Chemical composition and use thereof

This invention relates to novel compositions comprising a N-halodialkylamine as defined in the specification and an inorganic oxide. The compositions are useful as halogenating agents for phenolic compounds. The compositions have the advantage that they are milder halogenating agents than halogens or hydrogen halides.

The present invention relates to inorganic oxide derived compositions and 
to their use as halogenating agents for organic compounds, especially 
phenolic compounds. 
Chlorinated phenols, for example, are valuable industrial products having a 
variety of uses, which include their use as intermediates in the 
manufacture of dyestuffs, preservatives, disinfectants, germicides, 
insecticides and antifungal agents. 
Chlorinations of phenolic compounds have been carried out with a variety of 
chlorinating agents, catalysts and reaction conditions too numerous to 
mention in detail. Thus chlorophenols are obtained with chlorinating 
agents such as chlorine, chlorine oxide, SO.sub.2 Cl.sub.2, NaOCl, 
tertiary butyl hypochlorite etc. The ortho/para ratio is very dependent 
upon the nature of the chlorinating agents and the conditions. For 
example, the chlorination of phenol with tertiary butyl hypochlorite in 
CCl.sub.4 gives an ortho:para ratio of 1.04 (cf. D. R. Harvey and R. O. C. 
Norman, J. Chem. Soc., 1961, 3604) and this ratio also depends on the 
concentration of phenol (cf. W. D. Watson, J. Org. Chem., 1974, 39, 1160). 
Likewise, the chlorination of phenol with Chlorine in CCl.sub.4 gives an 
ortho:para ratio of 2.85 (cf. Y. Ogata et al, J. Chem. Soc. Perkin Trans 
II., 1984, 451). 
We have recently described in our published UK Patent Specification No. 
2155009, the use of novel halogenation compositions comprising an 
inorganic solid and one or more organic halogen-containing compounds, 
which halogenate aromatic substrates such as toluene under mild conditions 
and avoid the use of corrosive halogen or hydrogen halide. 
We have now found that compositions containing an N-halodialkylamine 
compound (cf. J. R. Lindsay Smith and L. C. McKeer, Tet. Letters, 1983, 
3117), such as for example N-chloropiperidine, and an inorganic oxide, 
such as for example silica gel, alumina or an aluminosilicate are highly 
effective halogenating agents and are especially useful for the 
halogenation of phenolic compounds. 
Accordingly, the present invention provides a composition for use as a 
halogenating agent which comprises at least one N-halodialkylamine and at 
least one inorganic oxide. 
By the term `N-halodialkylamine` is meant here and throughout the 
specification that the nitrogen atom in the compound is linked directly to 
(a) at least two separate hydrocarbyl units which may themselves be 
substituted by other groups and/or which may together form a heterocyclic 
ring with the nitrogen being the hetero atom, and (b) a halogen atom. 
A wide range of N-halodialkylamines may be employed including 
iodine-containing compounds, although chlorine- and bromine-containing 
compounds are preferred. Typical of the N-halodialkylamines which may be 
used in the composition of the present invention are N-chloropiperidine, 
N-chlorodiisopropylamine, N-chloromorpholine, N,N-dichloropiperazine, 
N-chlorobis(2-methoxyethyl)amine, N-chlorobis(2-chloroethyl)amine and 
N-chlorodiethylamine. It should be noted that 
N-chlorobis-(2-methoxyethyl)amine and N-chlorobis(2-chloroethyl)amine may 
have explosive properties when in their neat state and they should be 
handled with care. They may be handled with safety in the form of 
solutions or suspensions in appropriate solvents. These can be prepared in 
situ by reacting in aqueous solution the parent dialkylamines, e.g. 
bis(2-methoxyethyl)amine and bis(2-chloroethyl)amine respectively with 
sodium hyprochlorite. For further details on the preparation of 
N-halodialkylamines, the reader is referred to J. Am. Chem. Soc., 1933, 
55, 3001 by G. H. Coleman and Can. J. Chem., 1970, 48, 546 by K. U. 
Ingold. The aqueous reaction mixture may then be stirred in carbon 
tetrachloride dichloromethane or hydrocarbon solvents so as to extract the 
N-halodialkylamine directly into the organic solvent of choice. 
The inorganic oxides which may be employed include one or more of silica, 
alumina, silica/alumina, titania, zirconia and both natural and synthetic 
aluminosilicates. 
In the compositions of the present invention the amount of 
N-halodialkylamine to inorganic oxide may vary over a wide range. The rate 
of halogenation reaction will vary with the relative proportion of the two 
components. Typically, the composition may contain 0.2 to 10 moles, 
preferably 0.5 to 5 moles of the N-halodialkylamine per kilogram of the 
inorganic oxide. 
For example, in the case of a commercial silica (e.g. ex-British Drug 
Houses) a maximum rate of halogenation is achieved when using 0.65 mole of 
the N-halodialkylamine per kilogram of the silica. 
The halogentating properties of the resulting compositions are quite 
different from those of the individual components. Many of the 
compositions falling within the scope of the invention will also tolerate 
the presence of water. 
Such compositions are not only halogenating agents but also have the added 
advantage of preferentially forming the orthohalogenated isomer in the 
product during halogenation of phenols. Thus, for example chlorination of 
2-methylphenol in carbon tetrachloride at 25.degree. C. with a slight 
excess of N-chlorobis(2-chloroethyl)amine can give a 94% yield of 
chloro-2-methylphenols in the proportions 6-chloro-2methylphenol (81%), 
4-chloro-2-methylphenol (10%), 2,4-dichloro-2methylphenol (9%) [ratio of 
ortho substituted: para substituted=8:1]. Chlorination of phenol under the 
same conditions as above gives an ortho:para ratio of about 15:1. 
Ortho:para ratios in the product may be varied by varying the phenolic 
reactant to halogenating agent ratios, the concentration of the 
reactant(s), the reaction medium, e.g. solvent or the reaction conditions. 
Although the compositions are especially useful for the halogenation of 
simple or substituted phenols e.g. phenol, ortho-chlorophenol, 
para-chlorophenol, ortho-cresol and meta-cresol, they may also be used for 
the halogenation of other organic compounds, for example other aromatic 
compounds. 
The components in the composition may be used as a performed physical 
admixture or may be added sequentially to the halogenation reaction. 
The relative proportions of the halogenating composition and the phenolic 
compound may be varied over a wide range depending on the level of 
chlorination required. However, molar ratios of the phenolic 
compound:N-halodialkylamine in the range 3:1 to 1:3 are preferred. 
The halogenation reactions may be carried out over a range of temperatures, 
typically 0.degree.-80.degree. C., but are most conveniently carried out 
at 15.degree.-40.degree. C. Similarly, the most convenient pressure is 
atmospheric pressure, but sub-atmospheric or elevated pressures may be 
employed. 
Although the reactions are conveniently carried out in the presence of a 
solvent, this is not essential. The N-halodialkylamine may initially be 
deposited on the inorganic solid (with removal of any solvent employed for 
this purpose), and the reactant may be brought into contact with the 
supported halogenating agent in a gas flow, as a neat liquid or in 
solution. Solid-phase reactions are also possible.

The invention will now be further illustrated by reference to the following 
Examples. 
EXAMPLE 1 
Silica (3 g, 60-120 BSS mesh), carbon tetrachloride (10 ml), phenol (2.5 
mmol) and N-chlorobis(2-chloroethyl)amine (2.63 mmol) were gently stirred 
together at 25.degree. C. for 24 hours. The reaction mixture was filtered 
and the solid was washed with a little extra carbon tetrachloride and some 
methanol to give a filtrate containing ortho-chlorophenol (47%), 
2,6-dichlorophenol (10%), 2,4-dichlorophenol (5%), para-chlorophenol (3%) 
and unreacted phenol (34%), as estimated by gas chromatography. 
EXAMPLE 2 
The proceduure of Example 1 was repeated except that the reactant was 
p-chlorophenol instead of phenol. The filtrate obtained contained 
2,4-dichlorophenol (55%), 2,4,6-trichlorophenol (16%) and unreacted 
para-chlorophenol (29%), as estimated by gas chromatography. 
EXAMPLE 3 
The procedure of Example 1 was repeated except that ortho-chlorophenol was 
the reactant (instead of phenol), the reaction period was increased to 48 
hours and the reagent used was N-chlorodiethylamine. The filtrate obtained 
contained 2,6-dichlorophenol (32%), 2,4-dichlorophenol (22%), 
2,4,6-trichlorophenol (18%) and unreacted ortho-chlorophenol (28%), as 
estimated by gas chromatography. 
EXAMPLE 4 
The procedure of Example 1 was repeated except that the reactant was 
ortho-chlorophenol (instead of phenol) and the reaction period was 
increased to 48 hours. The filtrate obtained contained 2,6-dichlorophenol 
(41%), 2,4-dichlorophenol (8.5%), 2,4,6-trichlorophenol (12.5%) and 
unreacted ortho-chlorophenol (38%), as estimated by gas chromatography. 
EXAMPLE 5 
The procedure of Example 1 was repeated except that the reactant was 
ortho-cresol instead of phenol and the reaction period was increased to 48 
hours. The filtrate obtained contained 6-chloro-2-methylphenol (76%), 
4-chloro-2-methylphenol (9.5%), 4-6-dichloro-2-methylphenol (8.5%) and 
unreacted 2-methylphenol (6%), as estimated by gas chromatography.