Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Reexamination Certificate
1999-03-29
2001-06-05
Raymond, Richard L. (Department: 1624)
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
C544S347000
Reexamination Certificate
active
06242602
ABSTRACT:
TECHNOLOGICAL FIELD
The present invention pertains to a low cost method of preparing dihydrophenazine and dihydrophenazine derivatives, including substituted phenazines.
DESCRIPTION OF THE RELATED ART
Phenazines occupy a somewhat unique status in the field of organic chemistry. In his abortive attempt to synthesize quinine, Sir William Henry Perkin instead synthesized mauveine, an impure mixture of substituted phenazines and other compounds, which became the first successful synthetic dye. This synthesis, in the mid-19th century, is regarded as the beginning of the synthetic organic chemical industry.
In the phenazine series of dyestuffs, while consistency of product color, shade, and dyeing ability has been important, purity in the sense of preparing or isolating well defined compounds has not. See, e.g., “Azine Dyes”, J. Clyde Conger, Kirk Othmer C
ONCISE
E
NCYCLOPEDIA
O
F
C
HEMICAL
T
ECHNOLOGY
,© 1985, p. 142. The base structure shared by the phenazine dyes, phenazine itself,
has been prepared by several methods, in varying degrees of purity, and with some degree of difficulty. For example, early syntheses included the reaction of nitrobenzene with aniline in the presence of caustic. However, the reaction is dangerous and difficult to control, and the yield of the initial product, phenazine oxide, is low. Large quantities of azobenzene are formed. The phenazine oxide can be reduced to phenazine. Phenazine has also been prepared by the reduction of 1,1′-dinitrodiphenylamine. Eckert et al., Monatshefte für Chemie, 1914, pp. 1153-55.
In U.S. Pat. No. 2,292,808, phenazine is manufactured by the cyclization of ortho-nitrodiphenylamine, itself prepared by the lead oxide oxidation of ortho-amino diphenylamine. The cyclization is effected with a zero valent metal or low valent metal oxide such as chromous oxide or lead suboxide, which act as oxygen acceptors. The reaction involves the use of a nitro group-substituted organic compound which is potentially dangerous, and generates large quantities of environmentally suspect heavy metal-containing waste products.
Phenazine and 5,10-dihydrophenazine are prepared from catechol and o-phenylenediamine by J. S. Morley, J. C
HEM
. S
OC
. (1952), p. 4008-4014, following an earlier procedure reported by Ris, B
ER
., 1886 (19), p. 2206. In this reaction, catechol and o-phenylenediamine are heated under pressure in a sealed tube at 200-210° C. for 35-40 hours. The yield is modest, and somewhat lower after purification, ca. 60% overall. The product may be converted to phenazine by standard methods, for example by sublimation in a stream of oxygen. Dihydrophenazine is notoriously sensitive to oxidation. The method of Morely and Ris suffers from the disadvantage that the process is not amenable to large scale production, and from the further disadvantage that considerable quantities of unidentified impurities are formed.
In Wataya published Japanese application JP 48-144440 (laid open Jul. 29, 1975), 2-nitrophenylenediamine or substituted 2-nitrophenylenediamines are cyclized with the aid of highly basic metal alcoholates in dimethylsulfoxide solvent. The latter solvent is relatively expensive. However, Wataya indicates that other solvents, for example benzene, toluene, ethers, and hydroxylic solvents such as aliphatic alcohols, fail to work, or produce products only very slowly or in low yield. Purification from dimethylsulfoxide solvent-based reactions is difficult, requiring chromatographic methods.
All the foregoing syntheses are difficult on a commercial scale, involve use of expensive reagents, or generate undesirable byproducts. These difficulties may be reflected in the very high cost of phenazine, averaging ca. $1000/Kg or more. However, pure phenazine and dihydrophenazine and their derivatives have become increasingly useful, not only as dyestuffs, or dyestuff intermediates, but as pharmaceuticals and other products. For example, many 5,10-disubstituted dihydrophenazines, and 5,10-disubstituted dihydrophenazines bearing ring substituents in the 1-4 and/or 6-9 positions have been shown to exhibit electrochromic behavior, and can be used as chromophores in applications such as electrically dimmable mirrors (electrochromic mirrors), windows, and the like.
Importantly, some ring-substituted dihydrophenazines, when employed with other electrochromophores, can produce a color which varies from colorless to very dark gray without significant color shift during transitioning. Compositions such as these, and electrochromic devices containing them, are disclosed in copending U.S. patent application Ser. No. 08/832,596 filed Apr. 2, 1997, and entitled: Improved Electrochromic Medium Capable Of Producing A Preselected Color, herein incorporated by reference. To be useful in such applications, unlike the phenazine dyes of the nineteenth century, the electrochromophores must be produced in a high degree of purity. Unfortunately, the synthetic route to these ring-substituted dihydrophenazines begins by reducing expensive and not widely available phenazine. Moreover, ring-substituted dihydrophenazines such as alkyl, ring substituted-dihydrophenazines are inaccessible by this route, and are not presently commercially available.
It would be desirable to prepare dihydrophenazine, substituted dihydrophenazines, and analogous phenazines by a simple procedure, in acceptable yield, which procedure can be commercially practiced in large scale without the use of nitro group-substituted organic compounds, without requiring a pressurized autoclave, and without significant use of transition or heavy metals. It would be further desirable to provide a one pot synthesis of ring-substituted dihydrophenazines without employing expensive phenazine as starting material. It would be yet further desirable to provide a lower cost route to phenazine.
DISCLOSURE OF INVENTION
It has now been surprisingly discovered that dihydrophenazine and substituted dihydrophenazines can be prepared simply and in acceptable yields, by the solvent mediated reaction of substituted or unsubstituted catechols with substituted or unsubstituted 1,2-diaminoaryl compounds, particularly 1,2-diaminobenzenes (o-phenylenediamines). In addition to dihydrophenazines, bis[dihydrophenazines] can also be prepared. The products can be readily oxidized to the corresponding phenazines, and may optionally be derivatized at the 5 and/or 10 positions without oxidation to prepare N-substituted dihydrophenazines.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The phenazines and dihydrophenazines produced by the subject invention process preferably correspond to the formulas I and II, respectively:
wherein each R may be the same or different, and is a substituent which does not interfere with the condensation of the respective substituted catechols and 1,2-diaminobenzenes, and if the dihydrophenazine product is further N-alkylated or derivatized, does not interfere with the N-alkylation reaction or other N-derivatization. Thus, the substituents R may not, in general, be groups which react with aromatic amino groups or which react with aromatic hydroxyl groups to an extent which is more rapid than the cyclizing condensation of the latter groups with each other. Thus, oxirane groups, isocyanate groups, cyanate groups, and aziridine groups are not acceptable R substituents.
Examples of suitable R substituents include the most preferred alkyl, cycloalkyl, alkaryl, and aralkyl groups, alkoxy groups, and aryl groups; and may also include such groups as cyano, halo, haloalkyl, aryloxy, nitro, sulfonate, acyl, acyloxy, and the like. Most preferably, the substituents R are C
1-20
alkyl, C
4-20
cycloalkyl, C
7-20
alkaryl, C
7-20
aralkyl, and C
6-20
aryl, most preferably methyl, ethyl, propyl, isopropyl, butyl, t-butyl, 2-butyl, 2-ethylhexyl, nonyl, octadecyl, and the like. The alkyl, cycloalkyl, aralkyl, and aryl groups may also contain interspersed heteroatoms, particularly O, S, and N. Two or more of the R groups may also be linked to form a cyclic structure, an aromatic structure, i.e. a fused benzene
Baumann Kelvin L.
Byker Harlan J.
Giri Punam
Factor & Partners LLC
Gentex Corporation
Raymond Richard L.
Rees Brian J.
Schroeder Ben
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