MAGNESIUM AMALGAM
1
Magnesium Amalgam
Mg(Hg)
[37237-15-3]
InChI = 1/Mg
InChIKey = FYYHWMGAXLPEAU-UHFFFAOYAI
(reduction of metal halides, particularly for the synthesis of
organometallic compounds; preparation of a reduced titanium
species from TiCl
4
that is useful for the reductive dimerization of
ketones, aldehydes, their derived imines, and the chemoselective
reduction of nitro groups; preparation of bis(bromomagnesio)-
methanes; reductive dimerization of germane derivatives; deoxy-
genation of epoxides)
Preparative Methods:
prepared fresh, or generated in situ, from
Magnesium metal and typically 1–3 mol % of a mercury(II) salt
such as Mercury(II) Chloride in THF or aromatic hydrocarbon
solvent.
Handling, Storage, and Precautions:
mercury salts are toxic.
Proper disposal is required.
Reductions and Reductive Dimerizations. Mg(Hg) is the
classical reagent for the reductive dimerization of acetone to form
pinacol,
1
and still finds occasional use in that regard.
2,3
More re-
cently, the pinacol coupling has been effected by the combination
of Titanium(IV) Chloride and 2 equiv of Mg(Hg).
4
For exam-
ple, using the latter mixture, cyclohexanone is dimerized in 93%
yield (eq 1). The intramolecular dimerization can be facile, as il-
lustrated by the reductive cyclization of 2,5-hexanedione to the
cis
-cyclobutanediol (eq 2), and the intramolecular ketoaldehyde
cross coupling illustrated in eq 3. Other reagents for pinacol-type
coupling of carbonyl derivatives include a variety of reduced tita-
nium reagents,
5
–
7
Samarium(II) Iodide,
8
Niobium Trichloride,
9
and Aluminum Chloride–Zinc–Acetic Acid.
10
O
HO OH
(1)
THF, 0 °C, 0.5 h
93%
Mg(Hg)–TiCl
4
O
O
Me
Me
OH
OH
(2)
THF, 0 °C, 2.5 h
81%
Mg(Hg)–TiCl
4
H
O
CHO
H
OH
OH
(3)
THF, 0 °C, 1.5 h
90%
Mg(Hg)–TiCl
4
The Mg(Hg)–TiCl
4
mixture is also an effective reagent
for the stereoselective reductive dimerization of aldimines to
1,2-diamines.
11,12
For example (eq 4), treatment of the aldimine
derived from benzaldehyde leads to a 80:20 mixture of syn (±)
and anti (meso) isomers in 63% yield. Simple reduction of the
aldimine competes with the dimerization. Similarly, the N-ben-
zylimine derived from acetaldehyde affords a 90:10 syn:anti
mixture in 67% yield. Other reagents for the reductive dimer-
ization of imines include TiCl
4
–Mg,
13
. SmI
2
,
14,15
Niobium(IV)
Chloride,
16
Indium,
17
Ytterbium(0),
18
and Zinc.
19
(4)
N
H
R
1
R
1
R
2
R
1
NHR
2
NHR
2
NHR
2
NHR
2
R
1
R
1
+
syn
(±)
anti
(meso)
(a) R = Ph, R
2
= Me (63%)
(b) R
1
= Me, R
2
= CH
2
Ph (67%)
THF, 0 °C, 12 h
Mg(Hg)–TiCl
4
Rivière and Satge
20
reported the Mg(Hg)-mediated reductive
dimerizations of organogermanes. For example (eq 5), treatment
of phenylchlorogermane with Mg(Hg) (THF, 20
◦
C) affords the
diphenyl-1,2-digermane in 75% yield. Similarly, diphenylchloro-
germane affords tetraphenyl-1,1,2,2-digermane in 73% yield.
R Ge
H
Ph
Cl
R
H
Ph
R
Ge
H
Ph
Ge
(5)
R = H (75%), Ph (73%)
THF, 20–60 °C
Mg(Hg)
The Mg(Hg)–TiCl
4
mixture is an effective reagent for the
chemoselective reduction of the nitro group.
21
For example
(eq 6), chloro-, cyano-, and carboxy-substituted nitro aromat-
ics are each reduced in high yield by the Mg(Hg)–TiCl
4
mix-
ture (THF–t-butanol, 0
◦
C, 1 h). Aliphatic nitro compounds
are also efficiently reduced. Others have used this procedure
successfully.
22
–
24
Other reagents for this transformation include
Titanium(III) Chloride,
25
TiCl
4
–Te(i-Bu)
2
,
26
TiCl
4
–Sodium
Borohydride,
27
Palladium on Carbon–Ammonium Formate,
28
Raney Nickel–Hydrazine,
29
Chromium(II) Chloride,
30
Tin(II)
Chloride,
31
and Nickel Boride (Ni
2
B).
32
O
2
N
R
H
2
N
R
(6)
R = Cl (92%), CN (94%), C(O)OCH
2
CH=CH
2
(96%)
THF, 0 °C, 12 h
Mg(Hg)–TiCl
4
Mg(Hg) has been used occasionally for the reduction of
1,2-dihalides
33
and enones,
34
and has been extensively used for
the preparation of reduced organometallic complexes.
35
–
40
Preparation of 1,1-Diorganometallic Reagents. Mg(Hg) has
been widely used for the preparation of 1,1-dimagnesium
reagents
41
by reaction with methylene dibromides and diiodides.
For example (eq 7), Cainelli and co-workers
42
found that
treatment of Dibromomethane or Diiodomethane with Mg(Hg)
affords a solution of organomagnesium reagent. Bis(bromo-
magnesio)methane reacts with CO
2
to afford the malonic acid
and with aldehydes and ketones to give alkenes. This reagent
has found use in organic synthesis
43
–
47
and offers an alternative
to Methylenetriphenylphosphorane, Trimethylsilylmethyllith-
ium, Trimethylsilylmethylmagnesium Chloride, the Tebbe
reagent(µ-Chlorobis(cyclopentadienyl)(dimethylaluminum)-µ-
methylenetitanium), dimethyltitanocene (Bis(cyclopentadienyl)
dimethyltitanium),
48
CH
2
I
2
–CrCl
2
,
49
CH
2
I
2
–Zn–Me
3
Al,
50
CH
2
I
2
–Zn–TiCl
4
,
51,52
and CH
2
(AlR
2
)
2
,
53
reagents. Similarly,
Mg(Hg) has been used for the preparation of the 1,1-dimagnesium
Avoid Skin Contact with All Reagents
2
MAGNESIUM AMALGAM
species bis(bromomagnesio)trimethylsilylmethane
54
and bis
(bromomagnesio)bis(trimethylsilyl)methane.
55
(7)
R
1
C(O)R
2
R
1
= C
11
H
23
, R
2
=H (65%)
R
1
= Ph, R
2
= H (70%)
R
1
, R
2
= -(CH
2
)
5
- (68%)
X
MgX
MgX
R
1
X
R
2
Mg(Hg)
X = Br, I
Bickelhaupt and co-workers
56
reported the use of bis(bro-
momagnesio)methane as a reagent for the preparation of 1,3-
dimetallacyclobutanes. For example (eq 8), treatment of bis-
(bromomagnesio)methane (prepared using Mg(Hg) as described
above) with Cp
2
TiCl
2
and Dichlorodimethylsilane affords the
novel mixed 1,3-dimetallacyclobutane in quantitative yield.
(8)
Cp
2
TiCl
2
Cp
2
Ti
CH
2
MgBr
CH
2
MgBr
Cp
2
Ti
SiMe
2
MgBr
MgBr
Me
2
SiCl
2
quantitative
Miscellaneous. Mg(Hg) has been used in combination with
Magnesium Bromide as a reagent for the deoxygenation of
epoxides.
57
Yields are typically modest, for example 50% for the
formation of cyclohexene from cyclohexene oxide, and several
good alternative reagents are available for this transformation.
58
1.
Adams, R.; Adams, E. W., Org. Synth. 1941, 1, 459.
2.
Binks, J.; Lloyd, D., J. Chem. Soc. (C) 1971, 2641.
3.
Nichols, P. P., J. Org. Chem. 1979, 44, 2126.
4.
Corey, E. J.; Danheiser, R. L.; Chandrasekaran, S., J. Org. Chem. 1976,
41
, 260.
5.
Lenior, D., Synthesis 1989, 883.
6.
McMurry, J., Chem. Rev. 1989, 89, 1513.
7.
Pons, J.-M.; Santelli, M., Tetrahedron 1988, 44, 4295.
8.
Chiara, J. L.; Cabri, W.; Hanessian, S., Tetrahedron Lett. 1991, 32, 1125.
9.
Szymoniak, J.; Bescancon, J.; Moise, C., Tetrahedron 1992, 48, 3867.
10.
Jun, J.-G.; Shin, H. S., Synth. Commun. 1993, 23, 1871.
11.
Mangeney, P.; Tejero, T.; Alexakis, A.; Grosjean, F.; Normant, J.,
Synthesis 1988
, 255.
12.
Cuvinot, D.; Mangeney, P.; Alexakis, A.; Normant, J.-F., J. Org. Chem.
1989, 54, 2420.
13.
Betschart, C.; Schmidt, B.; Seebach, D., Helv. Chim. Acta 1988, 71,
1999.
14.
Enholm, E.; Forbes, D. C.; Holub, D. P., Synth. Commun. 1990, 20, 981.
15.
Imamoto, T.; Nishimura, S., Chem. Lett. 1990, 1141.
16.
Roskamp, E. J.; Pederson, S. F., J. Am. Chem. Soc. 1987, 109, 3152.
17.
Kalyanam, N.; Rao, G. V., Tetrahedron Lett. 1993, 34, 1647.
18.
Takai, K.; Tsubaki, Y.; Tanaka, S.; Beppu, F.; Fujiwara, Y., Chem. Lett.
1990, 203.
19.
Shono, T.; Kise, N.; Oike, H.; Yoshimoto, M.; Okazaki, E., Tetrahedron
Lett. 1992
, 33, 5559.
20.
Rivière, P.; Satge, J., Synth. Inorg. Metal-Org. Chem. 1972, 2, 57.
21.
George, J.; Chandrasekaran, S., Synth. Commun. 1983, 13, 495.
22.
Dijkstra, P. J.; Van Steen, B. J.; Reinhoudt, D. N., J. Org. Chem. 1986,
51
, 5127.
23.
Sanchez, I. H.; Larraza, M. I.; Rojas, I.; Brena, F. K.; Flores, H. J.;
Jankowski, K., Heterocycles 1985, 23, 3033.
24.
Pakusch, J.; Ruechardt, C., Chem. Ber. 1990, 123, 2147.
25.
Ho, T.-L.; Wong, C. M., Synthesis 1974, 45.
26.
Suzuki, H.; Manabe, H.; Enokiya, R.; Hanazaki, Y., Chem. Lett. 1986,
1339.
27.
Kano, S.; Tanaka, Y.; Sugino, E.; Hibino, S., Synthesis 1980, 695.
28.
Ram, S.; Ehrenkaufer, R. E., Tetrahedron Lett. 1984, 25, 3415.
29.
Yuste, F.; Saldana, M.; Walls, F., Tetrahedron Lett. 1982, 23, 147.
30.
Varma, R. S.; Varma, M.; Kabalka, G. W., Tetrahedron Lett. 1985, 26,
3777.
31.
Bellamy, F. D.; Ou, K., Tetrahedron Lett. 1984, 25, 839.
32.
Ganem, B.; Osby, J. O., Chem. Rev. 1986, 86, 763.
33.
Wiberg, K. B.; Ubersax, R. W., J. Org. Chem. 1972, 37, 3827.
34.
Celina, M.; Lazana, R. L. R.; Luisa, M.; Franco, T. M. B.; Herold, B. J.,
J. Chem. Soc., Faraday Trans. 1993
, 1327.
35.
McVicker, G. B., Inorg. Synth 1976, 16, 56.
36.
McVicker, G. B., Inorg. Chem. 1975, 14, 2087.
37.
Green, M. L. H.; Wong, L. L., J. Chem. Soc., Chem. Commun. 1989,
571.
38.
Hill, A. F.; Honig, H. D.; Stone, F. G. A., J. Chem. Soc., Dalton Trans.
1988, 3031.
39.
Morancais, J. L.; Hubert-Pfalzgraf, L. G., Transition Met. Chem. 1984,
9
, 130.
40.
Jones, R. F.; Fisher, J. R.; Cole-Hamilton, D. J., J. Chem. Soc., Dalton
Trans. 1981
, 2550.
41.
Bickelhaupt, F., Angew. Chem., Int. Ed. Engl. 1987, 26, 990.
42.
Bertini, F.; Grasselli, P.; Zubiani, G.; Cainelli, G., Tetrahedron 1970, 26,
1281.
43.
Georges, M.; MacKay, D.; Fraser-Reid, B., J. Am. Chem. Soc. 1982, 104,
1101.
44.
Cardillo, G.; Orena, M.; Porzi, G.; Sandri, S., J. Org. Chem. 1981, 46,
2439.
45.
Gewali, M. B.; Ronald, R. C., J. Org. Chem. 1982, 47, 2792.
46.
Welch, S. C.; Rao, A. S. C. P.; Gibbs, C. G.; Wong, R. Y., J. Org. Chem.
1980, 45, 4077.
47.
Yoshimura, J.; Sato, K.; Wakai, H.; Funabashi, M., Bull. Chem. Soc. Jpn.
1976, 49, 1169.
48.
Petasis, N. A.; Bzowej, E. I., J. Am. Chem. Soc. 1990, 112, 6392.
49.
Okazoe, T.; Takai, K.; Utimoto, K., J. Am. Chem. Soc. 1987, 109, 951.
50.
Takai, K.; Hotta, Y.; Oshima, K.; Nozaki, H., Bull. Chem. Soc. Jpn. 1980,
53
, 1698.
51.
Hibino, J.; Okazoe, T.; Takai, K.; Nozaki, H., Tetrahedron Lett. 1985,
26
, 5581.
52.
Lombardo, L., Tetrahedron Lett. 1982, 23, 4293.
53.
Piotrowski, A. M.; Malpass, D. B.; Boleslawski, M. P.; Eisch, J. J., J.
Org. Chem. 1988
, 53, 2829.
54.
Van de Heisteeg, B. J. J.; Schat, G.; Tinga, M. A. G. M.; Akkerman, O.
S.; Bickelhaupt, F., Tetrahedron Lett. 1986, 27, 6123.
55.
Hogenbirk, M.; Van Eikema Hommes, N. J. R.; Schat, G.; Akkerman, O.
S.; Bickelhaupt, F.; Klumpp, G. W., Tetrahedron Lett. 1989, 30, 6195.
56.
Van de Heisteeg, B. J. J.; Schat, G.; Akkerman, O. S.; Bickelhaupt, F., J.
Organomet. Chem. 1986
, 308, 1.
57.
Bertini, F.; Grasselli, P.; Zubiani, G.; Cainelli, G., J. Chem. Soc., Dalton
Trans. 1970
, 3, 144.
58.
Wong, H. N. C.; Fok, C. C. M.; Wong, T., Heterocycles 1987, 26, 1345.
James M. Takacs
University of Nebraska-Lincoln, Lincoln, NE, USA
A list of General Abbreviations appears on the front Endpapers