N-Dichloromethylene-N,N-dimethyliminium Chloride1

[33842-02-03]  · C3H6Cl3N  · N-Dichloromethylene-N,N-dimethyliminium Chloride  · (MW 162.46)

(converts alcohols into halides;5 useful in heterocycle synthesis;20-22 reacts with active methylenes to afford a-chloroenamines1,30)

Alternate Names: PI; phosgeniminium chloride.

Physical Data: mp ~186 °C (dec); 194-196 °C from acetonitrile (sublimation).2

Solubility: sol liquid SO2, thionyl chloride (for NMR measurements), nitromethane, acetonitrile; sparingly sol chloroform, dichloromethane, and polychloroethanes; insol benzene, ether, toluene; THF and dioxane are slowly decomposed; protic solvents and DMSO react violently.

Form Supplied in: white solid, commercially available. Dimethylcarbamoyl chloride and complexed HCl may be present.

Analysis of Reagent Purity: hydrolysis and titration, NMR (CD3NO2) d = 4.07 ppm.

Preparative Methods: chlorination of Dimethylthiocarbamoyl Chloride using Chlorine,1,2 Phosphorus(V) Chloride,2,3 Phosgene or Sulfuryl Chloride.1 When exposed to excess chlorine the title reagent forms a yellow complex, PI.Cl2.2,4 Dimethyldithiuram and dithiocarbamates are also cheap starting materials for the preparation of the reagent.3,4

Purification: washing with dry dichloromethane and drying on a rotary evaporator at 40-60 °C/12 mmHg.

Handling, Storage, and Precautions: moisture sensitive. In the absence of moisture, has a shelf life of a few years. The reaction apparatus should be flame dried. The hydrolysis product, dimethylcarbamoyl chloride, is reportedly mutagenic.

Reactions with Alcohols, Amines, and Thiols.

Alcohols are invariably converted to the corresponding alkyl halides since the intermediate alkoxychloromethyleniminium salts are unstable when treated with PI. With phenols and thiols, selective mono- and disubstitution are possible.5-7 Diols lead to cyclic iminium carbonates, which are opened by the chloride counterion in a strictly SN2 fashion. This has important implications in carbohydrate chemistry. One free hydroxy group is replaced stereo- and regioselectively by a chlorine atom, leading to chlorodeoxy sugars. Vic-diols form iminium carbonates, which give chloro-O-carbamoyldeoxy sugars in a selective fashion (eq 1).8

Bromodeoxy sugars are available on treatment with the PI-FeCl3 complex and subsequent addition of Lithium Bromide.9 Recent developments have been detailed by Copeland10 and Benazza.11 Carboxylic and even sulfonic acids are converted smoothly to the corresponding chlorides.1 Hydrogen Selenide affords N,N-dimethyldiselenocarbamate, which may be converted to 1,3-diselenolium salts, the starting materials for selenafulvalene-type organic conductors (eq 2).12

The reagent even reacts with unreactive primary and secondary amines, e.g. tosylamides,13 to give the corresponding chloroformamidines or chloroformamidinium salts.1

Primary enamines react both at the nitrogen and at the nucleophilic carbon atom, thereby forming versatile azapentamethine cyanines (eq 3).14

Substituted nitriles lead, in the presence of HCl, to analogous compounds (R = Cl).15 Dimethylcyanamide adds smoothly to PI giving 1,3-dichloro-2-azatrimethine cyanines, which have found widespread use in heterocyclic synthesis (eq 4).1,16 Carbodiimides form nonconjugated adducts (eq 5).17

Chloroazidoiminium salts are obtained from PI and Azidotrimethylsilane.18 They transfer a diazonium group to nucleophilic aromatic substrates, whereas diazo transfer occurs with activated methylene compounds.19

Heterocycle Synthesis.

PI salts have almost unlimited potential in heterocyclic chemistry, readily forming cyclic systems with 1,4- and 1,5-bisnucleophilic compounds (eqs 6-8).20-22

Ester or cyano groups (after prior addition of HCl) can also act as nucleophiles (eqs 9 and 10).23,24

ortho-Hydroxybenzonitriles lead, after hydrolysis, to 2-dimethylamino-1,3-benzoxazines.25 Aliphatic enamino esters and nitriles react completely analogously to their aromatic counterparts (eq 11).26,27

Reactions with Carbon Nucleophiles.

Ketones react smoothly with PI in refluxing chloroform to form the corresponding chlorides of 3-chloroacrylamides (eqs 12 and 13).1

Cyclic ketones react too, but the reagent is very sensitive to steric hindrance. Aliphatic ketones (e.g. acetone) lead to complicated mixtures. Acid chlorides probably react via ketene intermediates, affording a-chloro-b-chlorocarbonylenamines.28 Diphenylketene leads to 4,4-dichloroazetidin-2-one.28

Only very activated (hetero) aromatics undergo C-acylation with PI. Thus 1,3-dimethoxybenzene is acylated, generating the corresponding amide chloride, which can be hydrolyzed to the amide or, interestingly, thermolyzed to the nitrile (eq 14).29 In this manner, PI can be considered as a [CN]+ equivalent. Similar chemistry is observed with electron-rich indoles29 and pyrroles.30

Activated methylene groups condense readily with PI to form push-pull a-chloroenamines.1,30 This transformation is also successful for vinylogous methyl and methylene groups in ethylidene malononitriles and cyanoacetates (eq 15).31

Cyanoacetate condensation products cyclize spontaneously to aminocyanopyrones, via attack by the ester group.31 Tricyanomethane reacts at the cyano nitrogen.32

Enamines react readily with PI to give trimethine cyanines.1 Vinylogous aminofulvenes undergo attack on the cyclopentadiene moiety.33 1,2,3,4-Tetrachloro-1,3-cyclopentadiene34 and 4,5-dichlorocyclopent-4-ene-1,3-dione35 afford the corresponding chlorodimethylaminofulvene and fulvenequinone, respectively.

As a reasonably strong chlorinating agent, PI transforms tertiary amides into amide chlorides. Substituted acetamides react further to give the very versatile 1,3-dichlorotrimethine cyanines (eq 16).36 Vinylogous acetamides (e.g. crotonamide) react as well (eq 17).30,37 This reaction does not occur when R is a strong electron-withdrawing group (e.g. NO2, ester, CF3). Tertiary lactams produce unsymmetrical trimethine cyanines.1,30,38

Secondary acetamides (or ketenimines) lead to versatile N-a-chlorovinyl chloroformamidinium salts (eq 18).1,39


1. (a) Janousek, Z; Viehe, H. G. Advances in Organic Chemistry: Methods and Results. Iminium Salts in Organic Chemistry; Böhme, H; Viehe, H. G.; Eds.; Wiley: New York, 1976; Part 1. (b) Janousek, Z; Viehe; H. G. AG(E) 1971, 10, 573.
2. Kukhar, V. P; Pasternak, V. I; Kirsanov, A. V. ZOR 1971, 7, 2084.
3. Vilkas, M; Quasmi, D. SC 1990, 20, 2769.
4. Mironova, D. F; Vykrestyuk, N. I; Kukhar, D. F. JOU 1984, 20, 276.
5. Morris, J; Wiskha, D. G; Fang, Y. JOC 1992, 57, 6502.
6. Le Clef, B; Mommaerts, J; Stelander, B; Viehe, H. G. AG(E) 1973, 12, 404.
7. Copeland, C; Stick, R. V. AJC 1979, 32, 637; 1974, 37, 1483.
8. Klemer, A; Brandt, B; Hofmester, U; Rüter, E. R. LA, 1983, 1920.
9. Klemer, A; Brandt, B. LA, 1986, 932.
10. Copeland, C. M; Ghosh, J; McAdam, D. P; Skelton, B. W; Stick, R. V; White, A. H. AJC, 1988, 41, 549, 563.
11. Benazza, M; Uzan, R; Beaupère, D; Demailly, G. TL 1992, 33, 3192.
12. (a) Braam, J. M; Carlson, C. D; Stephens, D. A; Rehan, A. E; Corupton, S. J; Williams, J. M. Inorg. Synth. 1986, 24, 131. (b) Wudl, F; Nalewalek, D. CC 1980, 866.
13. Himbert, G; Schwickerath, W. LA 1982, 2105.
14. Guillot, N; Janousek, Z; Viehe, H. G. H 1988, 28, 879.
15. Stelander, B; Viehe, H. G. AG(E) 1977, 16, 189.
16. Shibua, I; Nakanishi, H. BCJ 1987, 60, 2686; Antus-Ercsényi, A; Bitter, I Acta Chim. Acad. Sci. Hung. 1979, 99, 29.
17. Elgavi, A; Viehe, H. G. AG(E) 1977, 16, 181.
18. Viehe, H. G;, George, P. C 1975, 29, 209.
19. Kokel, B; Viehe, H. G. AG(E) 1980, 19, 716.
20. Kokel, B; Lespagnol, C; Viehe, H. G. BSB 1980, 89, 651.
21. Hervens, F; Viehe, H. G. AG(E) 1973, 12, 405.
22. van Vyve, T; Viehe, H. G. AG(E) 1974, 13, 79.
23. Kokel, B; Menichi, G; Huber-Habart, M. TL 1984, 25, 1557.
24. Bitter, I; Szócs, L; Tóke, L. Acta Chim. Acad. Sci. Hung. 1981, 107, 57, 171.
25. Kokel, B; Menichi, G; Huber-Habart, M. TL 1984, 25, 3837.
26. Bondarchuk, N. D; Momot, V. V; Larukina, L. A; Pesotskaya, G. V; Kukhar, V. P. ZOR 1974, 10, 735.
27. Decock-Plancquaert, M.-A; Evariste, F; Guillot, N; Janousek, Z; Maliverney, Ch; Merényi, R; Viehe, H. G. BSB 1992, 101, 313. See also Neidlein, R; Sui, Z. S 1990, 959.
28. Viehe, H. G; Le Clef, B; Elgavi, A. AG(E) 1977, 16, 182.
29. Bergman, J; Pelcman, B. T 1988, 16, 5215.
30. Viehe, H. G. CI(L) 1977, 386.
31. Bouvy, D; Janousek, Z; Viehe, H. G. BSB 1993, 102, 129; TL, 1993, 34, 1779.
32. Kukhar, V. P; Pavlenko, N. G; Kirsanov, A. V. ZOR 1973, 9, 305.
33. Hafner, K.; Krimmer, H.-P. AG 1980, 92, 202.
34. Fick, F.-G.; Hartke, K. CB 1976, 109, 3939.
35. Seitz, G; Braun, H. AP 1976, 309, 34.
36. de Voghel, G. J.; Eggerichs, T. L.; Janousek, Z.; Viehe, H. G. JOC 1974, 39, 1233.
37. Huys-Francotte, M.; Janousek, Z.; Viehe, H. G. JCR(S) 1977, 100.
38. Toth, G; Bitter, I.; Bigam, G.; Strausz, O. MRC 1986, 24, 137.
39. Goffin, E.; Legrand, Y.; Viehe, H. G. JCR(S) 1977, 105.

Zdenek Janousek & Heinz G. Viehe

Université Catholique de Louvain, Louvain-la-Neuve, Belgium



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