Iodohydroxylation of olefins

Details Iodohydroxylation of olefins Iodohydroxylation of olefins

2003-01-31

2004-12-28

Richter, Johann R. (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Halogen containing

C570S246000, C570S243000, C570S190000, C570S216000, C570S217000

Reexamination Certificate

active

06835860

ABSTRACT:

FIELD OF THE INVENTION
The present invention is directed to the iodohydroxylation of olefins using aqueous iodine monochloride or aqueous iodine monobromide.
BACKGROUND OF THE INVENTION
Iodohydrins are useful as intermediates in the preparation of pharmaceutically active compounds. For example, U.S. Pat. No. 5,728,840 and WO 01/38332 disclose iodohydrins which are useful as intermediates in the preparation of HIV protease inhibitors. Another example is WO 95/16658, which discloses the use of iodohydrins in the preparation of allylic halides that are intermediates for the synthesis of antifungal agents. Iodohydrins are also useful in the preparation of bisperfluoroalkyldiols as described in U.S. Pat. No. 5,708,119, wherein the bisperfluoroalkyldiols and their derivatives can impart oil and water repellancy to various materials such as glass, wood, paper, leather, wool, cotton and polyester.
Iodohydrins have been prepared from olefins by a variety of methods. Ohta et al.,
Chem. Letters
1990, 733-736 reports the synthesis of iodohydrins from certain alkenes, alkenols, and alkenones by treatment with periodic acid (H
5
IO
6
) and sodium bisulfite (NaHSO
3
) under mild conditions. Masuda et al.,
J. Org. Chem
. 1994, 59: 5550-5555 provides further details on the preparation of iodohydrins using H
5
IO
6
+NaHSO
3
.
Sanseverino et al.,
Synthesis
1998 11: 1584-1586 discloses the preparation of &bgr;-iodo ethers and iodohydrins in relatively good yields by the reaction of alcohols and water respectively with alkenes in the presence of molecular iodine. The use of molecular iodine leads to the formation of HI during the reaction which in turn causes the reaction mixture to become increasingly acidic. This can trigger side reactions for acid sensitive reactions such as iodohydroxylation of 2-alkyl-4-enamides, as described in Maligres et al.,
Tetrahedron Letters
1995, 36: 2195. Furthermore, the presence of iodide can trigger additional side reactions as, for example, described in Sun et al,
Tetrahedron Letters
2001, 42: 8603.
De Corso et al.,
Tetrahedron Letters
2001, 42; 7245-7247 discloses the iodohydroxylation of various olefins by treatment with a mixture of molecular iodine and phenyliodine(III)bis(trifluoroacetate) in acetonitrile-H
2
O solvent. The drawbacks of this approach include the use of molecular iodine (see preceding paragraph) and the expense of the trifluoroacetate oxidant. Asensio et al.,
Org. Lett
. 1999, 1: 2125-2128 describes the formation of iodohydrins by the oxidation of iodomethane with dimethyldioxirane (DMDO) in acetone at −70° C., followed by addition of an olefin and slow warming of the mixture to room temperature. Unfortunately, very low temperatures are required due to the thermal instability of the reaction system. In addition, DMDO is a relatively expensive reagent.
U.S. Pat. No. 5,728,840 discloses the iodohydroxylation of an allyl acetonide by treating allyl acetonide 1 with N-iodosuccinimide (NIS) and aqueous sodium bicarbonate to provide iodohydrin 2, which is an intermediate in the preparation of indinavir, an HIV protease inhibitor:
Although NIS is a practical iodohydroxylation reagent, it becomes increasingly unstable above a pH of 8 and loses its ability to iodohydroxylate due to rapid decomposition. U.S. Pat. No. 5,981,759 discloses the iodohydroxylation of allyl acetonide 1 to provide iodohydrin 2 by treating the acetonide with an aqueous solution of alkali metal hypohalite (e.g., NaOCl) and an aqueous solution of an alkali halide (e.g., NaI). While this process is characterized by high yields, operability over a wide pH range, and minimal production of organic wastes, it does exhibit a mixing sensitivity (i.e., the level of conversion decreases with increasing mixing intensity). This mixing sensitivity can present a problem during process scaleup, because mixing intensity in large vessels will vary from vessel to vessel, and can be significantly higher than that employed in typical, small-scale laboratory vessels. The process also requires two addition lines, one for the hypohalite solution and one for the halide solution, to introduce the iodohydroxylation reagent.
SUMMARY OF THE INVENTION
The present invention is an improved process for the preparation of iodohydroxylated olefins. More particularly, the present invention is a process for preparing an iodohydroxylated olefin which comprises treating an olefin with an aqueous solution of an iodine monohalide selected from iodine monochloride (ICI) and iodine monobromide (IBr). While not wishing to be bound by theory, it is believed that hypoiodous acid (HOI) is the active agent in the process of the invention and is rapidly and cleanly generated in situ via hydrolysis of ICI or IBr to provide for efficient iodohydroxylation of the olefin. The process of the invention can be operated over a relatively wide range of pH, which can be adjusted to and maintained at (i.e., “tuned” to) a value that optimizes yield of the desired iodohydroxylated product and concomitantly minimizes or suppresses by-product formation. In addition, and in contrast with the NaOCl/NaI process of U.S. Pat. No. 5,981,759 (see Background), the process of the invention is relatively insensitive to the degree of mixing/agitation of the reaction mixture; i.e., the conversion of olefin to iodohydrin exhibits little or no dependence on mixing intensity over a wide range of intensities. Further in contrast with the NaOCl/NaI process of US '759, the process of the invention utilizes only one addition line (instead of two) for the iodohydroxylation reagent, which can reduce equipment complexity and costs.
Various embodiments, aspects and features of the present invention are either further described in or will be apparent from the ensuing description, examples, and appended claims.


REFERENCES:
patent: 5708119 (1998-01-01), Deisenroth et al.
patent: 5728840 (1998-03-01), Askin et al.
patent: 5981759 (1999-11-01), Sun et al.
patent: WO 95/16658 (1995-06-01), None
patent: WO 01/38332 (2001-05-01), None
H. Ohta et al., “Iodohydrin Synthesis from Simple and Functionalised Olefins on Treatment with Periodic Acid and Sodium Bisulfite,” Chemistry Letters 1990, pp. 733-736.
H. Masuda et al., “A New Synthetic Method of Preparing Iodohydrin and Bromohydrin Derivatives through in Situ Generation of Hypohalous Acids from H5IO6 and NaBrO3 in the Presence of NaHSO3,” J. Org. Chem. 1994, vol. 59, pp. 5550-5555.
A. M. Sanseverino et al., “An Improved Synthesis of Beta-Iodo Ethers and Iodohydrins from Alkenes,” Synthesis 1998, vol. 11, pp. 1584-1586.
A. R. De Corso et al., “Iodohydroxylation of Alkenes Promoted by Molecular and Hypervalent(III) Iodine,” Tetrahedron Letters 2001, vol. 42, pp. 7245-7247.
G. Arsensio et al., “Iodomethane Oxidation by Dimethyldioxirane: A New Route to Hypoiodous Acid and Iodohydrines,” Organic Letters 1999, vol. 1, No. 13, pp. 2125-2128.
K. J. Edgar et al., “An Efficient and Selective Method for the Preparation of Iodophenols,” J. Org. Chem. 1990, vol. 55, pp. 5287-5291.
Y. L. Wang et al., “Kinetics of Hydrolysis of Iodine Monochloride Measured by the Pulsed-Accelerated-Flow Method,” J. Am. Chem. Soc. 1989, vol. 111, pp. 7838-7844.
S. G. Yang et al., “A Practical Iodination of Aromatic Compounds Using Tetrabutylammonium Peroxydisulfate and Iodine,” Tetrahedron Letters. 1999, vol. 40, pp. 6051-6054.
P.E. Maligres et al., “Diastereoselective Syn-Epoxidation of 2-Alkyl-4-Enamides to Epoxymides: Synthesis of the Merck HIV-1 Protease Inhibitor Expoxide Intermediate”, Tetrahedron Letters. 1995, vol. 36, No. 13, pp. 2195-2198.
Carl R. LeBlond et al., “Harvesting Short-Lived Hypoiodous acid for efficient diastereoselective iodohydroxylation in Crixivan Synthesis”, Tetrahedron Letters. 2001, vol. 42, pp. 8603-8606.

Affiliated with

Also associated with

Rating

Iodohydroxylation of olefins does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Iodohydroxylation of olefins, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Iodohydroxylation of olefins will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3334951