MERCURY(II) CHLORIDE 1
enamines.11 By contrast, propargylic alcohols (HC
a"CCH2OH) un-
Mercury(II) Chloride1
dergo oxidative aminomercuration to afford bis-aminated alde-
hydes, e.g. (Z)-PhNHCH=C(NHPh)CH=O.12 Propargyl amines
HgCl2
(HCa"C CH2NR2) add HgCl2 in aqueous HCl to give ClCH=
C(HgCl) CH2NR2.13
Treatment of silyl enol ethers of µ-alkynic ketones or aldehydes
[7487-94-7] Cl2Hg (MW 271.49)
with HgCl2 (1.1 equiv) and Hexamethyldisilazane (0.2 equiv; acid
InChI = 1/2ClH.Hg/h2*1H;/q;;+2/p-2/f2Cl.Hg/h2*1h;/q2*-1;m
scavenger) induces cyclization (eq 3).14
InChIKey = LWJROJCJINYWOX-ZZJRNXLTCY
(electrophilic mercuration of multiple bonds;1 cleavage of
HgCl2
OTMS
vinyl sulfides and thioacetals;17 transmetalation;1 preparation of
HgCl
O
(TMS)2NH
amalgams30 33)
CH2Cl2
(3)
30 °C
Alternate Name: mercuric chloride.
ć% ć%
Physical Data: mp 277 C; bp 302 C; d 5.440 g cm-3.
Solubility: sol H2O, alcohol, ether, glycerol, acetic acid, acetone,
ethyl acetate; slightly sol benzene, pyridine, CS2.
Enol ethers derived from carbohydrates can be readily con-
Form Supplied in: white rhombic crystals.
verted into carbocycles via a HgCl2-mediated reaction which in-
Handling, Storage, and Precautions: violent poison; may be fa-
volves an electrophilic attack at the C=C bond to generate the
tal if swallowed in 0.2 0.4 g doses. Exposure to any mercury
corresponding ketoaldehyde, which cyclizes spontaneously via
reagent is to be avoided. Teratogen; mutagen; irritant. Reacts
an intramolecular aldol condensation (eq 4).15
violently with K, Na. Releases toxic Hg vapor when heated to
decomposition. Handle in a fume hood.
HgCl2
O OMe O
Me2CO H2O (1:2)
(4)
Electrophilic Attack on Multiple Bonds. Although less elec-
reflux
AcO OBn AcO OBn
trophilic than other HgII reagents, HgCl2 has been successfully
OBn OBn
employed in electrophilic cyclization of various dienes1,2 (see
also Mercury(II) Acetate) (eq 1);3 an allylic hydroxyl controls
the diastereoselectivity of the latter reaction.3 Aromatization of
Aldehydes RCH2CH=O (R=Me, Et) afford Ä…,Ä…-bischloro-
certain conjugated systems has also been observed on treatment
mercurated products on treatment with excess HgCl2.16
with HgCl2.4 Similar to TlI salts,5 HgCl2 promotes iodocycliza-
tion of alkenic alcohols.6 In the presence of a halogen (Cl2 or Br2),
Hydrolysis of Vinyl Sulfides and Thioacetals to Carbonyl
HgCl2 facilitates halogenation of a C=C bond.2
Compounds.17 Whereas the hydrolysis of vinyl sulfides to ke-
tones works well with a mixture of HgCl2 and an additive (HgO,
OH
HO OH
1. HgCl2, t-BuOH
CaCO3, or CdCO3), the reaction leading to aldehydes often gives
2. NaBH4
unsatisfactory results. In this case, yields can be dramatically im-
(1)
+
55%
proved if HCl is first added across the double bond of the vinyl
sulfide (RCH=CHSPh) to generate R CH2CH(Cl)SPh. The lat-
OH
ter intermediate is then quantitatively hydrolyzed by HgCl2 and
water to the aldehyde RCH2CH=O.18
Thioacetals19,20 and O,S-acetals21 are hydrolyzed by means
Intramolecular aminomercuration of ´,µ-unsaturated amines
of HgCl2 to the corresponding carbonyl compounds; addition of
has also been accomplished with HgCl27,8 (eq 2).8 The stere-
Calcium Carbonate usually improves the yields (see also Mer-
ochemistry of the reaction is solvent dependent8 and may be
cury(II) Chloride Cadmium Carbonate). This method, involving
reversible.9
spontaneous spirocyclization of the resulting keto group, has been
employed in the synthesis of talaromycin B (eq 5).20
1. HgCl2
+ (2)
Ph Ph Ph
2. NaBH4
N N
NHMe
1. HgCl2, MeCN
Me Me OH
2. Me2C(OMe)2
S S
THF 10:90 36%
OO
65%
THF, H2O 87:13 64%
OO
OH
Terminal alkynes (RCa"CH) add MeOH in the presence of Tri-
ethylamine and a catalytic amount of HgCl2 to give enol ethers
O
of the corresponding ketones (RC(OMe)=CH2).10 This reaction
Talaromycin B (5)
O
parallels the well-known HgSO4-catalyzed hydration of alkynes,
O O
producing ketones. 3-Alken-1-ynes undergo catalytic aminomer-
ć%
curation in the presence of HgCl2 at 70 C over 3 6 h to produce
Avoid Skin Contact with All Reagents
2 MERCURY(II) CHLORIDE
Methylthiomethyl (MTM) ethers can be converted into 2-me- R. C. Solvomercuration/Demercuration Reactions in Organic Synthesis;
Springer: Berlin, 1986.
thoxyethoxy (MEM), methoxymethyl (MOM), or ethoxymethyl
2. (a) Vardhan, H. B.; Bach, R. D., J. Org. Chem. 1992, 57, 4948.
(EOM) ethers on reaction with HgCl2 and MeOCH2CH2OH,
(b) Barluenga, J.; Martínez-Gallo, J. M.; Nájera, C.; Yus, M., J. Chem.
MeOH, or EtOH, respectively, in 70 80% yields.22
Soc., Chem. Commun. 1985, 1422.
Addition of HgCl2 to boronate ate complexes derived from O,S-
3. (a) Henbest, H. B.; Nicholls, B., J. Chem. Soc 1959, 227. (b) Henbest,
acetals induces B C migration. This sequence has been used to
H. B.; McElkinney, R. S., J. Chem. Soc 1959, 1834. (c) Matsuki, Y.;
obtain optically pure aldehydes (eq 6).23 Selenoacetals are simi-
Kodama, M.; Itô, S., Tetrahedron Lett. 1979, 2901.
larly hydrolyzed by HgCl2/CaCO3 in acetonitrile.24
4. Rozenberg, V. I.; Gavrilova, G. V.; Ginzburg, B. I.; Nikanorov, V. A.;
Reutov, O. A., Izv. Akad. Nauk SSSR, Ser. Khim. 1982, 1916; Bull. Acad.
Sci. USSR, Div. Chem. Sci. 1982, 31, 1707.
O
O
5. Ko%0ńovskż, P.; Pour, M., J. Org. Chem. 1990, 55, 5580.
1. HgCl2
PhS(MeO)CHLi
O
B
B
OMe
6. Forsyth, C. J.; Clardy, J., J. Am. Chem. Soc. 1990, 112, 3497.
O
2. H2O2
7. Périé, J. J.; Laval, J. P.; Roussel, J.; Lattes, A., Tetrahedron Lett. 1971,
PhS
4399.
8. Tokuda, M.; Yamada, Y.; Suginome, H., Chem. Lett. 1988, 1289.
CHO
(6)
9. Barluenga, J.; Perez-Prieto, J.; Bayon, A. M., Tetrahedron 1984, 40,
1199.
10. Barluenga, J.; Aznar, F.; Bayod, M., Synthesis 1988, 144.
11. (a) Barluenga, J.; Aznar, F.; Liz, R.; Cabal, M. P., J. Chem. Soc.,
Preparation of Organomercurials by Exchange Reac- Chem. Commun. 1985, 1375. Similar reaction occurs with (AcO)2Hg:
(b) Davtyan, S. Zh.; Chobanyan, Zh. A.; Badanyan, Sh. O., Arm. Khim.
tions. Among the methods developed for the synthesis of
Zh. 1983, 36, 508 (Chem. Abstr. 1984, 100, 67 447c). (c) Barluenga,
organomercurials is the transmetalation of other organometallics
J.; Aznar, F.; Valdez, C.; Cabal, M. P., J. Org. Chem. 1991, 56, 6166.
with HgCl2 (e.g. ArLi ArHgCl or RMgCl RHgCl),1,25
(d) Barluenga, J.; Aznar, F.; Liz, R.; Cabal, M. P., Synthesis 1986,
and reactions of aromatic diazonium salts with HgCl2 and
960.
copper (ArN2+ Cl- ArHgCl).26 The yields in the lat-
12. Barluenga, J.; Aznar, F.; Liz, R., J. Chem. Soc., Chem. Commun. 1986,
ter methods do not exceed 50%.25 Sodium p-toluenesulfinate
1180.
is also converted into the corresponding organomercurial
13. Larock, R. C.; Burns, L. D.; Varaprath, S.; Russell, C. E.; Richardson, J.
(MeC6H4HgCl) on reaction with HgCl2.27 Vinylmercury chlo- W., Jr.; Janakiraman, M. N.; Jacobson, R. A., Organometallics 1987, 6,
1780.
rides (RCH=CH HgCl) can be prepared by transmetalation
14. (a) Drouin, J.; Bonaventura, M.-A.; Coia, J.-M., J. Am. Chem. Soc. 1985,
of the corresponding vinylalanes, which, in turn, are available
107, 1726. (b) Conia, J. M.; LePerchec, P., Synthesis 1975, 1. (c) Forsyth,
from terminal alkynes; the transmetalation occurs with >98%
C. J.; Clardy, J., J. Am. Chem. Soc. 1990, 112, 3497.
retention of configuration.28 A stable metalated cubane deriva-
15. Chida, N.; Ohtsuka, M.; Nakazawa, K.; Ogawa, S., J. Chem. Soc., Chem.
tive has been obtained by lithiation of the diisopropylamide
Commun. 1989, 436.
of cubanecarboxylic acid with Lithium 2,2,6,6-Tetramethyl-
16. Korpar-Colig, B.; Popovic, Z.; Sikirica, M., Croat. Chem. Acta 1984, 57,
piperidide followed by transmetalation with HgCl2.29 Reversed
689 (Chem. Abstr. 1985, 102, 220 968m).
transmetalation (cubane HgCl cubane Li) has also been des-
17. Stachel, D. P. N., Chem. Soc. Rev. 1977, 6, 345.
cribed.29
18. Mura, A. J., Jr.; Majetich, G.; Grieco, P. A.; Cohen, T., Tetrahedron Lett.
1975, 4437.
Amalgams. Mercury(II) chloride has been extensively uti-
19. Seebach, D.; Beck, A. K., Org. Synth., Coll. Vol. 1988, 6, 316.
lized for the preparation of a variety of amalgams (e.g. Zn,30 Mg,31
20. (a) Schreiber, S. L.; Sommer, T. J., Tetrahedron Lett. 1983, 24, 4781.
and Al)32,33 to be employed in reductive processes such as Clem-
(b) Kozikowski, A. P.; Scripko, J. G., J. Am. Chem. Soc. 1984, 106,
mensen reduction (with Zn)30 or pinacol coupling (Mg),31 and to
353.
prepare, for example, aluminum ethoxide32 and t-butoxide.33 21. Jensen, J. L.; Maynard, D. F.; Shaw, G. R.; Smith, T. W., Jr., J. Org.
Chem. 1992, 57, 1982.
Miscellaneous. Penam derivatives result from the HgCl2- 22. Chowdhury, P. K.; Sharma, D. N.; Sharma, R. R., Chem. Ind. (London)
1984, 803.
promoted ring closure of azetidin-2-one.34 Mercury(II) chloride
23. (a) Brown, H. C.; Imai, T., J. Am. Chem. Soc. 1983, 105, 6285. (b) Brown,
seems to be a reagent of choice for isolation of histidine from a
H. C.; Imai, T.; Desai, M. C.; Singaram, B., J. Am. Chem. Soc. 1985, 107,
mixture of amino acids in the form of an insoluble complex.35 In
4980.
combination with iodine, HgCl2 facilitates Ä…-iodination of eno-
24. Burton, A.; Hevesi, L.; Dumont, W.; Cravador, A.; Krief, A., Synthesis
lizable ketones and aldehydes.36
1979, 877.
25. (a) Eaton, P. E.; Martin, R. M., J. Org. Chem. 1988, 53, 2728. (b) Wells,
Related Reagents. Mercury(II) Chloride Cadmium Carbo-
A. P.; Kitching, W., J. Chem. Soc., Perkin Trans. 1 1995, 527.
nate; Mercury(II) Chloride Silver(I) Nitrite.
26. Nesmeyanov, A. N., Org. Synth., Coll. Vol. 1943, 2, 432.
27. Whitmore, F. C.; Hamilton, F. H.; Thurman, N., Org. Synth., Coll. Vol.
1941, 1, 519.
28. Negishi, E.; Jadhav, K. P.; Daotien, N., Tetrahedron Lett. 1982, 23,
2085.
1. (a) Larock, R. C., Angew. Chem., Int. Ed. Engl. 1978, 17, 27. (b) Larock, 29. (a) Eaton, P.; Castaldi, G. U. S. Patent Appl. 613 708 (Chem. Abstr. 1986,
R. C., Tetrahedron 1982, 38, 1713. (c) Larock, R. C. Organomercury 105, 172 705n)(b) Eaton, P. E.; Cunkle, G. T.; Marchioro, G.; Martin,
Compounds in Organic Synthesis; Springer: Berlin, 1985. (d) Larock, R. M., J. Am. Chem. Soc. 1987, 109, 948.
A list of General Abbreviations appears on the front Endpapers
MERCURY(II) CHLORIDE 3
30. (a) Martin, E. L., Org. Synth., Coll. Vol. 1943, 2, 499. (b) Schwarz, R.; 35. Foster, G. L.; Shemin, D., Org. Synth., Coll. Vol. 1943, 2, 330.
Hering, H., Org. Synth., Coll. Vol. 1963, 4, 203. (c) Shriner, R. L.; Berger,
36. Barluenga, J.; Martinez-Gallo, J. M.; Najera, C.; Yus, M., Synthesis 1986,
A., Org. Synth., Coll. Vol. 1955, 3, 786.
678.
31. Adams, R.; Adams, E. W., Org. Synth., Coll. Vol. 1941, 1, 459.
32. Chalmers, W., Org. Synth., Coll. Vol. 1943, 2, 598.
Pavel Ko%0ńovskż
33. Wayne, W.; Adkins, H., Org. Synth., Coll. Vol. 1955, 3, 367.
University of Leicester, Leicester, UK
34. Sheehan, J. C.; Piper, J. V., J. Org. Chem. 1973, 38, 3492.
Avoid Skin Contact with All Reagents