CS257350B1 - Process for the preparation of 5-hydroxy-6'-formyl-7H-benzo (c) fluorene - Google Patents

Abstract

The solution relates to a method for producing 5-hydroxy-6-formyl-7H-benzo[c]fluorene consisting in the formylation of 5-hydroxy-7H-benzo[c]fluorene by the action of dichloromethylmethyl ether in a dichloroethane environment under the catalysis of aluminum chloride.

Description

The invention relates to a process for the preparation of 5-hydroxy-6-formyl-7H-benzo [c] fluorene of the formula I

Benzo (c) fluorene derivatives are a new class of pharmacologically active substances which, depending on the nature of the substituents and the position of substitution in the tetracyclic skeleton, have been found to have antitumor, antibacterial and antiviral effects, as found, for example, in AO 212 669 and 217 731; J. Křepelka, J. Roubik, J. Holubek, I. Vancurova, Collection Czechoslovak Chem. Commun. 47, 1258 (1982), I. Vančurová, J. Křepelka ,. F. Smejkal, Collection Czechoslovak Chem. Commun. 47, 1867 (1982).

For the above reasons, the compound of formula (I) is a valuable intermediate for the preparation of biologically active substances, in particular of the type where substitution at the 6-position is critical for eliciting a certain type of activity. By analogy with the above work, it follows that suitable substitution at the 5 and 6 positions results in antiviral and interferonogenic agents.

According to the invention, a compound of formula I is prepared by reacting a compound of formula IX

with dichloromethyl methyl ether of formula III or ₂ choch ₃ (III) used in an amount of 1.1 to 3 mol equivalents, preferably in an amount of 2 mol equivalents, in an environment of aliphatic chlorinated hydrocarbons, preferably dichloroethane, catalysed with aluminum chloride used in an amount of 1 to 2 mol equivalents Deň: 18 ° C.

The reaction of the compound of formula II with dichloromethyl methyl ether of formula III can be carried out in an environment of aliphatic chlorinated hydrocarbons such as dichloromethane, chloroform, dichloroethane, tetrachlomethane; the use of dichloroethane seems to be particularly advantageous from the point of view of the reaction.

After the reaction, the reaction mixture is worked up in the usual manner: for example after quenching with water and hydrochloric acid and after filtering off the solid, the organic portion is taken up in chlorinated solvent and after drying and evaporation of the solvent the crude product is purified by column chromatography. The compound of formula (II) is known and is described (see J. Křepelka, I. Vancurová, J. Holoubek, M. Melka, K. Řežábek, Coll. Czechoslovak Chem; Commum. 47, 1856 (1982)).

Other conventional organic chemistry methods introducing the formyl group adjacent to the aromatic hydroxy group can be used to prepare the compound of Formula I, starting from the compound of Formula II, but conventional methods provide complex reaction mixtures in which the desired compound is present at a low content.

More detailed information on the preparation of the compound of formula I will be apparent from the following non-limiting example.

Example

To a solution of 1.15 g (5 mmol) of 5-hydroxy-7H-benzo [t] fluorene in 50 ml of dichloroethane cooled to 0 ° C was added a solution of 1.15 g (10 mmol) of dichloromethyl methyl ether in 4 ml of dichloroethane over 10 minutes. 1.0 g (7.5 mmol) of aluminum chloride was added and the reaction mixture was stirred at 20 ° C for 4 hours. The reaction mixture was quenched with water and hydrochloric acid, and after filtering off the solids, the organic layer was separated from the filtrate, dried over anhydrous sodium sulfate and evaporated. The crude product was purified by silica gel column chromatography using chloroform as eluent. Combine the uniform fractions and crystallize the crude product to give the compound of formula I of m.p. Mp 166-170 ° C.

Claims (1)

Process for the preparation of 5-hydroxy-6-formyl-7H-benzo [c] fluorene of the formula I, characterized in that it is reacted 5-hydroxy-7H-benzo [c] fluorene of formula XI (II) 'with dichloromethyl methyl ether of formula III C 1 _{2 3} CKD (III) is used in an amount of 1.1 to 3 molar equivalents, preferably 2 molar equivalents, in an aliphatic chlorinated hydrocarbon, preferably dichloroethane, under catalysis by aluminum chloride used in an amount of 1-2 molar equivalents, at 20 ° C.