Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Patent
1997-11-19
1998-11-24
Shippen, Michael L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
570183, C07C 3334, C07C 2200
Patent
active
058410007
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to an industrially useful method for making trans-2-bromoindan-1-ol.
BACKGROUND ART
Trans-2-bromoindan-1-ol is a pharmaceutical intermediate for anti-HIV drugs, etc., and is useful as a starting material for making cis-1-aminoindan-2-ol. For example, in Japanese Patent Application 6-298619 which is a previous patent by the present applicants, it is stated that cis-1-aminoindan-2-ol can be obtained by reacting trans-2-bromoindan-1-ol under acid conditions with acetonitrile to give trans-1-(acetamide)-2-bromoindane, cyclizing this to make a cis-oxazoline derivative, and then hydrolysing. Similarly, in the method of Gagis et al. (J. Ore. Chem. 37, 3181 (1972)) cis-1,2-epoxyindane is obtained by treating trans-2-bromoindan-1-ol under basic conditions. In the aforementioned Japanese Patent Application 6-298619 it is shown that a derivative of cis-oxazoline is produced by reacting this epoxy compound under acid conditions with acetonitrile, and that cis-1-aminoindan-2-ol can be obtained by hydrolysing this.
To date, various methods have been disclosed for making trans-2-bromoindan-1-ol. For example, Porter et al. (J. Am. Chem. Soc. 57, 2022 (1935)) obtained trans-2-bromoindan-1-ol by reacting bromine water with indene; however, the yield was low at 31%. Similarly, Suter et al. (J. Am. Chem. Soc. 62, 3473 (1940)) obtained trans-2-bromoindan-1-ol with 94% yield by saturating an aqueous solution of sodium bromide with bromine and then reacting with indene in the presence of a large quantity of a dispersant. This method gives a comparatively good yield but efficiency is poor, and using a 5-litre reaction vessel only 204 g of the intended product is obtained. Moreover, there are industrial problems in that a large quantity of reaction mother liquor is produced, and the fact that the mother liquor is a mixture of sodium bromide and hydrogen bromide complicates treatment after the reaction. On the other hand, Guss et al. (J. Am. Chem. Soc. 77, 2549 (1955)) obtained trans-2-bromoindan-1-ol with a yield of 59% by reacting N-bromosuccinimide with indene in water at room temperature for 3 hours. Although this method is comparatively efficient, from the economic point of view N-bromosuccinimide needs to be regenerated by separating out by-product succinimide and then brominating.
As indicated above, no industrial and cheap method is known for making trans-2-bromoindan-1-ol.
DISCLOSURE OF THE INVENTION
The present invention offers an industrial and cheap method for making trans-2-bromoindan-1-ol.
It has been disclosed by Dalton et al. (J. Am. Chem. Soc. 90, 5498 (1968)) that when an alkene is brominated in water bromine cations attack the carbon-carbon double bond to produce a bromonium cation intermediate, and this intermediate is attacked by solvated anions (OH.sup.- anions in the case of a reaction in water) to produce a bromhydrin.
Thus, it is suggested that all of the prior art cited above includes this reaction mechanism. In the reaction of bromine water and indene of Porter et al., for example, Br.sup.+ OH.sup.- (produced by an equilibrium reaction between bromine and water) contained in the bromine water becomes the reaction reagent; a bromonium cation intermediate is first produced by Br.sup.+ attacking indene, and then trans-2-bromoindan-1-ol (indenebromohydrin) is produced by the action of OH.sup.-. However, because the concentration of Br.sup.+ OH.sup.- in water is small the yield is low. Similarly, Suter et al. dissolved bromine in sodium bromide in order to increase the concentration of Br.sup.+ OH.sup.- in the water. Moreover, Guss et al. used the reaction of indene with Br.sup.+ OH.sup.- generated from water and N-bromosuccinimide.
The present inventors have perfected the present invention as the result of pursuing concerted studies focusing on the importance of the concentration of bromonium cations produced as an intermediate stage of the synthesis of trans-2-bromoindan-1-ol.
There are 2 methods for generating bromonium cations in an indene system: 1-(sub
REFERENCES:
L. Benmenni, "Acta Cryst. Sec. C" vol. 50 (1994), pp. 1636-1638.
A. Gagis, "J. Org. Chem." vol. 37, No. 20 (1972), pp. 3181-3182.
Dale F. Shellhamer, "J. Chem. Soc. Perkin Trans 2" (1991), pp. 401-403.
T. Ho, "Synthesis" (1977), pp. 675-677.
W.E. Billups, "J. Org. Chem." vol. 45, No. 23 (1980), pp. 4636-4641.
G.E. Heasley, "J. Org. Chem." vol. 45, No. 23 (1980), pp. 5150-5155.
M.R. Detty, "J. Am. Chem. Soc." vol. 118, No. 2, Jan. 17, 1996 (17 Jan. 1996), pp. 313-318.
D.T. Sawyer, "J. Am. Chem. Soc." vol. 117, No. 1, Jan. 11, 1995 (11 Jan. 1995), pp. 106-109.
Asano Fumihiro
Igarashi Yoshio
Konno Yuzi
Nakano Shigeru
Ichikawa Gosei Chemical Co., Ltd.
Puttlitz, Jr. Karl J.
Shippen Michael L.
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