US3312708A - Manufacture of aminoquinolines - Google Patents

Manufacture of aminoquinolines Download PDF

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US3312708A
US3312708A US312365A US31236563A US3312708A US 3312708 A US3312708 A US 3312708A US 312365 A US312365 A US 312365A US 31236563 A US31236563 A US 31236563A US 3312708 A US3312708 A US 3312708A
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quinolinol
aminoquinoline
equipment
parts
ammonium
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US312365A
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Charles J Lind
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Honeywell International Inc
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Allied Chemical Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/38—Nitrogen atoms
    • C07D215/40—Nitrogen atoms attached in position 8

Definitions

  • Another object is to devise a process for the preparation of ar-aminoquinolines wherein corrosion of the equipment is practically nil.
  • Still another object is to devise a process for the manufacture of 8-aminoquinoline which is economical to operate and utilizes readily available equipment.
  • ar-aminoquinolines can be prepared in excellent yields by heating an ar-quinolinol and a salt of sulfurous acid in which at least one valence of the sulfurous ion is satisfied by ammonium and the other by ammonium, or an alkali metal (e.g., sodium or potassium) or an alkaline earth metal (e.g., magnesium, calcium, strontium or barium).
  • the reaction is carried out under moderate pressure, preferably in a stainless steel autoclave, at a temperature above 100 C., preferably between 140 and 160 C.
  • This amination step which is carried out in the absence of free ammonia, results in yields of excellent quality ar-aminoquinoline in excess of 75% of theory. Equally important, the corrosive attack of the metal equipment, which is characteristic of the known processes in which free ammonia is used, is greatly reduced in ordinary steel equipment and is effec tively eliminated in stainless steel equipment.
  • S-quinolinol in amount of about /3 mol. equivalent, is added to the mixture which then is heated, in a stainless steel autoclave, at about to C., for about 24 hours.
  • the autogenous pressure developed ranges between 60 and 80 p.s.i.g.
  • the mixture is cooled to ambient temperature and the solid product is separated from the aqueous reaction mixture and purified in a known manner, e.g., by steam distillation or by vacuum distillation.
  • This new process is carried out preferably in stainless steel equipment since the corrosion of such equipment by the reaction mixture is insignificant.
  • Various types of chromium/nickel steels can be used including equipment fabricated in whole or in part from 304, 316, 317, 347 and the like austenitic stainless steels.
  • the equipment can be fabricated from more than one type, e.g., the autoclave can be of 316 SS, the agitator from 347 SS, the piping from 304 SS, and the valves from Hastelloy steel.
  • the temperature at which the amination is effected can be varied over a wide range. Although it is preferred to operate at a temperature between 140 and 160 C., the reaction can be run at temperatures as low as about 100 C. and as high as 200 C. In the lower range, the reaction velocity is so slow as to be uneconomical whereas at temperatures in excess of 200 C., an undesirable amount of corrosion takes place.
  • the amount of ammonium sulfite salt which is used can also be varied over a broad range. Although theoretically the quinolinol and ammonium sulfite react in molecular equivalent amounts, i.e., one mol of quinolinol requires 1 mol of diammonium sulfite or 1 mol of sodium ammonium sulfite, an excess of the ammoniating agent is preferably used. Normally, between two and five times the theoretical quantity of the aminating agent is used since the use of less than this amount gives undesirably low yields, while more than this amount (5 molecular equivalents) does not give significantly increased yields.
  • Example 1 To a cold (5 C.) solution of 700 parts of sodium metabisulfite in 500 parts of water, 447 parts of 28% aqua ammonia are added slowly. The vigorous exothermic reaction causes the mass .to heat up to about 65 C., and thereafter it is cooled to about 30 C. The mass is neutral to slightly acidic to nitrazine yellow. The slurry of sodium ammonium sulfite thus obtained is transferred to a 316 stainless steel autoclave and 290.4 parts of 8-quinolinol are added. The mixture is heated to and maintained at 151 to 153 C., for 24 hours. The pressure developed in the autoclave during this reaction is between 63 and 76 p.s.i.g.
  • the mixture is cooled to ambient temperature and then removed from the autoclave as a thin slurry of finely divided greenish solid.
  • the autoclave is rinsed with 450 parts of water and the combined slurry and wash liquor is heated to 70 C., then agitated and cooled to about 25 C.
  • the resultant slurry is filtered and the filter cake is washed with 3000 parts of water.
  • the washed solids are reslurried in a mixture of 91.5 parts of 50 C., B. aqueous caustic soda and 1750 parts of water.
  • the slurry is heated to 70 C., and then cooled while agitating to about 25 C.
  • the resultant granular slurry is filtered and the filter cake is washed alkali free to nitrazine yellow with about 3000 parts of water.
  • the crude 8-aminoquinoline (M.P. 56.0 to 56.5 C.) is distilled in vacuo and gives 209 parts of pure 8-aminoquinoline of *M.-P. 66.0 to 66.5" C.
  • the autoclave in which this reaction was carried out shows no etching, pitting, crevice attack or other evidence of corrosion.
  • the corrosion rate is estimated to be 0.00054 inch per year (i.p.y.).
  • Example 2 In an analogous experiment in which a like amount of 8-quinolinol is reacted with diammonium sulfite (prepared in situ from 357 parts of aqua ammonia and 207 parts of sulfur dioxide) and free ammonia (357 parts of 28% aqua lamim-oinia) by heating this mixture for 8 hours at 148 C. to 150 C., with the pressure varying between 136 and 150 p.s.i.g. A yield of 209 parts of distilled 8- aminoquinoline, MJP. 64.5 C. to 65 C., is obtained. However, the 316 stainless steel autoclave shows severe pitting and considerable etching. The corrosion rate is estimated to be 0.0442 i.p.y.
  • Example 3 The procedure of Example 2 above is repeated but omitting the second addition of aqua ammonia from the autoclave charge.
  • the amination step is thus conducted in the'substantial absence of free ammonia.
  • the charge is heated at 150 C. to 155 C., in this instance for 8 hours.
  • the pressure developed varies between 72 and 78 p.s.i.g.
  • the yield of S-aminoquinoline from this experiment is somewhat less (163 parts) than that obtained in the preceding experiments but in contrast to the severe corrosion noted in Experiment 2, no evidence of corrosion (i.e., no pitting, etching, -etc.,) can be detected in this experiment.
  • the corrosion rate is estimated to be 0.0016 i.p.y.
  • My invention has been illustrated by several examples which include the best mode known to me of carrying out the process of my invention. It is, however, not to be limited to the details of these examples since various alternate details, some of which have been disclosed in the above description, can be made in the illustrative examples.
  • a catalyst such as copper powder, cupnous bromide and the lilne, can be used to fiacilihate the reaction.
  • Other variations in the procedure will be obvious to those skilled in this art and can be used without departing from the scope or spirit of this invention which is limited only by the appended claims.
  • ammonium salt is sodium ammonium sulfite.
  • HENRY R. JILES, Examiner.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

United States Patent This invention relates to improvements in the manufacture of ar-arninoquinolines. More particularly it relates to amination of 8-quinolinol with an ammonium salt of sulfurous acid in the substantial absence of free ammonia.
The preparation of ar-aminoquinolines and especially 8-aminoquinoline by the Bucherer Reaction in which 8- quinolinol is reacted with ammonium sulfite and ammonia under pressure is well known. This synthetic method, when carried out on a small scale, e.g., in the laboratory, is reported to give almost quantitative yields. Because of the relative ease of preparation of 8-quinolinol as compared with 8-chloroquinoline or 8-nitroquinoline, the Bucherer technique has been the preferred mode of preparing S-aminoquinoline. However, as the batch size is increased, certain unforeseen difficulties arise which cause the yield to drop. The major difliculty in the manufacture of S-aminoquinoline in full scale equipment results from corrosive attack of the pressure equipment used, by one or more of the reactants. Even in stainless steel equipment, etching and severe pitting as well as moderate crevice attack, all of which are evidences of corrosion, were noted when attempts were made to aminate 8-quino1ino1 with ammonium sulfite and free ammonia. In ordinary steel equipment, the yield of 8-aminoquinoline fell to below 25% of theory.
It is, therefore, a principal object of this invention to devise an improved process for the preparation of araminoquinolines.
Another object is to devise a process for the preparation of ar-aminoquinolines wherein corrosion of the equipment is practically nil.
Still another object is to devise a process for the manufacture of 8-aminoquinoline which is economical to operate and utilizes readily available equipment.
These and other objects and advantages ancillary thereto will be evident from the following description of my invention.
It has now been discovered that ar-aminoquinolines can be prepared in excellent yields by heating an ar-quinolinol and a salt of sulfurous acid in which at least one valence of the sulfurous ion is satisfied by ammonium and the other by ammonium, or an alkali metal (e.g., sodium or potassium) or an alkaline earth metal (e.g., magnesium, calcium, strontium or barium). The reaction is carried out under moderate pressure, preferably in a stainless steel autoclave, at a temperature above 100 C., preferably between 140 and 160 C. This amination step, which is carried out in the absence of free ammonia, results in yields of excellent quality ar-aminoquinoline in excess of 75% of theory. Equally important, the corrosive attack of the metal equipment, which is characteristic of the known processes in which free ammonia is used, is greatly reduced in ordinary steel equipment and is effec tively eliminated in stainless steel equipment.
Although the improved process is of particular benefit and interest in the production of S-aminoquinoline from 8-quinolinol, this technique is applicable also to the preparation of ar-aminoquinolines in general which may contain additional substituents such as lower alkyl (e.g., methyl, ethyl, butyl, hexyl, etc.) lower alkoxy (e.g., methoxy, ethoxy, isopropoxy, hexoxy, etc.) sulfamyl (e.g., sulfonamido, N-methyl sulfonamido, N,N-diethyl sulfonamido) and the like substituents. Quinolindiols also can be used to prepare the corresponding aminoquiuolinols and diaminoquinolines although mixtures of such products are usually obtained which are sometimes diflicult to separate.
As typical of the ar-quinolinols which can be used to produce corresponding ar-aminoquinolines, the following are mentioned:
S-quinolinol 6-quinolinol 7-quinolinol 2-m ethyl-8- quinolinol 6-ethyl-8-quinolinol 6-methyl-5-quinolinol 6-isopropyl-5-quinolinol 4-methyl-6-quinolinol 5-butyl-8-quinolinol 2,3 -dimethyl-8-quinolinol 3,4-dimethyl-8-quinolinol 5-hexyl-8-quinolinol 6-methoxy-8-quinolinol 7-propyl-8-quinolinol 5,6-quinolinediol 5,8-quinolinediol 6,8-quinolinediol 2-methy1-7,8-quinolinediol In accordance with a preferred mode of carrying out this improved process, aqua ammonia is added to an aqueous solution of sodium bisulfite until the mixture is practically neutral, i.e., pH is just 7. Thereafter S-quinolinol in amount of about /3 mol. equivalent, is added to the mixture which then is heated, in a stainless steel autoclave, at about to C., for about 24 hours. The autogenous pressure developed ranges between 60 and 80 p.s.i.g. Thereafter the mixture is cooled to ambient temperature and the solid product is separated from the aqueous reaction mixture and purified in a known manner, e.g., by steam distillation or by vacuum distillation.
Although freshly-prepared sodium ammonium sulfite is the preferred aminating agent in this novel process, other agents can be used. As examples of such alternatives, the following are mentioned:
diammonium sulfite potassium ammonium sulfite magnesium ammonium sulfite calcium ammonium sulfite strontium ammonium sulfite barium ammonium sulfite Mixtures of these and equivalent agents are also contemplated for use in the process of the instant invention.
The absence of free ammonia from the reaction mixture of this novel process has the advantage of reducing substantially the corrosive attack of the mixture on the equipment and also permits the reaction to becarried out at a considerably lower pressure. Inasmuch as equipment designed to withstand high pressure is relatively expensive to install and maintain, it will be readily appreciated that the more modest pressures developed in the course of the improved reaction permits the use of less expensive equipment and thus results in a considerable economic advantage.
This new process is carried out preferably in stainless steel equipment since the corrosion of such equipment by the reaction mixture is insignificant. Various types of chromium/nickel steels can be used including equipment fabricated in whole or in part from 304, 316, 317, 347 and the like austenitic stainless steels. As will be obvious the equipment can be fabricated from more than one type, e.g., the autoclave can be of 316 SS, the agitator from 347 SS, the piping from 304 SS, and the valves from Hastelloy steel.
The temperature at which the amination is effected can be varied over a wide range. Although it is preferred to operate at a temperature between 140 and 160 C., the reaction can be run at temperatures as low as about 100 C. and as high as 200 C. In the lower range, the reaction velocity is so slow as to be uneconomical whereas at temperatures in excess of 200 C., an undesirable amount of corrosion takes place.
The amount of ammonium sulfite salt which is used can also be varied over a broad range. Although theoretically the quinolinol and ammonium sulfite react in molecular equivalent amounts, i.e., one mol of quinolinol requires 1 mol of diammonium sulfite or 1 mol of sodium ammonium sulfite, an excess of the ammoniating agent is preferably used. Normally, between two and five times the theoretical quantity of the aminating agent is used since the use of less than this amount gives undesirably low yields, while more than this amount (5 molecular equivalents) does not give significantly increased yields.
The invention will-be illustrated by the following examples in which parts and percentages are by weight and temperatures are given in degrees centigrade. As will be obvious to those skilled in the art to which this invention pertains, changes may be made in the details of these purely illustrative examples without departing from the scope or spirit of the invention.
Example 1 To a cold (5 C.) solution of 700 parts of sodium metabisulfite in 500 parts of water, 447 parts of 28% aqua ammonia are added slowly. The vigorous exothermic reaction causes the mass .to heat up to about 65 C., and thereafter it is cooled to about 30 C. The mass is neutral to slightly acidic to nitrazine yellow. The slurry of sodium ammonium sulfite thus obtained is transferred to a 316 stainless steel autoclave and 290.4 parts of 8-quinolinol are added. The mixture is heated to and maintained at 151 to 153 C., for 24 hours. The pressure developed in the autoclave during this reaction is between 63 and 76 p.s.i.g. The mixture is cooled to ambient temperature and then removed from the autoclave as a thin slurry of finely divided greenish solid. The autoclave is rinsed with 450 parts of water and the combined slurry and wash liquor is heated to 70 C., then agitated and cooled to about 25 C. The resultant slurry is filtered and the filter cake is washed with 3000 parts of water. The washed solids are reslurried in a mixture of 91.5 parts of 50 C., B. aqueous caustic soda and 1750 parts of water. The slurry is heated to 70 C., and then cooled while agitating to about 25 C. The resultant granular slurry is filtered and the filter cake is washed alkali free to nitrazine yellow with about 3000 parts of water. The crude 8-aminoquinoline (M.P. 56.0 to 56.5 C.) is distilled in vacuo and gives 209 parts of pure 8-aminoquinoline of *M.-P. 66.0 to 66.5" C.
The autoclave in which this reaction was carried out shows no etching, pitting, crevice attack or other evidence of corrosion. The corrosion rate is estimated to be 0.00054 inch per year (i.p.y.).
Example 2 In an analogous experiment in which a like amount of 8-quinolinol is reacted with diammonium sulfite (prepared in situ from 357 parts of aqua ammonia and 207 parts of sulfur dioxide) and free ammonia (357 parts of 28% aqua lamim-oinia) by heating this mixture for 8 hours at 148 C. to 150 C., with the pressure varying between 136 and 150 p.s.i.g. A yield of 209 parts of distilled 8- aminoquinoline, MJP. 64.5 C. to 65 C., is obtained. However, the 316 stainless steel autoclave shows severe pitting and considerable etching. The corrosion rate is estimated to be 0.0442 i.p.y.
Example 3 The procedure of Example 2 above is repeated but omitting the second addition of aqua ammonia from the autoclave charge. The amination step is thus conducted in the'substantial absence of free ammonia. The charge is heated at 150 C. to 155 C., in this instance for 8 hours. The pressure developed varies between 72 and 78 p.s.i.g. The yield of S-aminoquinoline from this experiment is somewhat less (163 parts) than that obtained in the preceding experiments but in contrast to the severe corrosion noted in Experiment 2, no evidence of corrosion (i.e., no pitting, etching, -etc.,) can be detected in this experiment. The corrosion rate is estimated to be 0.0016 i.p.y.
It can thus be seen that an efficient and economical procedure for the manufacture of 8-aminoquinoline has been devised which process is capable of being operated in stainless steel equipment without the severe corrosion which characterized similar processes in which free ammonia was present.
My invention has been illustrated by several examples which include the best mode known to me of carrying out the process of my invention. It is, however, not to be limited to the details of these examples since various alternate details, some of which have been disclosed in the above description, can be made in the illustrative examples. For example, a catalyst such as copper powder, cupnous bromide and the lilne, can be used to fiacilihate the reaction. Other variations in the procedure will be obvious to those skilled in this art and can be used without departing from the scope or spirit of this invention which is limited only by the appended claims.
I claim:
1. The process of preparing an ar-aminoquinoline from the corresponding ar-quinolinol which comprises the step of .heating at a temperature not above 200 C. and under autogenous pressure a mixture of the ar-quinolinol and, as the sole aminating agent, an ammonium salt of sulfurous acid having the general formula lVI-(N I-L) 090 wherein M stands for a member of the group consisting of the ammonium group, alkali metals and alkaline earth metals and x stands for an integer equal to the valence of M.
2. The process as described in claim 1 in which the ar-quinolinol is 8-quinolinol.
3. The process as described in claim 1 in which the ammonium salt is sodium ammonium sulfite.
References Cited by the Examiner Hartshorn et al.: J. Am. Chem. Soc., vol. 68, 1562-3, (1946).
Kogan et al.: Chem. Abstracts, vol. 32, column 7031 (1938).
ALEX MAZEL, Primary Examiner.
HENRY =R. JILES, Examiner.
DONALD G. DAUS, Assistant Examiner,

Claims (1)

1. THE PROCESS OF PREPARING AN AR-AMINOQUINOLINE FROM THE CORRESPONDING AR-QUINOLINOL WHICH COMRPRISES THE STEP OF HEATING AT A TEMPERATUER NOT ABOVE 200*C. AND UNDER AUTOGENOUS PRESSURE A MIXTUE OF THE AR-QUINOLINOL AND, AS THE SOLE AMINATING AGENT, AN AMMONIUM SALT OF SULFUROUS ACID HAVING THE GENERAL FORMULA M(NH4)X(SO3)X WHEREIN M STANDS FOR A MEMBER OF THE GROUP CONSISTING OF THE AMMONIUM GROUP, ALKALI METALS AND ALKALINE EARTH METALS AND X STANDS FOR AN INTGEGER EQUAL TO THE VALENCE OF M.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3860599A (en) * 1972-12-14 1975-01-14 Koppers Co Inc Preparation of hydroxyquinolines

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3860599A (en) * 1972-12-14 1975-01-14 Koppers Co Inc Preparation of hydroxyquinolines

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