Synthesis and chemical characterisation of some new diheteroaryl thienothiophene derivatives

Article abstract of DOI:10.3390/molecules16097706

Treatment of 1-(5-acetyl-3,4-dimethythieno[2,3-b]thiophene-2yl)ethanone (1) with dimethylformamide dimethyl acetal afforded enaminone derivative 2, which reacted with amino derivatives to give the corresponding bis-pyrimidine, bis-pyrazole, bis-triazolo-p

Full text of DOI:10.3390/molecules16097706

Molecules 2011, 16, 7706-7714; doi:10.3390/molecules16097706
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Synthesis and Chemical Characterisation of Some New
Diheteroaryl Thienothiophene Derivatives
Yahia Nasser Mabkhot *, Abdullah Mohammad Al-Majid and Abdullah S. Alamary
Department of Chemistry, Faculty of Science, King Saud University, P.O. Box 2455, Riyadh 11451,
Saudi Arabia
* Author to whom correspondence should be addressed; E-Mail: yahia@ksu.edu.sa.
Received: 10 June 2011; in revised form: 15 August 2011 / Accepted: 5 September 2011 /
Published: 8 September 2011
Abstract: Treatment of 1-(5-acetyl-3,4-dimethythieno[2,3-b]thiophene-2yl)ethanone (1) with
dimethylformamide dimethyl acetal afforded enaminone derivative 2, which reacted with amino
derivatives to give the corresponding bis-pyrimidine, bis-pyrazole, bis-triazolo-pyrimidine and
bis-benzoimidazopyrimidine derivatives.
Keywords: bis-heterocycles; DMF-DMA; bis-pyrimidine; bis-pyrazole; bis-triazolo
pyrimidine
1. Introduction
In the last 30 years, annulated heterocyclic systems have attracted considerable attention both from
a theoretical standpoint and in view of their various practical applications [1-14]. Enaminones are
valuable intermediates in synthetic organic chemistry [15-18], and Mabkhot and others [19-26]
have reported a variety of syntheses of heteroaromatics developed using functionally substituted
enaminones as readily obtainable building blocks possessing multiple electrophilic and nucleophilic
moieties. This study was undertaken in continuation of our interest in the chemical and biological
properties of thienothiophene derivatives [27-29] and our work aimed at the synthesis of
a variety of heterocyclic systems for biological and pharmacological evaluation, we have found that
1-(5-acetyl-3,4-dimethylthieno[2,3-b]-thiophene-2-yl) ethanone (1) is a versatile, readily accessible
building block for the synthesis of several new bis-heterocyclic compounds.

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2. Results and Discussion
Treatment of 1-(5-acetyl-3,4-dimethythieno[2,3-b]thiophene-2-yl)ethanone (1) with dimethylformamide
dimethylacetal (DMF-DMA) in refluxing ethanol afforded 1,1'-(3,4-dimethylthieno[2,3-b]thiophene-
13
2,5-diyl)-bis(3(dimethylamino)prop-2-en-1-one (2) in high yield (Scheme 1). The C-NMR spectrum
of compound 2, revealed ten carbon types. The 1H-NMR spectrum displayed a singlet at δ 2.22 due to
methyl protons, a singlet at δ 2.82 due to the N,N-dimethyl protons and at δ 5.36, 5.40 (d, 2H, CH,
J = 16), 7.62, 7.66 (d, 2H, CH, J = 1) due to olefinic protons. The mass spectrum revealed a molecular
ion peak at m/z 363, corresponding to C18H22N2O2S2. When compound 2 was treated with hydrazine
hydrate or phenylhydrazine in refluxing ethanol/DMF the novel products 3a,b were obtained,
respectively, which then undergo intramolecular cyclization and subsequent aromatization via the loss
of dimethylamine and water molecules (Scheme 1). The structures of the latter products were deduced
from their elemental analyses and spectral data. The 1H-NMR spectrum of compound 3a, for example,
revealed signals at δ 5.47 (d, 2H, CH, J = 5.5), 7.86 (d, 2H, CH, J = 5.5) and 13.20 characteristic of
pyrazole CH protons and a NH proton, respectively.
Scheme 1. Synthesis of enaminone 2 and pyrazole thienothiophene derivatives 3a,b.
Me
Me
DMF - DMA
xylene
S
S
N
N
S
S
O
O
Me
2
Me
O
O
1
R
3
a
H
b
Ph
H
H
Me
H
H
H
Me
S
S
S
S
- 2H2O
N
N
O
O
N
N
-2NH-(Me)2
Me
H
N
R
N
R
Me
N-NH2
NH2-N
R
R
3a, b
When compound 2 was treated with guanidine, thiourea and or urea in refluxing EtOH/DMF, the
the expected derivatives 4a-c were not obtained, and rather the novel bis-thienothiophene derivatives
5a-c were formed, which then undergo intramolecular cyclization and subsequent aromatization via the
loss of dimethylamine and water molecules under the reaction conditions to give 5a-c, as depicted in
Scheme 2.

Molecules 2011, 16
Scheme 2. Synthesis of pyrimidine thienothiophene derivatives 5a-c.
7708
Me
Me
S
S
N
N
O
O
Me
2
Me
XH
NH2
X
HN
H2N
NH2
H
H
H
H
Me
Me
Me
S
S
Me
S
S
N
N
N
O
N
O
O
O
Me
Me
X
Me
N
Me
X
N
HN
H2N
NH
NH2
H2N
HX
NH2
XH
- 2H2O -2NH-(Me)2
- 2H2O
-2NH-(Me)2
H
H
H
H
S
S
S
S
N
N
X
N
N
N
XH
N
X
XH
NH
NH
4a-c
5a-c
x
5
a
b
NH
S
c
O
The structures of the latter products were deduced from their elemental analyses and spectral data.
The IR spectrum of compound 5a, for example, showed, the absence of carbonyl bands and revealed the
appearance of bands in the 3,417 and 3,100 cm−1 region due to NH2 groups. The structure of product 5a
was confirmed by the 1H-NMR spectrum, which displayed a new pair of doublet signals at δ 7. 83, 8.37
with J = 12 Hz corresponding to pyrimidine CH protons, as reported for such E-coupled protons [30-32].
The 1H-NMR spectrum also revealed one singlet corresponding to a methyl group at δ 2.21, in addition
to the NH2 protons at δ 4.83 in Scheme 2. The formation of compound 5a would involve an initial

Molecules 2011, 16
7709
addition of the amino group in guanidine to the activated double bond in enaminone derivative 2,
followed by deamination to an intermediate which then undergoes cyclization and aromatization via
loss of water affording the final isolable product (Scheme 2).
The compound 7,7'-(3,4-dimethylthieno[2,3-b]thiophene-2,5-diyl) bis-[1,2,4]triazolo[1,5-a] pyrimidine (6)
was formed initially via Michael type addition followed by elimination of dimethylamine and water
molecules when treatment of compound 2 with 5-amino-1,2,4-triazole in refluxing ethanol/DMF
afforded in (Scheme 3).
Scheme 3. Synthesis of triazolo and benzoimidazolo pyrimidine thienothiophene
derivatives 6 and 7.
1
In the H-NMR spectra of compound 6 the CH proton appeared as a pair of doublets at
7.66/7.69 ppm (d, 2H, CH, J = 12 Hz), and 9.09/9.12 ppm (d, 2H, CH, J = 12 Hz) due to vicinal
coupling with the two magnetically non-equivalent protons of the methylene group at position 5 and 6
1
of the pyrimidine ring. Also, the H-NMR spectrum showed one singlet corresponding to a methyl
group at δ 2.24, in addition to the CH proton of triazole at δ 8.62. The mass spectrum revealed a

Molecules 2011, 16
7710
molecular ion peak at m/z 404, corresponding to C18H12N8S2. In a similar manner, when 2 was treated
with 2-aminobenzimidazole, the corresponding compound 7 was obtained in high yield.
3. Experimental
3.1. General
All melting points were measured on a Gallenkamp melting point apparatus. The infrared spectra
were recorded in potassium bromide disks on a Pye Unicam SP 3300 or Shimadzu FT IR 8101 PC
infrared spectrophotometers. The NMR spectra were recorded on a Varian Mercury VX-400 NMR
1
13
spectrometer. H spectra were run at 400 MHz and C spectra were run at 75.46 MHz in dimethyl
sulphoxide (DMSO-d6). Chemical shifts were related to that of the solvent. Mass spectra were
recorded on a Shimadzu GCMS-QP 1000 EX mass spectrometer at 70 e.V. Elemental analyses were
carried out at the Microanalytical Center of King Saud University, Riyadh, Saudi Arabia.
1,1'-(3,4-Dimethylthieno[2,3-b]thiophene-2,5-diyl)bis(3-(dimethylamino)prop-2-en-1-one (2): A mixture
of compound 1 (10 mmol, 0.252 mg) and DMF-DMA (20 mmol, 5 mL) in 99.9% EtOH (20 mL) was
refluxed for 8 h, then left to cool to room temperature. The reddish-brown precipitate was filtered off,
washed with petroleum ether, and dried. Recrystallization from DMF/EtOH afforded the enaminone
derivative 2 in 97% yield, mp. 270–272 °C; IR 1620 (C=O) 1546 (C=C) cm−1; 1H-NMR δ 2.22 (s, 6H,
2CH3), 2.82 (12H, 2CH3), 5.36, 5.40 (d, 2H, CH, J = 16), 7.62, 7.66 (d, 2H, CH, J = 16); 13C-NMR δ
15.6, 44.3, 90.4, 136.0, 138.6, 141.5, 147.7, 186.9, 155.3; MS m/z (%): 363 (M+1, 37), 362 (M, 100),
347 (84), 318 (10), 284 (6), 98 (100). Anal. Calcd for C18H22N2O2S2 (362.51); C, 59.64; H, 6.12;
N, 7.73; S, 17.69. Found: C, 59.58; H, 5.82; N, 7.44; S, 17.39.
3.2. General Procedure for the Reaction of Compound 2 with Hydrazine Derivatives
Treatment of compounds 2 (1 mmol) with hydrazine hydrate or phenyl hydrazine (0.1 mL) in dry
ethanol (20 mL) under reflux for 7 h afforded the corresponding derivatives 3a and 3b, respectively.
The solid products were collected by filteration, washed with ethanol, dried and recrystallized from
DMF/EtOH.
3,3'-(3,4-Dimethylthieno[2,3-b]thiophene-2,5-diyl)bis(1H-pyrazole) (3a): White crystals; yield 92%;
mp > 320 °C; IR 3186 (NH), 1549 (C=N) cm−1; 1H-NMR δ 2.10 (s, 6H, 2CH3), 5.47, 5.50 (d, 2H, CH,
13
J = 5.5), 7.83, 7.86 (d, 2H, CH, J = 5.5), 13.20 (2H, pyrazole N-H); C-NMR δ 14.3, 103.2, 127.2,
130.2, 133.5, 145.7, 148.3, 161.9; MS m/z (%): 301 (M+1, 24), 300 (M, 100), 284 (19), 233 (68). Anal.
Calcd for C14H12N4S2 (300.40); C, 55.97; H, 4.03; N, 18.65; S, 21.35. Found: C, 55.67; H, 3.73;
N, 18.38; S, 21.05.
3,3'-(3,4-Dimethylthieno[2,3-b]thiophene-2,5-diyl)bis(1-phenyl-1H-pyrazole) (3b): Red crystals; yield
1
(87%); mp > 320 °C; IR 1568 (C=N) cm−1; H-NMR δ 2.18 (s, 6H, 2CH3), 6.28, 7.16, 7.42 (5H,
ArH’s), 6.77, 6.80 (d, 2H, CH, J = 12), 8,20, 8.23 (d, 2H, CH, J = 12); 13C-NMR δ 15.5, 105.5, 120.3,
121.8, 123.6, 125.4, 128.1, 131.5, 135.1, 146.8, 149.3, 162.1; MS m/z (%): 453 (M+1, 91), 452

Molecules 2011, 16
7711
(M, 100), 437 (39), 375 (25). Anal. Calcd for C26H20N4S2 (452.11); C, 69.00; H, 4.45; N, 12.38;
S, 14.17. Found: C, 68.70 H, 4.18; N, 12.08; S, 13.88.
3.3. General Procedure for the Reaction of Compound 2 with Guanidine, Thiourea and Urea
Treatment of compound 2 (1 mmol) with guanidine, thiourea or urea (2 mmol) after making sure
they dissolve in DMF (2 mL) in dry ethanol (20 mL, 99.9%), under reflux for 6-8 h. afforded the
corresponding derivatives 5a-c respectively. After the solid products were collected by filtration,
washed with ethanol, dried and recrystallized from DMF/EtOH.
4,4'-(3,4-Dimethylthieno[2,3-b]thiophen-2,5-diyl)bis(pyrimidine-2-amine) (5a): Brown crystals; yield
71%; mp. 304–306 °C; IR 3417, 3326 (NH2), 1556 (C=N) cm−1; 1H-NMR δ 2.21 (s, 6H, CH3), 4.83 (s,
4H, NH2), 7.83 (d, 2H, CH, J = 5.5 Hz), 8.37 (d, 2H, CH, J = 5.5 Hz); 13C-NMR δ 14.92, 102.6, 126.9,
134.1, 135.9, 144.5, 148.2, 158.5, 162.1; MS m/z (%): 355 (M+1, 7), 354 (M, 18), 339 (21), 322 (16).
Anal. Calcd for C16H14N6S2 (354.07); C, 54.22; H, 3.98; N, 23.71; S, 18.09. Found: C, 53.92 H, 3.68;
N, 23.68; S, 17.82.
4,4'-(3,4-Dimethylthieno[2,3-b]thiophen-2,5-diyl)bis(pyrimidine-2-thiol) (5b): Dark yellow crystals;
1
Yield (88%); mp. > 320 °C; IR 3282 (SH), 1622 (C=N) cm−1; H-NMR δ 2.28 (s, 6H, CH3), 7.12, (d,
13
2H, CH, J = 5.5 Hz), 8.35 (d, 2H, CH, J = 5.5 Hz), 11.82 (2H, SH); C-NMR δ 16.3, 107.7, 125.6,
136.3, 137.1, 144.8, 149.1, 159.7, 161.1; MS m/z (%): 389 (M+1, 67), 388 (M, 78), 354 (6), 277 (31).
Anal. Calcd for C16H12N4S4 (388.55); C, 49.46; H, 3.11; N, 14.42; S, 33.01. Found: C, 49.93; H, 2.82;
N, 14.32; S, 32.92.
4,4'-(3,4-Dimethylthieno[2,3-b]thiophen-2,5-diyl)bis(pyrimidine-2-ol) (5c): Dark brown crystals; yield
1
79%; mp > 320 °C; IR 3480 (OH), 1587 (C=N) cm−1; H-NMR δ 2.26 (s, 6H, CH3), 8.18(d, 2H, CH,
13
J = 5.5 Hz), 8.42 (d, 2H, CH, J = 5.5 Hz), 12.62 (2H, OH); C-NMR δ 15.9, 112.5, 126.3, 134.8,
136.1, 145.6, 147.4, 160.4, 162.5; MS m/z (%): 357 (M+1, 58), 356 (M, 18), 355 (2.5), 261 (11). Anal.
Calcd for C16H12N4O2S2 (356.42); C, 53.92; H, 3.39; N, 15.72; S, 17.99. Found: C, 54.00; H, 3.55; N,
15.64; S, 17.78.
3.4. General Procedure for the Synthesis of Compounds 6 and 7
Compound 2 (0.362 g, 1 mmol) in dry DMF (2 mL) was added to 4-amino-1,2,4-triazole (2 mmol,
0.168 gm) or 2-aminobenzimidazole (2 mmol, 0.266 mg), respectively, in dry 99.9% ethanol (20 mL)
under reflux for 6–7 h. Then the solid product were collected by filtration, washed with ethanol, dried
and recrystallized from (DMF/EtOH) to give 6 or 7.
7,7'-(3,4-Dimethylthieno[2,3-b]thiophene-2,5-diyl)bis-[1,2,4]triazolo[1,5-a]pyrimidine (6): Light yellow
crystals; yield 88%; mp > 320 °C; IR 1548, (C=N) cm−1; 1H-NMR δ 2.24 (s, 6H, 2CH3),7.66, 7.69 (d,
13
2H, CH, J = 12), 9.09, 9.12 (d, 2H, CH, J = 12), 8.62 (2H, =CH, triazole); C-NMR δ 16.3, 117.2,
128.8, 134.3, 142.0, 145.8, 148.2, 158.7,159.3, 162.1; MS m/z (%): 406 (M+2, 41), 405 (M+1, 56),
404 (100), 389 (14), 285 (31). Anal. Calcd for C18H12N8S2 (404.06); C, 53.45; H, 2.99; N, 27.70;
S, 15.86. Found: C, 53.44; H, 2.81; N, 27.76; S, 15.67.

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2,2'-(3,4-Dimethylthieno[2,3-b]thiophene-2,5-diyl)bis(benzo[4,5]imidazo[1,2-a]pyrimidine) (7): Dark
1
yellow crystals; yield 82%; mp > 320 °C; IR 1529 (C=N) cm−1; H-NMR δ 2.18 (s, 6H, 2CH3), 7.56,
7.59 (d, 2H, CH, J = 12), 8.37, 8.40 (d, 2H, CH, J = 12), 8.12, 8.86 (4H, CH, pyrimidine); 13C-NMR δ
15.81, 100.0, 112.1, 115.1, 122.5, 127.1, 131.3, 135.9, 139.1, 142.0, 148.0, 148.4, 156.0, 162.78; MS
m/z (%): 503 (M+1, 67), 502 (M, 100), 487 (9), 334 (12). Anal. Calcd for C28H18N6S2 (502.61);
C, 66.91; H, 3.61; N, 16.72; S, 12.76. Found: C, 66.86; H, 3.57; N, 16.86; S, 12.61
4. Conclusions
In summary, the reactivity of 1-(5-acetyl-3,4-dimethythieno[2,3-b]thiophene-2-yl)ethanone (1) as a
versatile and readily accessible building block for the synthesis of new bis-heterocycles incorporating
thieno[2,3-b]thiophene was investigated.
Acknowledgements
The authors extend their appreciation to the Deanship of Scientific Research at King Saud
University for funding the work through the research group project No. RGP-VPP-007.
References and Notes
1. Biederman, A.; Jacobson, P. Advances in heterocyclic chemistry. Chem. Ber. 1886, 19, 2444.
2. Litvinov, V.P.; Goldfarb, Y.A.L. The chemistry of Thienothiophenes and related systems. Adv.
Heterocycl. Chem. 1976, 19, 123-214.
3. Litvinov, V.P. The Chemistry of Thienothiophenes. Doctoral Thesis in Chemical Sciences,
Institute of Organic Chemistry, Academy of Sciences of the USSR: Moscow, USSR, 1975.
4. Konjaeva, I.P. The Chemistry of Thienothiophenes. Candidate Thesis in Chemical Sciences,
Institute of Organic Chemistry, Academy of Sciences of the USSR: Moscow, USSR, 1975.
5. Litvinov, V.P. In Topics in Organic Sulfur Chemistry, Tishler, M., Ed.; University Press:
Ljubljana, Slovenia, 1978; p. 157.
6. Dize, A.S.; Saidman, S.; Garay, R.O. Synthesis of a thienothiophene conjugated polymer.
Molecules 2000, 5, 555-557.
7. Krayushkin, M.M. The Chemistry and Biological Activity of Oxygen- and Sulfur-Containing
Heterocycles, Proceedings of II International Conference; ISB Press: Moscow, Russia, 2003;
Volume 1, p. 289.
8. Heeney, M.; Bailey, C.; Genevicius, K.; Shkunov, M.; Sparrowe, D.; Tierney, S.; Mculloch, I.
Stable polythiophene semiconductors incorporating thieno[2,3-b]thiophene. J. Am. Chem. Soc.
2005, 127, 1078-1079.
9. Henssler, J.T.; Xinnan, Z.; Adam, J. Thiophene/Thieno[3,2-b]thiophene co-oligomers: Fused ring
analogues of Sexithiophene. J. Org. Chem. 2009, 74, 9112-9119.
10. Shefer, N.; Rozen, S. The oxygenation of thieno[2,3-b]thiophenes. J. Org. Chem. 2010, 75,
4623-4625.
11. Henssler, J.T.; Adam, J. Facile and scalable synthesis of the fused-ring heterocycles
thieno[3,2-b]thiophene and thieno[3,2-b]furan. Org. Lett. 2009, 11, 3144-3147.

Molecules 2011, 16
7713
12. Jarak, I.; Kralj, M.; Piantanida, I.; Suman, L.; Zinic, M.; Pavelic, K.; Karminski-Zamola, G.
Novel cyano- and amidino-substituted derivatives of thieno[2,3-b]- and thieno[3,2-b]thiophene-
2-carboxanilides and thieno[3′,2′:4,5]thieno- and thieno[2′,3′:4,5]thieno[2,3-c]quinolones:
Synthesis, photochemical synthesis, DNA binding, and antitumor evaluation. Bioorg. Med. Chem.
2006, 14, 2859-2868.
13. Kim, H.S.; Kim, Y.H.; Kim, T.H.; Noh, Y.Y.; Pyo, S.; Yi, M.H.; Kim, D.Y.; Kwon, S.K.
Synthesis and studies on 2-hexylthieno[3,2-b]thiophene end-capped oligomers for OTFTs. Chem.
Mater. 2007, 19, 3561-3567.
14. He, M.; Li, J.; Sorensen, M.L.; Zhang, F.; Hancock, R.R.; Fong, H.H.; Pozdin, V.A.; Smilgies, D.;
Malliaras, G.G. Alkylsubstituted thienothiophene semiconducting materials: Structure property
relationships. J. Am. Chem. Soc. 2009, 131, 11930-11938.
15. Mabkhot, Y.N.; Kheder, N.A.; Al-Majid, A.M. Facile and convenient synthesis of new
thieno[2,3-b]-thiophene derivatives. Molecules 2010, 15, 9418-9426.
16. Mabkhot, Y.N. Synthesis and chemical characterisation of new bis-thieno[2,3-b]thiophene
derivatives. Molecules 2010, 15, 3329-3337.
17. Mabkhot, Y.N. Synthesis and analysis of some bis-heterocyclic compounds containing sulphur.
Molecules 2009, 14, 1904-1914.
18. Riyadh, S.M.; Abdelhamid, I.A.; Al-Matar, H.M.; Hilmy, N.H.; Elnagdi, M.H. Enamines as
precursors to polyfunctional heteroaromatic compounds; a decade of development. Heterocycles
2008, 75, 1849-1905.
19. Stanovnik, B.; Svete, J. Synthesis of heterocycles from alkyl 3-(dimethylamino) propenoates and
related enaminones. Chem. Rev. 2004, 104, 2433-2480.
20. Zhu, S.; Zhao, K.; Su, X.; Ji, S. Microwave-assisted synthesis of new spiro[indoline-3,4'-quinoline]
derivatives via a one-pot multicomponent reaction. Synth. Commun. 2009, 39, 1355-1366.
21. Loghmani-Khouzani, H.; Sabzyan, H.; Rezaei-Pooranari, A. Synthesis and structure of
α-azo-2-ketomethylquinolines. Dyes Pigm. 2008, 76, 447-454.
22. Mabkhot, Y.N.; Al-Majid, A.M.; Alamary, A.S.; Warad, I.; Sedigi, Y. Reactions of some new
thienothiophene derivatives. Molecules 2011, 16, 5142-5148.
23. Mabkhot, Y.N.; Kheder, N.A.; Farag, A.M. Synthesis and antimicrobial evaluation of some new
tetrahydropyrimidine derivatives. Heterocycles 2011, 83, 609-617.
24. Loghmani-Khouzani, H.; Sabzyan, H.; Rezaei-Pooranari, A. Synthesis and structure of
α-azo-2-ketomethylquinolines. Dyes Pigm. 2008, 76, 447-454.
25. Al-Omran, F.; Abdel Khalik, M.M.; ElKhair, A.A.; Elnagdi, M.H. Studies with functionally
substituted heteroaromatics: A novel route for the synthesis of 1-aryl-6-oxopyridazinones,
1-arylpyridazine-6-imines and 1-aryl-6-imino-4-pyridazinals. Synthesis 1997, 1997, 91-94.
26. Al-Mousawi, S.; Moustafa, M.S.; Elnagdi, M.H. Studies with enamines: Functionally substituted
enamines as aldehyde equivalents in Gewald reaction. ARKIVOC 2008, 10, 17-25.
27. Elassar, A.A.; El-Khair, A.A. Recent developments in the chemistry of enaminones. Tetrahedron
2003, 59, 8463-8480.
28. de Koning, C.B.; Michael, J.P.; Riley, D.L. Formal synthesis of (5R,8R,8aS)-indolizidine 209I via
enaminones incorporating weinreb amides. Heterocycles 2009, 79, 935-953.

Molecules 2011, 16
7714
29. Svete, J. Utilisation of chiral enaminones and azomethine imines in the synthesis of functionalised
pyrazoles. ARKIVOC 2006, 7, 35-56.
30. Al-Mousawi, S.M.; Moustafa, M.S.; Elnagdi, M.H. Green synthetic approaches: Solventless
synthesis of polyfunctionally substituted aromatics as potential versatile building blocks in
organic synthesis utilizing enaminones and enaminonitriles as precursors. Green Chem. Lett. Rev.
2011, 4, 185-193.
31. Abdel-Aziz, H.A.; Hamdy, N.A.; Farag, A.M.; Fakhr, I.M. Synthesis of some novel pyrazolo[1,5-
a]pyrimidine, 1,2,4-triazolo[1,5-a]pyrimidine, pyrido[2,3-d]pyrimidine, pyrazolo[5,1-c]-1,2,4-triazine
and 1,2,4-triazolo[5,1-c]-1,2,4-triazine derivatives incorporating a thiazolo[3,2-a]benzimidazole
Moiety. J. Heterocycl. Chem. 2008, 45, 1033-1037.
32. Mabkhot, Y.N.; Al-Majid, A.M.; Assem, B.; Alshahrani, S.; Siddiqui, Y. 1,1′-(3-Methyl-4-
phenylthieno[2,3-b]thiophene-2,5-diyl)diethanone as a building block in heterocyclic synthesis.
Novel synthesis of some pyrazole and pyrimidine derivatives. Molecules 2011, 16, 6502-6511.
Sample Availability: Samples of the compounds 1-7 are available from the authors.
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