DE3319978A1 - METHOD FOR PRODUCING 4-AZAPHTHALIDE COMPOUNDS - Google Patents

Description

Dr. F. Zuffi & ieirv sen. - Dr Eassmann Dipl.-Ing. F. Klingseisen - Or. F. Zumstein jun.

PATENT LAWYERS

APPROVED REPRESENTATIVES AT THE EUROPEAN PATENT OFFICE REPRESENTATIVES BEPQRE THE EU, ROPEAN PATENT OFFICE

CIBA-GEIGY AG ' Case 1-14377 / "+

Basel, Switzerland)

Process for the preparation of 4-azaphthalide compounds

The present invention relates to a new method of manufacture of azaphthalide compounds, which are used as color formers in printing or heat-sensitive recording materials can be used.

In pressure-sensitive, carbon-free copier systems is usually an oily solution of the chromogenic dye precursor such as crystal violet lactone, benzoyl leucomethylene blue, phthalides or fluorans, usually isolated in pressure breakable microcapsules, either on a separate transfer sheet may be present as a layer to form an interdependent pair of copy sheets, or which are on top of the sensitized side of the copy receiving sheet itself to form a self-reactive paper sheet.

In such pressure-sensitive copier systems is mostly used as chromogenic dye precursor crystal violet lactone [3,3-bis- (4'-dimethylaminophenyl) -6-dimethylaminophthalide] used. A print made with crystal violet lactone is known to fade a lot quickly when exposed to light, so that :; constant attempts to find a suitable Finding a substitute for it must be undertaken.

Good replacement products that have a satisfactory blueprint with showed improved lightfastness are azaphthalides, which in

3-position contain an aminophenyl and an indolyl substituent. However, the production of these color formers always results in isomeric structures of 4- and 7-azaphthalides. Although with these isomer mixtures an improvement in light fastness and, at the same time, a reduction the decrease in reactivity (CB decrease) can be achieved, however, undesirable discoloration of the die usually occurs in the production of pressure-sensitive recording materials chromogenic substance-containing microcapsules, which by the Presence of the 7-azaphthalide isomer in the isomer mixture caused will.

It has now been found that an isomer-free 4-azaphthalide compound can be obtained can be obtained if the reaction of quinolinic anhydride is used to prepare the isomer-free keto acid required as an intermediate with the indole compound in a specific organic Reaction medium and in the presence of a metal salt of a polyvalent Metal performs.

The present invention accordingly provides a method of production of 4-azaphthalide compounds of the formula

AA / A /

I A Il Il Il I. ...

· M)

^v V

Y. hydrogen, unsubstituted or by halogen, cyano, Hydroxyl or lower alkoxy substituted alkyl with at most 12 carbon atoms, acyl with 1 to 12 carbon atoms, Benzyl or thireh halogen, nitro, lower alkyl or Lower alkoxy substituted benzyl,

Z hydrogen, Nievlera] .yl odor phenyl,

X -OR. or preferably

R. and R-, independently of one another, each hydrogen, unsubstituted or by halogen, cyano, hydroxyl or lower alkoxy substituted alkyl with a maximum of 12 carbon atoms, cycloalkyl, phenyl, benzyl or by halogen, nitro, cyano, Lower alkyl, lower alkoxy or lower alkoxycarbonyl substituted phenyl or benzyl or

R-- and R "together with the nitrogen atom connecting them a five- or six-membered, preferably saturated, heterocyclic radical,

V denotes hydrogen, halogen, hydroxy, nitro, lower alkyl or lower alkoxy and

wherein the ring A is unsubstituted or by halogen, nitro, cyano, lower alkyl, lower alkoxy, lower alkoxycarbonyl, amino, mono-lower alkyliamino or di-lower alkylamino is substituted.

The method is characterized in that one is at one temperature of at most 65 ° C quinolinic anhydride with an indole compound of the formula

ί ^{Α 1} J L'-z

VY

wherein A, Y and Z have the meaning given, in the presence of one inorganic or organic metal salt of a polyvalent metal in an organic reaction mixture consisting of a lower aliphatic monocarboxylic acid or a nitrile of this acid, the reaction product obtained with a compound of the formula

V
wherein X and V have the meaning given, further condensed and

the resulting reaction mixture to a pH of at least 6 represents.

Lower alkyl and lower alkoxy are used in the definition of the radicals of the 4-azaphthalides as a rule such groups or group components represent, which have 1 to 5, in particular 1 to 3 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, η-butyl, sec-butyl or amyl or methoxy, ethoxy or isopropoxy.

Acyl is especially formyl, nicderalkylcarbonyl, such as acetyl or Propionyl, or benzoyl. Further acyl radicals can be lower alkylsulphonyl, such as methylsulphonyl or ethylsulphonyl and also phenylsulphonyl. Benzoyl and Phehylsulfonyl can be substituted by halogen, methyl, methoxy or ethoxy.

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

If the alkyl radicals in R .., R "and Y are substituted, it is especially cyanoalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl each preferably having a total of 2 to 4 carbon atoms, e.g. ß-cyanoethyl, ß-chloroethyl, ß-hydroxyethyl, ß-methoxyethyl or β-ethoxyethyl.

Examples of cycloalkyl in the meaning of R ₁ and R "are cyclopentyl or, preferably, cyclohexyl.

Preferred substituents in the benzyl group of R., R- and Y and in the phenyl group of R ₁ and R "are, for example, halogens, nitro, methyl or methoxy. Examples of such araliphatic or aromatic radicals are p-methylbo.u: -. Yl, o- or p-chlorobenzyl, o- or p-nitrobenzyl, o- or p-tolyl, xyIyI, o-, ra- or p- Chlorophenyl, o- or p-nitrophenyl

or ο- or p-methoxyphenyl.

If the substituents R ₁ and R_ together with the common nitrogen atom represent a heterocyclic radical, this is, for example, pyrrolidino, piperidino, pipecolino, morpholino, thioraorpholino or piperazines, for example N-methylpiperazino. Preferred heterocyclic radicals are pyrrolidino, piperidino or morpholino.

X is preferably the amino group of the formula -NR ₁ R ..

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

The substituents R ₁ and R- can be different from one another or are preferably identical. R, and R. are preferably benzyl or lower alkyl and in particular methyl or ethyl.

V is preferably hydrogen, methyl, methoxy or especially ethoxy.

The N-substituent Y is preferably benzyl, acetyl, propionyl or especially alkyl with 1 to 8 carbon atoms, such as n-octyl, n-butyl, Methyl or ethyl. A particularly preferred N-substituent Y is ethyl or n-octyl. Z is preferably phenyl or especially Methyl.

The benzene ring A is preferably not or also not further substituted substituted by halogen.

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

When carrying out the method according to the invention, the the substances involved in the reaction are preferably used in each case in molar amounts.

The preparation of the azaphthalide compounds of the formula (1) is according to the so-called one-pot process in two stages and continuously carried out.

The first stage, taking quinolinic anhydride with the indole compound of the formula (2) in organic solvents as defined and is reacted in the presence of an organic or inorganic metal salt is conveniently carried out at a temperature of

0 to 50 ⁰ C, preferably at room temperature (17 to 30 ⁰ C).

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

In the case of the reaction medium used in the process according to the invention The lower aliphatic monocarboxylic acid is conveniently a carboxylic acid which is liquid under the reaction conditions and which

May have 1 to 5 carbon atoms.

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

As corresponding nitriles, which are also used as the reaction medium in the invention Processes that can be used include, for example, acetonitrile, propionitrile or butyronitrile.

However, preferred solvents are aliphatic monocarboxylic acids with 2 to 4 carbon atoms, such as butyric acid, isobutyric acid, Propionic acid or especially acetic acid or mixtures of these carboxylic acids.

The metal salts used according to the invention are advantageously derived of polyvalent metals with an atomic weight of 24 to 210, preferably 26 to 140 and in particular 26 to 120. Examples 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. Aluminum, calcium, cadmium, iron, chromium, cobalt, copper, nickel, manganese, strontium, tin and zinc are preferred. The anionic constituent of these metal salts is expediently derived from mineral acids or else from organic acids

and represents e.g. a sulfate, halide, nitrate, formate, acetate, Propionate, citrate or stearate.

A fluoride, iodide, bromide or, preferably, can be used as the halide Chloride and also a pseudohalide such as a rhodanide into consideration come.

The metal salts can be used individually or as mixtures.

Preferred metal salts are sulfates or especially halides of metals from the aluminum, calcium, iron, cadmium, cobalt, copper, Manganese, nickel, tin and zinc, such as aluminum chloride, Calcium chloride, nickel chloride, cobalt chloride, iron 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 will be obtained in the presence of chlorides from aluminum, calcium, cobalt, iron, copper or zinc. Zinc chloride and aluminum chloride are of particular interest. One Mixture of calcium chloride and zinc chloride, the mixing ratio being is preferably 1: 9 to 2: 1, i ;; t also preferred.

The proportion of metal salt in the first reaction stage is advantageously at 10 to 100 mol%, preferably 12 to 50 mol%, based on the quinolinic anhydride used.

After the first reaction stage has ended, the reaction product (non-isolated keto acid) is further condensed directly with the compound of the formula (3). This second reaction step is preferably carried out so that one of an acidic EnLwässerungsmittels at a temperature of 20 ° to SO brings the Reaklionskomponenten in the presence of ⁰ C to the reaction. Examples of such condensing agents are

Sulfuric acid, phosphoric acid, phosphorus oxychloride and especially acetic anhydride. When using acetic anhydride temperatures are preferably between 20 ° and 60 ⁰ C. The reaction time of the second stage is generally 1 to 4 hours, preferably 1 1/2 to 3 hours.

The reaction mixture is finally to a pH of at least 6 posed. Suitable for this 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. A pH of 7 to 11 is preferably set.

The end product of the formula (1) is isolated in general in a known manner by separating the precipitate formed, washing and drying or by treating with suitable organic solvents, such as methanol or isopropanol and optionally recrystallization of the product.

If OR ₁ and / or V in the reaction product of the formula (1) are in each case hydroxyl, the hydroxyl group can be alkylated or aralkylated subsequently according to the definition of R and V.

The alkylation or aralkylation of the reaction products in which V and / or OR .. mean hydroxy, is usually according to known methods carried out. For example, the reaction will be in presence an acid binding agent such as an alkali metal carbonate or a tertiary nitrogen base such as triethylamine and optionally in Presence of an inert, organic solvent such as acetone, Isopropyl alcohol, chlorobenzene or nitrobenzene.

Suitable alkylating agents are alkyl halides such as methyl or Ethyl iodide or chloride, or dialkyl sulfates, such as dimethyl or diethyl sulfate. A particularly suitable aralkylating agent is Benzyl chloride and the corresponding substitution products, e.g. p-chlorobenzyl chloride or 2,4-diethylbenzyl chloride, which are preferably

in a non-polar, organic solvent such as benzene, Toluene or xylene can be used.

A particularly expedient embodiment of the new process consists in dissolving or suspended quinolinic anhydride in a saturated aliphatic CL-C, monocarboxylic acid, in particular acetic acid, or in acetonitrile, adding an indo compound of the formula (2) and converting the mixture into Presence of an inorganic metal salt, especially a metal halide, of a polyvalent metal with an atomic weight of 26 to 66, such as zinc chloride, calcium chloride, aluminum chloride, iron chloride, cobalt chloride or copper dichloride at room temperature, preferably 2 to 6 hours. Thereafter, the compound of formula (3) is added and the reaction mixture heated after the addition of acetic anhydride at 30 ° to 60 ⁰ C suitably 1 to 3 hours. A pH of 7.5 to 9 is then set using an alkali metal hydroxide or aqueous ammonia, for example. The precipitated 4-azaphthalide compound of the formula (1) is separated off and, if desired, recrystallized.

The preferred 4-azaphthalide compounds of formula (1), which are continuous produced according to the one-pot process according to the invention are those in which V is hydrogen, methyl, hydroxyl, methoxy or especially ethoxy and X is a group of the formula -NR R. represents in which R and R are methyl or ethyl or -NR R. pyrrolidino or Piperidino mean. Here: Y is preferably alkyl with 1 to 8 Carbon atoms, Z is primarily methyl and the ring A is preferably unsubstituted. Most preferred azaphthalide compounds of formula (1) are those in which the group

2-ethoxy-4-dimethylaminophenyl or 2-ethoxy-4-diethylsminophenyl Y is ethyl or octyl and Z is methyl and the ring A is unsubstituted.

- ys-

There is a great advantage of the method of the present invention in that it is technically easy to use and without insulation of the intermediately formed keto acids are pure end products with very good ones Yields. In particular, 4-A2aphthalide compounds are obtained, those entirely from the corresponding 7-azaphthalide isomers of the formula

I A Il Il Il I

are free. 7th

The 4-azaphthalide compounds prepared by the process according to the invention of formula (1) are normally colorless or at most faintly colored. They are especially suitable as fast developing ones Color former for use in a heat sensitive or, in particular, pressure-sensitive recording material which has both Can be copying as well as recording material. If these color formers are mixed with a preferably acidic developer, i.e. an electron acceptor, are brought into contact, so they result in intense, green-blue, blue or violet-blue color tones, both on clays, as well as special are sublimation and lightfast on phenolic substrates.

Compared to the previously from DK-OS 2 842 263 or DE-OS 3 116 815 known isomer mixtures of 4- and 7-azaphthalides, according to DE-OS 3 116 815 the disruptive 7-azaphthalide compound except for one 2% share is reduced, the e.r invention stand out isomer-free 4-azaphthalide produced by the advantage of that they do not cause any undesired early discoloration during manufacture or storage of the recording materials.

In the following examples, the percentages given relate to unless otherwise stated, by weight.

Example 1: 20.0 g Chinolinsäureanhydrid, 80 ml of acetic acid and 20.3 g of N-ethyl-2-methylindole and 2.74 g Ziikchlorid be eerührt for 5 hours at 20 ⁰ C. Then shall 23.6 g of 3- (N, N ~ diethylamino) -phenetol and 30 ml of acetic anhydride, warm and the reaction mixture to 50 to 60 ⁰ C and is stirred at this temperature for 2 hours. After addition of 170 ml of 30% aqueous ammonia and 100 ml of water fäll ^1: the product as a dough and "is separated The dough is mixed with .60 ml of isopropanol and boiled for 1 hour under reflux After cooling it.!. The recrystallized product is filtered off, washed with isopropanol and dried, giving 46.9 g of the i.; omeren-free 4-azaphthalide compound of the formula

:O

with a melting point of 156 ° bi :; 158 ° C.

Example 2: 6.0 g Chinolinsäureanhvdrid, 9.5 g of N-octyl-2-methylindole and 0.56 g of zinc chloride are stirred with 30 ml of glacial acetic acid for 5 hours at 2O ⁰ C. Then 6.6 g: 5-diethylaminophenetol and 8 ml acetic anhydride are added, whereupon the mixture is ^{stirred at 50 °} C. for 2 1/2 hours. After adding 30% aqueous ammonia, the product precipitates. This is separated off and recrystallized from isopropanol. 16.5 g of the isomer-free 4-azaphthalide compound of the formula are obtained

(12)

with a melting point of 113-118 ° C.

If 0.30 g of copper (II) dichloride or 0.53 g of aluminum trichloride are used instead of 0.56 g of zinc chloride and the procedure is otherwise as described in the example, 15.9 g or 16.8 g of the 4-azaphthalide compound are obtained of formula (12) with a melting point of 113-116 ⁰ C and 115-119 ° C.

ι
Example 3 : 1.5 g of quinolinic anhydride, 2.3 g of 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 ^{at 20 ° C. for 5 hours.} 1.6 g of 3-diethylaminophenetol and 2 ml of acetic anhydride are then added, whereupon the reaction mixture is ^{stirred at 50 °} C. for 2 1/2 hours. After adding 30% aqueous ammonia, the product precipitates. This is separated off from the aqueous phase and recrystallized from isopropanol. 3.8 g of the isomer-free 4-azaphthalide compound of the formula (12) with a melting point of 114-117 ° C. are obtained.

Use 0.19 g of iron trichloride or 0.14 g of cobalt dichloride instead of the specified metal salt mixture and otherwise proceed as Described in the example, 3.3 g or 3.8 g of the 4-azaphthalide compound are obtained of formula (12) with a melting point of 113-117 ° C or 113-116 ° C.

Example 4 : 8 g of quinolic anhydride, 1.1 g of zinc chloride, 40 ml of acetic acid and 9.95 g of n-butyl-2-methylindole are stirred at 20-23 ° C. for 5 hours. 9.3 g of 3- (N, N-diethylamino) phenetole are then added

and 7.5 ml of acetic anhydride were added. The reaction mixture is then stirred at 50-60 ° C. for 2 hours. Neutralized after the reaction has ended the acetic acid solution with 30% aqueous ammonia, whereby the reaction product separates out. After removing the watery Phase, the crude product is dissolved in glacial acetic acid and it is precipitated again with 30% aqueous ammonia. Obtained after recrystallization from ethanol 16.8 g of the isomer-free 4-azaphthalide compound of the formula

| 4 9

CII Ν (ϋ H)

LJJ ^{3 1} Y ί ^{2 5}

with a melting point of 152-154 ° C.

Example 5 ; A solution of 3 g of the 4-azaphthalide compound of the formula (11) in 80 g of diisopropylnaphthalene and 17 g of kerosene is microencapsulated in a manner known per se with gelatin and gum arabic by coacervation, after which the resulting microcapsules are not discolored. The microcapsules obtained are mixed with starch solution and brushed onto a sheet of paper. A second sheet of paper is coated on the front with phenolic resin as a color developer. The first sheet containing microcapsules and the color developer coated paper are placed on top of one another with the coatings adjacent. A pressure-sensitive copier paper is obtained which does not discolor even on storage. Pressure is exerted on the first sheet of paper by writing by hand or with a typewriter, and an intense blue copy that has excellent lightfastness develops immediately on the sheet which has been coated with the developer.

Corresponding non-discolored pressure-sensitive copier papers and Blue copies that are intense and lightfast through writing are also obtained using each of the others in Preparation Examples 2, 3 and 4 obtained color former.

Claims (16)

Claims ! ./ Process for the preparation of 4-azaphthalide compounds of the formula I A Il Il Il I _H X "> (1), A / Y hydrogen, unsubstituted or halogen, cyano, hydroxyl or lower alkoxy substituted alkyl with a maximum of 12 carbon atoms, acyl with 1 to \ 1 carbon atoms, benzyl or. benzyl substituted by halogen, nitro, lower alkyl or lower alkoxy, Z is hydrogen, lower alkyl or phenyl, X -OR ₁ or - R and R-, independently of one another, each hydrogen, unsubstituted or alkyl substituted by halogen, cyano, hydroxyl or lower alkoxy and having a maximum of 12 carbon atoms, cycloalkyl, Phenyl, benzyl or by halogen, nitro, cyano, lower alkyl, Phenyl substituted with lower alkoxy or Niederalkoj.ycarbonyl or benzyl or R and R ₀ together with the nitrogen atom leaving them form a five- or six-membered heterocyclic radical, V is hydrogen, halogen, hydroxy, nitro, lower alkyl or lower alkoxy mean and wherein the ring A is unsubstituted or substituted by halogen, nitro, cyano, lower alkyl, lower alkoxy, lower alkoxycarbonyl, amino, mono-lower alkylamino or di-lower alkylamino, characterized in that quinoline ^{is used at a temperature of at most 65 0 C} -th _ acid anhydride with an indole compound of the formula I A Il Il VV wherein A, Y and Z have the given meaning, in the presence of one 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 'obtained reaction product with a compound of the formula wherein X and V have the meaning given, further condensed and the resulting reaction mixture adjusts to a pH of at least 6. 2. The method according to claim 1, characterized in that X is the Amino groups of the formula -NR R “denotes. 3. The method according to any one of claims 1 and 2, characterized in that that R and R independently of one another lower alkyl or benzyl or R and R_ together with the nitrogen atom connecting them Represent pyrrolidino, piperidino or morpholino. 4. The method according to any one of claims 1 to 3, characterized in that that V denotes hydrogen, methyl, methoxy or ethoxy. 5. The method according to any one of claims 1 to 4, characterized in that that Y is alkyl with 1 to 8 carbon atoms, acetyl, propionyl or benzyl .. 6. The method according to any one of claims 1 to 5, characterized in that that Z denotes methyl or phenyl. 7. The method according to one of the claims] to 6, characterized in that that the ring A is unsubstituted. 8. The method according to any one of claims 1 to 7, characterized in that that the reaction of quinolic acid anhydride with the indole compound of the formula (2) at a temperature of from 0 to 50 ° C., preferably is carried out at room temperature. 9. The method according to any one of claims 1 to 8, characterized in that the organic reaction. ¹ medium an aliphatic monocarboxylic acid with 2 to 4 carbon atoms and preferably acetic acid is used. 10. The method according to any one of claims 1 to 9, characterized in that that the metal hall ·: from c in a polyvalent metal with a Atomic weight from 24 to 210, preferred; .tfeise 26 to 140 and in particular 26 to 120. 11. Procedure according to one of the Ans; irüche 1 to 10, characterized in that that as a metal salt a halogen of the metals aluminum, calcium, Iron, cadmium, cobalt, copper, may gan, nickel, or tin. Zinc used will. 12. Procedure according to one of the Ans; rüche 1 to 11, characterized in that the condensation of from Chinolinsäureanhydrid and the indole compound of formula (2) obtained ltenen reaction product with the compound of formula (3) in the opposite kind of an acidic dehydrating agent at a temperature of 2) ° to 80 ⁰ C is performed. 13. The method according to any one of claims 1 to 12, characterized in that there. ¹ ; ·; one finally adjusts the reaction ^ cmiscli to a pH value of 7 to 11. 14. The method according to claim 1, characterized in that quinolic anhydride is dissolved or suspended in a saturated aliphatic C -C monocarboxylic acid, an indole compound of the formula (2) is added and the mixture is in the presence of an inorganic metal salt of a polyvalent metal with an atomic weight stirred for 26 to 66 at room temperature, it is added the compound of formula (3) and the reaction mixture heated after the addition of acetic anhydride at 30 to 6O ⁰ C and then sets to a pH value of 7.5 to. 9 15. 4-azaphthalide compounds of the formula (1), characterized in that that it is produced by a process according to one of the claims Ibis 14 have been. 16. Use of a 4-Af.aphtiialidverbindungen according to claim 15 or of their mixtures as color formers in a pressure-sensitive or thermosensitive recording material. FO 7.1 / PE / mg *