PASE synthesis of 1-azolyl-1H-1,2,4-triazoles by the reaction of diazoazoles with ethyl isocyanoacetate

Article abstract of DOI:10.1016/j.mencom.2019.11.016

PASE (pot, atom and step economic) synthesis of 1-azolyl-1H-1,2,4-triazole derivatives in up to 91% yield has been accomplished by addition of 5-diazoazoles to ethyl isocyanoacetate.

Full text of DOI:10.1016/j.mencom.2019.11.016

Mendeleev
Communications
Mendeleev Commun., 2019, 29, 653–654
PASE synthesis of 1-azolyl-1H-1,2,4-triazoles by the reaction
of diazoazoles with ethyl isocyanoacetate
Elena V. Sadchikova,a,b Daria L. Alexeeva and Valentine G. Nenajdenko*c
a
a
Institute of Chemical Engineering, Ural Federal University, 620002 Ekaterinburg, Russian Federation.
E-mail: e.v.sadchikova@urfu.ru
Department of Pharmacy and Chemistry, Ural State Medical University, 620028 Ekaterinburg,
b
Russian Federation
c
Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russian
Federation. Fax: +7 495 932 8846; e-mail: nenajdenko@gmail.com
DOI: 10.1016/j.mencom.2019.11.016
N
PASE (pot, atom and step economic) synthesis of 1-azolyl-
H-1,2,4-triazole derivatives in up to 91% yield has been
accomplished by addition of 5-diazoazoles to ethyl
isocyanoacetate.
Y
Z
Z
N
CO2Et
+
CN
CO2Et
Y
N
1
X
acetonitrile
or acetone,
AcONa
N2
N
X
NH
up to 91%
X = N, Z = C, Y = C, N
Among heterocyclic compounds, five-membered nitrogen ones
are the most important as they represent a key structural part of
many natural products and modern drugs.1 Triazole derivatives
construct triazoles by the reaction of diazonium salts with
1
9
isocyanoacetate
as well as silver or copper catalyzed
–3
20
cycloadditions have been published. Meanwhile, no examples
of participation of heterocyclic diazo compounds possessing
4
–7
attract a lot of attention in the field of drug design,
8
9–11
21
agrochemistry and materials science.
Many triazole derived
specific reactivivty in such a cycloaddition can be found.
drugs such as Fluconazole, Itraconazole, Posaconazole,
Voriconasole, Ravuconazole (antifungal), Ribavirin (antiviral),
Rizatriptan (migraine headaches), Trapidil (hypotensive),
Trazodon, Etoperidone, Nefazodone (antidepressants), Vorozole,
Anastrozole, Letrozole (antineoplastics), Rilmazafone (sedative,
hypnotic), Etizolam (anticonvulsant) are currently on the market.
Various products containing the 1,2,4-triazole nucleus, e.g.,
Tebuconazole, Epoxiconazole, Difenoconazole (fungicides),
Diniconazole, Triazophose (pesticides), Amitrole, Epronaz,
Flupoxam (herbicides) and Paclobutrazole, Diclobutrazole
In the present work, we investigated the reaction of ethyl
isocyanoacetate 1 with 5-diazopyrazoles 2a–g (Scheme 1) and
5-diazoimidazoles 3a–d (Scheme 2). It is well known that the
coupling of 5-diazoazoles or relative diazonium salts with
CH-acids leads to the corresponding azol-5-ylhydrazones.2
Depending on the nature of the reactants and on the medium
pH value, these coupling products can either be isolated or be
directly cyclized to azolo[5,1-c][1,2,4]triazine or azolo[5,1-c]-
2,23
2
4,25
[1,2,4]triazin-4-one derivatives.
Coupling of ethyl isocyanoacetate 1 with 5-diazopyrazoles
2a–e and 5-diazoimidazoles 3a–d was performed in acetonitrile or
acetone in the presence of sodium acetate. To our delight, the
expected triazoles 4a–e and 5a–d were isolated in up to 91% yield.†
The structure of compounds 4a–e and 5a–d was confirmed
(plant growth regulators) find agricultural applications.
Numerous methods are available to obtain N-substituted
1
2–15
1
,2,4-triazoles.
However, some of them have restrictions.
For example, direct alkylation of 1,2,4-triazole usually affords a
mixture of isomeric products. This difficulty can in principle be
circumvented by introduction of an alkyl group before ring
closure, however few convenient routes are known. Coupling of
1
unambiguously by spectral data. The H NMR spectra of triazole
C(O)Y
N
C(O)Y
N2
N
1
6,17
aryldiazonium salts with methyl isocyanoacetate
or
tosylmethyl isocyanide is an efficient approach to produce
-aryl-1,2,4-triazoles. However, the heterocyclization takes
+
N
N
i
C–
N
18
EtO2C
+
EtO C
2
N
N
HN
1
1
3a–d
5a–d
place only for electron rich diazonium salts, otherwise
arenecarboxamides are formed.16 Recently flow modification to
a Y = OEt, 83%
b Y = pyrrolidin-1-yl, 75%
c Y = piperidin-1-yl, 78%
d Y = morpholin-4-yl, 91%
R2
R1
N
R2
N
+
N
i
R1
Scheme 2 Reagents and conditions: i, acetone, AcONa.
C–
N
EtO2C
+
EtO2C
N
N2
HN
N
†
N
General procedure for the synthesis of 4a–e and 5a–d. To a stirred
mixture of ethyl isocyanoacetate 1 (60 ml, 0.55 mmol)26 and sodium
1
2a–e
4a–e
acetate (45 mg, 0.55 mmol) in acetonitrile (3 ml) or acetone (3 ml), a cold
2
7,28
1
2
1
2
solution of the corresponding 5-diazopyrazole 2a–e (0.5 mmol)
in
in acetone
3 ml) was added dropwise at 0 °C for 5 min. The temperature of the
a R = Ph, R = H, 74%
d R = 4-ClC6H4, R = H, 82%
acetonitrile (3 ml) or 5-diazoimidazole 3a–d (0.5 mmol)2
9,30
1
2
1
2
b R = 4-MeC6H4, R = H, 81%
e R = H, R = CO2Et, 90%
(
1
2
c R = 4-MeOC6H4, R = H, 80%
mixture was raised to ambient, and the mixture was left until disappearing
of the starting diazoazole (3–4 days, TLC control). Activated charcoal
was added, the mixture was stirred for 15 min and filtered. The filtrate
Scheme 1 Reagents and conditions: i, acetonitrile, AcONa.
©
2019 Mendeleev Communications. Published by ELSEVIER B.V.
–
653 –
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.

Mendeleev Commun., 2019, 29, 653–654
5
S. Maddila, R. Pagadala and S. B. Jonnalagadda, Lett. Org. Chem.,
2013, 10, 693.
O
C(O)NHR
R
+
N
Y
i
Y
N
N
6 F. Ahmadi, M. R. Ghayahbashi, M. Sharifzadeh, E. Alipoiur, S. N. Ostad,
EtO
2
C
C–
+
X
X
M. Vosooghi, H. Reza Khademi and M. Amini, Med. Chem., 2015, 11,
6
N
2
N
N
H
N
9.
7 S¸ . G. Küçükgüzel and P. Çıkla-Süzgün, Eur. J. Med. Chem., 2015, 97,
30.
1
6a–d
7a–d
8
a X = N,Y = CH, R = H, 88%
b X = N,Y = CH, R = Me, 85%
c X = CH,Y = N, R = H, 83%
d X = CH,Y = N, R = Me, 90%
8
K. Shalini, N. Kumar, S. Drabu and P. K. Sharma, Beilstein J. Org.
Chem., 2011, 7, 668.
9
V. N. Bulut, C. Duran, A. Gundogdu, M. Soylak, N. Yildirim and
M. Tufekci, Bull. Chem. Soc. Ethiop., 2010, 24, 457.
Scheme 3 Reagents and conditions: i, acetone, AcONa.
1
1
1
0 A. Diaz-Ortiz, P. Prieto, J. R. Carrillo, R. Martin and I. Torres, Curr.
Org. Chem., 2015, 19, 568.
1 G. Aromi, L. A. Barrios, O. Roubeau and P. Gamez, Coord. Chem. Rev.,
part of these compounds revealed signals for CO Et fragment at
2
d 1.41–1.46 and 4.38–4.49 ppm, respectively, as well as singlet
of H(5) triazole ring at d 8.71–9.04 ppm. The 13C NMR spectra
contain triazole signals at 142.3–148.6 ppm for C(5) and 154.2–
2
011, 255, 485.
2 M. Balasubramanian, J. G. Keay, E. F. V. Scriven and N. Shobana,
Heterocycles, 1994, 37, 1951.
1
55.8 ppm for C(3).
13 A. Moulin, M. Bibian, A.-L. Blayo, S. El Habnouni, J. Martinez and
However, the reaction has some restrictions. The use of
J.-A. Fehrentz, Chem. Rev., 2010, 110, 1809.
1
1
1
4 S. C. Holm and B. F. Straub, Org. Prep. Proced. Int., 2011, 43, 319.
5 P. Kaur, R. Kaur and M. Goswami, Int. Res. J. Pharm., 2018, 9 (7), 1.
6 K. Matsumoto, M. Suzuki, M. Tomie, N. Yoneda and M. Miyoshi,
Synthesis, 1975, 9, 609.
5
-diazoazoles 6a–d containing 4-positioned NH-amide
groups afforded products of alternative transformation, viz.,
azolo[4,5-d][1,2,3]triazin-4(3H)-ones 7a–d (Scheme 3).
‡
In conclusion, it was demonstrated that the reaction of
1
7 A. V. Gulevich, A. G. Zhdanko, R. V. A. Orru and V. G. Nenajdenko,
5
-diazoazoles with ethyl isocyanoacetate is an efficient PASE
Chem. Rev., 2010, 110, 5235.
approach to the corresponding 1-azolyl-1H-1,2,4-triazole
derivatives. The reaction scope is rather broad. The prepared
hybrid heterocyclic compounds look highly attractive as
interesting ligands for coordination chemistry as well as
precursors for metal-organic frameworks (MOF) synthesis.
18 A. M. van Leusen, B. E. Hoogenboom and H. A. Houwing, J. Org.
Chem., 1976, 41, 711.
1
2
2
9 M. Baumann, A. M. R. Garcia and I. R. Baxendale, Org. Biomol. Chem.,
015, 14, 4231.
0 J.-Q. Liu, X. Shen,Y. Wang, X.-S. Wang and X. Bi, Org. Lett., 2018, 20,
930.
1 V. S. Mokrushin and E. V. Sadchikova, Khimiya geterotsiklicheskikh
diazosoedinenii (Chemistry of Heterocyclic Diazo Compounds),
Prospekt nauki, St. Petersburg, 2013 (in Russian).
2
6
This work was supported by the Russian Federation President
Grant for leading scientific schools (grant no. 4687.2018.3).
2
2
2 M. A. Bezmaternykh, V. S. Mokrushin, T. A. Pospelova and O. S. Eltsov,
Chem. Heterocycl. Compd., 1998, 34, 702 (Khim. Geterotsikl. Soedin.,
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi: 10.1016/j.mencom.2019.11.016.
1
998, 805).
3 E. V. Shchegol’kov, E. V. Sadchikova, Ya. V. Burgart and V. I. Saloutin,
Russ. Chem. Bull., Int. Ed., 2008, 57, 612 (Izv. Akad. Nauk, Ser. Khim.,
2
008, 599).
4 E. V. Sadchikova and V. S. Mokrushin, Chem. Heterocycl. Compd.,
014, 50, 1014 (Khim. Geterotsikl. Soedin., 2014, 1100).
5 E. V. Shchegol’kov, E. V. Sadchikova, Ya. V. Burgart and V. I. Saloutin,
Russ. J. Org. Chem., 2009, 45, 572 (Zh. Org. Khim., 2009, 45, 586).
6 R. Obrecht, R. Herrmann and I. Ugi, Synthesis, 1985, 400.
2
2
References
2
1
A. Ansari, A. Ali, M. Asif and Shamsuzzaman, New J. Chem., 2017, 41,
6.
1
2
3
L. D. Luca, Curr. Med. Chem., 2006, 13, 1.
I. A. Al-Masoudi, Y. A. Al-Soud, N. J. Al-Salihi and N. A. Al-Masoudi,
2
2
7 D. L. Alekseeva, V. Yu. Rakhimova, A. S. Minin, A. V. Belousova and
E. V. Sadchikova, Chem. Heterocycl. Compd., 2018, 54, 1145
Chem. Heterocycl. Compd., 2006, 42, 1377 (Khim. Geterotsikl. Soedin.,
2
006, 1605).
(
Khim. Geterotsikl. Soedin., 2018, 1145).
4
S. S. Kumar and H. P. Kavitha, Mini-Rev. Org. Chem., 2013, 10, 40.
2
2
8 Y. F. Shealy and C. A. O’Dell, J. Pharm. Sci., 1971, 60, 554.
9 K. E. Andersen and E. B. Pedersen, Liebigs Ann. Chem., 1986, 1012.
was concentrated under reduced pressure at a temperature below 40 °C.
The residue was treated with diethyl ether or hexane, the precipitate
formed was collected by filtration and purified by flash column
chromatography on silica gel (eluting with EtOAc–CH Cl mixture).
General procedure for the synthesis of 7a–d. To a stirred mixture of
ethyl isocyanoacetate 1 (60 ml, 0.55 mmol) and sodium acetate (45 mg,
30 E. V. Sadchikova and V. S. Mokrushin, Russ. Chem. Bull., Int. Ed., 2003,
52, 1600 (Izv. Akad. Nauk, Ser. Khim., 2003, 1516).
31 C. C. Cheng, R. K. Robins, K. C. Cheng and D. C. Lin, J. Pharm. Sci.,
1968, 57, 1044.
2
2
‡
32 M. F. G. Stevens, Prog. Med. Chem., 1976, 13, 205.
3
3 Y. F. Shealy, R. F. Struck, L. B. Holum and J. A. Montgomery,
J. Org. Chem., 1961, 26, 2396.
0
5
.55 mmol) in acetone (3 ml), a cold solution of the corresponding
-diazoazole 6a–d (0.5 mmol)2
8–30
in acetone (3 ml) was added dropwise
at 0 °C for 5 min. The mixture was left until disappearing of the starting
diazoazoles (TLC control). Activated charcoal was added, and the
mixture was stirred for 15 min and filtered. The filtrate was concentrated
under reduced pressure at a temperature below 40 °C. The residue was
3
1,32
crystallized from EtOH as white solid. Yield 60 mg (88%) for 7a,
6
4 mg (85%) for 7b,32 57 mg (83%) for 7c,
30,33
68 mg (90%) for 7d.
30
Physical and spectral characteristics of these compounds are identical to
the reported ones.3
0–33
Received: 14th June 2019; Com. 19/5952
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