Chemistry of cyclopropenones: synthesis of new pyrrolo[2,1-b]-1,3,4-oxadiazoles

Article abstract of DOI:10.1016/j.tetlet.2008.04.066

2,3-Diphenylcyclopropenone (1) reacts with ylidene-N-phenylhydrazine-carbothioamides 2a-e to form the pyrrolo[2,1-b]-1,3,4-oxadiazoles 5a-e.

Full text of DOI:10.1016/j.tetlet.2008.04.066

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 4060–4062
Chemistry of cyclopropenones: synthesis of new
pyrrolo[2,1-b]-1,3,4-oxadiazoles
a,
a
a
b
*
Ashraf A. Aly , Alaa A. Hassan , Mohamed A. Ameen , Alan B. Brown
a Chemistry Department, Faculty of Science, El-Minia University, 61519 El-Minia, Egypt
b Chemistry Department, Florida Institute of Technology, 150 West University Boulevard, Melbourne, FL 32901, USA
Received 22 December 2007; revised 28 March 2008; accepted 10 April 2008
Available online 13 April 2008
Abstract
2,3-Diphenylcyclopropenone (1) reacts with ylidene-N-phenylhydrazine-carbothioamides 2a–e to form the pyrrolo[2,1-b]-1,3,4-oxadi-
azoles 5a–e.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Ylidene-N-phenylhydrazine-carbothioamides; 2,3-Diphenylcyclopropenone; [2+3] Cycloaddition; Pyrrolo[2,1-b]-1,3,4-oxadiazoles
2,3-Diphenylcyclopropenone (1) has been found to react
with a wide range of imines and other compounds contain-
ing the C@N moiety, usually to form pyrrolinones via for-
mal [2+3] cycloaddition reactions.1–8 Whilst investigating
the utility of compound 1 in heterocycle synthesis, we have
reported the synthesis of pyridazinethiones and 1,2,4-triaz-
olo[4,3-b]pyridazine-thiones from the reaction of thiose-
micarbazides with 1.9 Additionally, we have shown that
1 reacts with N-imidoylthioureas to form pyrimidin-4(3H)-
ones.10 We also noted that N-[2-(40-[2.2]paracyclophanyl)-
ethylidene]methylamine N-oxide reacted with 2,3-diphenyl-
cyclopropenones to produce [2.2]paracyclophane-based
pyrrole(-2-one, -thione and -ylidene-malononitrile) in good
yields via formal [3p+3p] cycloaddition.11 As part of our
research to synthesize heterocyclic compounds, we recently
synthesized a series of 1,3-thiazines by reactions of N-
aroylsubstituted thioureas with ethyl propiolate, dimethyl
but-2-ynedioate and (E)-1,4-diphenylbut-2-ene-1,4-dione.12
Recent literature13 has shown the utility of 1,3,4-oxadiazole
derivatives as ancillary ligands for highly efficient
OLEDs.13 In this letter, we report the cycloadditions of
substituted
ylidene-N-phenylhydrazine-carbothioamides
with 2,3-diphenylcyclopropenone (1), possibly followed
by further in situ cyclization of the adducts. Thus, on add-
ing glacial acetic acid solutions of 114 to ylidene-N-phen-
ylhydrazine-carbothioamides 2a–e (2a,15 2b,16 2c,17 2d18
and 2e19) in the same solvent, the reaction proceeds to give
2,5,6,7-tetrasubstituted-pyrrolo[2,1-b](1,3,5-oxadiazolyl)-2-
amines 5a–e in 60–76% yields20 (Scheme 1). We chose
compounds 2a–e having aryl groups with electron donating
and withdrawing substituents on the benzene ring, in order
to examine their reactivity. Moreover, we chose the thienyl
derivative 2d in order to generalize the idea beyond benze-
noid aromatics, to heterocycle-substituted starting materi-
als. The structural proof of 5a–e was based upon the
1
mass, H NMR, 13C NMR and IR spectra as well as ele-
mental analyses. For example, mass spectrometry and ele-
mental analysis proved the molecular formula of 5a as
C30H23N3O2. The IR spectrum did not reveal any absorp-
tions due to C@S or OH groups. However, a sharp band
appeared at mmax = 3290 cmꢀ1 due to the presence of an
amino group. An absorption band at mmax = 1080 cmꢀ1
1
was assigned to C–O stretching. In the H NMR spectrum
of 5a, the aromatic protons resonated as two double dou-
blets and four multiplets, respectively. Distinctive 13C
NMR signals of 5a appeared at d = 156.4, 142.0, 122.2,
*
Corresponding author. Tel./fax: +20 862346876.
E-mail addresses: ashrafaly63@yahoo.com, ashraf160@yahoo.com
(A. A. Aly).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.066

A. A. Aly et al. / Tetrahedron Letters 49 (2008) 4060–4062
4061
R
O
H
H
H
H
N
H
H
N
Ph
N
C
AcOH
4-8 h
N
N
+
Ph
N
R
Ph
Ph
Ph
N
S
S
1
+
O
Ph
2a-e
H
3a-e
R
R
Yield of 5 (%)
R
2-5
5
H
a
b
c
d
e
4-H3CO-C6H4-
4-HO-C6H4-
4-Cl-C6H4-
2-Thienyl-
C6H5-
76
72
64
60
70
Ph
Ph
- H2S
N
N
N
2
PhHN
1
7a
PhHN
O
O
Ph
Ph
HS
5a-e
4a-e
Scheme 1. Mechanism for the formation of pyrrolo[2,1-b]-1,3,4-oxadiazoles 5a–e.
15. Prakash, K. M. M. S.; Prabhakar, L. D.; Reddy, D. V. Anal. Lett.
1987, 20, 959.
16. Wang, J. T.; Zhang, Y. W.; Xu, Y. M.; Wang, Z. W. Heteroat. Chem.
1995, 6, 443.
17. Bechert, R.; Gruner, M. G.; Seidel, I.; Kuban, R. Monatsh. Chem.
1989, 120, 1125.
18. Jouad, E. M.; Allain, M.; Khan, M. A.; Bouet, G. M. J. Mol. Struct.
2002, 604, 205.
19. Kaushik, N. K.; Mishra, A. K. Indian J. Chem. 2003, 42A, 2762.
20. General procedure: To a 250 cm3 two-necked round-bottomed flask
containing a solution of 2a–e (2 mmol) in glacial acetic acid (100 mL),
a solution of 1 (0.412 g, 2 mmol) in glacial acetic acid (10 mL) was
added dropwise with stirring. The mixture was stirred at room
temperature for 1 h, and then at reflux for 4–8 h (the reaction was
monitored by TLC). The solvent was evaporated under vacuum and
the solid residue was dissolved in dry acetone (30 mL) and the
solution was chromatographed on thin layer plates (silica gel) using
toluene/ethyl acetate (10:1). The mobile phases containing products
5a–e were extracted and the obtained products were recrystallized
from the stated solvents.
120.0, 117.0 and 51.0 corresponding to C-2, NH–Ph C, C-
7, C-5, C-7a and OCH3, respectively. Four carbon signals
of the thiophene moiety were assigned in the 13C NMR
spectrum of 5d at d = 136.6, 126.8, 125.6 and 124.2 corre-
sponding to thiophene-C-2, thiophene-C-3-H, thiophene-
C-5-H and thiophene-C-4-H, respectively. The structure
of the products obtained (Scheme 1) supports the formal
[2+3] cycloaddition pathway proposed by Eicher1–4 to
form adducts 3a–e. Thereafter, cyclization of 3a–e together
with aromatization of the pyrrole ring is proposed to
furnish intermediates 4a–e. Ultimately, intermediates 4a–e
lose a molecule of hydrogen sulfide to form the stable
heterocycles 5a–e (Scheme 1).
In conclusion, ylidene-N-phenylhydrazine-carbothioami-
des react with 2,3-diphenylcyclopropenone by way of an
initial [2+3] cycloaddition followed by a cyclization
process.
[6,7-Diphenyl-5-(40-methoxyphenyl)-pyrrolo[2,1-b]oxadiazolyl]-2-phe-
nylamine (5a). Orange crystals (0.70 g, 76%), mp 222 °C (ethanol). 1H
NMR (400 MHz, CDCl3): d = 8.82 (s, 1H, NH), 7.90 (dd, 2H, J =
8.00, 1.0 Hz, Ar-H), 7.50–7.20 (m, 9H, Ph–H), 7.00–6.84 (m, 6H, Ph–
H), 6.72 (dd, 2H, J = 8.0, 1.0 Hz, Ar-H), 3.90 (s, 3H, OCH3). 13C
NMR (400 MHz, CDCl3): d = 156.4 (C-2), 152.0 (Ar-C–O), 142.0
(NH–Ph C), 136.2 (O–Ph C), 134.8 (O–Ph 2CH), 134.4 (C-7, Ph C),
132.6 (C-6, Ph C), 132.0, 128.0 (ortho-2Ph CH), 127.2, 127.0, 126.6
(meta-Ph 2CH), 125.8 (O–Ph 2CH), 123.8, 123.6, 123.4 (para-Ph CH),
123.0 (C-6), 122.2 (C-7), 120.8 (C-2, NH–Ph 2CH), 120.0 (C-5), 117.0
(C-7a), 51.0 (OCH3). IR (KBr): mmax = 3290 (m, NH), 3080–3008 (w,
Ar-CH), 2980–2860 (m, aliph.-CH), 1612 (s, C@N), 1590 (m, C@C),
1080 (s, C–O) cmꢀ1. kmax (CH3CN, lge, nm): 440 (4.2). MS (EI): m/z
(%) = 457 [M+] (100), 440 (64), 380 (24), 338 (22), 302 (24), 279 (14),
220 (18), 178 (68), 152 (24), 119 (34), 85 (24), 77 (30). Anal. Calcd for
C30H23N3O2 (457.54): C, 78.76; H, 5.07; N, 9.18. Found: C, 78.86; H,
5.10; N, 9.10.
Acknowledgement
Professor Dr. Ashraf A. Aly thanks the DAAD founda-
tion for financial support to stay in Germany, Braun-
schweig University, Institute for Organic Chemistry.
References and notes
1. Eicher, T.; Weber, J. L. Top. Curr. Chem. 1975, 57, 1.
2. Eicher, T.; Weber, J. L. Tetrahedron Lett. 1974, 1381.
3. Eicher, T.; Abdesaken, F.; Franke, G.; Weber, J. L. Tetrahedron Lett.
1975, 3915.
4. Eicher, T.; Weber, J. L.; Chatila, G. Liebigs Ann. Chem. 1978, 1203.
5. Eicher, T.; Krause, D. Tetrahedron Lett. 1979, 1213.
6. Eicher, T.; Franke, G. Liebigs Ann. Chem. 1981, 1337.
7. Deem, M. L. Synthesis 1982, 701.
8. Musicki, B. J. Org. Chem. 1991, 56, 110.
9. Aly, A. A.; Hassan, A. A.; Gomaa, M. A.-M.; El-Sherief, E. M.
Arkivoc 2007, xiv, 1.
10. Aly, A. A.; Nour El-Din, A.-M.; Gomaa, M. A.-M.; Brown, A. B.;
Fahmi, M. S. J. Chem. Res. 2007, 439.
11. Aly, A. A. J. Chem. Res. 2007, 451.
12. Aly, A. A.; Ahmed, E. K.; El-Mokadam, K. M. J. Heterocycl. Chem.
2007, 44, 1431.
13. Chen, L.; You, H.; Yang, C.; Ma, D.; Qin, J. Chem. Commun. 2007,
1352.
14. Compound 1 was bought from Aldrich.
[6,7-Diphenyl-5-(20-hydroxyphenyl)-pyrrolo[2,1-b]oxadiazolyl]-2-phe-
nylamine ( 5b). Orange plates (0.64 g, 72%), mp 240–242 °C (meth-
anol). 1H NMR (400 MHz, CDCl3): d = 9.50 (s, 1H, OH), 8.80 (s, 1H,
NH), 7.56 (d, 1H, J = 1.0 Hz, ortho-OHAr-H), 7.45–7.30 (m, 4H, Ph–
H), 7.20–7.00 (m, 9H, Ph–H), 6.80–6.60 (m, 5H, Ph–H). 13C NMR
(100.6 MHz, CDCl3): d = 156.0 (C-3), 141.6 (NH–Ph C), 140.2 (HO-
Ar-C-40), 136.2 (HO-Ar-C-10), 134.0 (C-7, Ph C), 132.6 (C-6, Ph C),
132.4 (ortho-HOAr 2CH), 131.6, 127.8, 127.0 (ortho-2Ph CH), 127.0,
126.8, 126.4 (meta-Ph 2CH), 124.2, 124.0,123.6 (para-Ph CH), 123.4
(C-6), 122.5 (C-7), 120.6 (C-2, NH–Ph 2CH), 120.2 (C-5), 117.4 (C-7a).
IR (KBr): mmax = 3465 (m, OH), 3280 (m, NH), 3080–3012 (w, Ar-
CH), 1610 (s, C@N), 1594 (m, C@C), 1450 (s), 1075 (m, C–O) cmꢀ1
max (CH3CN, lge, nm): 460 (4.4). MS (EI): m/z (%) = 444 [M+1] (40),
.
k

4062
A. A. Aly et al. / Tetrahedron Letters 49 (2008) 4060–4062
443 [M+] (100), 426 (38), 412 (22), 380 (24), 330 (26), 192 (40), 118 (26),
94 (36), 77 (30). Anal. Calcd for C29H21N3O2 (443.51): C, 78.54; H,
4.77; N, 9.47. Found: C, 78.40; H, 4.70; N, 9.38.
(2-thiophene C), 133.6 (C-7, Ph C), 132.8 (C-6, Ph C), 128.6, 128.2,
127.8 (ortho-2Ph–CH), 127.6, 127.4, 127.0 (meta-2Ph–CH), 126.8 (3-
thiophene-CH), 126.4, 126.0, 125.8 (para-Ph–CH), 125.6 (5-thio-
phene-CH), 124.2 (4-thiophene-CH), 123.6 (C-7), 122.8 (C-6), 120.4
(C-5),118.0 (C-7a). IR (KBr): mmax = 3320 (s, NH), 3170–3020 (w,
Ar-CH), 1610 (s, C@N), 1586 (s, C@C), 1120 (C-S), 1070 (s, C–O),
cmꢀ1. kmax (CH3CN, lge, nm): 466 (3.6). MS (EI): m/z = 433 [M+]
(60), 350 (100), 304 (34), 226 (30), 192 (26), 118 (24), 92 (34), 124 (20),
77 (46). Anal. Calcd for C27H19N3OS (433.54): C, 74.80; H, 4.42; N,
9.69; S, 7.40. Found: C, 74.67; H, 4.50; N, 9.60; S, 7.30.
(5,6,7-Triphenyl-pyrrolo[2,1-b]-1,3,4-oxadiazolyl)-2-phenylamine ( 5e).
Orange crystals (0.60 g, 70%), mp 250 °C (ethyl acetate). 1H NMR
(400 MHz, DMSO-d 6): d = 8.90 (s, 1H, NH), 7.60–7.30 (m, 10H,
Ph–H), 7.10–6.90 (m, 5H, Ph–H), 6.80–6.74 (m, 5H, Ar-H). 13C NMR
(100.6 MHz, DMSO-d6): d = 156.0 (C-2), 142.0 (NH–Ph C), 134.0
(C-7, Ph C), 132.4 (C-6, Ph C), 132.0 (C-5, Ph C), 128.6, 128.0, 127.6,
127.4 (ortho-2Ph CH), 127.0, 126.6, 126.4, 126.2 (meta-Ph 2CH),
125.6, 124.8, 124.4, 123.8 (para-Ph CH), 123.5 (C-7), 122.6
(C-6), 120.6 (C-5), 118.2 (C-7a). IR (KBr): mmax = 3295 (m, NH),
3080–3008 (w, Ar-CH), 1612 (s, C@N), 1590 (m, C@C), 1450 (s), 1072
(m, C–O) cmꢀ1. kmax (CH3CN, lge, nm): 438 (4.4). MS (EI): m/z
(%) = 427 [M+] (100), 410 (20), 350 (34), 324 (22), 274 (34), 256 (18),
220 (18), 178 (68), 152 (24), 118 (40), 77 (36). Anal. Calcd for
C29H21N3O (427.51): C, 81.48; H, 4.95; N, 9.83. Found: C, 81.30; H,
4.90; N, 9.76.
[6,7-Diphenyl-5-(40-chlorophenyl)-pyrrolo[2,1-b]oxadiazolyl]-2-phen-
ylamine (5c). Orange crystals (0.59 g, 64%), mp 298 °C (acetonitrile).
1H NMR (400 MHz, CDCl3): d = 8.85 (s, 1H, NH), 7.46–7.22 (m,
9H, Ph–H), 6.90–6.70 (m, 8H, Ph–H), 6.50 (dd, 2H, J = 8.0, 1.0 Hz,
Ar-H). 13C NMR (100.6 MHz, CDCl3): d = 156.0 (C-2), 141.5 (NH–
Ph C), 133.4 (C-7, Ph C), 131.4 (C-6, Ph C), 130.0 (C-5, Ph C), 128.2,
128.0, 127.8 (ortho-2Ph CH), 127.0, 126.8, 126.4 (meta-Ph 2CH),
126.0 (Cl-Ar C), 123.8, 123.6, 123.0 (para-Ph CH), 122.6 (C-6), 122.0
(C-7), 121.8, 121.4 (Cl-Ar 2CH), 120.4 (C-5), 118.0 (C-7a). IR (KBr):
m
max = 3286 (m, NH), 3060–3000 (w, Ar-CH), 1610 (s, C@N), 1592
(m, C@C), 1070 (s, C–O), cmꢀ1. kmax (CH3CN, lge, nm): 442 (4.3).
MS (EI): m/z (%) = 463 [M+2] (34), 461 [M+] (100), 448 (24), 439
(64), 342 (26), 340 (32), 278 (14), 276 (18), 220 (18), 178 (60), 152 (20),
134 (30), 120 (34), 114 (32), 118 (34), 112 (34), 77 (26). Anal. Calcd for
C29H20ClN3O (461.96): C, 75.40; H, 4.36; Cl, 7.67; N, 9.10. Found:
C, 75.30; H, 4.30; Cl, 7.60; N, 9.12.
(6,7-Diphenyl-5-thiophen-20-yl-pyrrolo[2,1-b]oxadiazolyl)-2-phenyla-
mine (5d). Orange plates (0.52 g, 60%), mp 180 °C (methanol). 1H
NMR (400 MHz, CDCl3): d = 8.86 (s, 1H, NH), 7.66–7.52 (m, 7H,
Ph–H), 7.50 (dd, 1H, J = 7.6, 1.0 Hz), 7.30 (dd, 1H, J = 7.6, 1.0 Hz),
7.20–6.90 (m, 8H, Ph–H), 6.84 (t, 1H, J = 7.6 Hz). 13C NMR
(100.6 MHz, CDCl3): d = 156.8 (C-2), 141.8 (NH–Ph C), 136.6