FI76342B - FRAMEWORK FOR FRAME STATION 4-AZAFTALIDFOERENINGAR. - Google Patents

Description

7 6 3 4 2

Method for the preparation of 4-azaphthalide compounds For the preparation of 4-azaphthalide compounds

The invention relates to a new process for the preparation of azaphthalide compounds which can be used as colorants in pressure- or heat-sensitive markers.

In pressure-sensitive, carbon-free copying systems, an oily solution of a chromogenic color former, such as crystalline violet lactone, benzoyl leukomethylene, phthalides, or fluoranes, is conventionally isolated by self-sealing. on the sensitized side to form a self-reactive sheet of paper.

In such pressure-sensitive copying systems, crystal violet lactone [3,3-bis- (4'-dimethylaminophenyl) -6-dimethylaminophthalide) is most often used as the chromogenic color former. The printing produced with crystal violet lactone is known to fade so rapidly that constantly find a suitable substitute for it.

Good substitute products that form a satisfactory blue print with improved lightfastness include azaphthalides containing an aminophenyl and indolyl substituent at the 3-position. However, the preparation of these color formers always produces isomeric mixtures of 4- and 7-azaphthalides. Although these isomer mixtures can provide an improvement in light fastness and at the same time a decrease in reactivity (CB reduction), in the manufacture of pressure sensitive marking materials, undesirable discoloration of chromogenic microcapsules due to the presence of the 7-azaphthalide isomer generally occurs. .

2,76342

It has now been found that a isomer-free 4-azaphthalide compound can be obtained by reacting a quinoline anhydride with an indole compound in a specific organic reaction medium and in the presence of a polyvalent metal to prepare the isomer-free keto acid required as an intermediate.

The present invention therefore relates to a method of the formula Ϊ jsf '\ / \ / λ i A n_f: fi i v \ / \\ λ / y (1) *

i 11 5L

To prepare 4-azaphthalide compounds according to the formula, wherein Y represents hydrogen, alkyl having 1 to 12 carbon atoms, lower alkylcarbonyl having 1 to 4 carbon atoms or benzyl, Z represents hydrogen, lower alkyl or phenyl, xR1

X is -N

^ r 2

R1 and R2 independently of one another denote alkyl, cyclohexyl or benzyl having 1 to 12 carbon atoms or R1 and R2 together with the nitrogen atom connecting them denote pyrrolidino, piperidino or morpholino, V denotes hydrogen, lower alkyl or lower alkoxy and where ring A is substituted by halogen or halogen subs--substituted.

The process is characterized in that the quinolinic anhydride is reacted at a temperature of up to 65h £ .η with the formula 3 7 6 3 4 2 ___

i A fi M

VV (2),

Y

A, Y and Z are as defined above, in the presence of an inorganic or organic metal salt of a polyvalent metal in an organic reaction medium consisting of a lower aliphatic monocarboxylic acid or a nitrile of this acid, the reaction product obtained is further condensed. ,

V

with the substituents X and V as indicated and adjusting the pH of the resulting reaction mixture to at least 6.

Lower alkyl and lower alkoxy in the determination of 4-azaphthalide residues generally mean groups or parts of a group containing 1 to 5, in particular 1 to 3, carbon atoms, such as, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec. butyl, or amyl or vast, methoxy, ethoxy or isopropoxy.

If the substituents R 1, R 2 and Y denote alkyl groups, they can be straight-chain or branched alkyl radicals. Examples of such alkyl residues are methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, amyl, n-hexyl, 2-ethyl-hexyl, n-heptyl, n-octyl, isooctyl, n -nonyl, isonomyl or n-dodecyl.

V is preferably in the meta position with respect to the substituent X.

The substituents R 1 and R 2 may be different or are preferably identical. R 1 and R 2 preferably denote benzyl or lower alkyl and especially methyl or ethyl.

4,76342 V is preferably hydrogen, methyl, methoxy or, above all, ethoxy.

The N-substituent Y is preferably benzyl, acetyl, propionyl or especially alkyl having 1 to 8 carbon atoms, such as, for example, n-octyl, n-butyl, methyl or ethyl. A highly preferred N substituent Y is ethyl or n-octyl.

Z is preferably phenyl or above all methyl.

Preferably, the benzene ring A is further unsubstituted.

Halogen means, for example, fluorine, bromine or, preferably, chlorine.

In carrying out the process according to the invention, the reactants are preferably used in each case in molar amounts.

The preparation of azaphthalide compounds of the formula (1) is carried out in two steps in a so-called one-pot process (Eintopfver-fahren) and continuously.

The first step of reacting the quinoline anhydride with an indole compound of formula (2) in organic solvents as defined and in the presence of an organic or inorganic metal salt is conveniently carried out at a temperature of 0 to 50 ° C, preferably at room temperature (17 to 30 ° C).

The reaction time depends on the temperature and the metal salt and solvent used as a catalyst, and is usually 1 / 2-10, preferably 2-6 hours.

The lower aliphatic monocarboxylic acid used as the reaction medium in the process of the invention is suitably a liquid carboxylic acid which may contain 1 to 5 carbon atoms under the reaction conditions.

Suitable aliphatic monocarboxylic acids which form the reaction medium include formic acid, acetic acid, dichloroacetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid or mixtures of these acids.

Suitable nitriles which can likewise be used as reaction medium in the process according to the invention are, for example, acetonitrile, propionitrile or butyronitrile.

However, the most preferred solvents are aliphatic monocarboxylic acids containing 2 to 4 carbon atoms, such as, for example, butyric acid, isobutyric acid, propionic acid or especially acetic acid or also mixtures of these carboxylic acids. The metal protectors used according to the invention are preferably derived from polyvalent metals having an atomic weight of 24 to 210, more preferably 26 to 140 and especially 26 to 120. Examples of such metals are aluminum, barium, lead, cadmium, calcium, chromium, iron, gallium, cobalt. , copper, magnesium, manganese, molybdenum, nickel, mercury strontium, tantalum, titanium, vanadium, tungsten, zinc, tin and zirconium. In this case, aluminum, calcium, cadmium, iron, chromium, 25 cobalt, copper, nickel, manganese, strontium, tin and zinc are considered the best. The anionic part of these metal salts is suitably derived from mineral acids or also from organic acids and is, for example, sulphate, halide, nitrate, formate, acetate, propionate, citrate or stearate.

Suitable halides are fluoride, iodide, bromide or, preferably, chloride, as well as a pseudohalide such as rhodanide.

Metal salts can be used alone or in mixtures.

6,76342

Preferred metal salts include sulfates of metals belonging to the group of aluminum, calcium, iron, cadmium, cobalt, copper, manganese, nickel, tin and zinc, and above all halides, such as, for example, aluminum chloride, calcium chloride, nickel chloride, cobalt chloride, rhodium chloride, copper chloride, zinc chloride, tin chloride, tin bromide, manganese chloride, nickel bromide, calcium fluoride, cadmium iodide or mixtures thereof. In general, the best results are obtained in the presence of chlorides of aluminum, calcium, cobalt, iron, copper or zinc. Of particular interest are zinc chloride and aluminum chloride. Also preferred is a mixture of calcium chloride and zinc chloride, with a mixing ratio of preferably 1: 9 to 2: 1.

The proportion of the metal salt in the first reaction step is preferably 10 to 100 mol%, more preferably 12 to 50 mol%, relative to the quinolinic anhydride used.

At the end of the first reaction step, the reaction product 20 (uninsulated keto acid) is condensed directly with the compound of formula (3). This second reaction step is preferably carried out by reacting the reaction components in the presence of an acidic dehydrating agent at a temperature of 20 to 80 ° C. Examples of such condensing agents are sulfuric acid, phosphoric acid, phosphorus oxychloride and, above all, acetic anhydride. When using acetic anhydride, temperatures of 20 to 60 ° C are preferably used. The reaction time of the second step is generally 1 to 4 hours, preferably 1 to 3 hours.

The reaction mixture is finally adjusted to a pH of at least 6. Suitable for this purpose are alkalis, such as alkali metal hydroxides, e.g. sodium or potassium hydroxide, ammonia or alkali metal carbonates or bicarbonates, and mixtures of these compounds. Preferably, the pH is adjusted to 7-11.

7 76342

Isolation of the final product of formula (1) is carried out in a generally known manner by separating the precipitate formed, washing and drying or treating with organic solvents such as, for example, methanol or iso-5-propanil and, if appropriate, recrystallizing the product.

If 0R- | and / or V in each case in the reaction product of the formula (1) denotes hydroxyl, so that the hydroxyl group can be alkylated or aralkylated afterwards according to the substituents and the definition of V.

Alkylation or aralkylation of reaction products in which V and / or 0R represent hydroxy, are generally carried out according to known methods. For example, the reaction is carried out in the presence of an acid scavenger such as alkali carbonate or a tertiary nitrogen base such as triethylamine and optionally in the presence of an inert organic solvent such as acetone, isopropyl alcohol, clocribenzene and nitrobenzene.

Suitable alkylating agents are alkyl halides, such as, for example, methyl or ethyl iodide or chloride, or dialkyl sulfates, such as, for example, dimethyl or diethyl sulfate. Suitable aralkylating agents are, in particular, benzyl chloride and the corresponding substitution products, such as, for example, p-chlorobenzyl chloride or 2,4-dimethylbenzyl chloride, which are preferably used in a non-polar organic solvent such as, for example, benzene, toluene or xylene.

A very suitable embodiment of the new process is that the quinoline anhydride is dissolved or suspended in a saturated aliphatic C2-C4 monocarboxylic acid, especially acetic acid or also acetonitrile, a compound of formula (2) is added, in the presence of an inorganic metal salt of a metal, especially a metal halide such as, for example, zinc chloride, calcium chloride, aluminum chloride, ferric chloride, cobalt chloride or copper chloride at room temperature, preferably for 2-6 hours.

The compound of formula (3) is then added and, after the addition of acetic anhydride, the reaction mixture is heated to a temperature of 30 to 60 ° C, suitably for 1 to 3 hours. The pH is then adjusted to 7.5-9 with, for example, alkali metal hydroxide or aqueous ammonia. The precipitated 4-aza-phthalide compound of formula (1) is separated off and recrystallized if desired. Preferred 4-aza-phthalide compounds of formula (1) which are prepared continuously according to the one-pot process of the invention are those in which V represents hydrogen, methyl, hydroxyl, methoxy or, above all, ethoxy and X is a group of formula -NR-R 2. wherein R 1 and R 2 represent methyl Y is preferably alkyl of 1 to 8 carbon atoms, Z is primarily methyl and ring A is preferably unsubstituted. Most often, the preferred azaphthalide compounds of formula (1) are those in which the group

, / -X T

V

represents 2-ethoxy-4-dimethylaminophenyl or 2-ethoxy-4-diethylaminophenyl, Y represents ethyl or octyl and Z represents methyl and ring A is unsubstituted.

A great advantage of the process according to the invention is that it can be carried out technically easily and it produces pure end products without indirect isolation of pure keto acids in very good yields. In particular, 4-azaphthalodi compounds are obtained which are completely free of formula 9 76342

Y

t \ / \ / Z /% / * X

T · · · ·

I A I! Il II I

V '' ”\ / \ <(A). · A ^ f S | · 'of the corresponding 7-azaphthalide isomers according to $ 7.

The 4-azaphthalide compounds of formula (1) prepared according to the process of the invention are normally colorless or at most slightly colored.

5 They are particularly suitable for use as fast-developing color formers in heat-sensitive or, in particular, pressure-sensitive marking materials, which can be both copying and registration materials. When these color formers are contacted, preferably 10 acid generators, i. with an electron acceptor, so they form intense, green-blue, blue, or purple-blue hues that are both sublimation- and light-resistant on both clays and especially phenolic substrates.

15 Compared with the isomeric mixtures of 4- and 7-azaphthalides known to date from DE-A-2 842 263 or DE-A-3 116 815, in which the 7-azaphthalide compound which interferes with DE-A-3 116 815 has been reduced to 2%, The isomer-free 4-azaphthalide compounds prepared according to the invention are characterized by the advantage that they do not cause any undesired premature discoloration during manufacture or during storage of the labeling materials.

25 The percentages given in the following examples are by weight, unless otherwise indicated.

10 7 6 3 4 2

Example 1: 20.0 g of quinolinic anhydride, 80 ml of acetic acid, 20.3 g of N-ethyl-2-methylindole and 2.74 g of zinc chloride are stirred for 5 hours at 20 ° C.

23.6 g of 3- (Ν, Ν-diethylamino) phenethol 5 and 30 ml of acetic anhydride are then added, after which the reaction mixture is heated to 50-60 ° C and stirred for 2 hours at this temperature. 170 ml of 30% aqueous ammonia and 100 ml of water are added, after which the product precipitates as a dough and is separated. Add 160 ml of isopropanol to the dough and boil for one hour at reflux. After cooling, the recrystallized product is separated off, washed with isopropanol and dried. 46.9 g of isomer-free, of formula c2-5 are obtained

.0C H N

2 52 l IJ CH3 "fl il I

v \ ^ - \ / uu λ a; > '* ϊ% / - 4 azaphthalide compounds with a melting point of 15-15-158 ° C.

Example 2: 6.0 g of quinolinic anhydride, 9.5 g of N-octyl-2-methylindole and 0.56 g of zinc chloride are mixed with 30 ml of acetic acid for 5 hours at 20 ° C. 6.6 g of 3-diethylaminophenol and 8 ml of acetic anhydride are then added, after which the mixture is stirred for 2 hours at 50 ° C. 30% aqueous ammonia is added, after which the product precipitates. This is separated and recrystallized from isopropanol. 16.5 g of isomer-free n-C H K 17 OC H. CH 'of formula 11 76342 are obtained.

(C H 1 r ^ '7 2 5 3 N

<C2H5) 2N 'T; A 4-azaphthalide compound according to (V), having a melting point of 113-118 ° C.

If 0.30 g of copper (II) dichloride or 0.53 g of aluminum trichloride is used instead of 0.56 g of zinc chloride and the procedure is otherwise as described in the example, 15.9 g or the like are obtained. 16.8 g of a 4-azaphthalide compound of the formula (12) having a melting point of 113-116 ° C or the like. 115-119 ° C.

Example 3: 1.5 g of quinolinic anhydride, 2.3 g of 10 N-octyl-2-methylindole, 10 ml of glacial acetic acid and a mixture of 0.11 g of calcium chloride and 0.14 g of zinc chloride are stirred for 5 hours at 20 ° C. :in. 1.6 g of 3-diethylaminophenol and 2 ml of acetic anhydride are then added, after which the reaction mixture is stirred for 2 hours at 50 ° C. Li-15 is adjusted to 30% aqueous ammonia, after which the product precipitates. This is separated from the aqueous phase and recrystallized from isopropanol. 3.8 g of an isomer-free 4-azaphthalide compound of the formula (12) are obtained, m.p. 114-117 ° C.

If 0.19 g of ferric trichloride or 0.14 g of cobalt dichloride are used instead of the metal salt mixture shown and otherwise treated as described in the example, 3.3 g or the like are obtained. 3.8 g of a 4-aza-phthalide compound of formula (12), m.p. 113-117 ° C or resp. 113-116 ° C.

Example 4: 8 g of quinolinic anhydride, 1.1 g of zinc chloride, 40 ml of acetic acid and 9.95 g of N-butyl-2-methylindole are stirred for 5 hours at 20-23 ° C. After this 12,76342, 9.3 g of 3- (N, N-diethylamino) phenethol and 7.5 ml of acetic anhydride are added. The reaction mixture is then stirred for 2 hours at 50-60 ° C. After completion of the reaction, the acetic acid solution is neutralized with 30% aqueous ammonia, whereupon the reaction product separates. After removal of the aqueous phase, the crude product is dissolved in glacial acetic acid and reprecipitated with 30% aqueous ammonia. Recrystallization from ethanol gives 16.8 g of isomer-free, n-C, H149

A A A

(13) A 4-azaphthalide compound according to I ..... JJ CH3 '3 i N (C2H5) 2 v aV y i'Y>,, m.p. 152-154 ° C.

Example 5: A solution of 3 g of a 4-azaphthalide compound of formula (11) in 80 g of diisopropylnaphthalene and 17 g of kerosene is microencapsulated in a manner known per se with gelatin and acacia by coacervation, without any constituents. discoloration of microcapsules. The resulting microcapsules are mixed with the starch solution and applied to a sheet of paper. The second sheet of paper is coated on the front with feno-20 meat resin, which acts as a color developer. A first sheet of paper containing microcapsules and a second paper coated with a dye hit are superimposed on the coatings side by side. A pressure-sensitive copy paper is obtained which does not change color even during storage.

25 By typing by hand or typewriter, pressure is applied to the first sheet, and an intense blue copy, 13 76342, which is highly lightfast, immediately develops on the developer-coated sheet.

Corresponding non-color-changing pressure-sensitive copying papers and writing intense and light-resistant blue copies are also obtained using 5 other color formers obtained in Production Examples 2, 3 or 4.

Claims (13)

14,763,4 Claims; 1. Method of formula 1. ii ii ii i V ‘\ / \ <Λ A • 11? To prepare 4-azaphthalide compounds according to the formula, wherein Y represents hydrogen, alkyl having 1 to 12 carbon atoms, lower alkylcarbonyl or benzyl having 1 to 4 carbon atoms, Z represents hydrogen, lower alkyl or phenyl, / R 1 X is -N * 2 R1 and R2 independently of one another denote alkyl, cyclohexyl or benzyl having 1 to 12 carbon atoms or and R2 together with the nitrogen atom connecting them denote pyrrolidino, piperidino or morpholino, V denotes hydrogen, lower alkyl or lower alkoxy and wherein ring A is unsubstituted or halogen-substituted, characterized in that at a temperature of not more than 65 ° C the quinoline anhydride is reacted with an indole compound of the formula Y, wherein A, Y and Z are , 5 76342 are the same as above, in the presence of an inorganic or organic metal salt of a polyvalent metal in an organic reaction medium consisting of a lower aliphatic monocarboxylic acid or the nitrile of this acid, the resulting reaction product of formula (3) is further condensed. With a compound according to V, in which the substituents X and V are as defined, and adjusting the resulting reaction mixture to a pH of at least 6. Process according to Claim 1, characterized in that and R 2 independently of one another denote lower alkyl or benzyl or R 1 and R 2 together with the nitrogen atom connecting them denote pyrrolidino, piperidino or morpholino. Process according to Claim 1 or 2, characterized in that V represents hydrogen, methyl, methoxy or ethoxy. Process according to one of Claims 1 to 3, characterized in that Y represents alkyl, acetyl, propionyl or benzyl having 1 to 8 carbon atoms. Process according to one of Claims 1 to 4, characterized in that Z represents methyl or phenyl. Process according to one of Claims 1 to 5, characterized in that ring A is unsubstituted. Process according to one of Claims 1 to 6, characterized in that the reaction of the quinolinic anhydride with the indole compound of the formula (2) is carried out at a temperature of 0 to 50 ° C, preferably at room temperature. , 6 76342 Process according to one of Claims 1 to 7, characterized in that an aliphatic monocarboxylic acid having 2 to 4 carbon atoms and preferably acetic acid is used as the organic reaction medium. Process according to one of Claims 1 to 8, characterized in that the metal salt is based on a polyvalent metal having an atomic weight of 24 to 210, preferably 26 to 140 and in particular 26 to 120. Process according to one of Claims 1 to 9, characterized in that the metal salt used is aluminum, calcium, iron, cadmium, cobalt, copper, manganese, nickel, tin or zinc halide. Process according to one of Claims 1 to 10, characterized in that the condensation of the reaction product obtained from the quinoline anhydride and the indole compound of the formula (2) with the compound of the formula (3) is carried out in the presence of an acidic dehydrating agent at a temperature of 20 to 80 ° C. Process according to one of Claims 1 to 11, characterized in that the reaction mixture is finally adjusted to pH 7 to 11. Process according to Claim 1, characterized in that the quinolinic anhydride is dissolved or suspended in a saturated aliphatic C 2 -C 4 monocarboxylic acid, an indole compound of the formula (2) is added and the mixture is stirred with a polyvalent metal inorganic metal salt having an atomic weight of 26 to 66. in the presence of room temperature, a compound of formula (3) is then added and, after the addition of acetic anhydride, the reaction mixture is heated to 30-60 ° C and then adjusted to pH 7.5-9. 17 76342