proton Transfer), we have also prepared three compounds having another ortho-hydroxy
group at position 60. The X-ray molecular structures of five key representatives have been determined
and some important features related to their behavior discussed on the basis of solution and solid-state
NMR, as well as B3LYP/6-311þþG(d,p) computational results.
Received 9 November 2012
Received in revised form 17 January 2013
Accepted 31 January 2013
Available online xxx
Dedicated to our friend and pioneer of this
class of compounds John F. K. Wilshire
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
In the present paper we will report our studies about the
structure of Tinuvin P (drometrizole) and other Tinuvins [320
There are two main classes of UV absorbers, the 2-hydroxyaryl-
benzotriazoles of Ciba (Tinuvins)1 and the 2,4,6-triaryl-1,3,5-
triazines of BASF (Tinosorb S) (note that since Ciba and BASF
merged in April 2009 both photoprotectors now belong to BASF).2
They find application in many domains, one very active and eco-
nomically very profitable, as in polymers and ‘sun care’ products. The
photophysics of Tinuvin and related compounds has been extensively
studied,3 included by us.4
The protection mechanism isbased on theso-called ESIPT (Excited
State Intramolecular Proton Transfer) that we illustrated in Fig. 1 for
Tinuvin P. Ultraviolet absorbers, such as Tinuvin P achieve their ex-
ceptional photostabilities as a result of deactivation of excited singlet
states through excited state intramolecular proton transfer (ESIPT).5
(UV-320), 326 (bumetrizole), and 327] as well as other literature
compounds (Fig. 2). All these compounds, save 19, have one (1e15)
or two ortho-hydroxy groups (16e18). Besides Tinuvins 1e4,
the known compounds of Fig. 2 are reported in the following
papers: 5,5a 6,5a 7,6 8,6 9,6 10,6e8 11,6 12,6,8,9 13,8,10 14,10 16,7 18,6,11
and 19.7
Compounds 16e18 were designed for future studies of the ESIPT
mechanism (Fig. 3). The second hydrogen bond (HB) in PT1 should
favor the planar structure. A second proton transfer to afford PT2
seems highly improbable.
The nomenclature used in the text and in the experimental is
not in accordance with IUPAC rules. For all of the compounds with
phenolic hydroxyl groups, the phenol system has the highest pri-
ority; however, using IUPAC nomenclature here would be at the
expense of comparability and clearness. For instance, compound 18
would be 2-(2H-benzo[d][1,2,3]triazol-2-yl)-4,6-di-tert-butylben-
zene-1,3-diol under IUPAC rules, rather than 2-(2,6-dihydroxy-3,5-
di-tert-butylphenyl)-2H-benzotriazole. In order to prioritize com-
parability over correct nomenclature, we have named all of the
compounds as 2H-benzotriazole derivatives.
H
H O
N
O
hν*
N
N
N
N
+ heat
N
CH3
CH3
PT
Tinuvin P
H
N
O
Fig. 1. The ESIPT mechanism.
7
4
3'
7a
3a
2'
N
6
5
1
4'
1'
N 2
* Corresponding author. E-mail address: rclaramunt@ccia.uned.es (R.M.
3
6'
5'
Claramunt).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.01.096
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2
D. Santa María et al. / Tetrahedron xxx (2013) 1e12
HO
t-C4H9
HO
t-C4H9
t-C4H9
HO
t-C4H9
t-C4H9
HO
N
N
N
N
N
N
N
N
N
N
N
N
Cl
Cl
CH3
CH3
3 Tinuvin 326
4 Tinuvin 327
1 Tinuvin P
2 Tinuvin 320
HO
HO
t-C4H9
HO
HO
N
N
N
N
N
N
N
N
N
N
N
OH
CH3
N
H3C
HO
CH3
H3C
CH3
CH3
H3C
CH3
5
6
8
7
HO
t-C4H9
HO
HO
t-C4H9
N
N
N
N
N
N
N
N
N
N
N
N
H3C
t-C4H9
CH3
CH3
10
11
12
9
HO
HO
t-C4H9
HO
N
N
N
N
N
N
N
N
N
H3CO
t-C4H9
15
13
14
HO
t-C4H9
HO
t-C4H9
H3CO
HO
N
N
N
N
N
N
N
N
N
N
N
N
HO
HO
t-C4H9
H3CO
HO
16
17
19
18
Fig. 2. Tinuvins and related molecules. In red, X-ray structures already known. In blue structures determined in the present work.
H
N
H
H
H
O
O
O
O
R
hν*
hν*
R
R
N
N
N
N
N
N
H
+ heat
+ heat
N
N
O
O
H
16-18
PT2
PT1
Fig. 3. Possible ESIPT mechanism for compounds 16e18.
The structural characterization of these compounds is scarce. 1H,
nitrophenyl)-1H-tetrazole (21) via a 2-nitrodiphenylcarbodiimide
intermediate,15 a method that we had successfully applied to other
cases.4c,d The tetrazole was in turn formed by heating the corre-
sponding20-nitrobenzanilide(20) intoluenecontainingphosphorous
pentachloride to give N-(2-nitrophenyl)benzimidoyl chloride, which
was then treated with sodium azide in dry N,N0-dimethylformamide.
Demethylation of 19 yields 2,6-dihydroxy-2H-benzotriazole
(16), which under monomethylation affords 15.
13C, and 15N NMR data were reported for 1,4d but only 1H NMR for 5,5a
6,5a and 12.9 A search in the Cambridge Structural Data base (CSD)12
reveals that the X-ray structures of Tinuvin P (1, refcode NIQ-
DOG)4b,13 and of 12 (refcode KUCBUF) were twice determined.6,10
Surprisingly that of 7 was also determined by Rieker et al.6 but not
reported in the CSD. One of the most interesting results from the X-
ray determinations is the torsion angle about the phenyl and the 2H-
benzotriazolyl rings as defined by N1eN2eC10eC20: 1.4ꢀ (1), 89.3ꢀ
(7), 5.3ꢀ (12). In compounds 1 and 12 there is an OeH/N1 intra-
molecular hydrogen-bond (IMHB) that is absent in 7.
tert-Butylation of16 permitted, by varying the reaction conditions,
to obtain derivatives 17 and 18 as shown in the Experimental section.
2.2. X-ray structure determination of compounds 4, 15, 16, 18,
and 19
2. Results and discussion
2.1. Synthesis of benzotriazoles 15, 16, 17, and 18
Tinuvin 327, compound 4, was crystallized form chloroform/
ethanol. Crystals of 15, 16, and 19 were obtained by slow evapo-
ration of a chloroform solution, and those of 18 from chloroform/
hexane. The bond distances and angles of the hydrogen bonds for
compounds 4, 15, 16, and 18 are summarized in Table 1.
Compound 4 crystallizes in the triclinic Pꢁ1 space group with
one molecule per asymmetric unit (Fig. 5). The molecule is not
completely planar, the dihedral angle between the least-squared
Compound 18 was known and its synthesis started from
2-nitroaniline through the azo derivative 24.11 The procedure we
report here, inspired in tert-butylation of phenols using inorganic
supports,14 is simpler and more efficient. Fig. 4 summarizes the
overall synthetic pathways.
The 2-susbtituted benzotriazole 19 was prepared using the
thermal decomposition of the 5-(2,4-dimethoxyphenyl)-1-(2-
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D. Santa María et al. / Tetrahedron xxx (2013) 1e12
3
OCH3
H
OCH3
H3CO
NO2
N
i) PCl5
ii) NaN3/DMF
nitrobenzene
reflux
N
N
N
N
N
CH3O
CH3O
O
N
N
H3CO
20
19
21
NO2
reflux
HBr
HO
H3CO
(CH3)2SO4
N
N
N
N
NaOH aq.,
toluene
N
N
HO
HO
16
15
SiO2, K2CO3
t-C4H8Br
HO
t-C4H9
HO
t-C4H9
N
N
N
N
N
N
HO
t-C4H9
HO
18
17
Zn/NaOH
t-C4H9
NH2
NO2
i) NaNO2/HCl
HO
HO
t-C4H9
N
N
t-C4H9
ii)
22
23
OH
24
NO2
HO
t-C4H9
Fig. 4. Synthetic procedures followed to prepare compounds 15, 16, 17, and 18.
Table 1
Hydrogen bonds (A and ꢀ) for compounds 4, 15, 16, and 18
ꢁ
Compound DeH/A Symmetry d(DeH) d(H/A) d(D/A) <(DHA)
operations
4
O1eH1/N1
1.09
1.57
1.66
1.94
1.82
1.55
1.61
2.593(3) 153.9(1)
2.664(2) 177.3(1)
2.915(2) 172.0(1)
2.603(3) 126.5(1)
2.559(3) 152.6(1)
2.543(3) 146.3(1)
15
15
16
18
O1eH1/O3
x,ꢁyþ1/2,z 1.01
O3eH3A/N10 ꢁx,ꢁy,ꢁz
0.98
O1eH1/N1
O1eH1/N1
O2eH2/N3
x,ꢁyþ1/2,z 1.07
x,ꢁyþ1/2,z 1.08
1.04
planes that contain the benzotriazole fragment and the phenyl ring
being of 12.7(1)ꢀ. The bond distances of the benzotriazole moiety
present an extended electronic delocalization confirmed by its
planarity. The hydroxyl group shows some positional disorder be-
tween C9 (O1 with 80% occupancy) and C13 (O10 with 20% occu-
pancy). For this reason, the molecule presents intramolecular
hydrogen bonds O1/N1 and O10/N3 that might favor a major
planarity of the molecule.
Compound 15 crystallizes in the orthorhombic system, space
group Pnma. The asymmetric unit corresponds to half arylbenzo-
triazole molecule and half crystallization water molecule (Fig. 6),
the planar hydroxymethoxyphenyl group is located on the mirror
plane, with the planar benzotriazole moiety set perpendicularly.
The different molecules interact through the crystallization
water molecules with formation of intermolecular hydrogen bonds
Fig. 5. ORTEP plot (20% probability for the ellipsoids) of 4, showing the labeling
scheme. The white bonds correspond to the 20% occupancy of the disordered hydroxyl
and the 37% of the tert-butyl groups.
O1eH1A/O3eH3A/N10. In this way, each water molecule forms
three intermolecular hydrogen bonds with three different molecules,
one interaction through the hydroxyl group and the other two with
the N1 atoms giving rise to a chain along b-axis (Fig. 7).
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D. Santa María et al. / Tetrahedron xxx (2013) 1e12
4.4(1)ꢀ. The hydroxyl groups form 2 equiv intramolecular hydrogen
bonds O1eH1/N1.
The crystal structure of 18 (monoclinic P21/m space group)
consists of planar molecules since all the atoms, except C19 and
C16, and 16 H atoms of the methyl groups, are located on the
symmetry plane (Fig. 9). As in the previous structure, the hydroxyl
groups form two intramolecular hydrogen bonds O1eH1/N1 and
O2eH2/N3.
The compound 19 crystallizes in the orthorhombic Iba2 space
group with two molecules displayed almost perpendicularly in the
asymmetric unit. Both molecules are chemically equivalent but
crystallographically independent. In each molecule the benzo-
triazole moiety and the dimethoxyphenyl group are perpendicular
with dihedral angles of 86.5(1)ꢀ for molecule 1 and 86.6(1)ꢀ for
molecule 2 (Fig. 10). The bond distances and angles indicate that
both molecules are very similar, the main difference between them
being the relative positions of methyl groups, which are almost
coplanar with the phenyl ring in molecule 1 but shifted out of the
plane in molecule 2.
Fig. 6. ORTEP plot (20% probability) of 15, showing the labeling of the asymmetric unit.
Fig. 7. View of the crystal packing of 15 showing the chain formed by intermolecular H-bonds along the b-axis.
The derivative 16 also crystallizes in the Pnma orthorhombic
space group with half molecule per asymmetric unit. In this case,
the molecule is perpendicular to the mirror plane that passes
through N2, C8, and C11 (Fig. 8). The benzotriazole and dihydrox-
yphenyl rings are planar since both halves are related by the
reflection in the symmetry plane, however, the molecule is not
completely planar having a dihedral angle between the rings of
Fig. 8. ORTEP plot (20% probability) of 16, showing the labeling of the asymmetric unit.
Fig. 9. ORTEP plot (20% probability) of 18, showing the labeling of the asymmetric unit.
Dotted lines indicate the intramolecular hydrogen bonds.
Dotted lines indicate the intramolecular hydrogen bonds.
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D. Santa María et al. / Tetrahedron xxx (2013) 1e12
5
Fig. 10. ORTEP plot (30% probability) of 19, showing the labeling of the two molecules that form the asymmetric unit.
A comparison among the five crystal structures reported leads
to the following remarks:
gs-HMBC; those of N2 were obtained using the inverse gated 1H
decoupling technique.
In all compounds the benzotriazole fragment is planar exhibit-
ing an extended electronic delocalization. The bond distance
In solution, the rotation about the N2eC10 bond is fast in the
NMR time scale, consequently the chemical shifts of N1 and N3 are
average (Table 2), an average that disappears in the solid state
(Table 3). For compounds 3 and 4, although averaged, the signals
are different due to the effect of the chlorine atom. In Fig. 11 is
presented the 2D (1He15N) correlation experiment for compound 3
Tinuvin 326.
ꢁ
N2eC8 of about 1.43 A is very similar for 15, 16, 18, and 19, but it is
ꢁ
a bit shorter, 1.423(3) A, in 4. In this latter case such shortening can
be explained as due to the steric effect of the chlorine atom on the
crystalline packing.
The main differences observed are related to the coplanarity
between the benzotriazole and the phenyl rings. This coplanarity
appears when two intramolecular H-bonds between the hy-
droxyl groups and the triazole fragment are formed, as found in
16 and 18. On the contrary, when no intramolecular hydrogen
bonds are formed, derivatives 15 and 19, the two moieties of the
molecule tend to be perpendicular. Finally, compound 4 shows
an intermediate situation with formation of only one intra-
molecular H-bond leading to a torsion angle between both
fragments of 12.7ꢀ. This fact would indicate that the more stable
conformation, due to lower steric hindrance, is the perpendicular
one. The formation of intramolecular hydrogen bonds compen-
sates the loss in stability when the molecule adopts the planar
conformation.
Using the 13C chemical shifts in solution we have estimated the
degree of interannular conjugation. As shown in Fig. 12, we have
first determined the effects of the OH substituent from the exper-
imental data of Tinuvin P (1) and of 2-phenylbenzotriazole,4d tak-
ing those of the methyl group of 1 from the Kalinowski’s book (CH3:
Z1 9.2, Z2 0.7, Z3 ꢁ0.1, Z4 ꢁ3.1).16 Then, we have also calculated those
of the t-Bu group, and with these increments and those of the OCH3
group (Z1 31.4, Z2 ꢁ14.4, Z3 1.0, Z4 ꢁ7.7),16 the values gathered in
Table 4 were obtained.
For the solid state the conclusions were the same although there
are small differences in the dC-meta dC-ortho values: 10.8 (PhBzTr),
ꢁ
8.9 (1), 8.6 (3), 11.4 (4), 11.3 (16), 9.0 (17), 7.9 (18), and 3.2 (19). The
splitting of several signals in compound 19 corresponds to the
presence of two independent molecules in the unit cell (Fig. 10). In
the case of compound 4 the splitting of the NMR signals are due to
the existence of two atropisomers around the N2eC10 bond, and
from the intensities of the 15N NMR signals in solid state for N2 and
N3 (Table 3) the estimated proportions of both isomers are in
agreement with the values obtained from the X-ray diffraction
studies (Fig. 5).
The presence of additional substituents in the phenyl ring does
not affect the conformation of the molecule.
2.3. NMR studies
The results concerning the 15N and 13C NMR in solution as well
as in the solid state are given in Tables 2 and 3, respectively. 1H NMR
data in solution can be found in the electronic Supplementary data
(ESI). All assignments have been made taking into account the
multiplicity of the signals and 2D correlation experiments: (1He1H)
gs-COSY, (1He13C) gs-HMQC, (1He13C) gs-HMBC, and (1He15N) gs-
HMBC.
One important feature is the OH chemical shift that appears in
the range of 11.45e11.9 ppm in Tinuvin analogues presenting strong
intramolecular hydrogen bonds (IMHB). This fact has permitted to
detect the 15N NMR signals of N1 and N3 by means of (1He15N)
2.4. Computational results
We have calculated the geometries of all the compounds of Fig. 2
and reported the results in Table 5. In the case of compounds 3 and
4, due to the presence of the chlorine atom, there are two confor-
mations (Fig. 13) that differ only in 0.08 kJ molꢁ1. However, their
dipole moments are quite different, being twice for conformers 3
and 4 than for conformers 30 and 40.
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6
D. Santa María et al. / Tetrahedron xxx (2013) 1e12
Table 2
15N and 13C NMR chemical shifts (
d
in ppm) of 2H-benzotriazoles 3, 4, 15e19 in CDCl3 at 40 and 100 MHz, respectively. 1He13C coupling constants (J in Hz) are given in the ESI
3, R = Cl, R2' = OH, R6' = H, R3' = t-C4H9, R5' = CH3
R2'
R3'
7
4
4, R = Cl, R2' = OH, R6' = H, R3' = R5' = t-C4H9
15, R = H, R2' = OH, R6' = OCH3, R3' = R5' = H
16, R = H, R2' = R6' = OH, R3' = R5' = H
1
R
7a
3a
6
N
2
N
5
N
17, R = H, R2' = R6' = OH, R3' = t-C4H9, R5' = H
18, R = H, R2' = R6' = OH, R3' = R5' = t-C4H9
19, R = H, R2' = R6' = OCH3, R3' = R5' = H
3
R6'
R5'
Comp.
3
4
15
16
17
18
19
N1
N2
N3
C3a
C4
ꢁ78.9/ꢁ80.9
ꢁ106.6
ꢁ78.6/ꢁ80.8
ꢁ105.8
ꢁ65.5
ꢁ87.7
ꢁ110.9
ꢁ87.7
140.3
ꢁ87.8
ꢁ87.5
ꢁ58.8
n.d.
ꢁ109.9
ꢁ87.8
ꢁ109.2
ꢁ87.5
ꢁ124.6
ꢁ58.8
ꢁ78.9/ꢁ80.9
ꢁ78.6/ꢁ80.8
ꢁ65.5
141.1
118.6
141.1
118.7
143.9
140.2
116.8
140.0
116.7
144.5
118.3
118.1
116.8
C5
129.0
129.0
127.4
128.3
128.3
128.1
126.4
C6
C7
133.3 (Cl)
116.5
133.3(Cl)
116.6
127.4
118.1
128.3
116.8
128.3
116.8
128.1
116.7
126.4
118.3
C7a
C10
C20
C30
C40
C50
C60
Subs.
142.9
125.2
146.8 (OH)
139.2 (tBu)
129.1
142.9
125.0
143.9
117.8
151.9 (OH)
110.4
130.9
104.2
154.0 (OMe)
56.6 (OMe)
140.3
113.5
150.8 (OH)
109.2
130.6
109.2
150.8 (OH)
d
140.2
114.0
149.0 (OH)
129.2 (tBu)
128.1
140.0
114.7
144.5
119.2
156.1 (OMe)
104.0
131.5
104.0
156.1 (OMe)
56.0(OMe)
146.7 (OH)
138.7 (tBu)
125.5
147.6 (OH)
127.2 (tBu)
126.0
128.4 (Me)
119.4
141.8 (tBu)
116.2
107.7
127.2 (tBu)
147.6 (OH)
35.1 (tBu)
29.8 (tBu)
149.7 (OH)
34.8 (tBu)
29.6 (tBu)
35.4 (tBu)
29.5 (tBu)
20.9 (Me)
35.7 (tBu-3)
29.6 (tBu-3)
34.6 (tBu-5)
31.5 (tBu-5)
Table 3
15N and 13C NMR chemical shifts (
d in ppm) of 2H-benzotriazoles 3, 4, 16e19 in the solid state at 40 and 100 MHz, respectively
Comp.
3
4
16
17
18
19
N1
N2
N3
C3a
C4
C5
C6
C7
C7a
C10
C20
C30
C40
C50
C60
Subs.
ꢁ87.6
ꢁ86.7
ꢁ89.6
ꢁ106.5
ꢁ89.6
137.6
115.8
128.6
128.6
115.8
137.6
111.3
150.2 (OH)
110.3
130.4
110.3
150.2 (OH)
d
ꢁ89.2
ꢁ90.0
ꢁ108.9
ꢁ90.0
136.8
113.9
127.3
127.3
113.9
136.8
113.9
ꢁ53.0/ꢁ52.4
ꢁ118.9
ꢁ105.1
ꢁ67.9
ꢁ103.4/ꢁ104.2
ꢁ66.5/ꢁ68.2
140.0
ꢁ107.1
ꢁ89.2
ꢁ54.6/ꢁ53.9
141.6
116.9
129.1
134.5 (Cl)
115.2
141.6
124.5
146.5 (OH)
138.6 (tBu)
129.1
137.6
115.0
128.0
128.0
115.0
137.6
113.4
148.9 (OH)
128.0 (tBu)
129.9
144.9
118.3
130.7
135.1 (Cl)
115.5
142.6
118.4
128.5a
128.1a
117.4
144.9
119.0
124.1
145.5 (OH)
137.4 (tBu)
127.9
148.2 (OH)
125.9 (tBu)
124.4
155.3 (OMe)
104.4b
132.6
127.2 (Me)
120.1
140.0 (tBu)
115.5
108.7
127.3 (tBu)
148.2 (OH)
35.6/
104.7b
150.4 (OH)
156.5 (OMe)
54.8c (OMe-3)
56.9c (OMe-5)
36.0/29.8 (tBu)
18.6 (Me)
35.3/30.5 (tBu-3)
34.6/32.6 (tBu-5)
35.6/29.8 (tBu)
29.8&31.2 (tBu)
a
The assignment of these signals can be exchanged.
The assignment of these signals can be exchanged.
The assignment of these signals can be exchanged.
b
c
The interring CeN bond length is almost constant although it
intramolecular OeH/N1 HB (even weak) but an intermolecular
one. This explains why the calculated value (40.0ꢀ) is much lower
than the experimental one. There is a good qualitative agreement
with the DIC conclusions of Table 4.
was expected to be shorter in planar structures due to Nþ]C res-
onance forms.
H O
N
H O
N
We have calculated at the GIAO/B3LYP/6-311þþG(d,p) level all
R2
R2
N
N
N
N
the absolute shieldings (s, ppm) of 2-phenylbenzotriazole (PhBzTr)
R1
R1
and ortho-hydroxy derivatives 1e18 (Table 7). We have transformed
these values into chemical shifts ( , ppm) using empirical
s
d
relationships we have established from large collection of data (see
Supplementary data). As usual, the agreement is good with the
experimental results and will no longer commented save for some
selected examples.
Some interesting correlations were found between the experi-
mental and calculated data:
This is not the case, but the shorter distance corresponds to
¼12.7ꢀ) and the longest to compound 7
ꢁ
compound 4 (1.423 A,
q
ꢁ
(1.437 A,
q
¼89.3ꢀ). Concerning DIC, if one quantify Ext¼2, Med¼1,
Hin¼0, then there is some relationship between DIC and
q
(R2¼0.84).
The last three columns of Table 6 report the geometry of the
IMHB. The number of IMHB indicates their possible existence even
when due to the torsion they are weak or non-existent (compound
Eq. 1 (that includes three literature values also determined in
CDCl3) indicates that the calculations reproduce well the
7). In the X-ray structure of this compound (
q
¼89.3ꢀ) there is no
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D. Santa María et al. / Tetrahedron xxx (2013) 1e12
7
Fig. 11. 2D (1He15N) gs-HMBC spectrum of 3 in CDCl3.
147.5
Effects of the OH group:
140.4
H O
118.7
N
N
Z1 30.0
Z2 –10.6
Z3 1.6
131.2
N
128.9
129.4
N
N
N
124.8
129.6
CH3
121.1
120.6
Z4 –9.0
2-phenylbenzotriazole (PhBzTr)
Tinuvin P (1)
147.5
146.8
Effects of the t-Bu group:
H O
118.7
N
H O
N
t-Bu
139.2
129.1
128.4
CH3
119.4
N
N
Z1 20.5
131.2
129.6
CH3
121.1
Tinuvin P (1)
N
Z2 –2.1
N
124.8
Z3 –1.2
Cl
125.2
Z4 –1.7
ortho steric effect: 1.4
Tinuvin 326 (3)
Fig. 12. Calculation of the additive effects of the OH and t-Bu groups.
Table 4
Estimation of the degree of interannular conjugation (DIC): extensive (Ext), medium (Med), hindered (Hin). Aver: average values (all in ppm)
Compound
dC-ortho
dC-ortho Aver
dC-meta
dC-meta Aver
Dd¼
dC-metaedC-ortho
DIC
PhBzTr
1
120.6
120.6
119.7
129.4
129.4
129.4
8.8
9.7
Ext
Ext
147.5ꢁ30.0þ3.1¼120.6
118.7þ10.6þ0.1¼129.4
121.1ꢁ1.6ꢁ0.7¼118.8
129.6ꢁ9.2þ9.0¼129.4
3
146.8ꢁ30.0þ(2.1ꢁ1.4)þ3.1¼120.6
119.4ꢁ1.6þ1.7ꢁ0.7¼118.8
146.7ꢁ30.0þ(2.1ꢁ1.4)þ1.7¼119.1
116.2ꢁ1.6þ2.1þ1.7¼118.4
151.9ꢁ30.0ꢁ1.0¼120.9
119.7
118.8
121.0
139.2ꢁ20.5þ10.6þ0.1¼129.4
128.4þ9.0þ1.2ꢁ9.2¼129.4
138.7ꢁ20.5þ10.6þ1.2¼130.0
141.8ꢁ20.5þ9.0þ1.2¼131.5
110.4þ10.6þ7.7¼128.7
104.2þ14.4þ9.0¼127.6
109.2þ10.6þ9.0¼128.8
129.2ꢁ20.5þ10.6þ9.0¼128.3
107.7þ1.2þ10.6þ9.0¼128.5
127.2ꢁ20.5þ1.2þ10.6þ9.0¼127.5
104.0þ14.4þ7.7¼126.1
129.4
130.8
128.2
9.7
12.0
7.2
Ext
4
Ext
15
Med
154.0ꢁ31.4ꢁ1.6¼121.0
16
17
150.8ꢁ30.0ꢁ1.6¼119.2
119.2
119.0
128.8
128.4
9.6
9.4
Ext
Ext
149.0ꢁ30.0þ(2.1ꢁ1.4)ꢁ1.6¼118.1
149.7ꢁ30.0þ1.7ꢁ1.6¼119.8
147.6ꢁ30.0þ(2.1ꢁ1.4)þ1.7ꢁ1.6¼118.4
156.1ꢁ31.4ꢁ1.0¼123.7
18
19
118.4
123.7
127.5
126.1
9.1
2.4
Ext
Hin
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8
D. Santa María et al. / Tetrahedron xxx (2013) 1e12
Table 5
Table 6
Theoretically calculated geometries (distances in A, angles in ꢀ), total energies (in
hartrees, ZPE corrected), relative energies (in kJ molꢁ1) and dipole moments (in D).
B3LYP/6-311þþG(d,p) calculations. DIC conclusions from Table 4
Experimental geometries, DIC (degree of interannular conjugation) and number of
IMHB (intramolecular hydrogen bonds)
ꢁ
Number OeH (A) H/N1 (A) OHN (ꢀ)
IMHB
ꢁ
ꢁ
Comp.
X-ray
dCN
X-ray DIC
q
Comp.
HB
dCN
Torsion
q
Energy
Relative energy Dipole
PhBzTr
1
2
d
1.428
1.426
1.431
1.430
1.430
1.430
1.430
1.425
0.00
0.00
0.04
0.00
0.00
0.00
0.00
0.02
ꢁ627.08073
ꢁ741.24756
ꢁ1016.23836
d
d
d
0.34
1.60
1.31
1.93
0.98
2.00
1.01
1.36
2.03
1.70
1.16
1.61
1.64
1.07
1.27
1.63
1.40
1.94
3.03
3.05
3.07
1.28
PhBzTra 1.432
1.1
1.4
Ext
Ext
d
0
1
1
1
1
1
1
1
1
1
1
1
1
d
d
d
Yes
Yes
Yes
Yes
Yes
Yes
Yes
1b
2
1.430
d
1.00
1.767
142.7
d
3
ꢁ1357.99068 0.00
ꢁ1357.99064 0.08
ꢁ1475.84288 0.00
ꢁ1475.84281 0.08
3
d
d
Ext
Ext
d
30
4
5
1.423
d
12.7
d
1.09
1.57
153.9
4
40
6
d
d
d
c
c
c
5
6
7
8
ꢁ780.53751
ꢁ780.52749
ꢁ937.66688
ꢁ816.45456
ꢁ1055.50679
ꢁ701.95738
ꢁ780.53852
ꢁ898.38652
ꢁ859.09971
ꢁ859.09638
ꢁ816.43484
ꢁ777.17461
ꢁ934.31296
ꢁ1091.45076
ꢁ855.69916
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
7
8
1.437
d
89.3
d
d
Weak 1.432 36.75
Weak 1.435 40.00
Weak 1.429 29.88
Weak 1.438 44.98
Yes
Yes
Yes
Yes
Yes
d
9
d
d
d
10
11
12
d
d
d
9
d
d
d
10
11
12
13
14
15
16
17
18
19
1.426
1.427
1.430
1.427
1.430
0.00
0.00
0.00
0.00
0.00
1.427d
1.434e
d
5.3d
5.1e
d
d
0.81d
0.90e
1.84d
1.76e
151d
148e
13
14
15
16
17
18
d
1
1
1
2
2
2
d
d
d
1.432
1.434
d
89.2f
4.4
d
Med
Ext
Ext
Ext
0.98
1.07
1.94
1.82
172.0
126.5
Weak 1.425 34.19
Yes
Yes
Yes
d
1.423
1.427
1.431
0.00
0.00
0.00
1.432
0
1.08
1.04
d
1.55
1.61
d
152.6
146.3
d
1.427 64.76
19
1.429
1.431
86.5
86.6
Hin
0
a
X-ray, from Ref. 4d.
X-ray, from Ref. 4b.
No IMHB.6
From Ref. 6.
From Ref. 10.
b
c
d
e
f
Tinuvin 326
Cl
HO
t-C4H9
HO
t-C4H9
1
1
Hydrate (this work).
N
N
2 N
2
N
N
N
Cl
3
3
CH3
CH3
involved in the IMHB with two correcting terms. If two OH
groups (16, 17, 18) or two methoxy groups (19) are present cos2
decreases by approximately the same amount, that is, these
compounds are less planar than will be expected from the
chemical shift of N1.
3
3'
q
Tinuvin 327
HO
t-C4H9
HO
t-C4H9
1
N
2
1
Cl
N
2
N
N
N
N
Cl
cos2
q
¼ ꢁ ð0:33 ꢂ 0:04Þ ꢁ ð0:0178 ꢂ 0:0005Þ
d
15N calc: N1
3
3
t-C4H9
t-C4H9
4
4'
ꢁ ð0:40 ꢂ 0:02Þ½2 OHꢃ ꢁ ð0:48 ꢂ 0:00Þ½2 OCH3ꢃ;
Fig. 13. The two conformations of Tinuvin 326 and Tinuvin 327.
n ¼ 20; R2 ¼ 0:994
ð3Þ
Statistically, in the solid-state structure 3 fits better than 30 and
structure 4 better then 40, therefore they are 5-chloro and not
6-chloroderivatives (Fig. 13). Compounds 30 and 40 were not used
for calculated Eqs. 2 and 3. In solution, the data corresponds to
a w50/50 mixture of 3 and 30 and 4 and 40. The 15N chemical shifts
experimental value of the 1H chemical shift of the OH group
(measured only in solution) but that a corrective term should be
added when there is an OeH/N IMHB. Note that the intercept is
not significant.
t
are sensitive to the buttressing effect:17 for instance the Bu group
pushes the OH toward N1. Considering the N1 and N3 chemical
shifts, we observed that in compound 16 (no t-Bu) they resonate at
ꢁ96.6 ppm; in compound 18 (two t-Bu) at ꢁ98.6 ppm, finally, in
compound 17 (one t-Bu) at ꢁ98.8 ppm (near the t-Bu) and
ꢁ96.6 ppm (far from the t-Bu).
d
1H OH exp: ¼ ð1:1 ꢂ 2:0Þ þ ð0:75 ꢂ 0:20Þ
d
1H calc:
þ ð1:76 ꢂ 0:41Þ IMHB;
n ¼ 10; R2 ¼ 0:971
ð1Þ
Eq. 2 corresponds to all available data, both in solution and in
the solid state. There is a significant intercept because the empirical
equation to transform into
uses 15N chemical shifts from a large
variety of compounds while here the range is quite small (between
ꢁ49.4 and ꢁ114.9 ppm). The presence of HBs that affect N1 and N3
(but not N2) needs a rather important term (12.6 ppm).
To establish relationships similar to those of Table 4 it is
necessary to correct the calculated 13C chemical shifts of the
positions ortho and meta (20/30 and 60/50) for the substituent
effects. To avoid this semi-empirical approach, we have used the
calculated 15N chemical shifts of N3 (usually not involved in the
OeH/N IMHB). The equation needs a term for compounds
16e18 where N3 has also an IMHB and another for compound 19
that has no IMHB.
s
d
d
15N exp: ¼ ꢁð15:2 ꢂ 4:4Þ þ ð0:89 ꢂ 0:04Þ
d
15N calc:
þ ð12:6 ꢂ 0:9Þ N1 þ N3;
Using the 2-phenylbenzotriazole (PhBzTr) as a model we have
calculated the chemical shifts of the meta and ortho carbons as
n ¼ 33; R2 ¼ 0:985
ð2Þ
a function of the dihedral angle
q. The difference, Dd, was plotted
Finally, Eq. 3 shows that the torsion transformed into cos2
q
against
Fig. 14.
q and the calculated points roughly correspond to Eq. 4 and
(but when cos2
q increases so do q) depends on the N atom
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D. Santa María et al. / Tetrahedron xxx (2013) 1e12
9
Table 7
Some relevant calculated chemical shifts of the ortho-hydroxy derivatives 1e18 together with some experimental data in solution and in the solid state
Comp.
1a
2
15N1 (HB)
15N2
15N3
Average N1/N3
17O
1H OH
Solution N1/N3
Solution N2
Solution OH
11.10
Solid N1
Solid N2
Solid N3
ꢁ95.4
ꢁ97.7
ꢁ97.2
ꢁ99.1
ꢁ98.2
ꢁ106.9
ꢁ105.3
ꢁ103.8
ꢁ104.1
ꢁ104.0
ꢁ75.0
ꢁ74.5
ꢁ75.7
ꢁ74.0
ꢁ74.8
ꢁ85.2
ꢁ86.1
ꢁ86.4
ꢁ86.6
ꢁ86.5
77.9
83.5
83.5
83.6
83.6
11.16
12.14
11.88
11.88
11.88
ꢁ80.1
ꢁ110.1
ꢁ89.3
ꢁ107.3
ꢁ69.7
3
ꢁ87.6
ꢁ87.6
ꢁ105.1
ꢁ105.1
ꢁ67.9
ꢁ67.9
30
3/30
ꢁ80.9
ꢁ78.9
ꢁ106.6
ꢁ105.6
11.47
4
ꢁ97.3
ꢁ99.2
ꢁ98.2
ꢁ103.1
ꢁ103.4
ꢁ103.2
ꢁ76.1
ꢁ74.4
ꢁ75.2
ꢁ87.6
ꢁ86.8
ꢁ87.2
83.4
83.5
83.4
11.90
11.91
11.90
ꢁ86.7
ꢁ86.7
ꢁ103.8
ꢁ103.8
ꢁ66.8
ꢁ66.8
40
4/40
ꢁ80.8
ꢁ78.6
11.53
5
6
7
8
ꢁ96.0
ꢁ81.3
ꢁ81.3
ꢁ88.5
ꢁ77.2
ꢁ95.4
ꢁ96.1
ꢁ97.8
ꢁ95.4
ꢁ97.7
ꢁ85.2
ꢁ96.6
ꢁ98.8c
ꢁ106.5
ꢁ110.1
ꢁ109.7
ꢁ108.8
ꢁ110.2
ꢁ107.4
ꢁ106.4
ꢁ105.9
ꢁ106.2
ꢁ106.3
ꢁ114.9
ꢁ104.8
ꢁ104.0
ꢁ76.0
ꢁ53.9
ꢁ51.9
ꢁ60.1
ꢁ49.4
ꢁ74.7
ꢁ74.5
ꢁ74.3
ꢁ75.3
ꢁ74.0
ꢁ55.2
ꢁ96.6
ꢁ96.6
ꢁ86.0
ꢁ67.6
ꢁ66.6
ꢁ74.3
ꢁ63.3
ꢁ85.0
ꢁ85.3
ꢁ86.0
ꢁ85.4
ꢁ85.8
ꢁ70.2
ꢁ96.6
ꢁ97.7
77.6
62.4
64.3
72.5
61.5
81.3
77.8
83.5
78.0
86.8
68.0
82.1
88.4c
79.8
86.3
11.09
9.64
10.05
10.74
9.26
11.34
11.47
12.10
11.18
12.25
10.03
11.33
12.24c
11.30
12.25
11.04b
8.04b
9
10
11
12
13
14
15
16
17
ꢁ65.5
ꢁ87.7
ꢁ87.8
n.d.
8.93
d
ꢁ110.9
11.45
12.12c
11.34
11.90
ꢁ89.6
ꢁ89.2
ꢁ106.5
ꢁ107.1
ꢁ89.6
ꢁ89.2
ꢁ109.9
18
ꢁ98.6
ꢁ103.1
ꢁ98.6
ꢁ98.6
ꢁ87.5
ꢁ109.2
ꢁ90.0
ꢁ108.9
ꢁ90.0
a
From Ref. 4d.
From Ref. 6.
Near the t-Bu.
b
c
i.e., 1.2 larger than the calculated for PhBzTr (note that the sub-
stituents modify the geometry, for instance the interring NeC
distance). In the case of non-planar compounds 15 (
q
¼34.2ꢀ) and
19 (64.8ꢀ) the Eq. 4 predicts 5.1 ppm and 1.0 ppm, respectively,
lower than 7.2 ppm (ratio 7.2/5.1¼1.4) and 2.4 ppm (ratio 2.4/
1.0¼2.4), but still acceptable considering all the approximations
involved.
3. Conclusions
The study of the molecular structure of a large collection of
Tinuvins has been carried out. The behavior of these compounds
is mutually consistent proving that theoretical calculations for
the gas phase (isolated molecules) can be used to predict the
molecular properties of their ground states. Even subtle differ-
ences like those existing between 3 and 30 and between 4 and 40
can be determined theoretically agreeing with the experimental
results.
Fig. 14. Variation of Dd in function of the torsion angle
311þþG/(d,p) calculations.
q
in PhBzTr. GIAO/B3LYP/6-
4. Experimental
4.1. General
Melting points were determined with a ThermoGalen hot stage
microscope and are given uncorrected. Elemental analyses for
carbon, hydrogen, and nitrogen were performed by the Microana-
lytical Service of the Complutensian University of Madrid, using
a PerkineElmer 240 analyzer. Column chromatography was con-
ducted on silica gel (Merck 60, 70e230 mesh). Rf values were
measured on aluminum-backed TLC plates of silica gel 60 F254
(Merck, 0.2 mm) with the indicated eluent.
Tinuvin 326 (3) and Tinuvin 327 (4) are commercial products
from Aldrich and were used without further purification. Benzo-
triazoles 16 and 19 are known compounds and were prepared
according to the literature using the procedure described by Evans,7
with yields of 85% and 73%, respectively.
Dd ¼ ꢁð0:42 ꢂ 0:17Þ þ ð8:04 ꢂ 0:27Þcos2
n ¼ 19; R2 ¼ 0:98
q
;
(4)
In its ground state, the molecule is planar,
q
¼0ꢀ, and to this
conformation corresponds Dd¼8.14 ppm that compare well with
the experimental value of 8.8 ppm (Table 4). The conformation
q
¼90ꢀ is the transition state (19.0 kJ molꢁ1 including the zero-point
error correction) where Dd¼ꢁ0.35 ppm.
This curve shows that Dd is sensitive enough to determine the
torsion angle in 2-aryl-benzotriazoles with enough precision for
our purpose. The average Dd value of Table 4 for
q
¼0ꢀ is 9.8 ppm,
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10
D. Santa María et al. / Tetrahedron xxx (2013) 1e12
4.1.1. 2-(2-Hydroxy-6-methoxy)-2H-benzotriazole (15). A mixture
of 1.135 g (5 mmol) of 2-(2,6-dihydroxy)-2H-benzotriazole (16),
0.288 g (7.2 mmol) of NaOH in 20 mL of water, and 20 mL of toluene
was heated up to 100 ꢀC. Then a solution of 0.665 g (5.27 mmol) of
Me2SO4 in 30 mL of toluene was added at a rate of 12e15 drops per
min. A vigorous stirring was needed during the addition process
that takes about 1.5 h. Afterward, 0.3 g of NaOH in 30 mL of water
were added and the reaction mixture stirred, the alkaline aqueous
phase was separated and acidified to pH 6, with diluted HCl
affording a precipitate that was filtered and washed with water. The
crude product thus isolated was purified by column chromatogra-
phy on Merck silica gel 60 with chloroform as eluent. The first
fraction contained 0.22 g of the starting material (Rf: 0.56, chloro-
form), and the second one 0.25 g (19.7% yield) of 15, Rf: 0.15,
chloroform. Mp: 155e156 ꢀC (ethanol). Anal. Calcd for C13H11N3O2
(241.25): C, 64.72; H, 4.60; N, 17.42; found: C, 65.03; H, 4.54;
N, 17.0%.
million) are given from internal solvent, CDCl3, 7.26 for 1H and 77.0
for 13C; for 15N NMR nitromethane (0.00) was used as external
standard. 2D (1He1H) gs-COSY and inverse proton detected het-
eronuclear shift correlation spectra, (1He13C) gs-HMQC, (1He13C)
gs-HMBC and (1He15N) gs-HMBC, were carried out with the
standard pulse sequences19 to assign the 1H, 13C and 15N signals.
1D 15N NMR spectra were obtained with inverse gated 1H
decoupling technique.
Solid-state 13C (100.73 MHz) and 15N (40.60 MHz) CPMAS
NMR spectra were obtained on a Bruker WB 400 spectrometer at
300 K using a 4 mm DVT probehead. Samples were carefully
packed in a 4-mm diameter cylindrical zirconia rotor with Kel-F
end-caps. 13C spectra were originally referenced to a glycine
sample and then the chemical shifts were recalculated to the
Me4Si (for the carbonyl atom
d
(glycine)¼176.1 ppm) and 15N
spectra to 15NH4Cl and then converted to nitromethane scale
using the relationship:
d
15N(nitromethane)¼
d
15N(ammonium
chloride)ꢁ338.1 ppm. The typical acquisition parameters for 13C
CPMAS were: spectral width, 40 kHz; recycle delay, 5 s (75 s for
16); acquisition time, 39 ms; contact time, 2 ms; and spin rate,
12 kHz. In order to distinguish protonated and unprotonated
carbon atoms, the NQS (Non-Quaternary Suppression) experi-
ment by conventional cross-polarization was recorded; before
the acquisition the decoupler is switched off for a very short
4.1.2. 2-(2,6-Dihydroxy-3-tert-butylphenyl)-2H-benzotriazole
(17). To achieve the reaction, dryness conditions all through the
procedure must be maintained: a mixture of 0.454 g (2 mmol) of
2-(2,6-dihydroxy)-2H-benzotriazole (16) dried under vacuum at
60 ꢀC, 0.5 g (3.6 mmol) of dry finely powdered K2CO3, 0.822 g
(6 mmol) of tert-butyl bromide and 1 g of Merck silica gel 60
previously activated for 5 h under vacuum at 190 ꢀC, and 15 mL of
time of 25 m
s. The typical acquisition parameters for 15N CPMAS
ꢁ
were: spectral width, 29 kHz; recycle delay, 5 s (75 s for 16);
acquisition time, 35 ms; contact time, 6e9 ms; and spin rate,
6 kHz.
carbon tetrachloride freshly distilled and dried over 4 A molecular
sieves, was heated at 70e73 ꢀC with vigorous stirring during 24 h.
The reaction mixture was filtered at such temperature and after
thorough washing of the solid materials with dichloromethane, all
organic washings were joined to the filtrate and the solvent
evaporated off under reduced pressure. The crude residue was
then purified by column chromatography on Merck silica gel 60
with hexane/chloroform (6:4) as eluent. Rf¼0.48 (hexane/chloro-
form 6:4). Thus compound 17 was obtained, 0.25 g (44.2% yield).
Mp: 187e189 ꢀC (cyclohexane). Anal. Calcd for C16H17N3O2
(283.33): C, 67.83; H, 6.05; N, 14.83; found: C, 67.44; H, 6.12; N,
14.58%. Unreacted starting material 16 and traces of 18 were also
isolated.
4.3. Computational details
Optimization and frequency calculations were carried out at the
B3LYP20e22/6-31G(d) level;23 optimization and GIAO calcula-
tions24,25 were carried out at the B3LYP/6-311þþG(d,p) level;26,27
total (hartree) and relative (kJ molꢁ1) energies correspond to
B3LYP/6-311þþG(d,p) calculations. The Gaussian 09 package was
used for all the calculations.28
4.3.1. X-ray data collection and structure refinement. Data collec-
tion for all compounds were carried out at room temperature
4.1.3. 2-(2,6-Dihydroxy-3,5-di-tert-butylphenyl)-2H-benzotriazole
(18). To achieve this reaction dryness conditions all through the
procedure must be maintained: a mixture of 0.454 g (2 mmol) of
2-(2,6-dihydroxy)-2H-benzotriazole dried under vacuum at
60 ꢀC, 0.5 g (3.6 mmol) of dry finely powdered K2CO3, 2.46 g
(18 mmol) of tert-butyl bromide and 1.5 g of Merck silica gel 60
previously activated for 5 h under vacuum at 190 ꢀC, and 12 mL
on
a
Bruker Smart CCD diffractometer using graphite-
ꢁ
monochromated Mo-K
a
radiation (
l
¼0.71073 A) operating at
50 kV and 35 mA for 15, 16, and 18, 30 mA for 4 and 25 mA for 19.
In all cases, the data were collected over a hemisphere of the
reciprocal space by combination of three exposure sets; each
exposure was of 20 and covered 0.3ꢀ in
u. The first 100 frames
ꢁ
of carbon tetrachloride freshly distilled and dried over 4 A mo-
were recollected at the end of the data collection to monitor
crystal decay, and no appreciable decay was observed in all the
cases. A summary of the fundamental crystal and refinement data
is given in Table 8.
The structures were solved by direct methods and refined
by full-matrix least-square procedures on F2 (SHELXL-97).29 All
non-hydrogen atoms were refined anisotropically. All hydrogen
atoms were included in calculated positions and refined riding
on the respective carbon atoms, with some exceptions con-
cerning the hydroxyl groups. Thus, H1 and H3A for 15, H1 for
16 and H1 and H2 for 18 were located in a Fourier synthesis
map and refined riding on the respective oxygen bonded
atoms.
lecular sieves, was heated at 70e73 ꢀC with vigorous stirring
during 40 h. The reaction mixture was filtered at such temper-
ature and after thorough washing of the solid materials with
dichloromethane, all organic washings were joined to the filtrate
and the solvent evaporated off under reduced pressure. The
crude residue was purified by column chromatography on Merck
silica gel 60 with hexane/chloroform (6:4) as eluent. Rf¼0.81
(hexane/chloroform 6:4). The entitled compound 18 was ob-
tained, 0.55 g (81.0% yield). Mp: 203e204 ꢀC (cyclohexane). Lit.
(Ciba-Geigy):18 211 ꢀC (petroleum ether). Traces of 17 (5.6% yield)
were also isolated.
4.2. NMR spectroscopy
In compound 4 one of the tert-butyl groups is disordered over
two sites with 0.63:0.37 occupancies. The phenol group is also
disordered on C9 (O1 with 80% occupancy) and on C13 (O10 with
20% occupancy). The hydrogen atom, H1, bonded to O1, was located
in a Fourier synthesis map and refined riding on O1, while the
hydrogen atom bonded to O10 was not located.
Solution NMR spectra were recorded on a Bruker DRX 400
(9.4 T, 400.13 MHz for 1H, 100.62 MHz for 13C and 40.56 MHz for
15N) spectrometer with a 5-mm inverse-detection H-X probe
equipped with a z-gradient coil. Chemical shifts (d in parts per
Please cite this article in press as: Santa María, D.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.01.096

D. Santa María et al. / Tetrahedron xxx (2013) 1e12
11
Table 8
Crystal data and structure refinement for benzotriazoles 4, 15, 16, 18, and 19
Crystal data
4
15
16
18
19
Identification code
Empirical formula
Formula weight
Crystal system
CCDC-905042
CCDC-905043
C13H13N3O3
259.26
Orthorhombic
Pnma
CCDC-905044
C12H9N3O2
227.22
Orthorhombic
Pnma
CCDC-905045
C20H25N3O2
339.43
Monoclinic
P2(1)/m
CCDC-905046
C14H13N3O2
255.27
Orthorhombic
Iba2
C
20H24ClN3O
357.87
Triclinic
Pꢁ1
Space group
Unit cell dimensions
ꢁ
a (A)
6.043(2)
9.866(3)
16.089(5)
86.000(6)
88.945(6)
82.472(6)
948.6(5)
2
1.253
0.214
380
1.27 to 25.00
ꢁ7ꢄhꢄ7
ꢁ11ꢄkꢄ9
ꢁ19ꢄlꢄ19
6873
23.125(2)
7.0626(7)
7.9896(8)
d
22.392(11)
11.872(4)
3.800(2)
d
9.789(2)
6.874(1)
14.267(3)
d
19.676(1)
19.677(1)
13.790(1)
d
ꢁ
b (A)
ꢁ
c (A)
a
b
g
(ꢀ)
(ꢀ)
(ꢀ)
d
d
102.038(3)
d
d
d
d
d
3
ꢁ
Volume (A )
1304.9(2)
4
1.320
0.096
544
1.76 to 26.99
ꢁ29ꢄhꢄ26
ꢁ9ꢄkꢄ8
ꢁ10ꢄlꢄ10
11,070
1010.1(7)
4
1.494
0.106
472
1.82 to 27.00
ꢁ28ꢄhꢄ28
ꢁ11ꢄkꢄ15
ꢁ4ꢄlꢄ4
7784
939.0(3)
2
1.201
0.079
364
1.46 to 26.00
ꢁ12ꢄhꢄ10
ꢁ8ꢄkꢄ8
ꢁ17ꢄlꢄ17
7772
5339.1(7)
16
1.270
0.088
2144
1.46 to 26.99
ꢁ25ꢄhꢄ25
ꢁ23ꢄkꢄ25
ꢁ16ꢄlꢄ17
23,251
Z
Density (calculated) (Mg/m3)
Absorption coefficient (mmꢁ1
F(000)
)
Theta range (ꢀ) for data collection
Index ranges
Reflections collected
Independent reflec. [R(int)]
Completeness to theta (%)
Data/restraints/parameters
Goodness-of-fit on F2
3224 [0.1097]
96.5
3224/10/264
0.996
0.0565 (2006)
0.1706
1536 [0.0510]
100
1536/0/103
0.992
0.0396 (786)
0.1277
1145 [0.1296]
99.7
1145/0/82
0.997
0.0466 (565)
0.1619
1999 [0.0501]
99.5
1999/4/145
0.994
0.0438 (900)
0.1235
5702 [0.0575]
99.9
5702/1/343
0.998
0.0397 (3028)
0.0924
R1 (reflns obsd) [I>2sigma(I)]a
wR2 (all data)b
a
R1¼SjjFojꢁjFcjj/SjFoj.
b
wR2¼{S[w(F2oꢁFc2)2]/S[w(F2o)2]}.
6. Rieker, J.; Lemmert-Schmitt, E.; Goeller, G.; Roessler, M.; Stueber, G. J.; Schettler,
H.; Kramer, H. E. A.; Stezowski, J. J.; Holer, H.; Henkel, S.; Schmidt, A.; Port, H.;
Wiechmann, M.; Rody, J.; Rytz, G.; Slongo, M.; Birbaum, J.-L. J. Phys. Chem. 1992,
96, 10225e10234.
Acknowledgements
This work has been financed by the Spanish MICINN (CTQ2009-
ꢀ
7. Evans, N. E. Aust. J. Chem. 1981, 34, 691e695.
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13129-C02-02 and CTQ2010-16122) and Comunidad Autonoma de
Madrid (Project MADRISOLAR2, ref S2009/PPQ-1533). The authors
thank the CTI (CSIC) for allocation of computer time.
Supplementary data
11. Heller, H. J. Eur. Polym. J. (Suppl.) 1969, 105e132.
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