CH542866A - Isoquinolone prepn from homophthalic acid - Google Patents

Abstract

Isoquinolines, useful as starting materials for dyes and as fluorescent agents for marking mineral oils, of formula (I): (where R1, R2 and R3 each are an (ar- or cyclo)aliphatic or aromatic gp. and R1 can also denote H, halogen or -N(R4)2 where each R4 is an (ar)aliphatic or aromatic gp. or H) are prepared by reacting homophthalic acid cpds. (II) (where R5 is -COOH, -CN or -CONH2, R6 is -COOH, and R5 and R6 each can denote -COOR7 where R7 is an (ar- or cyclo) aliphatic or aromatic gp. or together they can form gp. -OC-O-CO-) with diamines H2N-R2NH-R3 (III) at 100-220 degrees C. - Pref. R1, R2 and R3 each are 1-6C alkyl(ene) 7-12C aralkyl(ene), 5-8C cyclalkyl(ene), phenyl(ene) or naphthyl(ene), R1 also denotes H, Cl or -N(R4)2, where each R4 is 1-6C alkyl, 2-5C aliphatic acyl, benzyl benzoyl, phenyl or H.

Description

  

  The invention relates to a process for the preparation of compounds of formula 1
EMI0001.0000
    in which R is a hydrogen atom or an alkyl group with 1 to 4 carbon atoms and n is the numbers 0 to 1, and the ring A can also be substituted by alkyl, alkoxy, phenyl, dialkylamino, phenylamino or acylamino. The process is characterized in that homophthalic acids of the formula 2a
EMI0001.0003
    or functional derivatives thereof with hydroxyalkylamines of formula 3
EMI0001.0004
    implements. Functional derivatives of homophthalic acids are z. B. the mono- or dinitriles, mono- or diesters, mono- or diamides, ester-nitriles, ester-amides, anhydrides or imides.



  The following connection types are listed in detail, for example:
EMI0001.0007
  
EMI0001.0008
    Individual compounds are, for example: homophthalic acid, 4-methyl-homophthalic acid, 3-, 4-, 5- or 6-phenyl-homophthalic acid, homophthalic acid dinitrile, 2-cyanomethylbenzoic acid, 5-tert-butyl-2-cyanomethyl-benzoic acid, 5-dimethyl -amino-2-cyanomethyl-benzoic acid, 4-phenylamino-2-cyanomethyl-benzoic acid, phenylacetamide-2-carboxylic acid, 4-benzamino-phenyl-acetamide-2-carboxylic acid, homophthalic acid diamide, homophthalimide, homophthalic anhydride, 2-carboxy-phenyl acetic acid , Methyl 2-cyano-phenylacetate, ethyl 2-cyanomethyl-benzoate, dibutyl homophthalate, N- [ß-hydroxyethyl] homophthalimide or N - [γ-hydroxy-propyl] homophthalimide.



  As radicals R are in addition to hydrogen z. B. methyl, ethyl, propyl or butyl.



  Hydroxyalkylamines are, for example: β-hydroxyethylamine, γ-hydroxypropylamine, β-hydroxypropylamine, β-hydroxy-butylamine, β-hydroxy-hexylamine or γ-hydroxy-butylamine. The process is expediently carried out by adding a component of the formula 1I with twice the molar amount or an excess (for example up to ten times the weight ratio) of the component of the formula III, optionally in the presence of a solvent, at normal pressure or under pressure heated to temperatures of 150 to 250 C, preferably 170 to 220 C before.



  As a solvent, for. B. into consideration: ethylene glycol, ethylene glycol butyl ether, diethylene glycol, diethylene glycol methyl ether, N-methylpyrrolidone, dimethylacetamide, tetramethylurea, trichlorobenzene or naphthalene.



  If the boiling point of component III is below the chosen reaction temperature, one can also proceed so that component II (together with part of component III) is initially charged, heated to the desired temperature and component III is gradually added at this temperature , an unreacted excess of III being distilled off together with reaction by-products such as water, alcohol or ammonia.



  The reaction products are obtained in crystalline form on cooling. An auxiliary solvent such as methanol, isobutanol or benzene can be added during the cooling process and the reaction products III are then obtained in greater purity.



  The compounds of the formula I show strong fluorescence in dilute solution. You can use as a fluorescent medium z. B. can be used to identify mineral oils. In addition, the process products are valuable starting products for dyes.



  It is known that homophthalic acid or homophthalic acid derivatives and primary amines result in N-substituted homophthalimides. Thus, from homophthalic acid or homophthalic anhydride with β-hydroxyethylamine or γ-hydroxypropylamine under the usual reaction conditions, N- [β-hydroxyethyl] - or N - [γ;

  -Hydroxypropyl] homophthalimide. It was surprising that when the action of hydroxyalkylamines on homophthalic acid or derivatives thereof is increased, a second amine molecule reacts with the addition of a further ring.



  <I> Example 1 </I> A mixture of 180 parts of homophthalic acid and 200 parts by volume of β-hydroxyethylamine is heated to 215 to 220 ° C. in a stirred flask with a descending cooler. Some of the excess amine is distilled off. A further 200 parts by volume of 2-hydroxyethylamine are now allowed to run in over the course of 4 hours. The temperature is then lowered to 150 ° C. and the remaining volatile constituents are removed under reduced pressure (water jet pump). The reaction product is poured into a bowl while it is still hot, where it crystallizes when it cools.



  Yield: 225 parts of 5-oxo-1- [ss-hydroxy-ethyl] -1.2.3.5-tetrahydro-imidazo [1.2-b] -isoquinoline. The compound melts after recrystallization from ethanol at 140 C and shows the following analysis: Analysis for C13HwN202 (230.3)
EMI0002.0016
  
    C <SEP> H <SEP> N <SEP> 0
<tb> Calculates <SEP> 67.8 <SEP> 6.1 <SEP> 12.2 <SEP> 13.9
<tb> Found <SEP> 67.7 <SEP> 6.2 <SEP> 12.2 <SEP> 13.6 Dilute solutions of the compound in ethanol fluoresce blue in daylight and UV light.



  The same compound is obtained if the homophthalic acid is replaced by an equivalent amount of homophthalic anhydride, homophthalic acid dinitrile, homophthalic acid diamide, homophthalimide or N- [β-hydroxyethyl] homophthalimide.



  <I> Example 2 </I> 236 parts of homophthalic acid diethyl ester are stirred at 200 ° C. in a stirred flask with a descending condenser. 750 parts by volume of ß-hydroxyethylamine are added dropwise to this in the course of 8 hours. During this process, ethyl alcohol, water and excess amine are distilled off. The remaining volatile constituents are then removed under reduced pressure (water jet pump) and the reaction mixture is boiled with 500 parts by volume of ethanol. The reaction product crystallizes out on cooling. It is filtered off with suction, washed with a little ethanol and dried.



  Yield: 189 parts of brownish crystals with a melting point of <B> 139 </B> to 140 C. The compound is identical to that described in Example 1.



  If, instead of diethyl homophthalate, an equivalent amount of monobutyl homophthalate or methyl 2-cyanomethylbenzoate is used, the same compound is obtained in a similar yield.



  <I> Example 3 </I> 161 parts of 2-cyanomethylbenzoic acid and 150 parts of β-hydroxyethylamine are introduced into 250 parts by volume of ethylene glycol and the mixture is stirred at 105 to 200 ° C. on the descending cooler for 6 hours. While cooling, the reaction mixture is then diluted with 250 parts by volume of methanol and 50 parts by volume of water. After standing overnight, the deposited crystals are filtered off with suction and washed with methanol. After drying, 161 parts of yellow-brownish crystals with a melting point of 140 ° C. are obtained.

      <I> Example 4 </I> 255 parts of [4- or 5-phenyl] phenylacetamide-2-carboxylic acid and 250 parts by volume of 2-hydroxyethylamine are mixed with a further 250 parts by volume of ss-hydroxy Ethylamine heated to 210 to 220 C for 6 hours on the descending cooler. The remaining excess amine is then distilled off under reduced pressure and the residue is boiled with 750 parts of ethanol.

   After cooling, suctioning off, washing with ethanol and drying, 218 parts of 5-oxo-1- [ss-hydroxyethyl] -7- or 8-phenyl-1.2.3.5-tetrahydro-imidazo [1.2-b] -isoquinoline are obtained Form of yellowish crystals with a melting point of 195 to 196 C.



  Analysis for C19H18N2O2 (306.4):
EMI0002.0040
  
    C <SEP> H <SEP> N <SEP> 0
<tb> Calculates <SEP> 74.5 <SEP> 5.9 <SEP> 9.2 <SEP> 10.5
<tb> Found <SEP> 74.6 <SEP> 6.0 <SEP> 9.0 <SEP> 10.8 <I> Example 5 </I> 298 parts of 4-benzoylamino-phenylacetamide-2-carboxylic acid are, as described in Example 4, reacted with β-hydroxy ethylamine. After working up, 178 parts of 5-oxo-1- [ss-hydroxy-ethyl] -7-amino-1.2.3.5-tetrahydro-imidazo [1.2-b] isoquinoline are obtained in the form of brownish crystals with a melting point of 208 C.

    Analysis for C13H15N3O2 (245.3):
EMI0003.0002
  
    C <SEP> H <SEP> N <SEP> 0
<tb> Calculates <SEP> 63.7 <SEP> 6.2 <SEP> 17.1 <SEP> 13.1
<tb> Found <SEP> 63.4 <SEP> 6.3 <SEP> 16.9 <SEP> 13.3 The benzoyl group was thus split off during the reaction by the excess amine. The compound fluoresces intensely yellow-green in dilute solution in daylight.



  <I> Example 6 </I> 204 parts of 2-cyanomethyl-5-dimethylamino-benzoic acid are reacted with β-hydroxyethylamine as described in Example 4. After working up, 245 parts of 5-oxo-1- [ss-hydroxy-ethyl] -7-dimethylamino-1.2.3.5-tetrahydro-imidazo [1.2-b] isoquinoline are obtained in the form of yellowish crystals with a melting point of 192 to 193C.



  Analysis for C15H19N3O3 (273.3):
EMI0003.0007
  
    C <SEP> H <SEP> N <SEP> 0
<tb> Calculates <SEP> 65.9 <SEP> 7.0 <SEP> 15.4 <SEP> 11.7
<tb> Found <SEP> 65.8 <SEP> 7.1 <SEP> 15.1 <SEP> 12.0 <I> Example 7 </I> In 200 parts by volume of ethylene glycol there are 150 parts of γ-hydroxypropylamine and 162 parts of homophthalic anhydride are carried and heated to 195 C. Over the next 4 hours, a further 150 parts of γ-hydroxy-propylamine are gradually added and the excess amine is then removed by distillation and under reduced pressure. While cooling, 300 parts by volume of methanol are added and the mixture is left to stand overnight. The crystal slurry is cooled with ice, filtered off with suction and washed with ice-cold methanol.

   After drying, 167 parts of 6-oxo-1 - [- hydroxypropyl] -1.2.3.5-tetrahydro-6H-pyrimido [1.2-b] isoquinoline are obtained. When recrystallizing from toluene, the compound is obtained in yellowish crystals with a melting point of 124.degree.



  Analysis for C15H18N2O2 (l58.3):
EMI0003.0013
  
    C <SEP> H <SEP> N <SEP> 0
<tb> Calculates <SEP> 69.8 <SEP> 7.0 <SEP> 10.8 <SEP> 12.4
<tb> Found <SEP> 69.5 <SEP> 7.1 <SEP> 10.7 <SEP> 12.8 The same compound is obtained if the homophthalic anhydride is replaced by equivalent amounts of dimethyl homophthalate, ethyl 2-cyanomethyl benzoate, Phenylacetamide-2-carboxylic acid or N - (γ-hydroxy-propyl] -homophthalimide.



  <I> Example 8 </I> A mixture of 90 parts of homophthalic acid and 100 parts of β-hydroxypropylamine is heated to 210 ° C. in a descending cooler. 200 parts of β-hydroxypropylamine are added dropwise to this over a period of 8 hours. Excess amine is then stripped off under reduced pressure and the residue is isolated. 125 parts of 5-oxo-1- (ss-hydroxypropyl] -2-methyl-1.2.3.5-tetrahydro-imidazo [1.2-b] -isoquinoline are obtained as a semi-solid glass-like mass.



  Analysis for C15H18N2O2 (258):
EMI0003.0019
  
    N
<tb> Calculates <SEP> 10.8
<tb> Found <SEP> 11.0

 

Claims (1)

PATENT CLAIM Process for the preparation of 5-oxo-1- (hydroxyalkyl) - 1,2,3,5-tetrahydroimidazo [1,2-b] isoquinolines and the corresponding tetrahydropyrimido-isoquinolines, characterized in that homophthalic acids of the formula 2a EMI0003.0022 or functional derivatives thereof with hydroxyalkylamines of formula 3 EMI0003.0023 to compounds of formula 1 EMI0003.0024 reacted, where R is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms and n is the number 0 or 1, and where. the ring A can also be substituted by alkyl, alkoxy, phenyl, dialkylamino, phenylamino or acylamino.