SPOTLIGHT
SYNLETT
Spotlight 467
This feature focuses on a reagent chosen by a postgraduate, highlighting the uses and
preparation of the reagent in
current research
██1043
spotlight
Mercury(II)
Chloride
Compiled by Felipe Fantuzzi
Felipe Fantuzzi was born in Rio de Janeiro, Brazil in 1987. He received his B.Sc. (2011) and M.Sc. (2013) in chemistry from the
Universidade Federal do Rio de Janeiro (UFRJ). He won the Sylvio
Canuto Award (2010) and the Presentation Prize at the Brazilian
Symposium on Theoretical Chemistry (2013). Currently, he is
working towards his Ph.D. in theoretical chemistry at UFRJ under
the advisory of Professor Marco A. Chaer Nascimento and the coadvisory of Dr. Thiago M. Cardozo. His research interests focus on
the nature of the chemical bond from the quantum interference perspective.
Introduction
Organomercurials were among the first prepared organometallic compounds, being known since the second half
of the 19th century.1,2 Despite their toxicity, mercury compounds are still used in the chemical and petrochemical
industries. For instance, the industrial synthesis of vinyl
chloride and acetaldehyde from acetylene is carried out
using mercury catalysts.3 Therefore, the study of environmental and health impacts of mercury and organomercurials, as well as the improvement of safety and handling
techniques, are of great importance.
Mercury(II) chloride, HgCl2, is a commercially available
mercury salt, and thus an important mercury(II) source.
Besides novel mercuration reactions with organic substrates,3–7 HgCl2 has been extensively used in a variety of
cyclization reactions, forming both carbocycles and heterocycles.8–10 Its use as inorganic thiophile has led to the
formation of several new products from organosulfur reactants, especially thiocarbonyl compounds.11–16 Finally,
the synthesis of mercury(II) alkynyls, mainly from HgCl2,
and their use as building blocks for supramolecular structures has been reviewed.17
Abstracts
(A) Preparation of Asymmetrical N,N'-Disubstituted Guanidines
Guanidine is a biologically relevant functional group, because it is
found in several natural products and in the amino acid arginine.
O’Donovan and Rozas reported a simple route to N,N′-asymmetrical
disubstituted guanidines from thiourea.14 The first step is the conversion of thiourea into N-Boc-protected N′-alkyl/aryl substituted thioureas, which are then treated with an amine in the presence of HgCl2
and triethylamine.
(B) Guanylation of N-Iminopyridinium Ylides
Cunha et al. reported the synthesis of five pyridinium N-benzoylguanidines in moderate to good yields.11 The N-aminopyridinium iodide
was subjected to modified guanylation reaction conditions, using
HgCl2 as inorganic thiophile. Among the two possible stereoisomers
(due to the C=N bond), only the E-configuration was detected in the
1
H NMR spectra. This study represents the first description of an
ylide as the nucleophilic partner in the guanylation reaction.
(C) Synthesis of Trisubstituted Triazines
Kaila et al. reported a one-pot synthesis of 1,3,5-trisubstituted triazines from isothiocyanates, N,N-diethylamidines, and carbamidines.10 An amidinothiourea intermediate is formed from the
reaction of the first two materials, which then reacts with the carbamidine in the presence of HgCl2 to generate the desired triazines.
SYNLETT 2014, 25, 1043–1044
Advanced online publication: 14.03.20140936-52141437-2096
DOI: 10.1055/s-0033-1340958; Art ID: ST-2014-V0474-V
© Georg Thieme Verlag Stuttgart · New York
1) NaH, Boc2O
2) NaH, TFAA
3) R1-NH2
S
R1
NH2 THF, 0 °C to r.t.
one-pot
H2N
HgCl2, Et3N
R2-NH2
S
N
H
Boc
N
H
N
R1
CH2Cl2, 0 °C to r.t.
16 h
28–91%
R2
N
N
H
H
49–91%
R1 = Pr, (CH2)2OH, (CH2)2OAc, Ph, 4-Me2NC6H4, 4-EtOC6H4
R2 = Pr, (CH2)2OH, (CH2)2OAc, Ph, 4-Me2NC6H4,
4-EtOC6H4, 6-(1,2,3,4-tetrahydronaphtalene)
O
S
N
H
N
H
HN
O
R
N
R
N
Et3N
N
N
N
NH2 I
NH
HgCl2
Et3N
DMF
70–90 °C
R = Ar, HetAr
E-configuration
56–77%
R2
R1
NCS
HCl
NH2
NEt2
+
+
HN
R2
HN
R3
HgCl2
Et3N, THF
r.t.
6h
N
R1
N
H
N
N
R3
13 examples
40–80% yield
Boc
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Instituto de Química, Universidade Federal do Rio de Janeiro,
Cidade Universitária, Av. Athos da Silveira Ramos 149, 21941-909
Rio de Janeiro, Brazil
E-mail: [email protected]
SPOTLIGHT
F. Fantuzzi
(D) Carbocyclization of Tethered Alkynedithioacetals
Biswas et al. reported a general route to five- and six-membered carbo- and heterocycles by HgCl2-mediated cyclization of tethered alkynedithioacetals.9 If the substrate is a terminal alkyne, the
formation of six-membered rings is preferential. On the other hand,
substitution at the alkyne terminus leads preferentially to five-membered rings. Moreover, it has been shown that the replacement of
HgCl2 by HgI2 interrupts the reaction at the dithioacetal intermediate.
(E) Intramolecular Cyclization of Ethynyl Phenols
Atta et al. reported a Hg(II)-specific intramolecular cyclization reaction of ethynyl phenols in semi-aqueous media at room temperature.8 The use of a malononitrile derivative as an electronwithdrawing group has led to the development of a Hg(II) selective
indicator that displays a color change from blue to pale yellow.
(F) Synthesis of α-Heteroatom-Substituted Nitrones
The application of nitrones range from biology to polymers and materials chemistry. Voinov and Grigor’ev reported the synthesis of an
α-mercurated cyclic aldonitrone with 55% yield.4 If only 0.5 equivalents of HgCl2 are used in the reaction, a disubstituted mercuric derivative is formed.5
R3
R1
R2
R3
X
S
S
R3
HgCl2
CaCO3
R1
MeCN–H2O
25 °C
R4
R2
O
X
(R = H, major)
or
O
R4
R3
R2
R4
4
S
S
X
R1
X = O, RN, R2C
R2
X
(R4 ≠ H, major)
EWG
EWG
HgCl
HgCl2 (2 equiv)
R
+
10 mM PBS buffer
(pH = 7.0)
OH
(H) Rearrangement of Ketoximes
The transformation of ketoximes into amides or lactams, known as
the Beckmann rearrangement, usually requires harsh conditions
which preclude sensitive oximes to react. Ramaligan and Park reported the use of HgCl2 in acetonitrile to obtain amides and lactams
from a variety of acyclic and cyclic ketoximes with good to excellent
yields under essentially neutral conditions.19
HCl
O
R
80–95% yield
Me
N
O
H
N
O
Li
N
s-BuLi
N
O
O
ClHg
N
HgCl2
N
N
N
Me
Me
Me
O
Hg
or
N
N
Me
55% yield
HgCl2 (1.0 equiv)
(G) Reduction of a Benzo[b]furan Ester
Varadaraju and Hwu reported the stereoselective reduction of a benzo[b]furan ester with metallic magnesium, catalytic HgCl2, and
methanol as the solvent.18 The product is a (±)-trans-dihydrobenzo[b]furan. The use of HgCl2 raised the yield from 30% to 82%. It
has been proposed that HgCl2 activates the magnesium and thus accelerates the reduction.
R4
R1
HgCl2 (0.5 equiv)
HO
CHO
CO2Me
CO2Me
Mg (40.0 equiv)
HgCl2 (0.10 equiv)
OMe
MeOH
r.t.
20 h
O
OMe
OMe
OMe
O
OMe
OMe
82% yield (with HgCl2)
N
R1
OH
H
N
HgCl2 (12 mol%)
MeCN
80 °C
8h
R2
R1 = H, F, OMe, Me, Cl, Br
R2 = Ph, Me, Et
R1
R2
O
71–98% yield
References
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
Frankland, E. Phil. Trans. R. Soc. 1852, 142, 417.
Larock, R. C. Angew. Chem., Int. Ed. Engl. 1978, 17, 27.
Cataldo, F.; Kanazirev, V. Polyhedron 2013, 62, 42.
Voinov, M. A.; Grigor'ev, I. A. Tetrahedron Lett. 2002, 43,
2445.
Voinov, M. A.; Shevelev, T. G.; Rybalova, T. V.; Gatilov, Y.
V.; Pervukhina, N. V.; Burdukov, A. B.; Grigor'ev, I. A.
Organometallics 2007, 26, 1607.
Liu, L.; Lam, Y.-W.; Wong, W.-Y. J. Organomet. Chem.
2006, 691, 1092.
Nagapradeep, N.; Verma, S. Chem. Commun. 2011, 47,
1755.
Atta, A. K.; Kim, S.-B.; Heo, J.; Cho, D.-G. Org. Lett. 2013,
15, 1072.
Biswas, G.; Ghorai, S.; Bhattacharjya, A. Org. Lett. 2006, 8,
313.
Kaila, J. C.; Baraiya, A. B.; Pandya, A. N.; Jalani, H. B.;
Sudarsanam, V.; Vasu, K. K. Tetrahedron Lett. 2010, 51,
1486.
Synlett 2014, 25, 1043–1044
(11) Cunha, S.; Rodrigues, M. T. Jr.; da Silva, C. C.; Napolitano,
H. B.; Vencato, I.; Lariucci, C. Tetrahedron 2005, 61,
10536.
(12) Kaila, J. C.; Baraiya, A. B.; Vasu, K. K.; Sudarsanam, V.
Tetrahedron Lett. 2008, 49, 7220.
(13) Kaila, J. C.; Baraiya, A. B.; Pandya, A. N.; Jalani, H. B.;
Vasu, K. K.; Sudarsanam, V. Tetrahedron Lett. 2009, 50,
3955.
(14) O'Donovan, D. H.; Rozas, I. Tetrahedron Lett. 2011, 52,
4117.
(15) O'Donovan, D. H.; Rozas, I. Tetrahedron Lett. 2012, 53,
4532.
(16) Insuasty, H.; Insuasty, B.; Castro, E.; Quiroga, J.; Abonia, R.
Tetrahedron Lett. 2013, 54, 1722.
(17) Wong, W-Y. Coord. Chem. Rev. 2007, 251, 2400.
(18) Varadaraju, T. G.; Hwu, J. R. Org. Biomol. Chem. 2012, 10,
5456.
(19) Ramaligan, C.; Park, Y.-T. J. Org. Chem. 2007, 72, 4536.
© Georg Thieme Verlag Stuttgart · New York
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
1044