Synthesis of guanidines

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An efficient guanylation of various amines with cyanamide proceeds in the presence of catalytic amounts of scandium(III) triflate under mild conditions in water without using preactivated guanylation reagents. Therefore, the method has practical utility for substrates that dissolve only in aqueous solutions, for example, peptides or pharmacologically important compounds.
K. Tsubokura, T. Iwata, M. Taichi, A. Kurbangalieva, K. Fukase, Y. Nakao, K. Tanaka, Synlett, 2014, 25, 1302-1306.

Simple lanthanide amides are highly efficient catalysts for the guanylation of both aromatic and secondary amines with a high activity under mild conditions. These catalysts are compatible with a wide range of solvents and substrates.
Q. Li, S. Wang, S. Zhou, G. Yang, X. Zhu, Y. Liu, J. Org. Chem., 2007, 72, 6763-6767.

Q. Li, S. Wang, S. Zhou, G. Yang, X. Zhu, Y. Liu, J. Org. Chem., 2007, 72, 6763-6767.

Ytterbium triflate is an efficient catalyst for the addition of a wide scope of amines to carbodiimides under solvent-free condition to provide N,N',N''-trisubstituted guanidines in good yields.
X. Zhu, Z. Du, F. Xu, Q. Shen, J. Org. Chem., 2009, 74, 6347-6349.

Ru(bpy)₃Cl₂ as a photocatalyst enables the conversion of various thioureas to the corresponding guanidines in a mixture of water and ethanol at room temperature under irradiation by visible light. Key benefits of this catalytic guanylation include the use low-toxicity solvents/base, ambient temperature, and an open-flask environment.
T. Saetan, M. Sukwattanasinitt, S. Wacharasindhu, Org. Lett., 2020, 22, 7864-7869.

An operationally simple and rapid copper-catalyzed three-component synthesis of trisubstituted N-aryl guanidines involving cyanamides, arylboronic acids, and amines is performed in the presence of K₂CO₃, a catalytic amount of CuCl₂·2H₂O, bipyridine, and oxygen (1 atm).
J. Li, L. Neuville, Org. Lett., 2013, 15, 6124-6127.

An efficient Pd-catalyzed cascade reaction of azides with isonitriles and amines provides N-sulfonyl-, N-phosphoryl-, and N-acyl-functionalized guanidines in excellent yield. In addition, the less reactive intermediate benzoyl carbodiimide could be isolated in moderate yield.
G. Qiao, Z. Zhang, B. Huang, L. Zhu, F. Xiao, Z. Zhang, Synthesis, 2018, 50, 330-340.

Carbamoyl isothiocyanates are ideal starting materials for the synthesis of multisubstituted guanidines. The nature of these carbamoyl thioureas permits creation of disubstituted and trisubstituted guanidines, as well as aromatic guanidines.
B. R. Linton, A. J. Carr, B. P. Orner, A. D. Hamilton, J. Org. Chem., 2000, 65, 1566-1568.

Treatment of an acylcyanamide with chlorotrimethylsilane generates a reactive N-silylcarbodiimide capable of guanylating a variety of amines. Typically the reaction is complete in 15 min for primary and secondary aliphatic amines at room temperature. Hindered amines and anilines are also competent nucleophiles but require extended reaction times.
R. E. Looper, T. J. Haussener, J. B. C. Mack, J. Org. Chem., 2011, 76, 6967-6971.

The use of cyanuric chloride (TCT) instead of classical HgCl₂ as activating reagent for di-Boc-thiourea provides an alternative route for the guanylation of amines and eliminates the environmental hazard of heavy-metal waste without appreciable loss of yield or reactivity.
A. Porcheddu, L. De Luca, G. Giacomelli, Synlett, 2009, 3368-3372.

Two new guanidinylation reagents, N,N′-bis(ortho-chloro-Cbz)-S-methylisothiourea and N,N′-bis(ortho-bromo-Cbz)-S-methylisothiourea, proved to be superior to already known reagents. The guanidinylations of amines with all reagents were accelerated by addition of DMAP.
T. Gers, D. Kunce, P. Markowski, J. Izdebski, Synthesis, 2004, 37-42.

A convenient one-step transformation of primary and secondary amines into the corresponding unprotected guanidines using 4-benzyl-3,5-dimethyl-1H-pyrazole-1-carboxamidine and its polymer-bound variant is described. The scopes and limitations of the method, the microwave-assistance of amidination as well as a recycling protocol are examined.
W. Solodenko, P. Bröker, J. Messinger, U. Schön, A. Kirschning, Synthesis, 2006, 461-466.

A one-pot multicomponent carbonylation/amination sequence enables a convenient synthesis of N-acylguanidines. A formation of an N-cyanobenzamide intermediate from the Pd(0)-catalyzed carbonylative coupling of cyanamide and aryl iodides or bromides is followed by amination with various amines to provide the final N-acylguanidines in good yields. Furthermore, various heterocycles were prepared from the N-acylguanidines.
L. Åkerbladh, L. S. Schembri, M. Larhed, L. R. Odell, J. Org. Chem., 2017, 82, 12520-12529.

The synthesis of 3,5-dimethyl-N-nitro-1-pyrazole-1-carboxamidine (DMNPC) has been optimised. A detailed protocol for the preparation of a range of guanidines via nitroguanidines is described using DMNPC as guanidinylating reagent.
J. A. Castillo-Meléndez, B. T. Golding, Synthesis, 2004, 1655-1663.

Primary amines are converted to protected N^G-hydroxyguanidines in a one-pot procedure using readily prepared materials. A high-yielding preparation of N^G-hydroxy-L-arginine, the intermediate in the enzymatic conversion of L-arginine to nitric oxide and L-citrulline by nitric oxide synthase, is described.
N. I. Martin, J. J. Woodward, M. A. Marletta, Org. Lett., 2006, 8, 4035-4038.