Organic Process Research & Development
Article
(14) Gazizov, M. B.; Khairullin, R. A.; Kadirova, R. F.; Lewis, E. S.;
Kook, A. M. J. Chem. Soc., Chem. Commun. 1990, 1133.
(15) For recent examples using air as the oxidant, see: (a) Zhang, T.;
Song, Z.; Chen, H.; Yu, X.; Jiang, Z. J. Biomater. Sci., Polym. Ed. 2008,
19, 509. (b) Feng, J.; Wang, P.; Li, F.; He, F.; Zhuo, R.-X. Gaodeng
Xuexiao Huaxue Xuebao 2006, 27, 567.
(16) For examples using peroxides as the oxidant, see: (a) Cui, Z.;
Zhang, B. Helv. Chim. Acta 2007, 90, 297. (b) Parang, K. Bioorg. Med.
Chem. Lett. 2002, 12, 1863.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Dr. David Conlon for helpful discussions, together
with the Chemical Development senior management for
support during the preparation of the manuscript.
(17) Makowiec, S.; Rachon, J. Heteroat. Chem. 2003, 14, 352.
(18) For examples using I2 in the synthesis of pro-nucleotides, see:
(a) Balaz, M.; Steinkruger, J. D.; Ellestad, G. A.; Berova, N. Org. Lett.
2005, 7, 5613. (b) Xiao, Q.; Sun, J.; Sun, Q.; Ju, Y.; Zhao, Y.-f.; Cui, Y.-
x. Synthesis 2003, 107. For other studies on iodine/pyridine complex,
see: (c) Uruska, I. Spectrochim. Acta 1980, 36A, 639. (d) Chen, K.
Name Reactions in Heterocyclic Chemistry; John Wiley & Sons, Inc.:
Hoboken, 2011; p 645. (e) Br2/pyridine was not effective for this
transformation.
(19) This impurity was observed by LC−MS but not quantified.
(20) For the formation of other pyrophosphates in a similar fashion,
see: Steinberg, G. M. J. Org. Chem. 1950, 15, 637.
(21) Downs, A. J.; Adams, C. J. Comprehensive Inorganic Chemistry;
Pergamon Press: Oxford, 1973; Vol. 2, p 1192.
(22) The reaction mixture with NaBO3 and KI remained colorless,
and only starting material was recovered, indicating no formation of
iodine (red or orange color).
(23) The color of the reaction mixture immediately changed from
colorless to red/orange upon adding the bleach, which then quickly
faded, indicating initial formation of iodine followed by oxidation to
iodate.
(24) The combination of I2 (0.5 equiv) and H2O2 was reported for
electrophilic iodination of pyrazoles; see: Kim, M. M.; Ruck, R. T.;
Zhao, D.; Huffman, M. A. Tetrahedron Lett. 2008, 49, 4026.
(25) Iodine is relatively stable in an acidic aqueous solution but
rapidly undergoes redox to iodide and iodate under basic conditions;
see: Cotton, F. A.; Wilkinson, G. Advanced Inorganic Chemistry, 5th ed.;
John Wiley & Sons: New York, 1988.
(26) The initial oxidation of cat. KI by H2O2 produces potassium
hydroxide, further increasing the pH of the aqueous phase as shown in
the chemical equation 2KI + H2O2 → I2 + 2KOH.
(27) For a report on CMCS → DCM conversion, see Power, N. P.;
Bethell, D.; Proctor, L.; Latham, E.; Dawson, P. Org. Biomol. Chem.
2004, 2, 1554.
(28) We have observed that the presence of residual CMCS in the
crude 3/DCM solution can lead to decomposition of 3 to the mono-
tert butyl derivative upon storage.
(29) The thermal conversion reached 100% upon adding CMCS over
1 min, indicating that there is no heat delay during the CMCS charge.
(30) King, R. B.; Sundaram, P. M. J. Org. Chem. 1984, 49, 1784.
(31) While 1H NMR was used to determine both the end of reaction
and final wt % of 3 in DCM, proof-of-concept was achieved to monitor
CMCS consumption by GC and determine the final wt % of 3 in
DCM by Raman spectroscopy.
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dx.doi.org/10.1021/op500066f | Org. Process Res. Dev. 2014, 18, 636−642