[7782-50-5]  · Cl2  · Chlorine  · (MW 70.91)

(powerful oxidizing and chlorinating agent)

Physical Data: yellowish-green gas, mp -101 °C, bp -34 °C; d 3.21 g cm-3 (gas, rt), 1.56 g cm-3 (liq, -35 °C).

Solubility: sl sol water (0.7 g in 100 mL at 20 °C); sol acetic acid, benzene, aliphatic hydrocarbons, chlorinated solvents, DMF.

Form Supplied in: packaged in cylinders with stainless steel or monel regulators.

Preparative Methods: chlorine is commercially available, but small quantities can be generated in the laboratory. The most common procedure involves the treatment of solid KMnO4 with conc HCl (0.89 g of KMnO4 and 5.6 mL of conc HCl per g of chlorine required).2 It is recommended that chlorine so generated be dried by passing in succession through gas-washing bottles containing H2O (to remove HCl), concd H2SO4 (to remove H2O), and glass wool (to remove spray).3 Preparations using conc HCl/MnO24 or by heating CuCl2 (anhyd)5 have also been reported.

Analysis of Reagent Purity: iodometric titration; the chlorine can be volatilized and the moisture and residue determined gravimetrically.1a

Purification: commercial chlorine should be purified with H2SO4, CaO, and P2O5 and subsequently condensed in a dry ice-acetone bath and vaporized, repeatedly, while the noncondensable gases are removed with a pump.4

Handling, Storage, and Precautions: 5 highly toxic, nonflammable gas. Forms explosive mixtures with hydrogen, acetylene, or anhydrous ammonia. It is corrosive when moist. Chlorine is a strong oxidant and reacts violently with combustible substances, reducing agents, organic compounds, phosphorus, and metal powders. Avoid skin contact. Use protective clothing and a full-face respirator equipped with a NIOSH-approved organic vapor-acid gas canister. Cylinders should be stored away from sources of heat. All reactions should be conducted in a well-ventilated fume hood. The amount of chlorine added to a reaction mixture can be determined by weighing the cylinder before and after addition, or by condensing the required volume into a calibrated vessel and subsequently allowing it to volatilize while connected to the reaction vessel, or by generation from a known quantity of KMnO4.

Substitution Chlorination.

Chlorine atoms, obtained from the dissociation of chlorine molecules by thermal or photochemical energy, react with saturated hydrocarbons by a radical chain mechanism. Chlorine reacts with methane to form methyl chloride, methylene chloride, chloroform, and carbon tetrachloride.1a Trialkylboranes have also been used to induce the radical chlorination of alkanes, e.g. chloro-2,3-dimethylbutanes are produced from 2,3-dimethylbutane.6 Ethers are also chlorinated by photoinduced radical substitution reactions (eq 1).7a

The chlorination of carboxylic acids with molecular chlorine is catalyzed by phosphorus and its trihalides.7b Chlorine has been used to chlorinate methyl esters of carboxylic acids to form monochloro esters.8 Chlorinations with chlorine favor the (o - 1)-position rather than the (o - 2)-position obtained with Sulfuryl Chloride.8 Thus the chlorination of methyl heptanoate with chlorine results mainly in methyl 6-chloroheptanoate, whereas chlorination with sulfuryl chloride results mainly in methyl 5-chloroheptanoate.8 Low temperatures are required for the chlorination of long-chain carboxylic acid methyl chlorides, as unsaturated compounds are formed at higher temperatures due to the elimination of HCl.

The main products of the chlorination of carbamates are the N-dichloro derivatives (eq 2).7c

Aromatic amines react readily with chlorine, e.g. aniline is chlorinated to give 2,4,6-trichloroaniline in high yield (eq 3).7d

Primary and secondary amides react with chlorine to give N-chloroamides and HCl.7e The reaction is reversible, and the products are favored by highly polar solvents.

a-Chlorination of aliphatic acids has been achieved with chlorine using enolizing agents like chlorosulfonic acid, H2SO4, HCl, or FeCl3 with a radical trapper like m-dinitrobenzene, oxygen, or chloranil.9 The imidyl hydrogen atoms of aldazines can be substituted with chlorine (eq 4).7f

Addition Chlorination.

Saturated chlorides are formed when chlorine reacts with alkenes, e.g. chlorination of ethylene results in ethylene dichloride and chlorination of vinyl chloride gives 1,1,2-trichloroethane.1a These alkyl chlorides are important synthetic intermediates, e.g. 1,1,2-trichloroethane can be converted into vinylidene chloride in an alkaline medium.1a The addition of chlorine to 1-trimethylsilyl-1-alkenes in CH2Cl2 at low temperatures, followed by the elimination of Me3SiX with methanolic sodium methoxide at 25 °C, produces vinyl chlorides in good yields (eq 5).10

The radical chain addition reactions of chlorine are initiated by light or the walls of the reaction vessel and inhibited by oxygen. Some ionic addition reactions are accelerated by Iron(III) Chloride, Aluminum Chloride, Antimony(V) Chloride, or Copper(II) Chloride.11

Chlorination of Aromatics.

Aromatic compounds may be chlorinated in the presence of Lewis acids like iron and iron(III) chloride. Low temperatures favor monochlorination, while high temperatures (150-190 °C) favor dichlorinated products.11 The chlorination of alkylbenzenes in alcoholic media can result in higher yields of monochloro derivatives than when FeCl3 is used.12 Chlorine diluted in water converts tyrosine into 3-chloro-4-hydroxybenzyl cyanide (eq 6);13 larger amounts of chlorine give 3,5-dichloro-4-hydroxybenzyl cyanide and 1,3-dichloro-2,5-dihydroxybenzene. The latter product can be converted into 2,6-dichloro-p-benzoquinone with additional aqueous chlorine.

Toluene is chlorinated by the radical mechanism to give benzyl chloride, benzal chloride, and benzotrichloride.11 Sulfuryl chloride, t-Butyl Hypochlorite, Hydrogen Chloride (in the presence of a copper-salt catalyst), and N-Chlorosuccinimide have also been used to chlorinate aromatics.11

Chlorination of phenol yields 2-chlorophenol and 4-chlorophenol in a ratio of 0.45:0.49, which is higher than the ortho/para ratio obtained with t-butyl hypochlorite.14 4-Alkylphenols react with chlorine in various solvents to form mainly 4-alkyl-4-chlorocyclohexa-2,5-dienones (in yields of 19-100%) and substitution products.15 Other chlorinating agents (alkyl hypochlorites, sulfuryl chloride, hypochlorous acid, and antimony pentachloride) have also been used, but they result in polychlorinated cyclohexadienones and cyclohexenones.15 The chlorination of dimethylphenols with chlorine in acetic acid containing HCl results in polychlorinated cyclohexenones (eq 7).16

The a-monochlorination of alkyl aryl ketones by chlorine gas occurs readily in a variety of solvents (e.g. CH2Cl2, CHCl3, CCl4, HOAc).17 a,a-Dichlorination of alkyl aryl ketones occurs with sodium acetate in refluxing acetic acid (5 h, 80-90% yield). Alternatively, DMF can be used as the catalyst (80-100 °C, 35-45 min) (eq 8).18

Chlorination of phenylenedibenzenesulfonamides by chlorine in nitrobenzene results in the formation of a mixture of dichloro derivatives.19 The more useful tetrachloro derivative can be prepared by successive oxidations and additions of HCl, or in one step using Cl2 in DMF (eq 9).19 The temperature must be kept below 60 °C when Cl2/DMF is used, or a runaway thermal reaction can result.20

Chlorine has been used for the chlorination of heterocycles,7i -k but the varied reactivity of substrates makes discussion of these reactions too lengthy for this review.

Oxidation of Alcohols.

Alcohols have been oxidized with complexes of chlorine with dimethyl sulfide,21 DMSO,22 iodobenzene,21 pyridine,23 and HMPA.21 Secondary hydroxyl groups are more readily oxidized than primary hydroxyl groups when the Chlorine-Pyridine (eq 10)23 and chlorine-HMPA complexes21 are used. The same results are obtained with 3-iodopyridine dichloride.23

Hydroxythiols undergo chlorination reactions with Cl2 in dichloromethane to form sultines and sulfinic esters after hydrolysis (eq 11).24

The oxidation of glycols usually results in C-C bond cleavage, but oxidation of the s-carbinol can be effected with a complex of a methyl sulfide (RSMe) and chlorine or NCS, or of DMSO and chlorine.25 The tricyclic a-ketol (2) (eq 12) can be prepared from the glycol (1) using these reagents.25


The C-C bond of short-chain hydrocarbons (<C3 and any partially chlorinated derivatives) can be cleaved by chlorine at high temperatures to give chlorinated products. 1,2-Dichloroethane and 1,2-dichloropropane are cleaved by chlorine to give carbon tetrachloride and tetrachloroethylene with HCl as a byproduct.11

C-S Bond Cleavage.

The benzylic group of alkyl benzyl sulfides can be selectively cleaved by chlorine in aqueous acetic acid to give alkanesulfonyl chlorides (eq 13).26

Excess chlorine has been used to cleave the secondary C-S bond in lactam (3) (eq 14) to give the azetidin-2-one (4) in nearly quantitative yield.27 When N-acyl groups are present, as in eq 15, the nitrogen lone pair electrons are inhibited, so cleavage of the tertiary C-S bond is favored over the azetidine C-S bond.27

Other Reactions.

Chlorine and Sodium Bromide are used to produce Bromine Chloride, which can be used in bromination reactions which are faster than those with elemental Bromine, and which take place in aqueous solution rather than acidic solvents; the bromination of 4-nitrophenol to 2,6-dibromo-4-nitrophenol is one example.28

Thiocyanogen, prepared in anhydrous conditions from silver or lead thiocyanate and bromine, cannot be used for addition reactions with halogenated alkenes and is too expensive for most commercial processes.29 Thiocyanogen can be prepared in a two-solvent system from Sodium Thiocyanate and chlorine.29 The thiocyanogen is extracted into the toluene layer and can be used for addition reactions to vinyl halides in the synthesis of haloalkylene bisthiocyanates.

Several methods for the preparation of Phosgene are known, e.g. the gas-phase reaction of chlorine with carbon monoxide on activated carbon, the decomposition of trichloromethyl chloroformate, and the reaction of carbon tetrachloride with oleum.30 Phosgene can be synthesized conveniently just before use by the reaction of chlorine with carbon monoxide in the presence of catalytic amounts of t-phosphine oxides, using carbon tetrachloride as the solvent.30

Chlorodimethylsulfonium chloride, generated in situ from Dimethyl Sulfide-Chlorine, is a useful reagent for the conversion of epoxides to a-chloro ketones (eq 16)31 and of aldoximes to nitriles,32 in the presence of tertiary amines. Bromodimethylsulfonium bromide, generated in the same way, can be used to form a-bromo ketones, but the yields are lower than those obtained for a-chloro ketones.31

Chlorine and Triphenylphosphine are used in the synthesis of lactams from cycloalkanone oximes in high yields (eq 17).33

Alkanesulfonyl chlorides, which are useful reagents and intermediates in organic synthesis, can be conveniently produced from dithiocarbonic acid esters (eq 18).34

The indirect oxidation of trialkyl phosphites to trialkyl phosphates can be achieved in high yield and purity with chlorine in the corresponding alcohol (eq 19).35 The indirect oxidation can also be effected by carbon tetrachloride, bromotrichloromethane, Carbon Tetrabromide, Chloroform, and hexachlorocyclopentadiene in alcohol.35 Cyclic phosphites may undergo ring opening during reactions with chlorine, depending on the size of the ring and its degree of substitution.7g

Cyclooctanone oxime can be synthesized from cyclooctane by a photochemical reaction with chlorine and nitrous oxide (eq 20).36 The oxime hydrochloride intermediate is converted into the oxime by aqueous sodium hydroxide.

Chlorine can be used for the synthesis of hydrazines from ureas, via diaziridinone intermediates (eq 21).7h

Related Reagents.

Bromine; Chlorine-Chlorosulfuric Acid; Dimethyl Sulfide-Chlorine; Chlorine-Pyridine; Iodine; Sulfuryl Chloride.

1. (a) Kirk-Othmer Encyclopedia of Chemical Technology, 3rd ed.; Grayson, M., Ed.; Wiley: New York, 1978; Vol. 1, p 833. (b) Stroh, R.; Hahn, W. MOC 1962, 5/3, 503. (c) Hudlicky, M.; Hudlicky, T. In The Chemistry of Halides, Pseudo-Halides and Azides; Patai, S., Rappoport, Z., Eds.; Wiley: New York, 1983; Part 2, Chapter 22, pp 1066-1101.
2. Fieser, L. F. Experiments in Organic Chemistry, 3rd ed.; Heath: Boston, 1957; p 296.
3. Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell, A. R. Vogel's Textbook of Practical Organic Chemistry, 5th ed.; Wiley: New York, 1989; p 424.
4. Schmeisser, M. In Handbook of Preparative Inorganic Chemistry, 2nd ed.; Brauer, G., Ed.; Academic: New York, 1963; Vol. 1, p 272.
5. Chemical Safety Sheets; Zawierko, J., Ed.; Kluwer: Dordrecht, 1991; p 201.
6. Hoshi, M.; Masuda, Y.; Arase, A. CL 1984, 195.
7. In Comprehensive Organic Chemistry; Pergamon: Oxford, 1979; (a) Vol. 1, p 840. (b) Vol. 2, p 642. (c) Vol. 2, p 1088. (d) Vol. 2, p 171. (e) Vol. 2, p 1021. (f) Vol. 2, p 460. (g) Vol. 2, p 1217. (h) Vol. 2, p 223. (i) Vol. 4, for example (cf. Vol. 6, pp 1110-1112). See also: (j) Ref. 1b, pp 1070-1076; (k) Ref. 1c, pp 1086-1087.
8. Korhonen, I. O. O.; Korvola, J. N. J. ACS(B) 1981, 35, 461.
9. Ogata, Y.; Harada, T.; Matsuyama, K.; Ikejiri, T. JOC 1975, 40, 2960.
10. Miller, R. B.; Reichenbach, T. TL 1974, 543 (FF 1981, 5, 556).
11. See Ref. 1a, Vol. 5, p 668.
12. Bermejo, J.; Cabeza, C.; Blanco, C. G.; Moinelo, S. R.; Martínez, A. J. Chem. Technol. Biotechnol. 1986, 36, 129.
13. Shimizu, Y.; Hsu, R. Y. CPB 1975, 23, 2179.
14. Watson, W. D. JOC 1974, 39, 1160.
15. Fischer, A.; Henderson, G. N. CJC 1979, 57, 552.
16. Hartshorn, M. P.; Martyn, R. J.; Robinson, W. T.; Vaughan, J. AJC 1986, 39, 1609.
17. FF 1981, 9, 182.
18. De Kimpe, N.; De Buyck, L.; Verhé, R.; Wychuyse, F.; Schamp, N. SC 1979, 9, 575.
19. Adams, R.; Braun, B. H. JACS 1952, 74, 3171.
20. Woltornist, A. Chem. Eng. News 1983, 61(6), 4.
21. Al Neirabeyeh, M.; Ziegler, J.-C.; Gross, B. S 1976, 811.
22. Corey, E. J.; Kim, C. U. JACS 1972, 94, 7586.
23. Wicha, J.; Zarecki, A. TL 1974, 3059.
24. King, J. F.; Rathore, R. TL 1989, 30, 2763.
25. Corey, E. J.; Kim, C. U. TL 1974, 287.
26. Langler, R. F. CJC 1976, 54, 498.
27. Sheehan, J. C.; Ben-Ishai, D.; Piper, J. U. JACS 1973, 95, 3064.
28. Obenland, C. O. J. Chem. Educ. 1964, 41, 566.
29. Welcher, R. P.; Cutrufello, P. F. JOC 1972, 37, 4478.
30. Masaki, M.; Kakeya, N.; Fujimura, S. JOC 1979, 44, 3573.
31. Olah, G. A.; Vankar, Y. D.; Arvanaghi, M. TL 1979, 38, 3653.
32. (a) Ohno, M.; Sakai, I. TL 1965, 4541. (b) Sakai, I.; Kawabe, N.; Ohno, M. BCJ 1979, 52, 3381.
33. Ho, T.-L.; Wong, C. M. SC 1975, 5, 423.
34. Barbero, M.; Cadamuro, S.; Degani, I.; Fochi, R.; Regondi, V. S 1989, 957.
35. Frank, A. W.; Baranauckas, C. F. JOC 1966, 31, 872.
36. Müller, E.; Fries, D.; Metzger, H. CB 1957, 90, 1188.

Veronica Cornel

Emory University, Atlanta, GA, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.