Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-03-13
2003-03-04
McKane, Joseph K. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C548S518000, C548S527000
Reexamination Certificate
active
06528659
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to a synthesis method involving the use of protecting groups which method can be useful in making dipyrromethanes (DPM), tripyrrodimethanes (TPM), as well as various bilanes, bilenes, and biladienes. Moreover, the inventive method provides a technique suitable for use in synthesizing. The present invention further relates to a variety of inventive compounds including a number of starting materials and intermediates.
Currently there is no commercial source of dipyrromethane due to its instability and its tedious and dangerous synthesis. The currently preferred procedure requires the use of thiophosgene, which is an extremely toxic and volatile nerve agent. This method can provide dipyrromethane in about a 40% yield in three steps. A more recent procedure discussed in literature can produce dipyrromethane in about 40% yield in one step from simple starting materials, however, the isolation involves a tedious chromatographic procedure requiring a base stabilizing agent. The pure material is not stable at room temperature for any extended periods of time. The initial reaction conditions, the isolation, and the instability of the resulting product do not make this route attractive for commercial scale production.
Attention is also directed towards the following patents and literature references which are incorporated by reference in their entirety for all purposes. U.S. Pat. No. 5,241,062 to Wijesekera et al.; U.S. Pat. No. 5,760,217 to Wijesekera et al.; U.S. Pat. No. 5,767,272 to Wijesekera et al.; U.S. Pat. No. 5,554,764 to Verkade et al.; U.S. Pat. No. 5,672,717 to Verkade et al; U.S. Pat. No. 5,124,449 to Franck et al.; U.S. Pat. No. 5,756,724 to Vogel et al.; JP 1238585 A, assigned to Maruyama K; JP 63238078 A, assigned to Central Glass Co. Ltd.; JP 63238057 A, assigned to Central Glass Co. Ltd.;
J. Am. Chem Soc.,
Abell et al., 120, 1741-1746 (1998);
Tetrahedron Letters,
Wang et al., 37, 3247-3250 (1996);
Tetrahedron Letters,
Kuroda et al., 30, 2411-2412 (1989);
Bull. Chem. Soc. Jpn.,
Kinoshita et al., 65, 2660-2667 (1992);
Chemistry Letters,
Kinoshita et al., 7, 1107-1108 (1989);
Synthesis,
Tietze et al., 851-857 (1996);
J. Porphyrin Phthalocyanines,
Bruckner et al., 2, 455-467 (1998),
BIORG KHIM
Isaeva et al., 5(7) 1146-1150 (1979);
Liebigs Ann. Chem.,
Triebs et al., 718, 183-207 (1968);
J. Porphyrin Phthalocyanines
Lin et al. 2, 363-368 (1998);
Porphyrins and Metalloporphyrins,
Smith, Chap. 2, 29-58 (1979);
Tetrahedron Letters,
Manka et al., 30, 6989-6992 (1989); and
Synlett
1999, Taniguchi et al., No. 1, 73-74 (1999).
Japanese patent applications JP 63238057 and JP 63238078 to Central Glass Co. Ltd. disclose methods of preparing unsymmetrically 3,4-disubstituted, 2-hydroxymethyl-pyrroles, with at least one perfluoroalkyl substituent. Japanese patent application 1238585 to Murmyama discusses a different method of preparation of unsymmetrical 3,4-disubstituted-2-hydroxymethylpyrroles with a variety of alkyl substituents.
U.S. Pat. No. 5,241,062 to Wijesekera et al. discloses methods of making and using compounds with “leaving group” substituents bonded to the oxygen of 3,4-disubstituted-2-hydroxyalkyl-pyrroles. The leaving groups disclosed included variously substituted benzoates and sulfonates.
Kinoshita et al. (in their 1989 and 1992 articles) disclose methods for the synthesis of substituted pyrroles which contain p-toluenesulfonate groups bonded to the pyrrole nitrogen atoms, and a variety of “leaving groups” on the 2-alkyl substituted pyrroles, including alkoxide, organo-nitrogen and mono-organo substituted sulfur groups.
Wang et al. disclose a method of reacting N-tosyl-protected 2-formyl-4-aryl-pyrroles, which are useful precursors of porphyrins with beta-aryl substituents.
Abell et al. disclose that various electron withdrawing protecting groups attached to the nitrogen atom of a pyrrole deactivate and stabilize pyrrole rings.
Tietze et al. disclose certain substituted hydroxymethyl pyrrole compounds with N-protecting groups, including tosyl and BOC protecting groups, and certain attempts to couple the substituted and protected hydroxymethylpyrrole compounds with unsubstituted pyrrole compounds.
Vogel et al. disclose the use of BOC groups to protect pyrrole nitrogens during a copper catalyzed coupling reaction of halo-pyrroles, to synthesize bipyrroles, and removal of the BOC groups from the bipyrroles by hydrogenation or thermal treatment.
Smith reviews numerous prior art methods of synthesizing substituted bilane and bilene compounds, including a number of methods that utilize dipyrromethane and tripyrromethane starting materials.
Franck et al. disclosed a synthesis of unusual “azaporphyrin” derivatives containing extra ethylene groups and nitrogen atoms bonded within the main porphyrin ring system.
Isaeva has disclosed a step-wise synthesis of porphyrins involving dipyrromethane, tripyrromethane, and biladiene intermediates which contain various protecting groups (including t-butoxycarbonyl) bonded to the carbon atoms of pyrrole rings.
The need still exists for an improved method for synthesis DPM as well as other compounds containing pyrrole sub-units.
SUMMARY OF THE INVENTION
The present invention is based, at least in part, on the surprising discovery that the use of protecting groups can greatly stabilize a variety of dipyrrolmethanes, tripyrromethanes, bilanes and bilenes. Moreover, these compounds can effectively, economically and rapidly be protected as needed for subsequent use with synthesis of porphyrins. This protection can thus provide for easier purification, isolation, storage and transportation of these compounds.
One aspect of the present invention relates to a method of forming chemical compounds and, in particular, chemical intermediates having one or more pyrrole sub-units and at least one protecting group bonded to an atom. within a pyrrole sub-unit. The method further involves removal of the protecting group so as to provide a desired chemical compound having one or more pyrrole sub-units.
Another aspect of the present invention relates to methods of making the protecting group containing compounds as well as the resulting chemical compounds and/or intermediates.
Yet another aspect of the invention relates to pyrrole intermediates and, in particular, sulfonium salt intermediates used in forming the protecting group-containing pyrrole compounds.
In particular, the present invention includes, but is not limited to, the following synthesis techniques for forming protective group containing compounds:
where R
1
, R
2
, R
3
, R
3
′, R
4
, R
5
, and R
6
include carbon atom-containing substituents including hydrogen, and hydrocarbon groups such as alkyl, aryl, alkenyl, alkynyl groups, which groups can optionally include substituents and heteroatoms in connection therewith, as well as a deprotection scheme such as that illustrated in connection with DPM:
where the protecting group, PG, is discussed in more detail below.
Moreover, the invention relates to a number of starting materials and intermediates including:
REFERENCES:
patent: 5124449 (1992-06-01), Franck et al.
patent: 5241062 (1993-08-01), Wijesekera et al.
patent: 5554764 (1996-09-01), Verkade et al.
patent: 5672717 (1997-09-01), Verkade et al.
patent: 5756724 (1998-05-01), Vogel et al.
patent: 5760217 (1998-06-01), Wijesekera et al.
patent: 5767272 (1998-06-01), Wijesekera et al.
patent: 63238078 (1988-04-01), None
patent: 63238057 (1988-10-01), None
patent: 1238585 (1989-09-01), None
Jerry March, Advanced Organic Chemistry, Fourth Ed., John Wiley & Sons, New York, pp. 352-354 and 421 (1992).*
Tietze et al, Synthesis, 1996 (7) 851-857 CAS Abstract Only.*
Abell, et al,. “Synthesis and Properties of Ring-Deactivated Deuterated(Hydroxymethyl)pyrroles,” J. Am. Chem. Soc., 120, 1741-1746 (1998).
Wang, et al., “A General Synthesis of &bgr;-Aryl and Heterorarylpyyroles by Palladium-catalyzed Coupling Reaction of &bgr;-Tributylstannylpyrrole with Aryl and Heteroaryl Halides,” Tetrahedron Letters, 37 (19
Liebeskind Lanny S.
Nickel Eric G.
Emory University
McKane Joseph K.
Needle & Rosenberg P.C.
Saeed Kamal
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