2-Chloro-1,3-dithiane

[57529-04-1]  · C4H7ClS2  · 2-Chloro-1,3-dithiane  · (MW 154.69)

(readily accessible electrophilic 1,3-dithiane reagent; formyl cation equivalent; reacts with alkyl- and arylmagnesium halides,1 enamines,2 1,3-dicarbonyl compounds,1,2 electron-rich aromatics,1,3 and with P,4,5 N,3 S,3 and Se6 nucleophiles)

Physical Data: mp 50 °C (dec).

Solubility: sol benzene, chloroform, THF, and ether.

Preparative Methods: the reagent can be easily obtained by chlorination of 1,3-Dithiane, either with N-Chlorosuccinimide (NCS) in benzene3 or with Sulfuryl Chloride in chloroform.5 The latter procedure generally gives a cleaner product7 and is described here.

Sulfuryl chloride (11 mmol) in 5 mL of chloroform is slowly added to 1,3-dithiane (10 mmol) in 25 mL of chloroform at -40 °C in a nitrogen atmosphere. A white precipitate (chlorosulfonium salt) forms instantly. This precipitate gradually dissolves when the reaction mixture is allowed to warm to rt in 30 min. After stirring for an additional 30 min the solvent is evaporated at 0 °C and 1.55 g of 2-chloro-1,3-dithiane (1) of better than 95% purity (1H NMR: C(2)-H d 6.20) is obtained as a white or pale-yellow solid. A (minor) impurity is the sulfenyl chloride ClCH2S(CH2)3SCl (d 4.80), formed by attack of chloride at the central carbon atom of the chlorosufonium salt.5

Handling, Storage, and Precautions: the reagent should be prepared shortly before use and rigidly protected against moisture, both in the solid form and in solution. Handle in a fume hood.

Reaction with Carbon Nucleophiles.

Organomagnesium (Aluminum) Reagents.

2-Chloro-1,3-dithiane (1) reacts readily with secondary and aromatic Grignard reagents,1 thereby providing products such as (2), (3), and (4) that are not readily available by classical 2-lithio-1,3-dithiane chemistry.8

Reaction with 3-substituted allylic aluminum reagents9 affords dithianes (5), which arise from an allylic rearrangement, free of any other isomer (eq 1). Alkylation of 2-lithio-1,3-dithiane with allylic halides would give the isomeric, nonrearranged products.8 The related reagent 1,3-dithienium tetrafluoroborate gives similar results in this reaction and affords better yields.9

The aluminum derivative of 1-bromo-2-propyne affords (6) upon combination with (1).9 The phenylacetylene derivative (7) had earlier been obtained by a Grignard reaction with (1).10

Reaction with Electron-Rich Arenes.

Reaction of (1), prepared with NCS, with phenol or dimethylaniline affords the crystalline 4-substituted 2-(1,3-dithianyl) derivatives (8) and (9), respectively.3

Excellent yields of products (10), (11), and (12) are obtained by combining the corresponding phenols with (1), prepared with sulfuryl chloride.1 In the reaction mixture obtained from phenol, 20% of the 2-substituted isomer was present (NMR).

In a study of 1,3-benzodioxole derivatives, the 6-substituted 2-(1,3-dithianyl) compound (13), obtained from reaction of the diol with (1) in 79% yield, served as starting material for the corresponding 6-methyl compound (reduction with Raney Nickel) as well as for the interesting 4,5-quinone (14) (eq 2).11

Reaction of the anion of N-(phenylsulfonyl)indole with (1) gives the 2-[2-(1,3-dithianyl)]indole (15) (65%) which, after deprotection, can be functionalized at C-2 to give (16) (eq 3).7

1,3-Dicarbonyl Compounds.

Reaction of (1) with the Na salts of malonic acid esters affords the 2-[2-(1,3-dithianyl)] derivatives (17) in excellent yields.1 Danishefsky and co-workers have applied this procedure for the introduction of a critical C-1 unit in their approach towards the synthesis of naphthyridinomycin alkaloids.12 Reaction of Na acetoacetic ester likewise affords (18).2 These compounds can be deethoxycarbonylated by treatment with NaCl in DMSO.2,13

Enamines.

Taylor and LaMattina have reported the synthesis of 2-[2-(1,3-dithianyl)]aldehydes (19) (R = H) and ketones by reaction of (1) with morpholino enamines (eq 4).2 This method has the advantage over classical methods for a-formylation of carbonyl compounds in that it directly introduces a base-stable protected formyl substituent.

Reaction with Phosphorus Nucleophiles.

Reagent (1) reacts with Triphenylphosphine to give phosphonium salt (20) (78%)5 and with Triethyl Phosphite to give diethyl phosphonate (21) (85%).4,5 Both compounds are excellent reagents for the synthesis of ketene dithioacetals by the Horner-Wittig reaction. The reactions of (20) are restricted to aldehydes (eq 5);5 however, (21) reacts well with both aldehydes and ketones (eq 6).5,14,15

Reaction with S, Se, and N Nucleophiles.

Reaction of (1) with thiophenol affords 2-phenylthio-1,3-dithiane in 90% yield.3 Reaction with Imidazole and with Succinimide affords the corresponding N-[2-(1,3-dithianyl)] compounds, also in excellent yields.3a Reaction of (1) with areneselenolate anions affords 2-arylseleno-1,3-dithianes (22) (eq 7).6 These compounds, like the earlier studied (7)10 and (1) itself,3 show a strong anomeric effect in solution.6

Other Applications.

Reagent (1) has found use in the preparation of 2-(1,3-dithianyl)-substituted polycarbonyl-metal complexes of Cr,16 W,16 and Mn.17


1. Kruse, C. G.; Wijsman, A.; van der Gen, A. JOC 1979, 44, 1847.
2. Taylor, E. C.; LaMattina, J. L. TL 1977, 2077.
3. (a) Arai, K.; Oki, M. BCJ 1976, 49, 553. (b) Arai, K.; Oki, M. TL 1975, 2183.
4. Mlotkowska, B.; Gross, H.; Costisella, B.; Mikolajzyk, M.; Grzejszczak, S.; Zatorski, A. JPR 1977, 319, 17.
5. Kruse, C. G.; Broekhof, N. L. J. M.; Wijsman, A.; van der Gen, A. TL 1977, 885.
6. (a) Pinto, B. M.; Sandoval-Ramirez, J.; Dev Sharma, R.; Willis, A. C.; Einstein, F. W. B. CJC 1986, 64, 732. (b) Pinto, B. M.; Johnston, B. D.; Sandoval-Ramirez, J.; Dev Sharma, R. JOC 1988, 53, 3766.
7. Rubiralta, M.; Casamitjana, N.; Grierson, D. S.; Husson, H.-Ph. T 1988, 44, 443.
8. Seebach, D.; Corey, E. J. JOC 1975, 40, 231.
9. Picotin, G.; Miginiac, P. JOC 1985, 50, 1299.
10. Arai, K.; Iwamura, H.; Oki, M. BCJ 1975, 48, 3319.
11. Dallacker, F.; Kramp, P.; Coerver, W. ZN(B) 1983, 38b, 752.
12. Danishefsky, S.; O'Neill, B. T.; Taniyama, E.; Vaughan, K. TL 1984, 25, 4199.
13. Kruse, C. G.; Janse, A. C. V.; Dert, V.; van der Gen, A. JOC 1979, 44, 2916.
14. Mikolajczyk, M.; Grzejszczak, S.; Zatorski, A. TL 1976, 2731.
15. The reactivity of the corresponding diphenylphosphine oxide is similar to that of (21): Juaristi, E.; Gordilla, B.; Valle, L. T. T 1986, 42, 1963.
16. Raubenheimer, H. G.; Kruger, G. J.; Viljoen, H. W. JOM 1987, 319, 361.
17. Löwe, C.; Huttner, G.; Zsolnai, L.; Berke, H. ZN(B) 1988, 43b, 25.

Arne van der Gen

Leiden University, The Netherlands



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