Transition-metal-free O-,S -, and N-arylation of alcohols, thiols, amides, amines, and related heterocycles

Article abstract of DOI:10.1021/jo1022052

A new protocol for the Ullmann-type arylation process of different aromatic heterocycles without any transition-metal catalyst, implying the use of a combination of an excess of potassium hydroxide and dimethyl sulfoxide, is described. The reaction can be performed between a broad range of starting nucleophiles including phenol, alcohols, amines, nitrogen-containing five-membered systems such as pyrazoles, imidazoles, and indoles, and amides with haloarenes, iodide and bromide derivatives giving the best results, the possible pathway involving the in situ generation of the corresponding benzyne intermediate. When the reaction was performed with 2-iodoaniline and either carboxamides or isothiocyanato derivatives, the corresponding benzoazole derivatives were obtained.

Full text of DOI:10.1021/jo1022052

pubs.acs.org/joc
Transition-Metal-Free O-, S-, and N-Arylation of Alcohols, Thiols,
Amides, Amines, and Related Heterocycles†
ꢀ
Rafael Cano, Diego J. Ramon,* and Miguel Yus
´ ´
Instituto de Sıntesis Organica (ISO) and Departamento de Quımica Organica, Facultad de Ciencias,
ꢀ
Universidad de Alicante, Apdo. 99, E-03080-Alicante, Spain
ꢀ
djramon@ua.es
Received November 8, 2010
A new protocol for the Ullmann-type arylation process of different aromatic heterocycles without
any transition-metal catalyst, implying the use of a combination of an excess of potassium hydroxide
and dimethyl sulfoxide, is described. The reaction can be performed between a broad range of starting
nucleophiles including phenol, alcohols, amines, nitrogen-containing five-membered systems such as
pyrazoles, imidazoles, and indoles, and amides with haloarenes, iodide and bromide derivatives giving
the best results, the possible pathway involving the in situ generation of the corresponding benzyne
intermediate. When the reaction was performed with 2-iodoaniline and either carboxamides or
isothiocyanato derivatives, the corresponding benzoazole derivatives were obtained.
1. Introduction
higher than 200 °C. Furthermore, the need of stoichiometric
amounts of copper salts to carry out the process decreased
the atom efficiency,3 and led to some waste problems.
However, these limitations have been partially overcome,
in the case of nitrogen-containing nucleophiles with the use
of catalytic systems derived from iron,4,5 cobalt,6 nickel,7
copper,8 and palladium.9 In many of the above protocols the
solvent of choice was a polar system, such as DMSO, in the
presence of stoichiometric amounts of bases at temperatures
The cross-coupling reaction between either amines or
N-heterocycles and aryl halides, also known as the Ullmann-
type reaction,1 as well as the related one using alcohols and
thiols as nucleophiles, is a well-documented process and very
important for the preparation of many compounds of inter-
est in biological, pharmaceutical, and material sciences.2
Historically, the common methods used for their prepara-
tion required very polar solvents, such as nitrobenzene,
N-methylpyrrolidone, or DMF, at high temperature, usually
(3)(a) Trost, B. M. Science 1991, 254, 1471–1477. (b) Green Chemistry:
Designing Chemistry for the Environment; Anastas, P. T., Williamson, T. C.,
Eds.; American Chemical Society: Washington, DC, 1996. (c) Trost, B. M.
Acc. Chem. Res. 2002, 35, 695–705. (d) Sheldon, R. A.; Arends, I.; Hanefeld,
U. Green Chemistry and Catalysis; Wiley-VCH: Weinheim, Germany, 2007.
†
ꢀ
Dedicated to Professor Carmen Najera on occasion of her 60th birthday and
after becoming Correspondent Member of the Real Academia de Ciencias
Exactas, Físicas y Naturales of Spain.
(1) Ullmann, F. Ber. Dtsch. Chem. Ges. 1903, 36, 2382–2384.
ꢀ
(e) Guillena, G.; Ramon, D. J.; Yus, M. Angew. Chem., Int. Ed. 2007, 46,
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2358–2364. (f) Guillena, G.; Ramon, D. J.; Yus, M. Chem. Rev. 2010, 110,
1611–1641.
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Lemaire, M. Chem. Rev. 2002, 102, 1359–1469. (b) Ley, S. V.; Thomas, A. W.
Angew. Chem., Int. Ed. 2003, 42, 5400–5449. (c) Beletskaya, I. P.; Cheprakov,
A. V. Coord. Chem. Rev. 2004, 248, 2337–2364. (d) Hartwig, J. F. Synlett
2006, 1283–1294. (e) Corbet, J.-P.; Mignani, G. Chem. Rev. 2006, 106, 2651–
2710. (f) Ma, D.; Cai, Q. Acc. Chem. Res. 2008, 41, 1450–1460. (g) Hartwig,
J. F. Acc. Chem. Res. 2008, 41, 1534–1544. (h) Monnier, F.; Taillefer, M.
Angew. Chem., Int. Ed. 2009, 48, 6954–6971.
(4) For recent representative examples, see: (a) Correa, A.; Elmore, S.;
Bolm, C. Chem.;Eur. J. 2008, 14, 3527–3529. (b) Guo, D.; Huang, H.; Xu,
J.; Jiang, H.; Liu, H. Org. Lett. 2008, 10, 4513–4516. (c) Lee, H. W.; Chan,
A. S. C.; Kwong, F. Y. Tetrahedron Lett. 2009, 50, 5868–5871. (d) Swapna,
K.; Kumar, A. V.; Reddy, V. P.; Rao, K. R. J. Org. Chem. 2009, 74, 7514–
7517.
654 J. Org. Chem. 2011, 76, 654–660
Published on Web 12/22/2010
DOI: 10.1021/jo1022052
r
2010 American Chemical Society

Cano et al.
JOCArticle
higher than 100 °C. The above copper-catalyzed protocol
with DMSO as solvent has been extended to other nucleo-
philes, such as phenols10 and sulfur-containing com-
pounds.11 In the last case, the use of polyfunctionalized
sulfur compounds allowed the synthesis of different inter-
esting heterocyclic compounds, such as phenothiazines12 and
benzothiazoles.13
TABLE 1. Reaction-Condition Optimization
Alternatively, a similar arylation transformation can be
performed by nucleophilic addition of the corresponding
nucleophilic compounds to an in situ generated aryne inter-
mediate under strong basic conditions.14,15
entry
X
solvent
base
T (°C)
t (h)
yield (%)a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
I
I
I
I
I
I
I
I
Br
Cl
F
I
I
I
DMSO
DMSO
DMSO
KOHb
KOH
KOHc
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
NaOH
KOtBu
K2CO3
KOH
120
120
120
120
120
120
120
120
120
120
120
120d
120
120
120
90
24
24
24
24
24
24
24
24
144
144
144
2
0
92
83
<5
0
<5
20
0
81
57
52
55
67
79
0
(5) For the catalytic role of contaminants, see: Buchwald, S. L.; Bolm, C.
Angew. Chem., Int. Ed. 2009, 48, 5586–5587.
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C.-Y.; Yang, L.-M. J. Org. Chem. 2008, 73, 1624–1627.
PhMe
Dioxane
MeCN
DMF
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S.; Adachi, Y.; Hayashi, M. Tetrahedron 2009, 65, 10459–10462. (l) Hirano,
K.; Biju, A. T.; Glorius, F. J. Org. Chem. 2009, 74, 9570–9572. (m) Cai, Q.;
Li, Z.; Wei, J.; Ha, C.; Pei, D.; Ding, K. Chem. Commun. 2009, 7581–7583. (n)
Guo, D.; Huang, H.; Zhou, Y.; Xu, J.; Jiang, H.; Chen, K.; Liu, H. Green
Chem. 2010, 12, 276–281. (o) Han, X. Tetrahedron Lett. 2010, 51, 360–362.
(p) Ali, M. A.; Punniyamurthy, T. Synthesis 2010, 908–910.
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
24
24
72
96
I
I
65
aIsolated yield. bThe reaction was carried out with only 40 mol % of
base. cThe reaction was carried out with 200 mol % of base. dThe
reaction was carried out with microwaves (80 W).
2. Results and Discussion
(9) For recent representative examples, see: (a) Urgaonkar, S.; Xu, J.-H.;
Verkade, J. G. J. Org. Chem. 2003, 68, 8416–8423. (b) Rataboul, F.; Zapf, A.;
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In our ongoing project on the use of copper-impregnated
magnetite,16 we realized that the transition-metal catalyst
could be eliminated in the N-Ullmann type reaction by the
correct choice of reaction conditions. Here, we report a simple,
mild, and uncatalyzed protocol to perform the arylation of
different oxygen-, nitrogen-, and sulfur-containing nucleophiles.17
2.1. Optimization of the Reaction Conditions. To optimize
the reaction conditions we studied the reaction between
pyrazol (1a) and different phenyl halides 2 to give the corre-
sponding compound 3a, as depicted in Table 1. The reaction
with stoichiometric amounts of all reagents failed after 1 day
of reaction at 120 °C, recovering the starting materials
unchanged (entry 1 in Table 1). However, increasing the
amount of base to 250 mol % allowed us to obtain the
expected product 3a in an excellent yield. A further increase
in the base amount to 500 mol % did not provoke any
improvement on the reaction time or on the yield (compare
entries 2 and 3). Once the optimal amount of base was
established, we studied the influence of the nature of solvent
(or their absence) and in all cases the reaction either failed or
gave a very low yield (compare entries 2 and 4-8 in Table 1).
Then, the influence of the halide at the phenyl ring in
compound 2 was evaluated (Table 1, entries 9-11), and in
all cases the reaction required longer reaction times and only
in the case of bromobenzene was the yield comparable with
ꢀ
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Vervest, I.; Leurs, S.; De Knaep, F. Org. Process Res. Dev. 2001, 5, 467–471.
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M. Synthesis 2010, 1983–1988. (f) Ding, Q.; He, X.; Wu, J. J. Comb. Chem.
2009, 11, 587–591.
ꢀ
(16)(a) Aliaga, M. J.; Ramon, D. J.; Yus, M. Org. Biomol. Chem. 2010, 8,
43–46. (b) Cano, R.; Ramon, D. J.; Yus, M. J. Org. Chem. 2010, 75, 3458–
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(14) For reviews on the use of arynes, see: (a) Pellissier, H.; Santelli, M.
~
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Tetrahedron 2003, 59, 701–730. (b) Pena, D.; Perez, D.; Guitian, E. Angew.
Chem., Int. Ed. 2006, 45, 3579–3581.
3460.
(17) The DMSO/KOH mixture was catalogued as a superbase and was
used, independently from our work, in the transition-metal-free prepara-
(15)(a) Bunnett, J. F.; Hrutfiord, B. J. J. Am. Chem. Soc. 1961, 83, 1691–
1697. (b)Biehl, E. R.;Lapis,S.;Reeves, P. C. J. Org. Chem. 1974, 39, 1900–1902.
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ꢀ
tion of cross-coupling products: Yuan, Y.; Thome, I.; Kim, S. H.; Chen,
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J. Org. Chem. Vol. 76, No. 2, 2011 655

Cano et al.
JOCArticle
that of the related iodobenzene. Also, the influence of micro-
waves was tested.18 We found that the reaction time could be
shortened to 2 h, albeit the yield was lower with a broad
range of different byproducts (compare entries 2 and 12 in
Table 1). The nature of the base also has a great importance
on the obtained yields (entries 13-15 in Table 1). Thus, the
yield was surprisingly lower in the case of using sodium
hydroxide, meanwhile potassium tert-butoxide19 gave simi-
lar results to potassium hydroxide, and the reaction failed
with a weaker base such as potassium carbonate. Finally,
decreasing the temperature decreased the chemical yield and
increased the reaction time (compare entries 2 and 16 in
Table 1).
TABLE 2. N-Arylation of Aromatic Nitrogenated Heterocycles
It should be pointed out that copper (0.001%) and nickel
(0.001%) are impurities present in the KOH. This minor
amount (0.0025 mol % of copper) might be the true catalyst,
as it was previously demonstrated for the iron cases.5 How-
ever, in the case of the potassium tert-butoxide, copper impu-
rities are not present, with the reaction results being similar.
Despite that, we performed ICP-MS studies of the obtained
solution after running the reaction as in entry 14 in Table 1,
finding that the amount of copper was 5 ꢀ 10-10 mol %, and
palladium was not detected. Therefore, we are confident that
the possible impurities are not responsible for the reaction
depicted in this process.
2.2. N-Arylation Process. Once the best conditions were
found for this Ullmann process (entry 2 in Table 1), the same
protocol was applied to other substrates in order to study the
scope of the reaction (Table 2). Similar results were obtained
when different 4-substituted haloarenes were used as arylat-
ing agent, obtaining in all cases a 1:1 mixture of 3- and
4-substituted arenes 3, independently of the electronic nature
of the substituent (entries 2-4 in Table 2), and indicating
that the reaction probably proceeded by hydrogen iodide
elimination to form the corresponding substituted aryne,
followed by statistic nucleophilic addition of pyrazole 1a at
both possible positions. When the reaction was carried out
with 2-bromopyridine (2h), only the isomeric 2-pyridyl com-
pound 3e was obtained (Table 2, entry 5). However, when the
same protocol was employed with 3-iodopiridine a 1:1 mix-
ture of 3-:4-isomers was obtained with good yield (Table 2,
entry 6). Instead of pyrazole derivatives, other heterocyclic
compounds such as imidazole 1b and the benzo derivatives
1c and 1d could be used in the arylation process with use of
either iodobenzene (2a) or 2-bromopyridine (2h) without any
substantial changes in the results obtained (entries 7-11 in
Table 2).
aIsolated yield after 24 h of reaction time. bReaction performed
during 48 h. cA 1:1 mixture of isomers at 3- and 4-position was
detected.
SCHEME 1. Phenylation of Amines and Amides
Owing to the excellent result obtained in the phenylation
of morpholine (4b), we focused on the problem of double
substitution in diiodobenzene derivatives 6 (Scheme 2). The
reaction, using in these cases a double amount of base as well
as amine, gave a mixture of the isomeric products 7. When
the reaction was performed with 1,4-diiodobenzene (6a), the
diamine products 7 were obtained in good yields (80%) as a
1:10 mixture of para- and meta-disubstituted compounds 7a
and 7b, respectively. Surprisingly, when the same reaction
was performed with the related 1,3-diiodobenze (6b) the only
amine detected from the reaction crude was compound 7b,
which was isolated in a 83% yield. Finally, the reaction with
1,2-diiodobenzene did not afford any of the possible amines,
giving a mixture of decomposition products.
A similar protocol could be employed with aliphatic
secondary amines 4a,b only increasing the reaction time
(Scheme 1), obtaining the corresponding N,N-disubstituted
aniline derivatives 5a and 5b with excellent results. In the
case of using benzamide (4c) the above protocol rendered
the expected N-phenylbenzamide (5c) albeit in a lower
yield (68%).
Although our hypothesis of reaction pathway involved
the formation of benzyne intermediate by dehydrohalogena-
tion on the reaction media, we did not have any empirical
proof of it, and to discard another possible mechanism, as for
instance a direct nucleophilic aromatic substitution, we per-
formed the reaction with a very electronic poor arene such as
pentafluoroiodobenzene (8 in Scheme 3). The reaction with
(18) For examples of microwave-assisted hetero Ullmann reaction,
see: (a) Chow, W. S.; Chan, T. H. Tetrahedron Lett. 2009, 50, 1286–1289.
(b) Rolfe, A.; Hanson, P. R. Tetrahedron Lett. 2009, 50, 6935–6937. (c)
´
Colacino, E.; Villebrum, L.; Martınez, J.; Lamaty, F. Tetrahedron 2010,
66, 3730–3735.
(19) For the unique example of amination of aryl chlorides using potas-
sium tert-butoxide as base in toluene at 135 °C, see: Beller, M.; Breindl, C.;
Riermeir, T. H.; Tillack, A. J. Org. Chem. 2001, 66, 1403–1412.
656 J. Org. Chem. Vol. 76, No. 2, 2011

Cano et al.
JOCArticle
SCHEME 2. Double Coupling Process with 1,n-Diiodobenzenes
TABLE 3. O-Phenylation of Phenols and Alcohols
entry
R
product 11
yield (%)a
1
2
3
4
Ph
11a
11b
11c
11d
80b
88
83
53
4-MeOC6H4
4-ClC6H4
Me(CH2)6
aIsolated yield after flash chromatography. bReaction performed
during 5 days.
SCHEME 3. Arylation Process with Pentafluoroiodobenzene
TABLE 4. S-Phenylation of Thiophenols and Thioalcohols
entry
R
product 13
yield (%)a
1
2
3
Ph
4-MeC6H4
Me(CH2)7
13a
13b
13c
92
97
99
aIsolated yield after flash chromatography.
TABLE 5. Synthesis of 2-Substituted Benzoimidazole Derivatives
pyrazol (1a), under standard conditions, gave compound 9a,
with an excellent result, in which the hydrogen is located
at the para-position, as it was probed by 19F NMR experi-
ments. The reaction with either 2-methylimidazole (1b) or
morpholine gave the same type of product 9b and 9c in
excellent yields.
2.3. O-Arylation Process. Once we demonstrated that this
new transition-metal-free protocol could be used for stan-
dard N-arylation processes, we faced the problem of the
arylation of alcohols and phenols (Table 3). The reaction
with these oxygenated nucleophiles 10 gave the expected
phenyl ethers 11 with, in general, good yields, although the
reaction times should be increased. The results were practi-
cally the same, for the case of phenol derivatives indepen-
dently of the presence of substituents at the para-position, as
well as the electronic nature of this substituent, with the
protocol allowing the use of chlorinated phenols. The reac-
tion with aliphatic alcohols also produced the desired pro-
duct, although in lower yield (entry 4).
2.4. S-Arylation Process. Not only oxygenated nucleo-
philes but also sulfur-containing nucleophiles could be used
with this protocol also with good results (Table 4). As in the
previous cases, the yields were not affected by the presence of
substitution at the aromatic ring. Moreover, in the case of
high nucleophilic thiols, the yield obtained for the aliphatic
derivatives was as high as the one obtained for aromatic
ones.
entry
R
product 15
yield (%)a
1
2
3
Ph
4-ClC6H4
tBu
15a
15b
15c
70
60b
51b
aIsolated yield after flash chromatography. bReaction performed
during 5 days.
moderate to good yields (Table 5). The reaction times
were somehow longer, due to the weaker nucleophilicity of
carboxamides (see Scheme
1 and the corresponding
comment). The following cyclization process could be diffi-
cult due to a nonselective reaction with the benzyne inter-
mediate. However, in fact the yields were higher than 50%
showing that the addition of amide was quite selective, with
the possible N-(3-aminophenyl) amide derivative not
being detected in the reaction crude by 1H NMR and GC-
MS. Moreover, no formation of the corresponding 2-sub-
stituted benzo[d ]oxazole seems to indicate that the benzyne
formation takes places prior to the aniline derivatization by
reaction with the carboxamide.
A similar reaction with equimolecular amounts of com-
pound 14 and different isothiocyanato derivatives 16 gave
the expected N-substituted benzo[d]thiazol-2-amine deriva-
tives 17 in good yields (Table 6). As in all previous cases, the
yields were not affected by the nature of the nucleophile
2.5. Synthesis of Benzoazole Derivatives. Finally, the pro-
tocol was tested in the tandem process of arylation and
cyclization to prepare benzoimidazole derivatives, starting
from 2-iodoaniline (14). The reaction of equimolecular
amounts of primary amides (4c-e) with compound 14
gave the expected 2-substituted-1H-benzo[d]imidazole 15 in
J. Org. Chem. Vol. 76, No. 2, 2011 657

Cano et al.
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TABLE 6. Synthesis of N-Substituted-2-Benzothiazoleamine
Derivatives
1-(4-Methoxyphenyl)-1H-pyrazole and 1-(3-methoxyphenyl)-
1H-pyrazole (3b):20 Rf 0.27 (hexane/ethyl acetate 4:1); IR (film) ν
1592, 1520, 1241 cm-1; 1H NMR (300 MHz, CDCl3) δ 3.74, 3.76
(2s, 3 and 3H, respectively), 6.39-6.45 (m, 2H), 6.76-6.88 (m,
1H), 6.96-7 (m with d at 6.97, J = 9.6 Hz, 3H), 7.13-7.16 (m,
1H), 7.24-7.26 (m, 1H), 7.56-7.6 (d, J = 9 Hz, 2H), 7.69-7.7
(m, 2H), 7.81-7.82 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 55.4,
55.6, 106.2, 107.2, 107.8, 114.5, 114.9, 116, 117.9, 121, 127,
130.3, 133.9, 138.3, 140.5, 140.6, 150.7, 158.3; EI-MS m/z 175
(Mþ þ 1, 12%), 146 (Mþ, 100), 159 (68), 131 (22), 77 (12).
1-(p-Tolyl)-1H-pyrazole and 1-(m-tolyl)-1H-pyrazole (3c):20
Rf 0.43 (hexane/ethyl acetate 4:1); IR (film) ν 1615, 1520
cm-1; 1H NMR (300 MHz, CDCl3) δ 2.36, 2.40 (2s, 3 and 3H,
respectively), 6.42-6.44 (m, 2H), 7.71 (m, 1H), 7.23 (d, J =
9 Hz, 2H), 7.28-7.33, 7.43-7.46, 7.54-7.57 (3 m, 1, 1 and 3H,
respectively), 7.7-7.71 (m, 2H), 7.85-7.89 (m, 2H); 13C NMR
(75 MHz, CDCl3) δ 20.8, 21.4, 107.2, 107.4, 116.1, 119.1, 119.9,
126.6, 126.7, 127.1, 129.1, 129.8, 136.1, 137.9, 139.4, 140, 140.7,
140.8; EI-MS m/z 159 (Mþ þ 1, 12%), 158 (Mþ, 100), 157 (27),
130 (30), 91 (13), 65 (10).
entry
R
product 17
yield (%)a
1
2
3
Ph
3,5-(CF3)2C6H3
tBu
17a
17b
17c
80b
77
74
aIsolated yield after flash chromatography. bReaction performed
during 5 days.
(aromatic or aliphatic) or by the presence of substituents in
the case of aromatic substituents. Contrary to the previous
case, two possible mechanism pathways could be active,
since isothiocyanato derivatives have a higher electrophilic
character compared to carboxamides 4c-e.
1-(4-Chlorophenyl)-1H-pyrazole and 1-(3-chlorophenyl)-1H-
pyrazole (3d):20 Rf 0.47 (hexane/ethyl acetate 4:1); IR (film)
1
ν 1597, 1514, 1092 cm-1; H NMR (300 MHz, CDCl3) δ 6.48
3. Conclusions
(m, 2H), 7.13-7.43 (m, 5H), 7.57-7.65 (m, 3H), 7.74-7.76
(m, 2H), 7.88-7.92 (m, 2H); 13C NMR (75 MHz, CDCl3)
δ 107.9, 108, 115.9, 116.9, 119.4, 120.2, 126.3, 126.7, 129.4,
129.7, 130.4, 135.1, 138.2, 141.3, 141.4, 154.5; EI-MS m/z 180
(Mþ þ 1, 33%), 179 (Mþ, 13), 178 (100), 151 (15), 116 (13), 111
(19), 89 (11), 75 (15).
In conclusion, we have demonstrated that the arylation
process of different nucleophiles, including oxygen, sulfur,
and nitrogen derivatives, even with the related heterocyclic
compounds, could be successfully performed under basic
conditions in DMSO without the presence of a transition-
metal catalyst. These conditions are quite similar (in terms of
reaction times, amount of base, and temperature) to others in
which the use of metallic catalysts was required, highlighting
the superfluous effect of some catalyst in these transforma-
tions. The reaction could be performed with a broad range
of substrates, keeping the high level of the results, and
permits the easy entry to the synthesis of interesting benzo-
condensed heterocycles. Finally, it should be pointed out
that the reaction seems to follow a pathway in which a
benzyne is involved.
2-(1H-Pyrazol-1-yl)pyridine (3e):4c Rf 0.57 (hexane/ethyl
acetate 4:1); IR (film) ν 1615, 1603, 1571 cm-1 1H NMR
;
(300 MHz, CDCl3) δ 6.45 (m, 1H), 7.13 (t, J = 5.9 Hz, 1H),
7.73-7.79 (m, 2H), 7.96-7.99 (m, 1H), 8.38 (d, J = 4.7 Hz, 1H),
8.57 (d, J = 2.6 Hz, 1H); 13C NMR (75 MHz, CDCl3)
δ 107.6, 112.2, 121.2, 126.8, 138.5, 141.9, 147.9, 151.4; EI-MS
m/z: 146 (Mþ þ 1, 10%), 145 (Mþ, 100), 118 (32), 78 (74).
3-(1H-Pyrazol-1-yl)pyridine (3f):4c Rf 0.47 (ethyl acetate); IR
(film) ν 1589, 1528 cm-1; 1H NMR (300 MHz, CDCl3) δ 6.34
(t, J = 1.9 Hz, 1H), 7.38-7.42 (m, 1H), 7.62 (d, J = 2 Hz, 1H),
7.97 (d, J = 2.5 Hz, 1H), 8.05-8.07 (m, 1H), 8.53-8.55 (m, 1H);
13C NMR (75 MHz, CDCl3) δ 108.4, 123.9, 126.6, 126.8, 136.5,
140.3, 141.9, 147.3; EI-MS m/z 146 (Mþ þ 1, 10%), 145 (Mþ,
100), 118 (23), 91 (12), 78 (14).
4. Experimental Section
4-(1H-Pyrazol-1-yl)pyridine (3f0):21 mp 63-67 °C (ethyl acet-
ate/hexane); Rf 0.33 (ethyl acetate); IR (KBr) ν 1600, 1524 cm-1
;
4.1. General Procedure for the Arylation Processes. A pressure
tube was charged with the corresponding nitrogenated hetero-
cycle (1), amine (4), amide (4), alcohol (10), thiol (12), or
isothiocyanato derivatives (16, 1 mmol), KOH (2.5 mmol, 140 mg),
haloarene (2 or 14, 1 mmol), and dry DMSO (1.5 mL) under
argon atmosphere. The resulting mixture was stirred in an oil
bath at 120 °C until the end of the reaction. The mixture was
quenched with a saturated solution of NH4Cl and extracted with
ethyl acetate (2 ꢀ 10 mL). The organic phase was dried over
MgSO4, followed by evaporation under reduced pressure to
remove the solvent. The product was purified by column
chromatography on silica gel (decreasing hexane/ethyl acetate
ratio). Analytical, physical, and spectroscopic data, as well as
literature for known compounds, follow:
1H NMR (300 MHz, CDCl3) δ 6.53-6.55 (m, 1H), 7.64-7.66
(m, 2H), 7.78-7.79 (m, 1H), 8.04-8.05 (m, 1H), 8.65-8.67
(m, 2H); 13C NMR (75 MHz, CDCl3) δ 109, 112.4, 126.5, 142.5,
145.9, 151.2; EI-MS m/z 146 (Mþ þ 1, 10%), 145 (Mþ, 100), 144
(13), 118 (17), 78 (13).
2-Methyl-1-phenyl-1H-imidazole (3g):8c Rf 0.7 (hexane/ethyl
acetate 3:2); IR (film) ν 1596, 1502 cm-1; 1H NMR (300 MHz,
CDCl3) δ 2.34-2.35 (m, 3H), 6.99-7.01, 7.26-7.28, 7.4-7.49
(3 m, 2, 2, and 3H, respectively); 13C NMR (75 MHz, CDCl3)
δ 13.4, 120.3, 125.2, 127.2, 127.9, 129.2, 137.6, 144.3; EI-MS
m/z 159 (Mþ þ 1, 12%), 158 (Mþ, 100), 157 (29), 131 (10), 130
(39), 117 (15), 90 (22), 77 (28).
1-Phenyl-1H-benzo[d]imidazole (3h):17c Rf 0.13 (hexane/ethyl
1-Phenyl-1H-pyrazole (3a):4d Rf 0.82 (hexane/ethyl acetate
acetate 4:1); IR (film) ν 1712, 1589, 1509 cm-1 1H NMR
;
4:1); IR (melted) ν 1716, 1597 cm-1 1H NMR (300 MHz,
;
(300 MHz, CDCl3) δ 7.30-7.37, 7.43-7.6, 7.87-7.9 (3 m, 2, 6
and 1H, respectively), 8.12 (s, 1H); 13C NMR (75 MHz, CDCl3)
δ 110.4, 120.5, 122.8, 123.7, 124, 128, 130, 133, 136.3, 142.2,
143.9; EI-MS m/z 195 (Mþ þ 1, 14%), 194 (Mþ, 100), 193 (23).
1-(Pyridin-2-yl)-1H-benzo[d]imidazole (3i):8b Rf 0.5 (ethyl
CDCl3) δ 6.46 (t, J = 2 Hz, 1H), 7.28 (t, J = 8 Hz, 1H),
7.35-7.37, 7.68-7.72 (2 m, 2 and 3H), 7.92 (d, J = 2 Hz, 1H);
13C NMR (75 MHz, CDCl3) δ 107.6, 119.2, 126.4, 126.7, 129.4,
140.2, 141; EI-MS m/z 145 (Mþ þ 1, 11%), 144 (Mþ, 100), 143
(12), 117 (15), 116 (19), 90 (20), 77 (33), 50 (21).
acetate); IR (film) ν 1669, 1588 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 7.14-7.17 (m, 1H), 7.29-7.35 (m, 2H), 7.42 (d, J =
(20) Teo, Y. C.; Chua, G.-L. Chem.;Eur. J. 2009, 15, 3072–3075.
658 J. Org. Chem. Vol. 76, No. 2, 2011
(21) Khan, M. A.; Polya, J. B. J. Chem. Soc. C 1970, 85–91.

Cano et al.
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8.2 Hz, 1H), 7.72-7.76, 7.83-7.86, 8-8.03, 8.49-8.51 (4 m, 1, 1,
1 and 1H, respectively), 8.54 (s, 1H); 13C NMR (75 MHz,
CDCl3) δ 112.4, 113.7, 120.1, 121.3, 122.8, 123.7, 131.6, 138.5,
140.9, 144.2, 148.9, 149.3; EI-MS m/z 196 (Mþ þ 1, 14%), 195
(Mþ, 100), 194 (53), 169 (43), 78 (10).
(400 MHz, CDCl3) δ 2.32 (s, 3H), 6.96-6.97 (m, 1H), 7.12-
7.13 (m, 1H), 7.26 ppm (tt, 2JHF = 9.6 Hz, 3JHF = 7.2 Hz); 13
C
NMR (400 MHz, CDCl3) δ 12.8, 106.7 (t, 2JCF = 23 Hz), 118 (t,
2JCF = 15 Hz), 120.7, 129, 142.5 (ddd, 1JCF = 254 Hz, 2JCF = 14
Hz, 3JCF = 6 Hz), 145.8, 146.1 ppm (dtd, 1JCF = 252 Hz, 2JCF
=
1-Phenyl-1H-indole (3j):4b Rf 0.67 (hexane/ethyl acetate 4:1);
IR (film) ν 1591 cm-1; 1H NMR (300 MHz, CDCl3) δ 6.67 (d,
J = 2.6 Hz, 1H), 7.14-7.22, 7.31-7.33, 7.47-7.48 (3 m, 2, 2 and
4H, respectively), 7.55 (d, J = 7.9 Hz, 1H), 7.68 (d, J = 7.5 Hz,
1H); 13C NMR (75 MHz, CDCl3) δ 103.5, 110.5, 120.3, 121.1,
122.3, 124.3, 126.4, 127.9, 129.3, 129.6, 135.8, 139.8; EI-MS m/z
194 (Mþ þ 1, 15%), 193 (Mþ, 100), 192 (16); 165 (21).
1-(Pyridin-2-yl)-1H-indole (3k):9e Rf 0.6 (hexane/ethyl acetate
4:1); IR (film) ν 1688, 1606 cm-1; 1H NMR (300 MHz, CDCl3) δ
6.71-6.72, 7.14-7.22, 7.27-7.31, 7.48-7.51, 7.65-7.67, 7.72-
7.73, 7.79-7.83, 8.19-8.22, 8.56-8.58 (9 m, 1, 2, 1, 1, 1, 1, 1, 1
and 1H, respectively); 13C NMR (75 MHz, CDCl3) δ 105.4,
112.9, 114.3, 119.9, 120.9, 121.1, 123, 125.8, 130.3, 134.9, 138.2,
148.7, 152.3; EI-MS m/z 195 (Mþ þ 1, 15%), 194 (Mþ, 100), 193
(57), 167 (12).
3JCF = 11 Hz, JCF = 6 Hz); 19F NMR (282 MHz, CDCl3)
δ -137.3 (m, 2F), -146.5 (m, 2F); EI-MS m/z 231 (Mþ þ 1, 11%),
230 (Mþ, 12), 229 (11), 211 (28), 203 (10), 189 (15), 162 (18), 149
(21), 99 (23). HRMS calcd for C10H6F4N2 230.0467, found
230.0479. Anal. Calcd for C10H6F4N2: C, 52.18; H, 2.63; N, 12.17.
Found: C, 52.22; H, 2.64; N, 12.21.
4
4-(2,3,5,6-Tetrafluorophenyl)morpholine (9c):22 mp 81-85 °C
(ethyl acetate/hexane); Rf 0.6 (hexane/ethyl acetate 4:1); IR
(KBr) ν 1643, 1607, 1270, 1108, 1031, 947, 871 cm-1 1H
;
NMR (300 MHz, CDCl3) δ 3.27-3.29 (m, 4H), 3.82 (m, 4H),
6.71 (tt, 2JHF = 9.8 Hz, 3JHF = 7.2 Hz); 13C NMR (75 MHz,
CDCl3) δ 51.2, 67.3, 99 (t, 2JCF = 23 Hz), 130.5 (t, 2JCF = 11
Hz), 142.2 (ddt, 1JCF = 245 Hz, 2JCF = 13 Hz, 3JCF = 5.2 Hz),
146.5 (dtd, 1JCF = 245 Hz, 2JCF = 3JCF = 14 Hz, 4JCF = 4.4
Hz); 19F NMR (282 MHz, CDCl3) δ -140.7 (m, 2F), -151.6 (m,
2F); EI-MS m/z 235 (Mþ, 61%), 178 (12), 177 (100), 176 (69),
149 (14), 99 (10).
1-Phenylpyrrolidine (5a):4b Rf10.8 (hexane/EtOAc 4:1); IR
(film) ν 1609, 1509, 1362 cm-1; H NMR (300 MHz, CDCl3)
δ 1.87-2.06 (m, 4H), 3.15-3.33 (m, 4H), 6.53-6.55, 6.62-6.66,
7.18-7.22 (3 m, 2, 1 and 2H, respectively); 13C NMR (75 MHz,
CDCl3) δ 25.4, 47.4, 111.5, 115.2, 129, 147.8; EI-MS m/z 147
(Mþ, 72%), 146 (100), 104 (15), 91 (41), 77 (23).
Diphenyl ether (11a):8f Rf 0.9 (hexane/ethyl acetate 4:1); IR
(film) ν 1580, 1485, 1235, 867 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 6.95-7.02, 7.06-7.1, 7.25-7.38 (3 m, 4, 2 and 4H,
respectively); 13C NMR (75 MHz, CDCl3) δ 118.8, 123.2, 129.7,
157.2; EI-MS m/z 171 (Mþ þ 1, 13%), 170 (Mþ, 100), 169 (24),
142 (28), 141 (51), 115 (12), 77 (17).
4-Phenylmorpholine (5b):4d Rf 0.23 (hexane/ethyl acetate 4:1);
1
IR (film) ν 1591, 1502, 1253, 1110 cm-1; H NMR (300 MHz,
1-Methoxy-4-Phenoxybenzene (11b):8f Rf 0.63 (hexane/ethyl
CDCl3) δ 3.13-3.15 (m, 4H), 3.84-3.86 (m, 4H), 6.86-6.92,
7.23-7.29 (2 m, 3 and 2H, respectively); 13C NMR (75 MHz,
CDCl3) δ 49.2, 66.8, 115.6, 119.9, 129.1, 151.2; EI-MS m/z 163
(Mþ, 75%), 106 (10), 105 (100), 104 (41), 77 (24).
1
acetate 4:1); IR (film) ν 1585, 1230, 1183, 1154, 831 cm-1; H
NMR (300 MHz, CDCl3) δ 3.74 (s, 3H), 6.83-6.85, 6.91-6.97,
6.98-7.02, 7.24-7.27 (4 m, 2, 4, 1 and 2H, respectively); 13C
NMR (75 MHz, CDCl3) δ 55.4, 114.8, 117.5, 120.7, 122.3, 129.6,
150, 155.8, 158.4; EI-MS m/z 201 (Mþ þ 1, 15%), 200 (Mþ, 100),
185 (50), 129 (24), 77 (40), 51 (12).
N-Phenylbenzamide (5c):4d mp 138-143 °C (ethyl acetate/
hexane); Rf 0.53 (hexane/ethyl acetate 3:2); IR (KBr) ν 3339,
1656, 1596, 1522 cm-1 1H NMR (300 MHz, CDCl3) δ
;
1-Chloro-4-phenoxybenzene (11c):8f Rf 0.77 (hexane/ethyl
7.11-7.29, 7.32-7.38, 7.41-7.53, 7.57-7.65, 7.83-7.86, 8.09-
8.11 (6 m, 1, 2, 4, 2, 1 and 1H, respectively); 13C NMR (75 MHz,
CDCl3) δ 120.3, 124.6, 127, 128.7, 129, 131.8, 134.8, 137.8, 166;
EI-MS m/z 197 (Mþ, 52%), 105 (100), 77 (45), 51 (10).
1,4-Dimorpholinobenzene (7a):7a Rf 0.13 (hexane/ethyl acetate
3:2); IR (film) ν 1585, 1514, 1294, 1111, 850 cm-1; 1H NMR (300
MHz, CDCl3) δ 3.06-3.09, 3.85-3.88 (2 m, 8 and 8H, respec-
tively), 6.90 (s, 4H); 13C NMR (75 MHz, CDCl3) δ 50.4, 67,
117.3, 145; EI-MS m/z 249 (Mþ þ 1, 17%), 248 (Mþ, 100), 190
(36), 132 (34), 131 (11).
1
acetate 4:1); IR (film) ν 1578, 1234, 1161, 1092 cm-1; H NMR
(300 MHz, CDCl3) δ 6.82-6.93, 6.97-7, 7.07-7.12, 7.23-7.27,
7.3-7.34 (5 m, 2, 2, 1, 2 and 2H, respectively); 13C NMR (75 MHz,
CDCl3) δ118.9, 120, 123.6, 128.1, 129.7, 129.8, 155.9, 156.8; EI-MS
m/z 206 (33%), 205 (Mþ þ 1, 15%), 204 (Mþ, 100), 169 (10), 141
(46), 77 (25).
Heptyloxybenzene (11d):23 Rf 0.8 (hexane/ethyl acetate 4:1);
IR (film) ν 1603, 1509, 1241, 1034 cm-1; 1H NMR (300 MHz,
CDCl3) δ 0.89 (t, J = 6.9 Hz, 3H), 1.28-1.39, 1.41-1.48, 1.74-
1.81 (3 m, 6, 2 and 2H, respectively), 3.94 (t, J = 6.6, 2H),
6.88-7.02, 7.23-7.29 (2 m, 3 and 2H); 13C NMR (75 MHz,
CDCl3) δ 14.1, 22.6, 26, 29, 29.3, 31.8, 67.9, 114.5, 120.4, 129.4,
159.1; EI-MS m/z 192 (Mþ, 19%), 94 (100).
1,3-Dimorpholinobenzene (7b):19 Rf 0.2 (hexane/ethyl acetate
3:2); IR (film) ν 1585, 1264, 1116, 867 cm-1 1H NMR
;
(300 MHz, CDCl3) δ 3.13-3.16, 3.83-3.86, 6.46-6.49, 7.15-
7.25 (2 m, 8, 8, 3 and 1H, respectively); 13C NMR (75 MHz,
CDCl3) δ 49.6, 66.9, 103.8, 108.1, 129.7, 152.3; EI-MS m/z 249
(Mþ þ 1, 16%), 248 (Mþ, 100), 247 (11), 233 (24), 191 (15), 190
(41), 132 (48), 104 (10).
Phenylsulfanylbenzene (13a):11c Rf 0.77 (hexane/ethyl acetate
4:1); IR (film) ν 1568, 1479, 1437, 677 cm-1; 1H NMR (300 MHz,
CDCl3) δ 6.84-7.11, 7.18-7.35 (2 m, 6 and 4H, respectively);
13C NMR (75 MHz, CDCl3) δ 126.9, 129, 130.9, 135.7; EI-MS
m/z 187 (Mþ þ 1, 16%), 186 (Mþ, 100), 185 (78), 184 (33).
4-Phenylsulfanyltoluene (13b):11f Rf 0.77 (hexane/ethyl ace-
tate 4:1); IR (film) ν 1585, 1495, 1469, 690 cm-1; 1H NMR (300
MHz, CDCl3) δ 2.29 (s, 3H), 7.05-7.1, 7.11-7.15, 7.18-7.24,
7.25-7.29 (4 m, 2, 1, 4 and 2H, respectively); 13C NMR
(75 MHz, CDCl3) δ 21, 126.3, 128.9, 129.7, 130, 131.2, 132.2,
137, 137.4; EI-MS m/z 201 (Mþ þ 1, 16%), 200 (Mþ, 100), 199
(26), 185 (33), 184 (32), 167 (11), 91 (16).
1-(2,3,5,6-Tetrafluorophenyl)-1H-pyrazole (9a): Rf 0.73
(hexane/ethyl acetate 4:1); IR (KBr) ν 1650, 1618, 1194, 1179
cm-1; 1H NMR (300 MHz, CDCl3) δ 6.53-6.55 (m, 1H), 7.17
(tt, 2JHF = 9.7 Hz, 3JHF = 7.1 Hz), 7.72-7.73 (m, 1H), 7.83-
7.84 ppm (m, 1H); 13C NMR (300 MHz, CDCl3) δ 105 (t,
2
2JCF = 22.7 Hz), 107.7, 120.9 (t, JCF = 15 Hz), 132, 141.8
1
(ddd, JCF = 254 Hz, JCF = 16 Hz, JCF = 3.8 Hz), 142.3,
2
3
146.2 ppm (dtd, 1JCF = 249.1 Hz, 2JCF=3JCF=11 Hz, 4JCF
=
4.6 Hz); 19F NMR (282 MHz, CDCl3) δ -138.1 (m, 2F), -148.6
(m,2F);EI-MSm/z217 (Mþþ1, 10%), 216 (Mþ, 100), 189 (13), 162
(24), 149(23), 99(22);HRMScalcdforC9H4F4N2 216.0311, found
216.0310. Anal. Calcd for C9H4F4N2: C, 50.01; H, 1.87; N,
12.96. Found C, 50.09; H, 1.79; N, 12.89.
Octylsulfanylbenzene (13c):11b Rf 0.87 (hexane/ethyl acetate
4:1); IR (film) ν 1582, 691 cm-1; 1H NMR (300 MHz, CDCl3)
δ 0.87 (t, J = 6.6 Hz, 3H), 1.18-1.32, 1.36-1.43, 1.58-1.66
2-Methyl-1-(2,3,5,6-tetrafluorophenyl)-1H-imidazole (9b):
mp 131-135 °C (ethyl acetate/hexane); Rf 0.13 (hexane/ethyl
(22) Koppang, R. J. Fluorine Chem. 1975, 5, 323–333.
(23) Gasparini, F.; Caglioti, L.; Misiti, D.; Palmieri, G.; Ballini, R.
Tetrahedron 1982, 38, 3609–3613.
acetate 4:1); IR (KBr) ν 1513, 1072, 942 cm-1 1H NMR
;
J. Org. Chem. Vol. 76, No. 2, 2011 659

Cano et al.
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(3 m, 8, 2 and 2H, respectively), 2.88 (t, J = 7.3, 2H), 7.09-7.13,
7.2-7.24, 7.28-7.3 (3 m, 1, 2 and 2H, respectively); 13C NMR
(75 MHz, CDCl3) δ 14, 22.6, 28.8, 29, 29.1, 31.7, 33.4, 125.4,
128.6, 128.7, 137; EI-MS m/z 222 (Mþ, 50%), 123 (20), 110
(100), 109 (11).
CDCl3) δ 7.11-7.19 (m, 2H), 7.26 (s, 1H), 7.27-7.29, 7.31-
7.35, 7.39-7.43, 7.49-7.52, 7.57-7.59, 7.62-7.64 (5 m, 1, 2, 2,
1, and 1H, respectively); 13C NMR (75 MHz, CDCl3) δ 119.3,
120.2, 120.8, 122.4, 124.3, 126.1, 129.6, 129.8, 139.8, 151.3, 164.7;
EI-MS m/z 227 (Mþ þ 1, 15%), 226 (Mþ, 74), 225 (100).
N-(3,5-Bis(Trifluoromethyl)phenyl)benzo[d]thiazol-2-amine
(17b):13b mp 150-155 °C (ethyl acetate/hexane); Rf 0.43
(hexane/ethyl acetate 3:2); IR (KBr) ν 3188, 1615, 1579, 754,
715 cm-1; 1H NMR (300 MHz, acetone-d6) δ 7.1-7.14 (m, 1H),
7.26-7.30 (m, 1H), 7.5 (s, 1H), 7.59-7.61 (m, 1H), 7.67-7.7 (m,
1H), 8.42 (s, 2H), 9.97 (s, br, 1H); 13C NMR (75 MHz, CDCl3) δ
115.2, 118.2, 121, 121.7, 124, 124.3 (q, 1JCF = 271.4 Hz), 126.8,
131.1, 132.2 (2JCF = 32.2 Hz), 143.1, 152.6, 161.2; EI-MS m/z
363 (Mþ þ 1, 20%), 362 (Mþ, 100), 361 (85), 343 (11).
2-Phenyl-1H-benzo[d]imidazole (15a):8g mp 225-227 °C
(ethyl acetate/hexane); Rf 0.13 (hexane/ethyl acetate 3:2);
IR (KBr) ν 3416, 1585, 1538 cm-1 1H NMR (300 MHz,
;
DMSO-d6) δ 7.18-7.22, 7.46-7.5, 7.52-7.56, 7.66-7.68,
8.17-8.2 (5 m, 2, 1, 3, 1 and 2H, respectively), 13 (s, br,
1H); 13C NMR (75 MHz, DMSO-d6) δ 111.4, 118.9, 121.7,
122.6, 126.5, 129, 129.8, 130.2, 135, 143.8, 151.3; EI-MS m/z
195 (Mþ þ 1, 15%), 194 (Mþ, 100), 193 (26).
2-(4-Chlorophenyl)-1H-benzo[d]imidazole (15b):24 mp 282-
285 °C (ethyl acetate/hexane); Rf 0.4 (hexane/ethyl acetate
3:2); IR (KBr) ν 3423, 1602, 1598, 1534, 1082 cm-1; 1H NMR
(300 MHz, DMSO-d6) δ 7.2-7.26, 7.53-7.55, 7.62-7.65,
7.67-7.68, 8.18-8.21 (5 m, 2, 1, 2, 1 and 2H, respectively), 13
(s, br, 1H); 13C NMR (75 MHz, DMSO-d6) δ 111.9, 119.4, 122.3,
123.2, 128.6, 129.5, 135, 135.5, 144.2, 150.6, 170.8; EI-MS m/z
230 (34%), 229 (Mþ þ 1, 18), 228 (Mþ, 100), 227 (10), 193 (13).
2-tert-Butyl-1H-benzo[d]imidazole (15c):25 mp 287-290 °C
(ethyl acetate/hexane); Rf 0.43 (hexane/ethyl acetate 3:2); IR
N-tert-butylbenzo[d]thiazol-2-amine (17c):26 mp 91-95 °C
(ethyl acetate/hexane); Rf 0.6 (hexane/ethyl acetate 3:2); IR
(KBr) ν 3241, 1597, 1538, 754 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 1.49 (s, 9H), 5.25 (s, br, 1H), 7.03-7.09, 7.24-7.3,
7.52-7.55 (3 m, 1, 1 and 2H, respectively); 13C NMR (75 MHz,
CDCl3) δ 29, 53.3, 119, 120.4, 121.4, 125.7, 130.7, 152.4, 164.6;
EI-MS m/z 206 (Mþ, 23%), 151 (11), 150 (100).
Acknowledgment. This work was financially supported
by the Spanish Ministerio de Ciencia y Tecnologıa (Proyects
´
(KBr) ν 1592, 1535, 1400, 1365 cm-1 1H NMR (300 MHz,
;
CTQ2007-65218/BQU and Consolider Ingenio 2010 CSD2007-
00006) and Generalitat Valenciana (G.V. PROMETEO/
2009/039 and FEDER). R.C. thanks G.V. for a fellowship
through the PROMETEO program.
DMSO-d6) δ 1.4 (s, 9H), 7.1 (d, J = 3.9 Hz, 2H), 7.41 (d, J =
6.5 Hz, 1H), 7.53 (d, J = 6.5 Hz, 1H), 12.1 (s, br, 1H); 13C NMR
(75 MHz, DMSO-d6) δ 29.7, 33.6, 111.2, 118.7, 121.1, 121.8,
135, 143.2, 162.6; EI-MS m/z 174 (Mþ, 34%), 173 (24), 160 (12),
159 (100), 119 (13).
N-Phenylbenzo[d]thiazol-2-amine (17a):15a mp 161-163 °C
(ethyl acetate/hexane); Rf 0.13 (hexane/ethyl acetate 4:1); IR
1
Supporting Information Available: Copies of H and 13C
NMR for all compounds 3, 5, 7, 9, 11, 13, 15, and 17, as well as
copies of 19F NMR for compounds 9, and General Information.
This material is available free of charge via the Internet at http://
pubs.acs.org.
(KBr) ν 3230, 1621, 1597, 748 cm-1 1H NMR (300 MHz,
;
(24) Bahrami, K.; Khodaei, M. M.; Naali, F. J. Org. Chem. 2008, 73,
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(25) Deng, X.; McAllister, H.; Mani, N. S. J. Org. Chem. 2009, 74, 5742–
5745.
(26) Qian, W.; Jin, E.; Bao, W.; Zhang, Y. J. Chem. Res. 2005, 613–616.
660 J. Org. Chem. Vol. 76, No. 2, 2011