SU334697A1 - METHOD OF OBTAINING COMPLEX ETHERS OF 7-NITRO-8-OXYHINOLINE - Google Patents

Description

The invention relates to the field of the preparation of new compounds, the nitro-8-hydroxyquinoline esters, which possess valuable pharmacological properties. A known method for the preparation of okaghinoline esters by the interaction of undecyl acid or its derivatives, anhydride or acid chloride, with 8-axiquinoline.

However, P: they only get one specific 8-hydroxyquinoline ester. Using the analogue method and using other acids as starting compounds, the authors synthesized Z-hydroxyquinoline esters of a very diverse structure. The described process for the preparation of 7-nitro-8-hydroxyquinoline esters of the formula:

straight chained or branched chain

R is a hydrogen atom, aryl or a residue of the formula:

g

ten

K1

where RI and R2 is a hydrogen atom, halogen, nitro, OXI, amino, alkoxygroup or alkyl, or if RI is a hydrogen atom, then R2 is phenyl, phenoxy, phenylthio or alkylthio, or a residue of the formula: 25 -h. where Ra, R4, R5 is an alkyl or alkoxy group, Rg is a hydrogen atom or Rs, R4, Rs, R6-alkyl or

Sbn

where R is a hydrogen atom or a chlorine atom, Ra is a hydrogen atom, a methyl, halogen or nitro group, Rg is a hydrogen atom "whether phenyl, Rio is a hydrogen atom, methyl or NH2-group, Rn-agom of hydrogen, or methyl, Ri2-atom hydrogen, methyl or alkoxy, oxygen, sulfur or NH - group, consists in that 7-nitro-8-hydroxyquinols, n are reacted with an acid of the formula:

R-X-COOH.

where R and X are as defined above, with the isolation of the target product by known techniques.

7-nitro-8-hydroxy, nolin is obtained by hydrolysis of 7-nitro-8-ca. iquinoline-5-1 sulfonic acid.

It is known that 7-nitro-8-hydroxy-inolin-5-sulfonic acid can be obtained by nitration of 8-oxyquinoline-5-sulfonic acid. However, under the previous conditions, nitration was of little effect and significant amounts of 5,7 dinitro-8-hydroxyquinoline were formed as a by-product. Tener, on the other hand, revealed that the by-product is formed in essentially insignificant quantities when

nitration is carried out at a temperature of from -5 ° C to 4-5 ° C. In addition, it is better to nitrate by adding dropwise a 30-50% aqueous solution of nitric acid to a cooled solution of 8-hydroxyquinoline-5 sulfonic acid in concentrated sulfuric acid for 4-8 hours

Example 1. 7-nitro-8-hydroxyquinoline-5-sulfonic acid.

45 g (0.2 mol of 8-acid, nolin-5-sulfonic acid is dissolved in 126 ml of cold concentrated sulfuric acid. Maintaining the temperature of this solution in the range of -5 ° C to + 5 ° C, 77 ml of 30-50% An aqueous solution of nitric acid is added over 8 h. The reaction mixture is then poured onto 400 g of ice.

The resulting precipitate is collected by filtration and washed B: ode. 43-48 g of crude 7-nitro-8-hydroxyquinoline-5-sulfonic acid, melting at 264 ° C with decomposition (80-90% of the theoretical yield) are obtained. This product is used for the next stage, without purification, although the letters contain a small amount of 5,7din, itro-8-about 10 quinoline. 7-nitro-8-oxyquinoline.

A solution of 54 g of 7-nitro-8-hydroxyquinoline-5-sulfonic acid is heated in 290 ml of 60% sulfuric acid for 6 hours. at a temperature

150 ° C. The solution is poured onto 500 g of ice, filtered to remove 5,7-dinitro-8-hydroxyquinoline (5-10 g; the starting material contains this impurity). Sub-temperature is below 20 ° C, the filtrate is neutralized at pH 5-6

alkali, such as NaOH or NH4OH.

The precipitate is collected by centrifugation and dried. The OH melts at a temperature of 162-163 ° C after crystallization from 40% acetic acid. Output: 27-30 g (70-80% of theoretical).

Analysis: Found in% C 56.76; P 3.41; N 14.65.

Calculated for CgHgNaOa: C 56.84; H 3.18; N 14.73.

The following examples illustrate the process for the preparation of 7-nitro-8-oxy, inolinic esters.

Example 2. 7-nitro-8-benzoylloxyquinoline. To a solution of 5.7 g (0.03 mol) of 7-nitro-8-hydroxyquinoline in 50 ml of pyridine, cooled to 15 ° C, 4.2 g (0.03 mol) of benzoyl chloride are added dropwise over 5 minutes. The mixture is maintained at a temperature of 15 ° C for 3 hours, then poured into cold water. Rounded with water. 6.75 g of product are obtained. Bringing the pH of the mother liquors to 2 get 0.800 g of 7-nitro-8-hydroxyquinoline. , calculated on the basis of the actually reacted starting materials, is 89% of the theoretical. The 7-nitro-8-benzoylloxyquinoline thus obtained is soluble in cold acetone, chloroform, and in hot methanol, ethanol, and gasoline. It is not soluble in ether and is not soluble in water. The melting point of this substance is in the range of 184-5 ° C, which does not change after crystallization in gasoline. Example 3. 7-nitro-8-acetoxyquinoline. Suanenzy 5.7 g (0,, 3 tol} 7-nitro-8-1o "of quinoline in 20 ml of acetic anhydride is treated in a reflux condenser for one hour and then the reaction mixture is poured into water. The resulting precipitate is collected by filtration and yellow is obtained 7 -nitro-8-acetoxyquinoline at a practically theoretical yield. This, the substance has a melting point of 159-160 ° C, which remains "altered after crystallization in gasoline. This substance is soluble in cold acetone and chloroform, as well as in hot methanol , ethanol and gasoline. It is not very soluble in ether and Example 4. 7-nitro-8-phenoacetoxyquinoline. To 19 g (0.01 mol 7 HITi-8-01 sihihiolin) in 35 ml of anhydrous gasoline add 0.48. (0.01 mol) oleaginous 50% - suspension of sodium hydride and the mixture is treated in a reflux condenser for 2 hours while stirring.The mixture is then cooled to 20 ° C and 1.54 g (0.01 mol} of fanacetylchloride n is added to the pei in a reflux condenser). , e 20 h. Then the solvent is distilled off in vacuo, the residue is washed with water, dried and mixed with a very small amount of ethyl acetate; get a thin suspension, which is poured onto a column of silica gel. Ethyl acetate is eluted from the column. The eluate is evaporated and 4.32 g of product are obtained with a melting point of 110-112 ° C. The distinguishing characteristics of the compounds obtained in Examples 2, 3 and 4, as well as other compounds prepared in the same way, are given in Tables I and P (see below). The compounds obtained in examples 2, 3 and 4 are compounds nos. 1, 34 and 33, respectively, listed in the tables. The minimum concentrations of some of the compounds mentioned in table. 1 and 2, which inhibit the growth of various microorganisms, are given in Table. 3

ohhh

liv:, r ,, -

OR

Continued table. I

And - ethyl acetate; B-benzine; D-dioxane; L ligroin.

Continued tab. one

table 2

May

Continued table. 2 A -

Continued table. 2

5) Str. pyosenes humanus (Sr. A). stylacetate; B-benzine; D-dioxane; L - ligroin; P - petroleum ether. The minimum concentration in mg1ml inhibit invitro bacteria and fungi. Table 3

g

15

 g

sixteen

Subject invention

The method of producing the 7-nitro-oxyquinolip esters of the formula:

where X is a simple bond or a hydrocarbon residue of an aliphatic row, saturated or unsaturated, having a straight or branched chain;

R is a hydrogen atom, aryl or a residue of the formula:

Ra

{/

ode RI and Ra-aTCM hydrogen, halogen, nitro, hydroxy, amine, alkoxy, or alkyl, or, if Ri is a hydrogen atom, then H2-phenyl, phenoxy, phenylthio or alkylthio, or a residue of the formula:

Cs

//

five

Bb

"ER9

N

f

KPK sh

where Rs, R4, R5-alkyl or alkoxygroup, Reatom hydrogen. Or Rs, R4, Rs, R6-alkyl, Or R-substituted or unsubstituted heterocyclic residues of the formula:

where R is a hydrogen atom or a chlorine atom, Ra is a hydrogen atom, methyl, halogen or nitro, Rg is a hydrogen atom or phenyl, Rjo is a hydrogen atom, methyl or NH2-rpynna, Ru is a hydrogen atom or methyl, Ri2 is a hydrogen atom, methyl or alkoxy, Z is oxygen, sulfur or NH-rpynna, characterized in that the 7-nitro-8-hydroxyquinoline is reacted with an acid of the formula:

R-X-COOH

where R. and X are as defined above, with isolation of the desired product by known techniques.