Mercury(II) Chloride1

HgCl2

[7487-94-7]  · Cl2Hg  · Mercury(II) Chloride  · (MW 271.49)

(electrophilic mercuration of multiple bonds;1 cleavage of vinyl sulfides and thioacetals;17 transmetalation;1 preparation of amalgams30-33)

Alternate Name: mercuric chloride.

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.

Form Supplied in: white rhombic crystals.

Handling, Storage, and Precautions: violent poison; may be fatal 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 electrophilic than other HgII reagents, HgCl2 has been successfully 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 certain conjugated systems has also been observed on treatment with HgCl2.4 Similar to TlI salts,5 HgCl2 promotes iodocyclization of alkenic alcohols.6 In the presence of a halogen (Cl2 or Br2), HgCl2 facilitates halogenation of a C=C bond.2

Intramolecular aminomercuration of d,ε-unsaturated amines has also been accomplished with HgCl27,8 (eq 2).8 The stereochemistry of the reaction is solvent dependent8 and may be reversible.9

Terminal alkynes (RC&tbond;CH) add MeOH in the presence of Triethylamine and a catalytic amount of HgCl2 to give enol ethers of the corresponding ketones (RC(OMe)=CH2).10 This reaction parallels the well-known HgSO4-catalyzed hydration of alkynes, producing ketones. 3-Alken-1-ynes undergo catalytic aminomercuration in the presence of HgCl2 at 70 °C over 3-6 h to produce enamines.11 By contrast, propargylic alcohols (HC&tbond;CCH2OH) undergo oxidative aminomercuration to afford bis-aminated aldehydes, e.g. (Z)-PhNHCH=C(NHPh)CH=O.12 Propargyl amines (HC&tbond;C-CH2NR2) add HgCl2 in aqueous HCl to give ClCH=C(HgCl)-CH2NR2.13

Treatment of silyl enol ethers of ε-alkynic ketones or aldehydes with HgCl2 (1.1 equiv) and Hexamethyldisilazane (0.2 equiv; acid scavenger) induces cyclization (eq 3).14

Enol ethers derived from carbohydrates can be readily converted into carbocycles via a HgCl2-mediated reaction which involves an electrophilic attack at the C=C bond to generate the corresponding ketoaldehyde, which cyclizes spontaneously via an intramolecular aldol condensation (eq 4).15

Aldehydes RCH2CH=O (R = Me, Et) afford a,a-bischloromercurated products on treatment with excess HgCl2.16

Hydrolysis of Vinyl Sulfides and Thioacetals to Carbonyl Compounds.17

Whereas the hydrolysis of vinyl sulfides to ketones works well with a mixture of HgCl2 and an additive (HgO, CaCO3, or CdCO3), the reaction leading to aldehydes often gives unsatisfactory results. In this case, yields can be dramatically improved if HCl is first added across the double bond of the vinyl sulfide (RCH=CHSPh) to generate R-CH2CH(Cl)SPh. The latter 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 of HgCl2 to the corresponding carbonyl compounds; addition of Calcium Carbonate usually improves the yields (see also Mercury(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

Methylthiomethyl (MTM) ethers can be converted into 2-methoxyethoxy (MEM), methoxymethyl (MOM), or ethoxymethyl (EOM) ethers on reaction with HgCl2 and MeOCH2CH2OH, MeOH, or EtOH, respectively, in 70-80% yields.22

Addition of HgCl2 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 similarly hydrolyzed by HgCl2/CaCO3 in acetonitrile.24

Preparation of Organomercurials by Exchange Reactions.

Among the methods developed for the synthesis of organomercurials is the transmetalation of other organometallics with HgCl2 (e.g. ArLi -> ArHgCl or RMgCl -> RHgCl),1,25 and reactions of aromatic diazonium salts with HgCl2 and copper (ArN2+ Cl- -> ArHgCl).26 The yields in the latter methods do not exceed 50%.25 Sodium p-toluenesulfinate is also converted into the corresponding organomercurial (MeC6H4HgCl) on reaction with HgCl2.27 Vinylmercury chlorides (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 derivative has been obtained by lithiation of the diisopropylamide of cubanecarboxylic acid with Lithium 2,2,6,6-Tetramethylpiperidide followed by transmetalation with HgCl2.29 Reversed transmetalation (cubane-HgCl -> cubane-Li) has also been described.29

Amalgams.

Mercury(II) chloride has been extensively utilized 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 Clemmensen reduction (with Zn)30 or pinacol coupling (Mg),31 and to prepare, for example, aluminum ethoxide32 and t-butoxide.33

Miscellaneous.

Penam derivatives result from the HgCl2-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, HgCl2 facilitates a-iodination of enolizable ketones and aldehydes.36

Related Reagents.

Mercury(II) Chloride-Cadmium Carbonate; Mercury(II) Chloride-Silver(I) Nitrite.


1. (a) Larock, R. C. AG(E) 1978, 17, 27. (b) Larock, R. C. T 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. JOC 1992, 57, 4948. (b) Barluenga, J.; Martínez-Gallo, J. M.; Nájera, C.; Yus, M. CC 1985, 1422.
3. (a) Henbest, H. B.; Nicholls, B. JCS 1959, 227. (b) Henbest, H. B.; McElkinney, R. S. JCS 1959, 1834. (c) Matsuki, Y.; Kodama, M.; Itô, S. TL 1979, 2901.
4. Rozenberg, V. I.; Gavrilova, G. V.; Ginzburg, B. I.; Nikanorov, V. A.; Reutov, O. A. IZV 1982, 1916; BAU 1982, 31, 1707.
5. Ko&cbreve;ovský, P.; Pour, M. JOC 1990, 55, 5580.
6. Forsyth, C. J.; Clardy, J. JACS 1990, 112, 3497.
7. Périé, J. J.; Laval, J. P.; Roussel, J.; Lattes, A. TL 1971, 4399.
8. Tokuda, M.; Yamada, Y.; Suginome, H. CL 1988, 1289.
9. Barluenga, J.; Perez-Prieto, J.; Bayon, A. M. T 1984, 40, 1199.
10. Barluenga, J.; Aznar, F.; Bayod, M. S 1988, 144.
11. (a) Barluenga, J.; Aznar, F.; Liz, R.; Cabal, M. P. CC 1985, 1375. Similar reaction occurs with (AcO)2Hg: (b) Davtyan, S. Zh.; Chobanyan, Zh. A.; Badanyan, Sh. O. Arm. Khim. Zh. 1983, 36, 508 (CA 1984, 100, 67 447c). (c) Barluenga, J.; Aznar, F.; Valdez, C.; Cabal, M. P. JOC 1991, 56, 6166. (d) Barluenga, J.; Aznar, F.; Liz, R.; Cabal, M. P. S 1986, 960.
12. Barluenga, J.; Aznar, F.; Liz, R. CC 1986, 1180.
13. Larock, R. C.; Burns, L. D.; Varaprath, S.; Russell, C. E.; Richardson, J. W., Jr.; Janakiraman, M. N.; Jacobson, R. A. OM 1987, 6, 1780.
14. (a) Drouin, J.; Bonaventura, M.-A.; Coia, J.-M. JACS 1985, 107, 1726. (b) Conia, J. M.; LePerchec, P. S 1975, 1. (c) Forsyth, C. J.; Clardy, J. JACS 1990, 112, 3497.
15. Chida, N.; Ohtsuka, M.; Nakazawa, K.; Ogawa, S. CC 1989, 436.
16. Korpar-Colig, B.; Popovic, Z.; Sikirica, M. Croat. Chem. Acta 1984, 57, 689 (CA 1985, 102, 220 968m).
17. Stachel, D. P. N. CSR 1977, 6, 345.
18. Mura, A. J., Jr.; Majetich, G.; Grieco, P. A.; Cohen, T. TL 1975, 4437.
19. Seebach, D.; Beck, A. K. OSC 1988, 6, 316.
20. (a) Schreiber, S. L.; Sommer, T. J. TL 1983, 24, 4781. (b) Kozikowski, A. P.; Scripko, J. G. JACS 1984, 106, 353.
21. Jensen, J. L.; Maynard, D. F.; Shaw, G. R.; Smith, T. W., Jr. JOC 1992, 57, 1982.
22. Chowdhury, P. K.; Sharma, D. N.; Sharma, R. R. CI(L) 1984, 803.
23. (a) Brown, H. C.; Imai, T. JACS 1983, 105, 6285. (b) Brown, H. C.; Imai, T.; Desai, M. C.; Singaram, B. JACS 1985, 107, 4980.
24. Burton, A.; Hevesi, L.; Dumont, W.; Cravador, A.; Krief, A. S 1979, 877.
25. (a) Eaton, P. E.; Martin, R. M. JOC 1988, 53, 2728. (b) Wells, A. P.; Kitching, W. JCS(P1) 1995, 527.
26. Nesmeyanov, A. N. OSC 1943, 2, 432.
27. Whitmore, F. C.; Hamilton, F. H.; Thurman, N. OSC 1941, 1, 519.
28. Negishi, E.; Jadhav, K. P.; Daotien, N. TL 1982, 23, 2085.
29. (a) Eaton, P.; Castaldi, G. U.S. Patent Appl. 613 708 (CA 1986, 105, 172 705n) (b) Eaton, P. E.; Cunkle, G. T.; Marchioro, G.; Martin, R. M. JACS 1987, 109, 948.
30. (a) Martin, E. L. OSC 1943, 2, 499. (b) Schwarz, R.; Hering, H. OSC 1963, 4, 203. (c) Shriner, R. L.; Berger, A. OSC 1955, 3, 786.
31. Adams, R.; Adams, E. W. OSC 1941, 1, 459.
32. Chalmers, W. OSC 1943, 2, 598.
33. Wayne, W.; Adkins, H. OSC 1955, 3, 367.
34. Sheehan, J. C.; Piper, J. V. JOC 1973, 38, 3492.
35. Foster, G. L.; Shemin, D. OSC 1943, 2, 330.
36. Barluenga, J.; Martinez-Gallo, J. M.; Najera, C.; Yus, M. S 1986, 678.

Pavel Ko&cbreve;ovský

University of Leicester, UK



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