CH439298A - Process for the preparation of 2,3-dihydrofuro (3,2-c) quinoline derivatives - Google Patents

Description

  

  



  Process for the preparation of 2,3-dihydrofuro [3,2-c] quinoline derivatives
The present invention relates to a method ZU3 production of 2, 3-DiSydrofuro [3, 2-c] quinoline Deriva th of the structural form
EMI1.1
 where R is water (toff, lower alkyl, e.g. methyl, ethyl,
Propyl, isopropyl, butyl, pentyl or lower alkenyl e.g. B. vinyl, 1-methylvinyl, allyl, 2-methylallyl, butenyl, R 'and R "each hydrogen or lower alkyl, e.g.



  Methyl, ¯thyl, propyl, isopropyl, butyl, pentyl, and X is hydrogen, halogen, e.g. B. chlorine, bromine, iodine, lower alkyl, e.g. B. methyl, ¯thyl, propyl, isopropyl, butyl, pentyl, or lower alkoxy, z. B. methoxy, ¯thoxy, propoxy, isopropoxy, butoxy, is.



   These compounds obtained according to the invention have various pharmacological properties.



   The above, process according to the invention is shown in the following reaction scheme:
EMI1.2

EMI1.3
 in which R, R ', R "and X have the same meanings as listed above, and is characterized in that a quinolyl alcohol of the above formula II is heated.



   The Cbiholylalkdhol (II) used as starting material can be made from the corresponding ChinoylÏther.



   The quinolyl ether is for this purpose at a
Temperature of about 150 to about 200 C heated, where as an intermediate product. The quinolyl alcohol (II), which is generally contaminated with a considerable amount of the desired 2,3-dihydrofuro [3, 2-c] quinolm (I), is obtained. This quinolyl alcohol (II) is then heated, m. usually to a temperature higher than about 200¯ C, usually 200-300 C, which leads to the expected product, the 2,3-dihydrofuro [3,2-c] quinoline (I).

   In order to improve the yield and / or lower the reaction temperature, a catalyst such as a Lewis acid, eg. B. pyridine hydrochloride, zinc chloride, boron fluoride, aluminum chloride, hydrogen bromide - acetic acid used. If desired, the reaction can be carried out in an inert organic solvent which has a relatively high boiling point, such as dialkylaniline, diphenyl ether, nerobenzene and methylnaphthalene.



   In a non-demanding process, the desired product can be obtained by heating the quinolyl ether to a temperature higher than about 200 ° C, usually 200-300 ° C, and advantageously in the presence of the above-mentioned catalyst.



   The 2, 3-dihydrofuro [3, 2-c] quinoline (I) produced in this way can be converted into its acidic addition salts, e.g. B. by treating this body with an acid, such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfur, nitric, phosphorus, thiocyan, carbon, vinegar, propion, oxal, citric , Tartaric, succinic, salicylic, benzoic or palmitic acid, in a suitable solvent such as water, methanol, ethanol, ether, benzene and toluene.



   The 2,3-dihydrofuro [3, 2-c] quinoline (I) thus obtained and its non-toxic acidic addition salts are useful as analgesic and anti-inflammatory agents.



   The above-mentioned process according to the invention is illustrated in more detail by the following examples.



   example 1
0.5 g of 2-methyl-3-allyl-4-oxyquinoline are mixed with 0.35 g of pyridine hydrochloride and the resulting mixture is heated at 220 ° C. for 15 minutes. After cooling, the reaction mixture is dissolved in water, made alkaline with sodium hydroxide and extracted with ether. The ether extract is then washed with water, dried over anhydrous magnesium sulfate and the solvent evaporated. The residue is crystallized from pelrolite and gives 0.4 g, which is in 80% yield, 2,4-dimethyl-2,3-dihydrofuro [3, 2-c] quinoline in colorless stalks with F. is =
68.5 to 69.5 C.



   IR: v CHCl3 max cm-1 1259, 1087, 1037.



   UV:? C2H5OH max mÁ (log?) 214 (4.29), 229.5 (4.69),
3.72 (286), 3.75 (292) 3.66 (302.5), 3.50 (310),
316 (3, 36).



   Analysis calculated for C13H13ON:
C 78.36 H6.58 N7.03 found: C78.12 H6.64 N6.79
Picrat: F. = 178.5 to 179.5 C.



   Hydrochloride: F. = 263 to 264 C.



   The abovementioned starting material can be obtained by heating 3.0 g of 2-methyl-4-allyloxyquinoline at 180 ° C. for 30 minutes. After cooling, the reaction product is treated with benzene and the material which is insoluble in benzene is crystallized from aqueous ethanol, with 2.8 g, d i. in 93.3% yield, of 2-methyl-3-allyl-4-oxyquinoline in colorless little stalks, with F. = 284-285 C.



   IR: v max cm-1 3273, 1641, 993, 921.



   UV:? C2H5OH max mÁ (log?) 240 (4, 50), 247, 5 (4, 49),
321, 5 (4, 10), 334 (4, 10).



   Analysis calculated for C13H13ON:
C78.36 H6.58 N7.03 found: C78.05 H6.62 N6.96
Example 2
0.1 g of 2-methyl-3-allyl-4-oxyquinoline are heated at 250 to 270¯ C for 30 minutes. The reaction product is then banded with benzene and the material which is soluble in benzene, after chromatographic purification on alumina, is crystallized from petroleum spirit and yields 23 mg of 2,4-dimethyl-2,3-dihydrofuro [3,2-c] quinoline.



   Example 3
0.5 g of 2-methyl-3- (2-methylalqyl-4-oxyquinolline are mixed with 0.25 g of pyridine hydrochloride and the mixture thus obtained is heated at 220 ° C. for 15 minutes. After cooling, the reaction mixture is gelatinized in water ¯st, made alkaline with sodium hydroxide and extracted with ¯ther. The ether extract is then washed with water, dried over anhydrous magnesium sulfate and the solvent evaporated.



  The residue is crystallized from petroleum spirit and yields 0.35 g, i.e. i. in 87.5% yield as colorless stems, with F. = 96.5 to 97.5 C, 2.2, 4 trimethyl-2,3-dihydrofuro [3, 2c] quinolih.



   IR: v CHCl3 max cm-1 1287, 1080, 1020. max 214 (4, 51), 229, 5 (4, 73),
285 (3, 76), 292 (3, 80), 302, 5 (3, 71), 309, 5 3, 59),
315, 5 (3, 42).



   Analysis calculated for C14H15ON:
C 78.84 H 7.09 N 6.57 found: C 78.99 H 7.23 N 6.77
Hydrochloride: F. = 262 to 263 C.



   The starting material can be obtained by heating 3.0 g of 2-methyl-4- (2-methylallyloxy) -quinoline at 180¯ C for 30 minutes. After cooling, the reaction product is treated with benzene and the material, which is insoluble in benzene, is recrystallized from aqueous ethanol. 2.66 g are obtained, that is in 88.6% yield, 2-methyl-3- (2-methylallyl) -4-oxyquinoline in the form of colorless stems with F. = 283 to 284 C.



   IR: v Nuiol max cm-1 3280, 1641, 894.



   UV:? C2H5OH max mÁ (log?) 240 (4, 46), 247 (4, 44),
321 (4, 05), 335, 5 (4, 06).



     Analysis, calculated for Ci4HI50N:
C 78.84 H 7.09 N 6.57 found: C 79.07 H 7.16 N 6.49
The material soluble in benzene can be crystallized from petroleum benzine after evaporation of the solvent and yields 240 mg, that is 8.0%, of 2, 2, 4-trimethyb2, 3-dihydrofuro [3, 2-c] quinoline.



   Example 4
0.4 g of 2-methyl-3- (1-methylallyl) -4-oxyquinoline are mixed with 0.25 g of pyridine hydrochloride and the resulting mixture is heated at 220 ° C. for 15 minutes. After cooling, the reaction mixture is dissolved in water, made alkaline with sodium hydroxide and extracted with ether. The ether extract is then washed with water, dried over anhydrous magnesium sulfate, and the solvent is evaporated.



  The residue obtained is crystallized from petroleum benzine and gives 0.32 g, which is in 80% yield, 2, 3, 4-trimethyl-2, 3-dihydrofuro [3, 2-c] quinoline as colorless prisms with F. is = 74.5 to 75.5 C.



   IR:? CHCl3 max cm-1 1253, 1090, 1020.



   UV:? C2H5OH max mÁ (log?) 214 (4, 48), 230 (4, 75),
285, 5 (3, 76), 291, 5 (3, 79), 302 (3, 69), 308 (3, 57),
315 (3, 37).



   Analysis calculated for C14H15ON:
C 78.84 H 7.09 N 6.57 found: C 78.75 H7.18 N6.73
Hydrochloride: F. = 247 to 248 C.



   The starting material can be obtained by heating 3.0 g of 2-methyl-4- (2-butenyloxy) quinoline at 180¯ C for 30 minutes. After cooling, the reaction product is treated with benzene and the material, which is insoluble in benzene, is crystallized from aqueous ether. 2.69 g, that is in 89.7% yield, of 2-methyl-3- (1-methylallyl) -4-oxyquinoline, are obtained as colorless flakes which melt at over 300.degree.



   IR: v Nuiol max cm-1 3285, 1638, 995, 910.



   UV:? C2H5OH max mÁ (log?) 241 (4, 47), 248 (4, 47),
321, 5 (4, 05), 334, 5 (4, 06).



   Analysis calculated for C14H15ON:
C 78.84 H 7.09 N 6.57 found: C 79.05 H 7.12 N 6.59
The material, which is soluble in benzene, is crystallized from petroleum benzine after the solvent has evaporated, and 51 mg are obtained, that is 1.7%, 2, 3, 4-tri-methyl-2, 3-dihydrofuro [3, 2-c] quinolih.



   Example 5
1 g of 2- (3-butenyl) -3-allyl-4-oxyquinoline is heated at a temperature higher than the melting point of 243-244 ° C. for 20 minutes. The reaction product is dissolved in benzene, then purified by chromatography on alumina and crystallized from petroleum spirit; they give 0.29 g, that is 29%, 2-methyl-4- (3-butenyl) -2,3-dihydrofuro [3, 2-c] quinoline.



   Example 6
1.5 g of 2- (3-butenyl) -3-allyl-4-oxyquinoline are combined with 0.5 g of zinc chloride and the resulting mixture is heated at 200-210 ° C. for 3 hours. After cooling, dilute ammonia water is added to the reaction mixture and shaken with chloroform.



  The CMoroform layer is washed with water, dried, evaporated under reduced pressure and purified by chromatography on alumina; 0.13 g, that is 8.7%, of 2-methyl-4- (3-butenyl) 2,3-dihydrofuro [3,2-c] quinoline are obtained.

 

Claims (1)

PATENT CLAIM Process for the production of. 2,3-Dihydrofuro [3,2-c] quinoline derivatives of the formula: EMI3.1 where R is hydrogen, lower alkyl or lower alkenyl, R 'and R "are each hydrogen or lower alkyl and X is hydrogen, halogen, lower alkyl or lower alkoxy, characterized in that a quinolyl alcohol of the structural formula: EMI3.2 heated. SUBClaims 1. The method according to claim, characterized ge kanoizeichnet that the reaction is carried out at a temperature of 150 to 300 C. 2. Process according to claim for the preparation of the acidic addition salts of 2,3-dihydrofuro [3,2-c] quinoline derivatives, characterized in that these quinoline derivatives are treated with a corresponding acid.