Potassium Nitrosodisulfonate1


[14293-70-0]  · K2NO7S2  · Potassium Nitrosodisulfonate  · (MW 268.35)

(oxidizing reagent for synthesis of quinones from phenols,2 naphthols,9 and anilines;18 oxidant for conversion of benzylic alcohols to aldehydes or ketones30 and amino acids to a-keto acids;31 preparation of heterocyclic quinones;20-22 oxidative aromatization29)

Alternate Name: Fremy's salt.

Solubility: sol H2O.

Form Supplied in: orange powder; widely available.

Preparative Methods: see Zimmer et al.1

Handling, Storage, and Precautions: in solid form, this reagent is rather unstable. It sometimes undergoes spontaneous decomposition which occasionally results in a violent explosion attributed to impurities such as chloride ion, manganese dioxide, or nitrite ion. Stored in a desiccator over calcium oxide in the presence of ammonium carbonate to provide an ammoniacal atmosphere, it is stable for several months.

Phenol Oxidations.

This reagent oxidizes phenols to the corresponding 1,2- or 1,4-quinones under mild conditions and usually in good yield. The substituents on the aromatic ring control the ratio of ortho- and para-quinones.2 para-Unsubstituted phenols bearing a variety of substituents in the ortho and meta positions (e.g. alkyl,3,4 alkyloxy and/or bromine,5 crown ether substituents,6 and p-hydroxybenzylamines and primary p-hydroxybenzamides7) are generally converted to 1,4-quinones. Phenols with easy-to-displace para substituents, such as CH2OH, Br, Cl, CO2H, CONH2, and CH(OH)CN, undergo oxidation to form 1,4-quinones. 1,2-Quinones are formed if the para substituents are alkoxy, alkyl, or aryl.8 See also Lead(IV) Oxide and Salcomine.

Naphthol Oxidations.

a-Naphthols can be oxidized to 1,2- or 1,4-naphthoquinones by Fremy's salt.9 Again, the nature of the para substituent is critical. 1,4-Naphthoquinones predominate if the para position is unsubstituted.10 1,2-Naphthoquinones are formed if an alkyl or aryl group occupies the para position,9 if there is a hydroxy group in the 2-position,9 or if the para position is hindered.11 Approximately equal amounts of 1,2- and 1,4-naphthoquinones are obtained if a hydroxy group occupies the 5-position.9 It has been reported that 1,4-naphthoquinones are produced from oxidation of 2- or 9-SMe substituted phenols.12 b-Naphthols are generally oxidized to 1,2-naphthoquinones (eq 1).13

The methyl ether of a b-naphthol has been reported to afford a 1,2-quinone (eq 2).14

Aniline Oxidations.

1,4-Quinones are formed by the reaction of 2,6-disubstituted and 2,3,6-trisubstituted anilines and Fremy's salt.15 Other ortho or meta methoxy-substituted aromatic amines were converted to the corresponding 1,4-quinones16 and 1,2-quinones.17 In one case the oxidation intermediate, a quinone imine which subsequently undergoes hydrolysis to the quinone, has been isolated (eq 3).18

Hypoxanthine analogs were formed by Fremy's salt oxidation (eq 4).19

Oxidations to Quinoline Quinones.

Quinolinols are converted to quinoline quinones (eq 5).20

In an approach to streptonigrin, Fremy's salt was utilized to oxidize a methoxy aniline by a phase-transfer procedure (eq 6).21

Oxidations to Indole Derivatives.

The derivatives of ortho-hydroxy phenethylamine were converted into indoles (eq 7).22 Presumably the primary oxidation product is protected from secondary oxidation by protonation at lower pH. Likewise, in solution at different pH, 2-methylindole dimerizes to different products (eq 8).23

The derivatives of ortho-aminophenethylamine were converted to indoline 1,4-quinone imides (eq 9).24 No oxidation at the 3-position or 4-position was observed if the a-position was occupied by two alkyl groups.

A novel route to heterocyclic quinones, based on Fremy's salt promoted oxidation, has been developed recently (eq 10).25

With this methodology, isoquinoline derivatives were converted with ring contraction to the 1,2-quinone indoles in a buffered (pH 6.1) two-phase (CH2Cl2-H2O) system (eq 11).

5-Hydroxybenzofuran is oxidized to the 4,5-ortho-quinone.26 Bisquinones27 and other heterocyclic quinones28 were prepared by Fremy's salt oxidation.

Tetrahydroisoquinoline Oxidation.

Papaveraldine could be produced by Fremy's salt oxidation over 7 days in 30% yield (eq 12). The corresponding N-alkyl tetrahydroisoquinolines give cleavage products (eq 13).29

Other Reactions.

Benzylic alcohols could be selectively oxidized to aldehydes or ketones in the presence of allylic alcohols and saturated alcohols by Fremy's salt in a phase-transfer system.30

Some a-amino and a-hydroxy acids were oxidized to the corresponding a-keto acids (dehydrogenation) and/or to the acids or amides (with decarboxylation) (eq 14).31

1. Zimmer, H.; Lankin, D. C.; Horgan, S. W. CRV 1971, 71, 229.
2. Deya, P. M.; Dopico, M.; Raso, A. G.; Morey, J.; Saa, J. M. T 1987, 43, 3523.
3. Teuber, H.-J.; Thaler, G. CB 1959, 92, 667.
4. (a) Magnusson, R. ACS 1966, 18, 759. (b) Engler, T. A.; Sampath, U.; Naganathan, S.; Velde, D. V.; Takusagawa, F.; Yohannes, D. JOC 1989, 54, 5712.
5. (a) Saa, J. M.; Llobera, A.; Garcia-Raso, A.; Costa, A.; Deya, P. M. JOC 1988, 53, 4263. (b) Singh, S. B.; Pettit, G. R. JOC 1989, 54, 4105.
6. (a) Chapoteau, E.; Czech, B. P.; Kumar, A.; Pose, A. JOC 1989, 54, 861. (b) Hayakawa, K.; Kido, K.; Kanematsu, K. JCS(P1) 1988, 511.
7. Saa, J. M.; Llobera, A.; Deya, P. M. CL 1987, 771.
8. Begley, M. J.; Fish, P. V.; Pattenden, G.; Hodgson, S. T. JCS(P1) 1990, 2263.
9. Teuber, H.-J.; Gotz, N. CB 1954, 87, 1236. Teuber, H.-J.; Lindner, H. CB 1959, 92, 921 and 927.
10. Ashnagar, A.; Bruce, J. M.; Lloyd-Williams, P. JCS(P1) 1988, 559.
11. (a) Ciufolini, M. A.; Byrne, N. E. JACS 1991, 113, 8016. (b) Ciufolini, M. A.; Byrne, N. E. TL 1989, 30, 5559.
12. Coll, G.; Morey, J.; Costa, A.; Saa, J. M. JOC 1988, 53, 5345.
13. (a) Pataki, J.; Raddo, P. D.; Harvey, R. G. JOC 1989, 54, 840. (b) Ray, J. K.; Kar, G. K.; Karmakar, A. C. JOC 1991, 56, 2268. (c) Ramesh, D.; Kar, G. K.; Chatterjee, B. G.; Ray, J. K. JOC 1988, 53, 212. (d) Sharma, P. K. SC 1993, 23, 389. (e) Chang, H. M.; Chui, K. Y.; Tan, F. W. L.; Yang, Y.; Zhong, Z. P. Lee, C. M.; Sham, H. L.; Wong, H. N. C. JMC 1991, 34, 1675.
14. He, Y.; Chang, H. M.; Lau, Y. K.; Cui, Y. X.; Wang, R. J.; Mak, T. C. W.; Wong, H. N. C.; Lee, C. M. JCS(P1) 1990, 3359.
15. Teuber, H. J.; Hasselbach, M. CB 1959, 92, 674.
16. (a) Helissey, P.; Giorgi-Renault, S.; Renault, J.; Cros, S. CPB 1989, 37, 675. (b) Kende, A. S.; Ebert, F. H.; Battista, R.; Boatman, R. J.; Lorah, D. P.; Lodge, E. H 1984, 21, 91. (c) Brown, P. E.; Lewis, R. A.; Waring, M. A. JCS(P1) 1990, 2979.
17. Cambie, R. C.; Grimsdale, A. C.; Rutledge, P. S.; Woodgate, P. D. AJC 1990, 43, 485.
18. Horner, L.; Sturm, K. CB 1955, 88, 329.
19. (a) Lee, C. H.; Gilchrist, J. H.; Skibo, E. B. JOC 1986, 51, 4784. (b) Dempcy, R. O.; Skibo, E. B. JOC 1991, 56, 776.
20. (a) Boger, D. L.; Yasuda, M.; Mitscher, L. A.; Drake, S. D.; Kitos, P. A.; Thompson, S. C. JMC 1987, 30, 1918. (b) Saito, H.; Hirata, T.; Kasai, M.; Fujimoto, K.; Ashizawa, T.; Morimoto, M.; Sato, A. JMC 1991, 34, 1959. (c) Kozikowski, A P.; Sugiyama, K.; Springer, J. P. JOC 1981, 46, 2426. (d) see Ref. 11.
21. (a) Kende, A. S.; Ebert, F. H.; Battista, R.; Boatman, R. J.; Lorah, D. P.; Lodge, E. H 1984, 21, 91. (b) Kende, A. S.; Ebetino, F. H. TL 1984, 25, 923.
22. Teuber, H.-J.; Glosauer, O. CB 1965, 98, 2648.
23. Teuber, H.-J.; Staiger, G. CB 1955, 88, 1066.
24. Teuber, H.-J.; Glosauer, O. CB 1965, 98, 2939.
25. Saa, J. M.; Capo, M.; Marti, C.; Garcia-Raso, A. JOC 1990, 55, 288.
26. Lee, J.; Tang, J.; Snyder, J. K. TL 1987, 28, 3427.
27. Yang, B.; Liu, L.; Katz, T. J.; Liberko, C. A.; Miller, L. L. JACS 1991, 113, 8993.
28. Giorgi-Renault, S.; Renault, J.; Gebel-Servolles, P.; Baron, M.; Paoletti, C.; Cros, S.; Bissery, M.-C.; Lavelle, F.; Atassi, G. JMC 1991, 34, 38.
29. Castedo, L.; Puga, A.; Saa, J. M.; Suau, R. TL 1981, 22, 2233.
30. Morey, J.; Dzielenziak, A.; Saa, J. M. CL 1985, 263.
31. Garcia-Raso, A.; Deya, P. M.; Saa, J. M. JOC 1986, 51, 4285.

Kathlyn A. Parker & Dai-Shi Su

Brown University, Providence, RI, USA

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