Hydrazinium Carbazate-H₂O₂: An Ideal Combination for Diimide Reduction of Base-Sensitive Unsaturated Peroxides [¹]

Abstract

The utility of a hydrazinium carbazate (N₂H₃COON₂H₅) and H₂O₂ combination for the double bond reduction of base-sensitive unsaturated 1,2,4-trioxanes, 1,2,4-trioxepanes, and their precursors β- and γ-hydroxyhydroperoxides is presented. The method is superior to the conventional diimide reduction using N₂H₄˙H₂O-H₂O₂ and catalytic hydrogenation.

Key words

diimide reduction - hydrazinium carbazate - hydrogen peroxide - β-/γ-hydroxyhydroperoxides - 1,2,4-trioxanes

1

CDRI communication number: 7233.

References

• For reviews on artemisinin and its analogues, see:
• 2a Klayman DL. Science  1985,  228:  1049 
• 2b Zhou WS. Xu XX. Acc. Chem. Res.  1994,  27:  211 
• 2c Cumming JN. Ploypradith P. Posner GH. Adv. Pharmacol.  1997,  37:  2253 
• 2d Bhattacharya AK. Sharma RP. Heterocycles  1999,  51:  1681 
• 2e Borstnik K. Paik I. Shapiro TA. Posner GH. Int. J. Parasitol.  2002,  32:  1661 
• 2f Ploypradith P. Acta Trop.  2004,  89:  329 
• 2g O’Neill PM. Posner GH. J. Med. Chem.  2004,  47:  2945 
• 2h Haynes RK. Ho W.-Y. Chan H.-W. Fugmann B. Stetter J. Croft SL. Vivas L. Peters W. Robinson BL. Angew. Chem. Int. Ed.  2004,  43:  1381 
• 3 Singh C. Tetrahedron Lett.  1990,  31:  6901 
• For alternative methods for the preparation of 1,2,4-trioxanes, see:
• 4a Jefford CW. Jaggi D. Boukouvalas J. Kohmoto S. J. Am. Chem. Soc.  1983,  105:  6498 
• 4b Kepler JA. Philip A. Lee YW. Morey MC. Caroll FI. J. Med. Chem.  1988,  31:  713 
• 4c Avery MA. Jennings-White C. Chong WKM. J. Org. Chem.  1989,  54:  1792 
• 4d Bloodworth AJ. Shah A. J. Chem. Soc., Chem. Commun.  1991,  947 
• 4e Posner GH. Oh CH. Milhous WK. Tetrahedron Lett.  1991,  32:  4235 
• 4f Bunnelle WH. Isbell TA. Barnes CL. Qualls S. J. Am. Chem. Soc.  1991,  113:  8168 
• 4g Bloodworth AJ. Johnson KA. Tetrahedron Lett.  1994,  35:  8057 
• 4h O’Neill PM. Pugh M. Davies J. Ward SA. Park BK. Tetrahedron Lett.  2001,  42:  4569 
• 4i Griesbeck AG. El-Idreesy TT. Fiege M. Brun R. Org. Lett.  2002,  4:  4193 
• 4j O’Neill PM. Mukhtar A. Ward SA. Bickley JF. Davies J. Bachi MD. Stocks PA. Org. Lett.  2004,  6:  3035 
• 5a Singh C. Pandey S. Saxena G. Srivastava N. Sharma M. J. Org. Chem.  2006,  71:  9057 
• 5b Singh C. Pandey S. Puri SK. Bioorg. Med. Chem.  2008,  16:  1816 
• For alternative methods for the preparation of 1,2,4-tri­-oxepanes, see:
• 6a Adam W. Duran N. J. Chem. Soc., Chem. Commun.  1972,  798 
• 6b Dussault PH. Davies DR. Tetrahedron Lett.  1996,  37:  463 
• 6c Ushigoe Y. Kano Y. Nojima M. J. Chem. Soc., Perkin Trans. 1  1997,  5 
• 6d Ushigoe Y. Torao Y. Masuyama A. Nojima M. J. Org. Chem.  1997,  62:  4949 
• 6e Ushigoe Y. Masuyama A. Nojima M. McCullough KJ. Tetrahedron Lett.  1997,  38:  8753 
• 6f Oh CH. Kang JH. Tetrahedron Lett.  1998,  39:  2771 
• 6g Dussault PH. Trullinger TK. Noor-e-Ain F. Org. Lett.  2002,  4:  4591 
• 6h Ahmed A. Dussault PH. Org. Lett.  2004,  6:  3609 
• 6i Amewu R. Stachulski AV. Berry NG. Ward SA. Davies J. Labat G. Rossignol JF. O’Neill PM. Bioorg. Med. Chem. Lett.  2006,  16:  6124 
• 7a Singh C. Misra D. Saxena G. Chandra S. Bioorg. Med. Chem. Lett.  1992,  2:  497 
• 7b Singh C. Misra D. Saxena G. Chandra S. Bioorg. Med. Chem. Lett.  1995,  5:  1913 
• 7c Singh C. Gupta N. Puri SK. Bioorg. Med. Chem.  2004,  12:  5553 
• 7d Singh C. Malik H. Puri SK. J. Med. Chem.  2006,  49:  2794 
• 7e Singh C. Kanchan R. Sharma U. Puri SK. J. Med. Chem.  2007,  50:  521 
• 8a Singh C. Malik H. Org. Lett.  2005,  7:  5673 
• 8b Singh C. Malik H. Synthesis  2006,  3485 
• For reviews on diimide reduction, see:
• 9a Aylward F. Sawistowska M. Chem. Ind. (London)  1962,  484 
• 9b Hünig S. Muller HR. Their W. Angew. Chem., Int. Ed. Engl.  1965,  4:  271 
• 9c Pasto DJ. Taylor RT. Org. React.  1991,  40:  91 
• For diimide reduction of unsaturated peroxides, see:
• 10a Adam W. Eggelte HJ. J. Org. Chem.  1977,  42:  3987 
• 10b Adam W. Balci M. Angew. Chem., Int. Ed. Engl.  1978,  17:  954 
• 10c Adam W. Balci M. J. Am. Chem. Soc.  1979,  101:  7537 
• 10d Kepler JA. Philip A. Lee YW. Morey MC. Carroll FI. J. Med. Chem.  1988,  31:  713 
• 10e Bachi MD. Korshin EE. Hoos R. Szpilman AM. Ploypradith P. Xie S. Shapiro TA. Posner GH. J. Med. Chem.  2003,  46:  2516 
• 11a Paget H. J. Chem. Soc.  1938,  828 
• 11b Dussault PH. Kreifels S. Lee IQ. Synth. Commun.  1995,  25:  2613 
• 11c O’Neill PM. Bishop LPD. Searle NL. Maggs JL. Storr RC. Ward SA. Park BK. Mabbs F. J. Org. Chem.  2000,  65:  1578 
• 13 Kurzer F. Wilkinson M. Chem. Rev.  1970,  70:  111 
• 14 Schmidt EW. Hydrazine and its Derivatives: Preparation, Properties, Applications   2nd ed., Vol. 1:  Wiley; New York: 2001. 
• 17a Lin X. Pan Q. Rempel GL. Appl. Catal., A  2004,  263:  27 
• 17b Erlenmeyer H. Flierl C. Sigel H. J. Am. Chem. Soc.  1968,  91:  1065 

1

CDRI communication number: 7233.

12

The progress of the reaction was monitored by TLC of the samples drawn at regular time intervals of 15 min. At no stage of the reaction was the required saturated trioxane observed.

15

The pH values of 1% aqueous solutions of N₂H₄˙H₂O and N₂H₃COON₂H₅ at 25 ˚C (glass electrode) were found to be 9.79 and 7.51, respectively.

16

The stereochemistry assigned to the diastereomers is only relative and is based upon coupling constants and NOESY experiments.

18

Due to intramolecular hydrogen bonding in diols 11, 15, 19, and 23, ^¹H NMR spectra of these compounds show complex multiplicity pattern. Conversion of these diols into the corresponding diacetates, on the other hand, provides clear multiplicity pattern in ^¹H NMR spectra.

19

Diimide reduction of ascaridole using dipotassium azodicarboxylate is known to furnish dihydroascaridole in ∼40% yield: see reference 10a.

20

In our hands all these peroxides have behaved well, but the usual precautions for handling of peroxides are recommended.