Categories: Synthesis of N-Heterocycles >
Synthesis of 1H-tetrazoles
A series of 1-substituted 1H-1,2,3,4-tetrazole compounds have been synthesized in good yields from amines, triethyl orthoformate, and sodium azide through the catalyzed reaction with Yb(OTf)3.
W.-K. Su, Z. Hong, W.-G. Shan, X.-X. Zhang, Eur. J. Org. Chem., 2006, 2723-2726.
The reaction of sodium azide with nitriles to give 1H-tetrazoles proceeds readily in water with zinc salts as catalysts. The scope of the reaction is quite broad; a variety of aromatic nitriles, activated and unactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides are all viable substrates.
Z. P. Demko, K. B. Sharpless, J. Org. Chem., 2001, 66, 7945-7950.
Treatment of organic nitriles with NaN3 in the presence of iodine or silica-supported sodium hydrogen sulfate as a heterogeneous catalyst enables an advantageous synthesis of 5-substituted 1H-tetrazoles.
B. Das, C. R. Reddy, D. N. Kumar, M. Krishnaiah, R. Narender, Synlett, 2010, 391-394.
L-proline as a catalyst enables a simple and efficient route for the synthesis of a series of 5-substituted 1H-tetrazoles from a broad range of substrates, including aliphatic and aryl nitriles, organic thiocyanates, and cyanamides. This environmentally benign, cost effective, and high-yielding L-proline-catalyzed protocol offers simple experimental procedure, short reaction time, simple workup, and excellent yields.
S. B. Bhagat, V. N. Telvekar, Synlett, 2018, 29, 874-879.
An efficient microwave-accelerated method allows the conversion of inactive nitriles into 5-substituted 1H-tetrazoles in DMF.
H. Yoneyama, Y. Usami, S. Komeda, S. Harusawa, Synthesis, 2013, 45, 1051-1059.
5-Substituted tetrazoles were prepared in very good yields and short reaction times by treatment of nitriles with sodium azide and triethylammonium chloride in nitrobenzene in a microwave reactor. Even sterically hindered tetrazoles, as well as those deactivated by electron-donating groups, can be prepared.
J. Roh, T. V. Artamonova, K. Vávrová, G. I. Koldobskii, A. Hrabálek, Synthesis, 2009, 2175-2178.
Aryl and vinyl nitriles have been prepared in very high yields from the corresponding bromides using palladium-catalyzed reactions under microwave irradiation. Furthermore, flash heating was used successfully for the conversion of these nitriles into aryl and vinyl tetrazoles by cycloaddition reactions. One-pot transformation of aryl halides directly to the aryl tetrazoles could also be accomplished.
M. Alterman, A. Hallberg, J. Org. Chem., 2000, 65, 7984-7989.
Thiocyanates and nitriles are converted efficiently into the corresponding 5-substituted 1H-tetrazoles in the presence of zinc(II) chloride and sodium azide in isopropanol, n-propanol, or n-butanol. The procedure offers mild reaction conditions, short reaction times, and very good yields for a wide range of substrates.
S. Vorona, T. Artamonova, Y. Zevatskii, L. Myznikov, Synthesis, 2014, 46, 781-786.
Activation of the nitrile substrate by the Brřnsted or Lewis acid catalyst is responsible for rate enhancement in azide-nitrile cycloaddition. Lewis acids such as Zn or Al salts perform in a similar manner, activating the nitrile moiety and leading to an open-chain intermediate that subsequently cyclizes to produce the tetrazole nucleus. The desired tetrazole structures were obtained in high yields within 3-10 min employing controlled microwave heating.
D. Cantillo, B. Gutmann, C. O. Kappe, J. Am. Chem. Soc., 2011, 133, 4465-4475.
An organocatalyst, 5-azido-1-methyl-3,4-dihydro-2H-pyrrolium azide, generated in situ from N-methyl-2-pyrrolidone (NMP), sodium azide, and trimethylsilyl chloride, enables the formation of tetrazoles by cycloaddition of sodium azide with organic nitriles under neutral conditions and microwave heating. The organocatalyst accelerates the azide-nitrile coupling by activating the nitrile substrate.
D. Cantillo, B. Gutmann, C. O. Kappe, J. Am. Chem. Soc., 2011, 133, 4465-4475.
An operationally simple, direct conversion of arylboronic acids to tetrazoles is catalyzed by a ONO pincer-type Pd(II) complex under mild, open flask reaction conditions. The palladium complex was reused up to four cycles.
A. Vignesh, N. S. P. Bhuvanesh, N. Dharmaraj, J. Org. Chem., 2017, 82, 887-892.
An easy and efficient one-pot, three-component reaction of aldehydes, hydroxylamine, and [bmim]N3 enables the synthesis of 5-substituted 1H-tetrazole derivatives.
M. M. Heravi, A. Fazeli, H. A. Oskooie, Y. S. Beheshtiha, H. Valizadeh, Synlett, 2012, 23, 2927-2930.
5-substituted 1H-tetrazole derivatives can be prepared in good to excellent yields from various oximes and sodium azide by using indium(III) chloride as a Lewis acid catalyst. The method has significant advantages, such as an inexpensive catalyst, low catalyst loading, mild reaction conditions, and a convenient experimental procedure.
S. D. Guggilapu, S. K. Prajapti, A. Nagarsenkar, K. K. Gupta, B. N. Babu, Synlett, 2016, 27, 1241-1244.
5-Substituted 1H-tetrazoles were effectively synthesized in short reaction times from aldoximes and diphenyl phosphorazidate (DPPA) under reflux conditions in xylenes. Various aldoximes underwent the cycloaddition reaction to afford the corresponding 5-substituted 1H-tetrazoles in good yields. Chiral aldoximes gave aminotetrazoles with almost no racemization.
K. Ishihara, M. Kawashima, T. Matsumoto, T. Shiori, M. Matsugi, Synthesis, 2018, 50, 1141-1151.
Aromatic and aliphatic aldoximes underwent a cycloaddition with diphenyl phosphorazidate (DPPA) to afford the corresponding 5-substituted 1H-tetrazoles with ease and efficiency.
K. Ishihara, M. Kawashima, T. Shioiri, M. Matsugi, Synlett, 2016, 27, 2225-2228.
1N-PMB-protected tetrazoles undergo C-H deprotonation with the turbo Grignard reagent without retro [2 + 3] cycloaddition as side reaction to provide a metalated intermediate, that can be used for reactions with electrophiles such as aldehydes, ketones, Weinreb amides, and iodine. The PMB-protecting group at the tetrazole can be cleaved using oxidative hydrogenolysis and acidic conditions.
K. Grammatoglou, A. Jirgensons, J. Org. Chem., 2022, 87, 3810-3816.
N-Protected (1H-tetrazol-5-yl)zinc pivalates are storable solids with appreciably air and moisture stability. They are obtained in high yields by deprotonation using the mixed zinc-magnesium base TMPZnClˇMg(OPiv)2. Subsequent cross-couplings and copper-catalyzed electrophilic aminations using hydroxylamine benzoates give access to functionalized 1H-tetrazoles.
C. P. Tüllmann, S. Steiner, P. Knochel, Synthesis, 2020, 52, 2357-2363.
In a synthesis of tetrazoles from amides, diphenyl phosphorazidate or bis(p-nitrophenyl) phosphorazidate act as both the activator of amide-oxygen for elimination and azide source. Various amides were converted into 1,5-disubstituted and 5-substituted 1H-tetrazoles in good yields without the use of toxic or explosive reagents.
K. Ishihara, T. Shioiri, M. Matusugi, Org. Lett., 2020, 22, 6244-6247.
A Pd/Cu cocatalytic system enables a mild, direct C-H arylation of 1-substituted tetrazoles with readily available aryl bromides to 5-aryltetrazoles. The methodology tolerates a wide range of functionalities and avoids late-stage usage of azides.
Y. Zhang, J. C. H. Lee, M. R. Reese, B. P. Boscoe, J. N. Humphrey, C. H. Helal, J. Org. Chem., 2020, 85, 5718-5723.
The reaction of various nitrones with bis(p-nitrophenyl) phosphorazidate provides 1,5-disubstituted tetrazoles in the presence of 4-(dimethylamino)pyridine without the need for toxic or explosive reagents.
K. Ishihara, T. Shioiri, M. Matsugi, Synlett, 2022, 33, 781-784.
Cascade reactions starting from isocyanides allow a straightforward synthesis of five-membered ring heterocycles. Addition of sodium azide on isocyanide dibromides followed by electrocyclization and a Suzuki coupling affords tetrazoles scaffolds, whereas addition of tetrazoles on isocyanide dibromides followed by Huisgen rearrangement and a Suzuki coupling gives triazoles scaffolds.
L. El Kaim, L. Grimaud, P. Patil, Org. Lett., 2011, 13, 1261-1263.
A general method for the synthesis of 1,5-disubstituted tetrazoles from imidoylbenzotriazoles involves mild reaction conditions and short reaction times.
A. R. Katritzky, C. Cai, N. K. Meher, Synthesis, 2007, 1204-1208.
Bu4NI catalyzes regioselective N2-alkylations and N2-arylations of tetrazoles using tert-butyl hydroperoxide as a methyl source, alkyl diacyl peroxides as primary alkyl source, alkyl peresters as secondary and tertiary alkyl sources, and aryl diacyl peroxides as arylating source. These reactions proceed without pre-functionalization of the tetrazoles and in the absence of any metal catalysts.
S. Rajamanickam, C. Sah, B. A. Mir, S. Ghosh, G. Sethi, V. Yadav, S. Venkateramani, B. K. Patel, J. Org. Chem., 2020, 85, 2118-2141.
The reaction of cyanogen azide and primary amines generates imidoyl azides as intermediates in acetonitrile/water. After cyclization, these intermediates gave 1-substituted aminotetrazoles in good yield.
Y.-H. Joo, J. M. Shreeve, Org. Lett., 2008, 10, 4665-4667.
A formal (3 + 2) cycloaddition enables a regioselective synthesis of biologically interesting tetrazolium salts employing simple amides and azides as starting materials. The mild conditions tolerate a broad range of functional groups.
V. Tona, B. Maryasin, A. de la Torre, J. Sprachmann, L. González, N. Maulide, Org. Lett., 2017, 19, 2662-2665.
A versatile and highly efficient Zn(OTf)2-catalyzed one-pot reaction of alkenes, NBS, nitriles, and TMSN3 gives various 1,5-disubstituted tetrazoles containing an additional α-bromo functionality of the N1-alkyl substituent.
S. Hajra, D. Sinha, M. Bhowmick, J. Org. Chem., 2007, 72, 1852-1855.
Sequential Pd(0)/Fe(III) catalysis enables a rapid and efficient synthesis of aminotetrazoles from aryl azides, isocyanides, and TMSN3. The reaction sequence utilizes a Pd-catalyzed azide-isocyanide denitrogenative coupling to generate an unsymmetric carbodiimide, which reacts with TMSN3 in the presence of FeCl3 in a single pot.
R. S. Pathare, A. J. Ansari, S. Verma, A. Maurya, A. K. Maurya, V. K. Agnihotri, A. Sharon, R. T. Pardasani, D. M. Sawant, J. Org. Chem., 2018, 83, 9530-9537.
The use of N-Boc-protected hydrazine in the Ugi tetrazole reaction provides a library of highly substituted 5-(hydrazinomethyl)-1-methyl-1H-tetrazoles in good yield.
P. Patil, J. Zhang, K. Kurpiewska, J. Kalinowska-Tłuścik, A. Dömling, Synthesis, 2016, 48, 1122-1130.