MERCURY(II) CHLORIDE

1

Mercury(II) Chloride

1

HgCl

2

[7487-94-7]

Cl

2

Hg

(MW 271.49)

InChI = 1/2ClH.Hg/h2*1H;/q;;+2/p-2/f2Cl.Hg/h2*1h;/q2*-1;m
InChIKey = LWJROJCJINYWOX-ZZJRNXLTCY

(electrophilic mercuration of multiple bonds;

1

cleavage of

vinyl sulfides and thioacetals;

17

transmetalation;

1

preparation of

amalgams

30

–

33

)

Alternate Name:

mercuric chloride.

Physical Data:

mp 277

◦

C; bp 302

◦

C; d 5.440 g cm

−

3

.

Solubility:

sol H

2

O, alcohol, ether, glycerol, acetic acid, acetone,

ethyl acetate; slightly sol benzene, pyridine, CS

2

.

Form Supplied in:

white rhombic crystals.

Handling, Storage, and Precautions:

violent poison; may be fa-

tal if swallowed in 0.2–0.4 g doses. Exposure to any mercury
reagent is to be avoided. Teratogen; mutagen; irritant. Reacts
violently with K, Na. Releases toxic Hg vapor when heated to
decomposition. Handle in a fume hood.

Electrophilic Attack on Multiple Bonds. Although less elec-

trophilic than other Hg

II

reagents, HgCl

2

has been successfully

employed in electrophilic cyclization of various dienes

1,2

(see

also Mercury(II) Acetate) (eq 1);

3

an allylic hydroxyl controls

the diastereoselectivity of the latter reaction.

3

Aromatization of

certain conjugated systems has also been observed on treatment
with HgCl

2

.

4

Similar to Tl

I

salts,

5

HgCl

2

promotes iodocycliza-

tion of alkenic alcohols.

6

In the presence of a halogen (Cl

2

or Br

2

),

HgCl

2

facilitates halogenation of a C=C bond.

2

HO

OH

OH

OH

(1)

1. HgCl

2

, t-BuOH

2. NaBH

4

+

55%

Intramolecular aminomercuration of δ,ε-unsaturated amines

has also been accomplished with HgCl

2

7,8

(eq 2).

8

The stere-

ochemistry of the reaction is solvent dependent

8

and may be

reversible.

9

(2)

NHMe

Ph

Ph

N
Me

Ph

+

N
Me

1. HgCl

2

THF
THF, H

2

O

10:90 36%
87:13 64%

2. NaBH

4

Terminal alkynes (RC≡CH) add MeOH in the presence of Tri-

ethylamine and a catalytic amount of HgCl

2

to give enol ethers

of the corresponding ketones (RC(OMe)=CH

2

).

10

This reaction

parallels the well-known HgSO

4

-catalyzed hydration of alkynes,

producing ketones. 3-Alken-1-ynes undergo catalytic aminomer-
curation in the presence of HgCl

2

at 70

◦

C over 3–6 h to produce

enamines.

11

By contrast, propargylic alcohols (HC≡CCH

2

OH) un-

dergo oxidative aminomercuration to afford bis-aminated alde-
hydes, e.g. (Z)-PhNHCH=C(NHPh)CH=O.

12

Propargyl amines

(HC≡C–CH

2

NR

2

) add HgCl

2

in aqueous HCl to give ClCH=

C(HgCl)–CH

2

NR

2

.

13

Treatment of silyl enol ethers of ε-alkynic ketones or aldehydes

with HgCl

2

(1.1 equiv) and Hexamethyldisilazane (0.2 equiv; acid

scavenger) induces cyclization (eq 3).

14

HgCl

2

(TMS)

2

NH

CH

2

Cl

2

OTMS

O HgCl

(3)

30 °C

Enol ethers derived from carbohydrates can be readily con-

verted into carbocycles via a HgCl

2

-mediated reaction which in-

volves an electrophilic attack at the C=C bond to generate the
corresponding ketoaldehyde, which cyclizes spontaneously via
an intramolecular aldol condensation (eq 4).

15

O

OMe

OBn

AcO

OBn

O

OBn

AcO

OBn

(4)

HgCl

2

Me

2

CO–H

2

O (1:2)

reflux

Aldehydes RCH

2

CH=O (R=Me, Et) afford α,α-bischloro-

mercurated products on treatment with excess HgCl

2

.

16

Hydrolysis of Vinyl Sulfides and Thioacetals to Carbonyl

Compounds.

17

Whereas the hydrolysis of vinyl sulfides to ke-

tones works well with a mixture of HgCl

2

and an additive (HgO,

CaCO

3

, or CdCO

3

), the reaction leading to aldehydes often gives

unsatisfactory results. In this case, yields can be dramatically im-
proved if HCl is first added across the double bond of the vinyl
sulfide (RCH=CHSPh) to generate R–CH

2

CH(Cl)SPh. The lat-

ter intermediate is then quantitatively hydrolyzed by HgCl

2

and

water to the aldehyde RCH

2

CH=O.

18

Thioacetals

19,20

and O,S-acetals

21

are hydrolyzed by means

of HgCl

2

to the corresponding carbonyl compounds; addition of

Calcium Carbonate usually improves the yields (see also Mer-
cury(II) Chloride–Cadmium Carbonate). This method, involving
spontaneous spirocyclization of the resulting keto group, has been
employed in the synthesis of talaromycin B (eq 5).

20

O

O

O

O

S

S

OH

O

O

O

O

OH

(5)

1. HgCl

2

, MeCN

2. Me

2

C(OMe)

2

Talaromycin B

65%

Avoid Skin Contact with All Reagents

2

MERCURY(II) CHLORIDE

Methylthiomethyl (MTM) ethers can be converted into 2-me-

thoxyethoxy (MEM), methoxymethyl (MOM), or ethoxymethyl
(EOM) ethers on reaction with HgCl

2

and MeOCH

2

CH

2

OH,

MeOH, or EtOH, respectively, in 70–80% yields.

22

Addition of HgCl

2

to boronate ate complexes derived from O,S-

acetals induces B → C migration. This sequence has been used to
obtain optically pure aldehydes (eq 6).

23

Selenoacetals are simi-

larly hydrolyzed by HgCl

2

/CaCO

3

in acetonitrile.

24

(6)

B

O

O

B

O

O

OMe

PhS

CHO

1. HgCl

2

PhS(MeO)CHLi

2. H

2

O

2

Preparation of Organomercurials by Exchange Reac-

tions.

Among the methods developed for the synthesis of

organomercurials is the transmetalation of other organometallics
with HgCl

2

(e.g. ArLi → ArHgCl or RMgCl → RHgCl),

1,25

and reactions of aromatic diazonium salts with HgCl

2

and

copper (ArN

2

+

Cl

−

→

ArHgCl).

26

The yields in the lat-

ter methods do not exceed 50%.

25

Sodium p-toluenesulfinate

is also converted into the corresponding organomercurial
(MeC

6

H

4

HgCl) on reaction with HgCl

2

.

27

Vinylmercury chlo-

rides (RCH=CH–HgCl) can be prepared by transmetalation
of the corresponding vinylalanes, which, in turn, are available
from terminal alkynes; the transmetalation occurs with >98%
retention of configuration.

28

A stable metalated cubane deriva-

tive has been obtained by lithiation of the diisopropylamide
of cubanecarboxylic acid with Lithium 2,2,6,6-Tetramethyl-
piperidide followed by transmetalation with HgCl

2

.

29

Reversed

transmetalation (cubane–HgCl → cubane–Li) has also been des-
cribed.

29

Amalgams.

Mercury(II) chloride has been extensively uti-

lized for the preparation of a variety of amalgams (e.g. Zn,

30

Mg,

31

and Al)

32,33

to be employed in reductive processes such as Clem-

mensen reduction (with Zn)

30

or pinacol coupling (Mg),

31

and to

prepare, for example, aluminum ethoxide

32

and t-butoxide.

33

Miscellaneous.

Penam derivatives result from the HgCl

2

-

promoted ring closure of azetidin-2-one.

34

Mercury(II) chloride

seems to be a reagent of choice for isolation of histidine from a
mixture of amino acids in the form of an insoluble complex.

35

In

combination with iodine, HgCl

2

facilitates α-iodination of eno-

lizable ketones and aldehydes.

36

Related Reagents. Mercury(II) Chloride–Cadmium Carbo-

nate; Mercury(II) Chloride–Silver(I) Nitrite.

1.

(a) Larock, R. C., Angew. Chem., Int. Ed. Engl. 1978, 17, 27. (b) Larock,
R. C., Tetrahedron 1982, 38, 1713. (c) Larock, R. C. Organomercury
Compounds in Organic Synthesis

; Springer: Berlin, 1985. (d) Larock,

R. C. Solvomercuration/Demercuration Reactions in Organic Synthesis;
Springer: Berlin, 1986.

2.

(a) Vardhan, H. B.; Bach, R. D., J. Org. Chem. 1992, 57, 4948.
(b) Barluenga, J.; Martínez-Gallo, J. M.; Nájera, C.; Yus, M., J. Chem.
Soc., Chem. Commun. 1985

, 1422.

3.

(a) Henbest, H. B.; Nicholls, B., J. Chem. Soc 1959, 227. (b) Henbest,
H. B.; McElkinney, R. S., J. Chem. Soc 1959, 1834. (c) Matsuki, Y.;
Kodama, M.; Itô, S., Tetrahedron Lett. 1979, 2901.

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.

5.

Koˇcovský, P.; Pour, M., J. Org. Chem. 1990, 55, 5580.

6.

Forsyth, C. J.; Clardy, J., J. Am. Chem. Soc. 1990, 112, 3497.

7.

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4399.

8.

Tokuda, M.; Yamada, Y.; Suginome, H., Chem. Lett. 1988, 1289.

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.,
Chem. Commun. 1985

, 1375. Similar reaction occurs with (AcO)

2

Hg:

(b) Davtyan, S. Zh.; Chobanyan, Zh. A.; Badanyan, Sh. O., Arm. Khim.
Zh. 1983

, 36, 508 (Chem. Abstr. 1984, 100, 67 447c). (c) Barluenga,

J.; Aznar, F.; Valdez, C.; Cabal, M. P., J. Org. Chem. 1991, 56, 6166.
(d) Barluenga, J.; Aznar, F.; Liz, R.; Cabal, M. P., Synthesis 1986,
960.

12.

Barluenga, J.; Aznar, F.; Liz, R., J. Chem. Soc., Chem. Commun. 1986,
1180.

13.

Larock, R. C.; Burns, L. D.; Varaprath, S.; Russell, C. E.; Richardson, J.
W., Jr.; Janakiraman, M. N.; Jacobson, R. A., Organometallics 1987, 6,
1780.

14.

(a) Drouin, J.; Bonaventura, M.-A.; Coia, J.-M., J. Am. Chem. Soc. 1985,
107

, 1726. (b) Conia, J. M.; LePerchec, P., Synthesis 1975, 1. (c) Forsyth,

C. J.; Clardy, J., J. Am. Chem. Soc. 1990, 112, 3497.

15.

Chida, N.; Ohtsuka, M.; Nakazawa, K.; Ogawa, S., J. Chem. Soc., Chem.
Commun. 1989

, 436.

16.

Korpar-Colig, B.; Popovic, Z.; Sikirica, M., Croat. Chem. Acta 1984, 57,
689 (Chem. Abstr. 1985, 102, 220 968m).

17.

Stachel, D. P. N., Chem. Soc. Rev. 1977, 6, 345.

18.

Mura, A. J., Jr.; Majetich, G.; Grieco, P. A.; Cohen, T., Tetrahedron Lett.
1975, 4437.

19.

Seebach, D.; Beck, A. K., Org. Synth., Coll. Vol. 1988, 6, 316.

20.

(a) Schreiber, S. L.; Sommer, T. J., Tetrahedron Lett. 1983, 24, 4781.
(b) Kozikowski, A. P.; Scripko, J. G., J. Am. Chem. Soc. 1984, 106,
353.

21.

Jensen, J. L.; Maynard, D. F.; Shaw, G. R.; Smith, T. W., Jr., J. Org.
Chem. 1992

, 57, 1982.

22.

Chowdhury, P. K.; Sharma, D. N.; Sharma, R. R., Chem. Ind. (London)
1984, 803.

23.

(a) Brown, H. C.; Imai, T., J. Am. Chem. Soc. 1983, 105, 6285. (b) Brown,
H. C.; Imai, T.; Desai, M. C.; Singaram, B., J. Am. Chem. Soc. 1985, 107,
4980.

24.

Burton, A.; Hevesi, L.; Dumont, W.; Cravador, A.; Krief, A., Synthesis
1979, 877.

25.

(a) Eaton, P. E.; Martin, R. M., J. Org. Chem. 1988, 53, 2728. (b) Wells,
A. P.; Kitching, W., J. Chem. Soc., Perkin Trans. 1 1995, 527.

26.

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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.

29.

(a) Eaton, P.; Castaldi, G. U. S. Patent Appl. 613 708 (Chem. Abstr. 1986,
105

, 172 705n)(b) Eaton, P. E.; Cunkle, G. T.; Marchioro, G.; Martin,

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.;
Hering, H., Org. Synth., Coll. Vol. 1963, 4, 203. (c) Shriner, R. L.; Berger,
A., Org. Synth., Coll. Vol. 1955, 3, 786.

31.

Adams, R.; Adams, E. W., Org. Synth., Coll. Vol. 1941, 1, 459.

32.

Chalmers, W., Org. Synth., Coll. Vol. 1943, 2, 598.

33.

Wayne, W.; Adkins, H., Org. Synth., Coll. Vol. 1955, 3, 367.

34.

Sheehan, J. C.; Piper, J. V., J. Org. Chem. 1973, 38, 3492.

35.

Foster, G. L.; Shemin, D., Org. Synth., Coll. Vol. 1943, 2, 330.

36.

Barluenga, J.; Martinez-Gallo, J. M.; Najera, C.; Yus, M., Synthesis 1986,
678.

Pavel Koˇcovský

University of Leicester, Leicester, UK

Avoid Skin Contact with All Reagents