Oxazoles formation during O-alkylation of isonitroso-naphthols. X-ray structure of [1,2]naphthoquinone 1-[O-(4-tert-Butyl-benzyl)oxime] and 2-(4-tert-Butyl-phenyl)napth[1,2-d]oxazole

Article abstract of DOI:10.1002/jhet.5570410618

1-Nitroso-2-naphthol and 2-nitroso-1-naphthol, both in the isonitroso form, react with benzyl bromides in THF and in the presence of triethylamine affording, in low yields, the corresponding O-benzyl oximes and 2-aryl naphthoxazoles in a 1:1 ratio, approximately. The structures of O-benzyl oximes and naphthoxazoles isolated have been determined by X-ray analysis.

Full text of DOI:10.1002/jhet.5570410618

Nov-Dec 2004
971
Oxazoles Formation During O-Alkylation of Isonitroso-naphthols.
X-Ray Structure of [1,2]Naphthoquinone 1-[O-(4-tert-Butyl-benzyl)-
oxime] and 2-(4-tert-Butyl-phenyl)Napth[1,2-d]Oxazole
a
a
a
a*
Paola Astolfi, Patricia Carloni, Riccardo Castagna, Lucedio Greci,
b
a
Corrado Rizzoli and Pierluigi Stipa
a
Dipartimento di Scienze dei Materiali e della Terra, Università Politecnica delle Marche, via Brecce Bianche,
b
I-60131 Ancona, Italy; Dipartimento di Chimica Generale ed Inorganica, Chimica Analitica, Chimica Fisica,
Università, Viale delle Scienze, I-43100 Parma, Italy
Received December 5, 2003
1-Nitroso-2-naphthol and 2-nitroso-1-naphthol, both in the isonitroso form, react with benzyl bromides in
THF and in the presence of triethylamine affording, in low yields, the corresponding O-benzyl oximes and
2-aryl naphthoxazoles in a 1:1 ratio, approximately. The structures of O-benzyl oximes and naphthoxazoles
isolated have been determined by X-ray analysis.
J. Heterocyclic Chem., 41, 971 (2004).
Introduction.
and oxazoles 5 and 7 as shown in Scheme 1. Yields of the
products isolated together with their analytical and spectro-
scopic data are reported in the experimental section.
X-Ray analyses were performed on compounds 4b and
5b in order to establish or confirm the structure of com-
pounds 4, 5, 6 and 7. X-Ray experimental details, selected
bond distances and angles for compounds 4b and 5b are
reported in Tables 1 and 2
The molecular geometry observed for both compounds
is as expected. In particular, in compound 4b (Figure 1)
the values of the bond distances are consistent with a dou-
ble bond character of the N1-C1 (1.302(3) Å), O1-C2
(1.220(3) Å), and C3-C4 (1.316(4) Å) bonds. These val-
ues are in good agreement with those reported in the litera-
ture for the corresponding bonds in naphthoquinone-1-
oxime systems (mean values 1.36(2), 1.236(10), and
1.328(12) Å respectively, calculated over four entries [5]
from the Cambridge Crystallographic Databank). The imi-
noxyl moiety deviates significantly from planarity, the
maximum deviation being observed for the O1 atom
(0.272(2) Å). The C12…C17 aromatic ring is oriented
almost perpendicular to the least-square mean plane
through the atoms of the iminoxyl moiety, the dihedral
Aminoxyls, both aliphatic and aromatic [1], are good
precursors of N-alkoxyamines, which, in the last decades,
have received great attention because of their importance
as initiators and intermediates in "living"/controlled free
radical polymerization [2]. Furthermore, the kinetics of
polymerizations involving aminoxyl radicals are closely
related to a general phenomenon, the so-called persistent
radical effect, characterized by a highly specific formation
of the cross-reaction products of transient and persistent
radicals, when simultaneously formed in the reaction sys-
tem [3].
Since iminoxyls are persistent radicals [4], alkylation of
isonitroso-naphthols was attempted in order to obtain
alkoxyimines to be possibly used, just like alkoxyamines,
in radical polymerization. The reactions here described
afforded the expected alkoxyimines, although in low
yields, together with unexpected new naphthoxazoles.
Results and Discussion.
Compounds 1 and 2 react with benzylbromides 3a and 3b
at room temperature in THF and in the presence of triethyl-
amine giving the corresponding alkylated iminoxyls 4 and 6
Scheme 1

972
P. Astolfi, P. Carloni, R. Castagna, L. Greci, C. Rizzoli and P. Stipa
Vol. 41
Table 1
bond character of the N1-C11 bond (1.295(6) Å). The
oxazole ring system is almost planar (maximum deviation
from planarity: 0.042(5) Å for C6 and C7). The
C12…C17 aromatic ring is nearly co-planar with the oxa-
zole system, the dihedral angle they form being 2.8(1)°.
Conformation and geometry of the naphthoxazole com-
pare well with those found in the literature [6].
For both compounds, crystal packing is mainly deter-
mined by van der Waals interactions, the shortest hydro-
gen contacts observed being C9…O2, 2.786(4) Å;
H9…O2, 2.20 Å; C9-H9…O2, 120.8° and C17…O1,
2.816(6) Å; H17…O1, 2.50 Å; C17-H17…O1, 100.2° for
4b and 5b, respectively.
Experimental Data for the X-ray Diffraction Study on Crystalline
Compounds Compounds 4b and 5b
Compound
4b
5b
formula
a, Å
b, Å
C
H
NO
C H NO
21 19
21 21
2
10.168(2)
15.292(3)
11.611(2)
98.39(2)
1786.1(6)
4
13.637(3)
10.995(2)
11.209(2)
90
1680.7(6)
4
301.4
Pca2
20
c, Å
β, °
V, Å
3
Z
formula weight
space group
t, °C
319.4
P2 /c
1
1
20
λ, Å
0.71073
1.188
0.76
1.54178
1.191
5.66
-3
ρ
, g cm
calc
-1
µ, cm
transmission coefficient
R [a]
0.984-0.989
0.068
0.148
1.016
1660
3891
3234
214
0.873-0.903
0.061
0.155
1.137
1107
1688
1575
203
wR
2
GOF
N-observed [b]
N-independent [c]
N-refinement [d]
variables
[a] Calculated on the observed reflections having I > 2σ(I);
[b] N-observed is the total number of the independent reflections
having I > 2σ(I); [c] N-independent is the number of independent
reflections; [d] N-refinement is the number of reflection used in
the refinement having I >0.
Table 2
Selected Bond Distances (Å) and Angles (°) for
Compounds 4b and 5b
Compound
4b
5b
O1-C2
O1-C11
O2-N1
O2-C11
N1-C1
N1-C11
C1-C2
C1-C10
C2-C3
C3-C4
1.220(3)
-
1.385(2)
1.473(2)
1.302(3)
-
1.524(3)
1.463(3)
1.437(3)
1.316(4)
1.385(6)
1.378(6)
-
-
1.402(5)
1.295(6)
1.370(6)
1.420(6)
1.391(6)
1.361(8)
Figure 1. An ORTEP view (50% probability ellipsoids) of compound 4b.
Disorder affecting the t-Bu group has been omitted for clarity.
In order to improve the selectivity of the reactions and
therefore to obtain higher yields of the alkylated oxime or
of the oxazole, different combinations of solvents and
bases were used, i.e. DMSO in the presence of KOH or
C2-O1-C11
N1-O2-C11
O2-N1-C1
C1-N1-C11
N1-C1-C2
N1-C1-C10
C2-C1-C10
O1-C2-C1
O1-C2-C3
C1-C2-C3
C2-C3-C4
-
104.0(3)
-
-
107.5(1)
114.1(2
-
109.5(2)
131.1(2)
119.4(2)
121.7(2)
122.4(2)
115.9(2)
122.6(2)
104.4(4)
109.3(4)
130.7(4)
120.0(4)
107.6(4)
127.6(4)
124.8(4)
115.6(4)
acetone in the presence of K CO . However, the selectiv-
2
3
ity was not improved and both products were obtained in
lower yields together with high reaction tar.
Alkylated iminoxyls 4 and 6 were tested in "living"/con-
trolled radical polymerization of styrene, but it was estab-
lished that homolytic cleavage of the oxygen-carbon bond,
responsible for their activity, does not occur up to 170 °C
in DMSO or chlorobenzene. Such a high temperature for
oxygen-carbon bond cleavage prevents their use because
styrene can be thermally polymerized at 140 °C without
catalysis [7].
angle they form being 94.4(1)°. The presence of an oxa-
zole moiety in compound 5b (Figure 2) is confirmed by
the aromaticity of the C1…C10 system and by the double

Nov-Dec 2004
Oxazoles Formation During O-Alkylation of Isonitroso-naphthols
973
with cyclohexane/ethyl acetate 8:2. The isolated products were
subsequently purified on preparative plates eluting with the same
solvents.
Thus, the formation of oxazoles 5 and 7 in these reac-
tions may be considered the most interesting result
because of the biological activity described for some ben-
zoxazole [8] and naphthoxazole [9] derivatives.
Mechanicistic studies on these reactions are currently
underway and will be reported in due course.
The reaction carried out in acetone/K CO under reflux
2
3
afforded the same products in low yields whereas those in
DMSO/KOH at room temperature were much faster but with
more impurities.
[1,2]Naphthoquinone 2-(O-Benzyl-oxime) (4a).
This compound was obtained as yellowish needles, 136 mg
(0.5 mmol, 26%), mp 87-88 °C (ligroin); FT-IR: 1659 (C=O),
-1
1
1519 (C=N), 987 (N-O) cm ; H NMR (200 MHz, CDCl , 25
3
°C): δ = 5.60 (s, 2H, CH ), 6.38-6.43 (m, 1H, CH); 7.36-7.48 (m,
2
+
9H, aromatic), 8.69 (m, 1H, CH); MS (EI ): m/z = 263 (5), 246
(48), 156 (28), 91 (100).
Anal. Calcd for C
H NO : C, 77.55; H, 4.98; N, 5.32.
17 13 2
Found: C, 77.53; H, 5.02; N, 5.36.
[1,2]Naphthoquinone 1-[O-(4-tert-Butyl-benzyl)-oxime] (4b).
This compounds was obtained as yellowish needles, 96 mg
(0.3 mmol, 15%), mp 124-125 °C (ligroin); FT-IR: 1666 (C=O),
-1
1
1526 (C=N), 987 (N-O) cm ; H NMR (200 MHz, CDCl , 25
3
°C): δ = 1.33 (s, 9H, t-Bu), 5.57 (s, 2H, CH ), 6.39-6.44 (m, 1H,
2
+
CH); 7.37-7.47 (m, 9H, aromatic), 8.69 (m, 1H, CH); MS (EI ):
m/z = 319 (2), 302 (45), 156 (35), 147 (100).
Anal. Calcd for C
H NO : C, 78.97; H, 6.63; N, 4.39.
21 21 2
Found: C, 78.95; H, 6.60; N, 4.41.
2-Phenyl-naphth[1,2-d]oxazole (5a).
This compound was obtained as white prisms, 142 mg (0.58
mmol, 29%), mp 133-135 °C (ligroin); FT-IR: 1551 and 1485
Figure 2. An ORTEP view (50% probability ellipsoids) of compound 5b.
Disorder affecting the t-Bu group has been omitted for clarity.
-1
1
(C=N), 1238 (C-O) cm ; H NMR (200 MHz, CDCl , 25 °C): δ
3
= 7.53-7.82 (m, 7H, aromatic), 7.98 (d, 1H, J = 8.3 Hz, aromatic),
8.32-8.39 (m, 2H, aromatic), 8.61 (d, 1H, J = 8.3 Hz, aromatic);
+
MS (EI ): m/z = 245 (100), 114 (52).
EXPERIMENTAL
Anal. Calcd for C
H NO: C, 83.25; H, 4.52; N, 5.71.
17 11
Found: C, 83.28; H, 4.55; N, 5.74.
Melting points are uncorrected and were measured with an
Electrothermal apparatus. IR spectra were recorded on a Nicolet
2-(4-tert-Butyl-phenyl)naphth[1,2-d]oxazole (5b).
Fourier Transform Infrared 20-SX spectrophotometer equipped
This compound was obtained as white prisms, 156 mg (0.52
mmol, 26%), mp 134-135 °C (ligroin); FT-IR: 1495 (C=N) 1270
1
with a Spectra Tech Collector for DRIFT measurements.
H
NMR spectra were recorded at room temperature in CDCl solu-
3
-1 1
(C-O) cm ; H NMR (200 MHz, CDCl , 25 °C): δ = 1.39 (s, 9H,
3
tion on a Varian Gemini 200 spectrometer (δ in ppm referred to
t-Bu), 7.57 (d, 2H, J = 8.4 Hz, aromatic), 7.63-7.85 (m, 4H,
tetramethylsilane). Mass spectra were performed on a Carlo Erba
aromatic), 8.01 (d, 1H, J = 8.4 Hz, aromatic), 8.29 (d, 2H, J = 8.4
+
QMD 1000 mass sperctrometer in EI mode. Elemental analyses
+
Hz, aromatic), 8.63 (d, 1H, J = 8.4 Hz, aromatic); MS (EI ): m/z
were performed with a Carlo Erba CHNSO E.A. 1108 elemental
analyser.
Nitroso-naphthols 1 and 2, alkyl halides 3a-b and triethyl-
amine were Aldrich commercial reagent grade products and used
as received. Potassium carbonate, potassium hydroxide and all
solvents were Carlo Erba or Aldrich RP-ACS grade.
= 301 (80), 286 (100), 258 (30), 114 (40).
Anal. Calcd for C
H NO: C, 83.69; H, 6.35; N, 4.65.
21 19
Found: C, 83.71; H, 6.32; N, 4.67.
[1,2]Naphthoquinone 2-(O-Benzyl-oxime) (6a).
This compound was obtained as greenish needles, 142 mg (0.54
mmol, 27%), mp 108-110 °C (ligroin); FT-IR: 1675 (C=O), 1590
General Procedure for the Reaction of Nitroso-naphthols 1 and 2
with Alkyl Halides 3a-b in THF in the Presence of
Triethylamine.
-1
1
(C=N), 971 (N-O) cm ; H NMR (200 MHz, CDCl , 25 °C): δ =
3
5.52 (s, 2H, CH ), 6.84 (d, 1H, J = 10.4 Hz, CH), 7.11 (d, 1H, J =
2
10.4 Hz, CH), 7.31-7.61 (m, 8H, aromatic), 8.19-8.23 (m, 1H, aro-
+
Alkyl halide (3 mmoles in 1 mL of THF) was added to a solu-
tion of nitroso-naphthol (2 mmoles in 3 mL of THF containing 5
mmoles of triethylamine) under stirring at room temperature.
After 3 hrs the reaction mixture was poured into 20 mL of water
and extracted with chloroform (2x20 mL). The organic layer was
dried over anhydrous sodium sulfate and evaporated to dryness;
the residue was chromatographed on silica gel column eluting
matic); MS (EI ): m/z = 263 (3), 246 (79), 157 (20), 91 (100).
Anal. Calcd for C
H NO : C, 77.55; H, 4.98; N, 5.32.
17 13 2
Found: C, 77.58; H, 4.96; N, 5.34.
[1,2]Naphthoquinone 2-[O-(4-tert-Butyl-benzyl)-oxime] (6b).
This compound was obtained as yellowish needles, 179 mg
(0.56 mmol, 28%), mp 93-94 °C (ligroin); FT-IR: 1673 (C=O),

974
P. Astolfi, P. Carloni, R. Castagna, L. Greci, C. Rizzoli and P. Stipa
Vol. 41
-1
1
anisotropically refined for all the non-H atoms except for the
methyl carbon atoms of the t-Bu group, which were found to be
disordered over two positions (called A and B) isotropically
refined with site occupation factors of 0.75 and 0.25, respectively.
During the refinement the C-C bond distances involving the disor-
dered atoms were constrained to be 1.54(1) Å. The hydrogen
atoms were put in geometrically calculated positions and intro-
duced as fixed contributors in the last stage of refinement with
1520 (C=N), 963 (N-O) cm ; H NMR (200 MHz, CDCl , 25
3
°C): δ = 1.33 (s, 9H. t-Bu), 5.49 (s, 2H, CH ), 6.82 (d, 1H, J =
10.1 Hz, CH), 7.11 (m., 1H, J = 10.1 Hz, CH), 7.28-7.62 (m, 7H,
aromatics), 8.20 (m, 1H, aromatic); MS (EI ): m/z = 319 (15),
302 (45), 147 (100), 132 (66).
2
+
Anal. Calcd for C
H NO : C, 78.97; H, 6.63; N, 4.39.
21 21 2
Found: C, 78.99; H, 6.65; N, 4.37.
2-Phenyl-naphth[2,1-d]oxazole (7a).
U
assigned to be 1.2 times those of the attached C atoms. The
iso
2
This compound was obtained as white prisms, 98 mg (0.4
mmol, 20%), mp 87-88 °C (ligroin); FT-IR: 1548 and 1485
(C=N), 1250 (C-O); H NMR (200 MHz, CDCl , 25 °C): δ =
structure was refined on F values (SHELX93) [11] by using the
weighting scheme w = 1/[σ (F )+(0.109 P) ] (with P = (F +2
2
2
2
2
o
o
1
2
F )/3). For 1107 unique reflections having I > 2(I) collected at T
3
c
7.55-7.60 (m, 4H, aromatic), 7.62-7.71 (m, 1H, aromatic), 7.78-
7.9 (m, 2H, aromatic), 7.97-8.02 (m, 1H, aromatic), 8.31-8.38
(m, 3H, aromatic); MS (EI ): m/z = 245 (100), 114 (52).
= 293(2) K on a Enraf-Nonius CAD4 diffractometer (3 < 2θ <
140°) the final R is 0.061 (wR2 = 0.155 calculated over 1575
reflections having I > 0; S = 1.137). The choice of the noncen-
+
Anal. Calcd for C
H NO: C, 83.25; H, 4.52; N, 5.71.
trosymmetric space group (Pca2 ) should be considered correct
17 11
1
Found: C, 83.28; H, 4.55; N, 5.74.
on the basis of the successful structure refinement. Moreover,
although the molecule shows a C pseudo-symmetry, the corre-
sponding centrosymmetric space group (Pbcm) results incompati-
ble with the orientation of the molecule within the unit cell.
m
2-(4-tert-Butyl-phenyl)naphth[2,1-d]oxazole (7b).
This compound was obtained as white prisms, 210 mg (0.7
mmol, 35%), mp 118-119 °C (ligroin); FT-IR: 1495 (C=N), 1270
1
(C-O); H NMR (200 MHz, CDCl , 25 °C): δ = 1.40 (s, 9H, t-
3
REFERENCES AND NOTES
Bu), 7.55-7.57 (m, 4H, aromatic), 7.77-7.89 (m, 2H, aromatic),
7.97-8.01 (m, 1H, aromatic), 8.25-8.35 (m, 3H, aromatic); MS
*
To whom the correspondence should be addressed; E-mail:
l.greci@univpm.it
[1] On the basis of their reactivity, we divide stable aminoxyls
+
(EI ): m/z = 301 (85), 286 (100), 258 (60), 114 (53).
Anal. Calcd for C
H NO: C, 83.69; H, 6.35; N, 4.65.
21 19
Found: C, 83.67; H, 6.37; N, 4.62.
into two different classes: aliphatic aminoxyls with the nitroxide func-
3
tion between two sp carbons, such as tetramethyl-piperidino, pyrro-
Crystal data for [1,2]Naphthoquinone 1-[O-(4-tert-Butyl-ben-
zyl)-oxime] (4b) (CCDC-225801).
lidino and imidazolino derivatives and aromatic aminoxyls whose
nitroxide function is conjugated with an aromatic ring, such as
indolinonic and quinolinic derivatives.
[2a] H. Fisher, Macromolecules, 30, 5666 (1997); [b] C. J.
Hawker, Acc. Chem. Res. , 30, 373 (1997); [c] D. Benoit, V. Chaplinski,
R. Braslau and C. J. Hawker, J. Am. Chem. Soc., 121, 3904 (1999).
[3] H. Fischer, Chem. Rev., 101, 3581 (2001) and references
reported therein.
C
H
NO , M = 319.4, monoclinic, space group 2 /c,
=
=
P
a
V
21 21
2
r
1
10.168(2), = 15.292(3), = 11.611(2) Å, β = 98.39(2)°,
1786.1(6) Å , = 4, ρ = 1.188 g cm ; λ(Mo-Kα) = 0.71073 Å,
Mo-Kα
µ(
b
3
c
-3
Z
-1
0.76 cm : yellow prism, crystal dimensions 0.15 x
) =
0.18 x 0.32 mm. The structure was solved by direct methods
(SIR97) [10] and anisotropically refined for all the non-H atoms.
The methyl carbon atoms of the t-Bu group were found to be dis-
ordered over two positions (called A and B) anisotropically
refined with site occupation factors of 0.75 and 0.25, respec-
tively. During the refinement the C-C bond distances involving
the disordered atoms were constrained to be 1.54(1) Å. The
hydrogen atoms were put in geometrically calculated positions
and introduced as fixed contributors in the last stage of refine-
[4] A. Zrzˇan, D. R. Crist and V. Horák, J. Phys. Org. Chem., 9,
695 (1996).
[5a] J.C.A.Boeyens, J. Cryst. Mol. Struct., 6, 217,(1976); [b] H.
Saarinen, J. Korvenranta and E. Nasakkala, Acta Chem. Scand., 31,
213, (1977); [c] H. Saarinen and J. Korvenranta, Finn. Chem. Lett.,
223, (1978); [d] R. Graziani, U. Casellato, P. A. Vigato, S .Tamburini
and M. Vidali, J .Chem. Soc., Dalton Trans., 697, (1983).
[6a] V. Malatesta, R. Millini and L. Montanari, J. Am. Chem.
Soc., 117, 6258, (1995); [b] P. Uznanski, C. Amiens, M. Bardaji, B.
Donnadieu, Y. Coppel, B. Chaudret and A. Laguna, New J. Chem., 25,
1495, (2001).
ment with U assigned to be 1.2 times those of the attached C
iso
2
atoms. The structure was refined on F values (SHELX93) [11]
2
2
2
by using the weighting scheme w = 1/[σ (F )+(0.074
(with
P) ]
= (F +2 F )/3). For 1660 unique reflections having I > 2(I)
o
2
2
P
o
c
[7] P. J. Flory, J. Am. Chem. Soc., 59, 241 (1937) and refer-
ences reported therein.
collected at T = 293(2) K on a Philips PW1100 diffractometer (3
< 2θ ° the final is 0.068 ( = 0.148 calculated over
< 54 )
R
wR2
[8a] E. A. Sener, Ö. T. Arpaci, I. Yalçin and N. Altanlar, Il
Farmaco, 55, 397 (2000); [b] D. Kumar, M. R. Jacob, M. B. Reynolds
and S. M. Kerwin, Bioorg. Med. Chem., 10, 3997 (2002).
[9] I. Minami, Y. Kozai, H. Nomura and T. Tashiro, Chem.
Pharm. Bull., 30, 3106 (1982).
[10] A. Altomare, M. C. Burla, M. Camalli, G. Cascarano, C.
Giacovazzo, A. Guagliardi, A. G. G. Moliterni, G. Polidori and R.
Spagna, J. Appl. Cryst., 32, 115 (1999).
3234 reflections having I > 0; S = 1.016).
Crystal data for 2-(4-tert-Butyl-phenyl)naphth[1,2-d]oxazole
(5b) (CCDC-225802).
C H NO, M = 301.4, orthorhombic, space group
2 ,
=
Pca
a
Z
21 19
r
1
3
13.637(3), = 10.995(2), = 11.209(2) Å, = 1680.7(6) Å ,
=
b
c
V
-3
-
4, ρ = 1.191 g cm ; λ(Cu-Kα) = 1.54178 Å, Cu-Kα
µ(
cm
) = 5.66
1
: pale yellow prism, crystal dimensions 0.18 x 0.20 x 0.40 mm.
The structure was solved by direct methods (SIR97) [10] and
[11] Sheldrick, G.M. SHELXL93. Program for crystal structure
refinement. University of Göttingen, Germany, 1993.