(R = Br)

[36469-73-5]  · C3H3BrCl2  · 3-Bromo-1,1-dichloro-1-propene  · (MW 189.87) (R = CH2OH)

[42134-33-8]  · C4H6Cl2O  · 4,4-Dichloro-3-buten-1-ol  · (MW 141.00)

(chloroalkene annulating agent for synthesis of cycloalkane carboxylic acids,1 halogenated vinyl epoxides,2 halogen-substituted allylglycines,3 and 1,1-dichloro terminal alkenes4)

Physical Data: R = Br: bp 65-66.5 °C/17 mmHg; nD20 1.5363; d25 1.7593 g L-1. R = CH2OH: bp 80-81.5 °C/10 mmHg.

Form Supplied in: R = Br: not available commercially; pale yellow liquid. R = CH2OH: not available commercially; liquid.

Preparative Methods: R = Br: can be prepared by N-Bromosuccinimide/Dibenzoyl Peroxide bromination in CCl4 of 1,1-dichloropropene with >60% yield.1,2,5 Other methods of preparation are Hydrogen Bromide bromination of 1,1,3-trichloropropene (Copper(I) Chloride/Copper(II) Chloride or Iron(III) Chloride catalyzed halogen exchange, 90% yield)6 or 1,1-dichloropropen-3-ol (65% yield).7 NMR, dipole moment, and IR studies of the reagent show that it exists in a gauche conformation in solution.8 R = CH2OH: can be prepared by the condensation of Chloral (hypnotic, sedative) and Malonic Acid,9 followed by acetylation (Acetyl Chloride/Pyridine), Zinc dechloroacetoxylation, and Lithium Aluminum Hydride reduction to produce 4,4-dichloro-3-buten-l-ol in 30% yield.1

Electrophilic Reactions.

These substituted alkenes are known for their utility in chloroalkene annulation reactions, which provide a useful synthesis of cycloalkanecarboxylic acids.1,10 One example is the octalincarboxylic acid synthesis outlined in eq 1. A 1,1-dichloroalkene intermediate (2) is formed by alkylation of 1-Pyrrolidino-1-cyclohexene (1) with 3-bromo-1,1-dichloro-1-propene. The ketone intermediate (2) is then converted to a mixture of isomeric octalincarboxylic acids (3) in two steps. First, Vinylmagnesium Bromide yields an allylic alcohol which then undergoes cyclization to (3) on treatment with Formic Acid at reflux. The cis,cis- and cis,trans-2-decalincarboxylic acids were obtained after hydrogenation of (3) with Pt catalyst in acetic acid.

A related procedure employing 4,4-dichloro-3-buten-1-ol provides an efficient route to cyclopentanecarboxylic acid (6) (eq 2).1,10 4,4-Dichloro-3-buten-1-ol is first converted to the mesylate (4) (with Methanesulfonyl Chloride), which in turn is used to alkylate deoxybenzoin to form ketone (5). Reduction of ketone (5) to the alcohol followed by formolysis (97% HCOOH, reflux overnight) results in cyclization to give trans,trans-2,3-diphenylcyclopentanecarboxylic acid (6).

Advantages of this methodology are the inertness of the chloroalkene side chain toward a variety of reagents and the relatively mild formolysis conditions required for cyclization. Chloroalkene reagents may be homologated to allow for generation of rings with more than six members. The method is general and has been used with other related haloalkene reagents.11

3-Bromo-1,1-dichloro-1-propene is also used to form halovinyl epoxides. A haloallylsulfonium salt (8) is prepared by reaction of tetrahydrothiophene (7) with 3-bromo-1,1-dichloro-1-propene in anhydrous acetone (eq 3).2 Halogenated vinyl epoxides (9) are formed upon condensation of (8) with RCHO (R = MeCH=CH-, CH2=C(Me)-, Ph). Other allylic chlorides and bromides have also been used in this reaction.2

Halogenated allylic reagents have been used to synthesize substituted allylglycines.3 Diethyl formamidomalonate (10) was alkylated with 3-bromo-1,1-dichloro-1-propene to form intermediate (11) (eq 4). The amino acid (12) is then obtained by hydrolysis with dilute HBr (reflux, 4 h).

The 1,1-dichloropropen-3-yl ester of hexanoic acid has been found to be an antagonist of insect juvenile hormone.4 This ester is prepared (93%) by reaction (K2CO3/55 °C/3 h/HMPA) of 3-bromo-1,1-dichloro-1-propene with hexanoic acid. Several patents have been filed for 1,1-dichloroalkene-substituted compounds which have antitumor, herbicide, or pesticide activity and are prepared using 3-bromo-1,1-dichloro-1-propene.

Nucleophilic Reactions.

It has been demonstrated that the 1,1-dichloroalkene moiety may also be introduced into organic molecules via conversion of the reagent to a nucleophile.1,10 For example, 4,4-dichloro-3-buten-1-ylmagnesium bromide, obtained from bromide (13) (Cl2C=CH(CH2)2OH/PBr3), reacts with deoxybenzoin to yield alcohol (14) (eq 5). Formolysis of (14) in refluxing HCO2H then provides the same cyclopentanecarboxylic acid (6) as was obtained in chemistry described earlier where Cl2C=CH(CH2)2OMs was employed as an electrophilic reagent (eq 2). The overall yields of the two reactions are similar and the same advantages of chloroalkene side-chain inertness and mild formolysis conditions apply. Other related chloroalkene reactions have been described in the literature.11

1. Lansbury, P. T.; Stewart, R. C. TL 1973, 1569.
2. Beny, J. P.; Pommelet, J. C.; Chuche, J. BSF(2) 1981, 369.
3. Shapir, J.; Dittmer, K. JACS 1960, 82, 1495.
4. Quistad, G. B.; Cerf, D. C.; Kramer, S. J.; Bergot, B. J.; Schooley, D. A. J. Agric. Food Chem. 1985, 33, 47.
5. Hatch, L. F.; Zimmerman, S. D. JACS 1957, 79, 3091.
6. (a) Kost, V. N.; Freidlina, R. Kh. Izv. Akad. Nauk SSSR, Otdel. Khim. Nauk 1961, 1252 (CA 1962, 56, 1328i). (b) Morlyan, N. M.; Muradyan, A. G.; Badanyan, Sh. O. Arm. Khim. Zh. 1975, 28, 633 (CA 1976, 84, 16 684w).
7. Turgarina, R. Izv. Akad. Nauk Kaz. SSR, Ser. Khim. 1980, 6, 75 (CA 1981, 94, 208 285v).
8. Lere-Porte, J. P.; Chorro, C.; Petrissans, J. CR(2) 1982, 295, 1105.
9. Hurd, C. D.; Hayao, S. JACS 1954, 76, 5564.
10. Fieser, M.; Fieser, L. F. FF 1975, 5, 191.
11. (a) Bott, K.; Hulmann, H. AG(E) 1966, 5, 870. (b) Lansbury, P. T. ACR 1972, 5, 311. (c) Lansbury, P. T.; Wovkulich, P. M.; Gallagher, P. E. TL 1973, 65. (d) Bott, K. AG(E) 1980, 19, 171. (e) Gesson, J.-P.; Jacquesy, J.-C.; Renoux, B. T 1989, 45, 5853. (f) Mayr, H.; Heilmann, W.; Bauml, E.; Vorbruggen, H. CB 1991, 124, 203. (g) Fraser, F. A.; Proctor, G. R.; Redpath, J. JCS(P1) 1992, 445. (h) Zhu, L.; Shaughnessy, K. H.; Rieke, R. D. SC 1993, 23, 525.

Theresa S. Chamblee

The Coca-Cola Company, Atlanta, GA, USA

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