Organic compounds -- part of the class 532-570 series – Organic compounds – Four or more ring nitrogens in the bicyclo ring system
Reexamination Certificate
2000-03-22
2001-06-05
Raymond, Richard L. (Department: 1624)
Organic compounds -- part of the class 532-570 series
Organic compounds
Four or more ring nitrogens in the bicyclo ring system
C544S219000
Reexamination Certificate
active
06242598
ABSTRACT:
This invention pertains to novel methods for the preparation of tris-aryl-o-hydroxy-phenyl-s-triazines using cyanuric chloride as a starting material. Particular o-hydroxy-phenyl-s-triazines which can be made by these new methods are: bis-aryl-resorcinol based s-triazines; mono-aryl-bis-resorcinol based s-triazines; and tris-resorcinol-s-triazines.
BACKGROUND OF THE INVENTION
Tris-aryl-o-hydroxyphenyl-s-triazines are intermediates for or are themselves UV absorbers useful for the protection of natural or synthetic materials from the adverse action of actinic radiation. There are many methods described for the preparation of such s-triazines as seen from the publications of S. Tanimoto and M. Yamagata, Senryo to Yakuhim, 1995, 40(12), 325-339 and of H. Brunetti and G. E. Luethi, Helv. Chim. Acta, 1972, 55(5), 1566-1595.
The most versatile method is to employ one or more Friedel-Crafts reactions starting from cyanuric chloride. A major obstacle in this approach is the fact that Friedel-Crafts reactions of aryl groups and cyanuric chloride are non-selective. This is a problem when the goal is to prepare an asymmetric tris-aryl-s-triazine. This is explained in the Tanimoto and Brunetti publications mentioned above and in U.S. Pat. Nos. 5,084,570 and 5,106,972. However, it is well-known that substitution reactions between nucleophiles and cyanuric chloride are selective as taught by E. M. Smolin and L. Rapoport, s-Triazines and Derivatives in The Chemistry of Heterocyclic Compounds, A. Weissberger Ed., Interscience Publishers, New York, 1959, pp. 53-57.
One possible approach to prepare asymmetric tris-aryl-s-triazines selectively would be to (a) replace one or two chlorine atoms of cyanuric chloride with an appropriate protecting group in a nucleophilic manner, (b) replace the remaining chlorine atom(s) with the desired aryl group via a Friedel-Crafts reaction; (c) displace the protecting group(s) with chlorine, and finally (d) replace the newly formed chlorine(s) with the second aryl group in a Friedel-Crafts manner. U.S. Pat. Nos. 5,084,570 and 5,106,972 disclose this strategy for the preparation of 2,(2,4-dihydroxyphenyl)-4,6-diaryl-s-triazine. The protecting group chosen in these two patents is methyl mercaptan. The process outlined is four steps starting from cyanuric chloride.
Another drawback of Friedel-Crafts reactions of aryl groups and cyanuric chloride in addition of non-selectivity is the fact that large amounts of Lewis acid are necessary to mediate the reaction, normally equimolar amounts. The Lewis acid most commonly used is aluminum chloride. These reactions produce prodigious amounts of aluminum waste which is environmentally hard to handle.
Japanese Hei 9-59263 discloses a three-step synthetic approach for the preparation of asymmetric tris-aryl-hydroxyphenyl-s-triazines. The preferred method of the Japanese reference is a one-pot process using a Lewis acid to mediate all three steps. This reference will be discussed in more detail later in this application.
A welcome addition to the art therefore would be to (a) provide a method of performing Friedel-Crafts reactions between aryl groups and s-triazines using protic acids instead of Lewis acids, and to (b) provide a method of preparing asymmetric tris-aryl-s-triazines in less than four synthetic steps.
OBJECTS OF THE INVENTION
One object of the invention is a process in which protic acids may be employed as Friedel-Crafts catalysts for the reaction between aryl groups and s-triazines.
Another object of the invention is a method for the preparation of asymmetric tris-aryl-s-triazines in less than four synthetic steps.
A third object of the invention is a process combining the two processes mentioned above.
DETAILED DESCRIPTION OF THE INVENTION
Strong protic acids, such as hydrogen chloride, sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid as well as solid-supported protic acids such as AMBERLYST® (Rohm & Haas), AMBERLITE® (Rohm & Haas) and NAFION® (duPont) catalysts, may be employed as effective Friedel-Crafts catalysts to form carbon-carbon bonds between aryl groups and s-triazines. Active leaving groups are halogen, alkoxy and aryloxy. Preferred leaving groups are chlorine, phenoxy and substituted phenoxy moieties.
The simpliest example of a reaction of this type is replacing the chlorine atoms on cyanuric chloride with resorcinol to prepare a tris-2,4,6-(2,4-dihydroxyphenyl)-s-triazine. U.S. Pat. Nos. 3,118,887 and 3.244.708 describe such syntheses, but where large amounts of aluminum chloride are used. Indeed, no added catalyst at all is required as the hydrogen chloride gas released during the initial nucleophilic reaction between resorcinol and cyanuric chloride serves as the catalyst for the carbon-carbon bond formation as seen below:
X in these formulae is hydrogen, alkyl, phenylalkyl or halogen.
This reaction may be performed in a solvent or it may be done in neat molten resorcinol. A wide variety of solvents may be used, for example, non-polar hydrocarbons such as xylene or polar solvents such as tetramethylene sulfone. The reaction will work over a wide temperature range from −30° C. to 250° C. An effective temperature range is from 70° C. to 200° C. The most effective temperature range is 100° C. to 170° C.
This reaction may also be performed on mono-aryl-bis-chloro-s-triazines and bis-aryl-mono-chloro-s-triazines as seen below.
R
1
, R
2
and R
3
are each independently hydrogen, alkyl of 1 to 12 carbon atoms, hydroxy, alkoxy of 1 to 12 carbon atoms, halogen, phenyl or phenyl substituted by alkyl of 1 to 12 carbon atoms, hydroxy, alkoxy of 1 to 12 carbon atoms or halogen. The solvents and temperature ranges are those given supra. O-Attached resorcinol groups on the s-triazine ring are observed as transient intermediates during the course of these reactions.
Similar Friedel-Crafts reactions may also be employed with alkoxy or aryloxy moieties as the leaving group. In these cases an external protic acid is added to the mixture. The most effective protic acids are hydrogen chloride gas and methanesulfonic acid. As with halogen, one or more alkoxy or aryloxy groups may be replaced in this fashion. Phenoxy and/or substituted phenoxy groups are especially suitable leaving groups as seen in the reactions outlined below.
R
1
, R
2
and R
3
are as defined above. The solvents and temperature ranges used are as above using chlorine as the leaving group.
The instant process also pertains to the preparation of asymmetric tris-aryl-s-triazines in only three steps while avoiding the selectivity problem of Friedel-Crafts reactions with cyanuric chloride. U.S. Pat. Nos. 5,084,570 and 5,106,972 describe a four-step process to overcome this selectivity problem. The key to the new three step process is to take advantage of a nucleophilic substitution step on cyanuric chloride which is selective (E. M. Smolin et al., loc cit). The nucleophile introduced into the triazine ring will also perform as a leaving group under Friedel-Crafts conditions. It is a poor leaving group compared to chlorine. In this way selectivity under Friedel-Crafts condition is achieved This allows one to avoid having to rechlorinate the triazine ring prior to subsequent Friedel-Crafts reactions thus reducing the number of synthetic steps. Effective nucleophiles which also serve as Friedel-Crafts leaving groups are alkoxy and aryloxy groups. Especially effective are phenoxy and substituted phenoxy.
For example, in order to prepare a mono-resorcinol-bis-aryl-s-triazine, cyanuric chloride is reacted with one mole of phenol or substituted phenol under nucleophilic (basic) conditions.
R
1
, R
2
and R
3
are defined as above.
As mentioned above, the phenoxy group is an active Friedel-Crafts leaving group. It is a weaker one than chlorine thus allowing for the introduction of a relatively weak Friedel-Crafts substrate such as m-xylene, toluene, benzene, chlorobenzene or biphenyl while leaving the phenol group intact.
In the third step, the phenoxide may be replaced with a strong Friedel-Crafts substrate such as resorcinol.
X, R
1
,
Ackerman Michael
Hayoz Pascal
Meuwly Roger
Oswald John Francis
Schregenberger Christian
Balasubramanian Venkataraman
Ciba Specialty Chemicals Corporation
Raymond Richard L.
Stevenson Tyler A.
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