Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
2002-10-30
2004-06-29
Shah, Mukund J. (Department: 1624)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C568S629000, C568S630000, C568S662000, C568S774000
Reexamination Certificate
active
06756512
ABSTRACT:
The invention relates to a novel process for preparing 2-alkyl-3-chlorophenols.
2-Alkyl-3-chlorophenols are intermediates which can be used, for example, for preparing crop protection agents (cf. WO 98/21189).
It is already known that 3-chloro-2-methylphenol can be obtained by reacting 2-chlorotoluene with sodium methoxide in hexamethylphosphoramide (HMPA) as solvent and treatment of the reaction solution with sodium isopropylthiolate. One disadvantage of this process is the use of HMPA as solvent, since it is highly carcinogenic. Also, the sodium isopropylthiolate used and the isopropylthiol released during the work-up are very odorous. For these reasons, this process is not applicable on the industrial scale.
In another process (cf. Justus Liebigs Ann. Chem., 350, 1906, 112), the preparation of 3-chloro-2-methylphenol takes place starting from 2-amino-6-chlorotoluene. Diazotization using nitrous acid and subsequent hydrolysis in a boiling mixture of water and sulphuric acid gives 3-chloro-2-methylphenol.
A significant disadvantage of this process is that the starting material cannot be prepared in isomerically pure form. High levels of by-products are isolated, which results in low yields. Also, the diazonium salt formed is of limited solubility so that the process must be operated in high dilution, which makes the preparation of 3-chloro-2-methylphenol on the industrial scale more difficult. A further disadvantage is that a steam distillation must be carried out, whose operation, particularly on the industrial scale, is costly and inconvenient.
It has been found that 2-alkyl-3-chlorophenols of the general formula (I)
where
R is C
1
-C
6
-alkyl, are obtained
when alkyldichlorobenzene derivatives of the general formula (II)
where
R has the above meanings, are reacted
a1) with a base in a high-boiling organic diluent of the general formula (III)
R
1
—OH (III),
where
R
1
is
R
2
—O—(CH
2
)
2
—O—(CH
2
)
2
—,
R
2
—O—(CH
2
)
2
—O(—CH
2
)
2
—O—(CH
2
)
2
—,
R
2
—O—(CH
2
)
2
—O(—CH
2
)
2
—O—(CH
2
)
2
—O—(CH
2
)
2
— or
—C
6
to C
10
-alkyl,
where R
2
is hydrogen, methyl or ethyl,
optionally in the presence of a catalyst, and the water released by the reaction is continuously removed,
or are reacted
a2) with a base in a high-boiling organic diluent of the general formula (III)
R
1
—OH (III),
where
R
1
has the above meanings,
optionally in the presence of a catalyst, and any water released during the reaction is continuously removed,
and the resulting compounds of the formula (IV)
where
R and R
1
have the above meanings, are treated with relatively highly concentrated acid,
or are reacted
b1) with a base in a primary alcohol having 1 to 3 carbon atoms used as a diluent under pressure,
or are reacted
b2) with a base in a primary alcohol having 1 to 3 carbon atoms used as a diluent under pressure,
and the resulting compounds of the formula (IV)
where
R and R
1
have the above meanings,
are treated with relatively highly concentrated acid.
After operation of the process variants a1) and b1), the reaction mixture is acidified with a dilute acid.
In the compounds of the formula (II), R is in particular methyl, ethyl, n- or i-propyl.
In the compounds of the formula (II), R is more preferably methyl.
In the compounds of the formula (III), R
1
is more preferably HO—(CH
2
)
2
—O—(CH
2
)
2
—.
The radical definitions listed above or given as preferred meanings apply both to starting compounds of the formulae (II) and (III) and correspondingly to the final products of the formula (I) and the intermediates of the formula (IV).
The specific radical definitions given for the combinations or combinations of radicals in question are, independently of the combination of the radicals given, alternatively arbitrarily replaced by radical definitions of other preferred meanings.
It is particularly surprising to note that, in the process of the invention, 2-alkyl-3-chlorophenols are obtained in high yields and high purity, since, for other comparable reactions, more drastic reaction conditions, such as hydrolysis to give phenols in a boiling mixture of water and sulphuric acid, are required.
The process of the invention has a whole series of advantages. For instance, 2-alkyl-3-chlorophenols can be prepared using non-carcinogenic solvents and without the reaction having to be carried out at high dilution. Therefore, the novel process is particularly suitable for industrial scale applications.
The compounds of the general formula (IVa) are hitherto unknown and as novel chemical compounds also form part of the subject-matter of the present invention
In the compounds of the formula (IVa),
R
1
is R
2
—O—(CH
2
)
2
—O—(CH
2
)
2
—,
R
2
—O—(CH
2
)
2
—O—(CH
2
)
2
—O—(CH
2
)
2
—, or
R
2
—O—(CH
2
)
2
—O—(CH
2
)
2
—O—(CH
2
)
2
—O—(CH
2
)
2
—,
where R
2
is hydrogen, methyl or ethyl.
In the compounds of the formula (IVa), R
1
is more preferably HO—(CH
2
)
2
—O—(CH
2
)
2
—.
The alkyldichlorobenzene derivatives of the general formula (II) and all other starting compounds are currently commercially available products or can be prepared from these by simple processes.
Examples of preferred diluents of the general formula (III) for operating the process variants a1) and a2) include diethylene glycol, triethylene glycol, tetraethylene glycol or higher-boiling primary alcohols. The process variants a1) and a2) are preferably carried out using diethylene glycol.
The process variants a1) and a2) of the invention are operated in the presence of a suitable acid acceptor. Examples of preferred acid acceptors include alkaline earth metal or alkali metal hydroxides, alkoxides or carbonates, such as sodium methoxide, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate. The process variants a1) and a2) are preferably carried out using sodium hydroxide or, in particular, potassium hydroxide.
The process variants a1) and a2) of the invention are optionally carried out in the presence of a suitable catalyst. Preferred catalysts include tertiary amines, such as trimethylamine, triethylamine, tributylamine, N,N-dimethylaniline, N,N-dimethylbenzylamine, pyridine, picoline, 2-methyl-5-ethylpyridine, N-methylpiperidine, N-methylmorpholine, N,N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclononene (DBN) or diazabicycloundecene (DBU).
The process variant a1) of the invention is operated using dilute acids, in particular mineral acids, preferable examples of which include sulphuric acid, phosphoric acid, and in particular hydrochloric acid.
The process variant a2) of the invention is preferably carried out using more highly concentrated acids, in particular mineral acids, preferable examples of which include sulphuric acid or hydrochloric acid or hydrobromic acid; and also Lewis acids, preferable examples of which include aluminium trichloride, boron trichloride or boron tribromide. The process variant a2) is preferably carried out using sulphuric acid.
The reaction temperatures during the operation of the process variant a1) of the invention can be varied within a relatively wide range. In general, operation is effected at temperatures of from 100 to 250° C., preferably at temperatures of 160 to 230° C., more preferably at temperatures of 180 to 220° C.
The reaction temperatures during the operation of the process variant a2) of the invention can be varied within a relatively wide range. In general, operation is effected at temperatures of from 100 to 250° C., preferably at temperatures of from 120 to 230° C., more preferably at temperatures of from 140 to 200° C.
The process variants a1) and a2) of the invention are generally operated under atmospheric pressure. However, it is also possible to work under pressure, in general from 1 bar to 10 bar.
To operate the process variant a1) of the invention for preparing the compounds of the formula (I), generally from 2 to 10 mol, preferably from 2 to 4 mol of base are used per mole of the compounds of the formula (II).
To carry out the process variant a2) of the invention for preparing the co
Hübsch Walter
Lantzsch Reinhard
Müh Thorsten
Weintritt Holger
Bayer Aktiengesellschaft
Henderson Richard E. L.
Shah Mukund J.
Tucker Zachary C.
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