CH628922A5 - Process for the preparation of 2-(disubstituted methyl)-5-aminobenzoic acids and their phthalides, and use of these substances - Google Patents

Description

628922

CLAIMS 1. Process for the preparation of a compound of formula III

COOH

in which R represents a hydrogen atom or a non-tertiary alkyl group of 1 to 4 carbon atoms, ben-zyl or benzyl substituted on the benzene ring by one or is two halogen or alkyl radicals of 1 to 3 carbon atoms; X represents a hydrogen or halogen atom; Y represents a monovalent radical having one of the formulas (A) to (H)

20

(AT)

(B)

25

30

35

(B) RJ (G)

where Ri represents a hydrogen atom or a non-tertiary alkoxy group of 1 to 4 carbon atoms, dialkylamino or N-alkylbenzylamino where the alkyl groups are non-tertiary alkyl groups of 1 to 4 carbon atoms; R2 represents a hydrogen atom or an alkyl group of 1 to 3 carbon atoms or non-tertiary alkoxy of 1 to 4 carbon atoms; R3 represents a hydrogen atom or an alkyl group of 1 to 3 carbon atoms, non-tertiary alkoxy of 1 to 4 carbon atoms, a halogen atom or a dialkylamino group in which the alkyl groups are non-tertiary alkyl groups from 1 to 4 carbon atoms; R4 represents one or two hydrogen radicals, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, halogen or nitro; R5 represents a hydrogen atom, a non-tertiary alkyl group of 1 to 8 carbon atoms, alkenyl of 2 to 4 carbon atoms, benzyl or benzyl substituted on the benzene ring by 1 or 2 halogen or alkyl radicals from 1 to 3 carbon atoms; R6 represents a hydrogen atom or an alkyl group of I to 3 carbon atoms or phenyl; and R7 and Rs represent hydrogen atoms or alkyl groups of 1 to 3 carbon atoms, characterized in that a compound of formula II is condensed

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45

50

with a compound of formula Z-H in the presence of an alkaline or acidic condensing agent.

2. Process for the preparation of a compound of formula IV

(D)

(F)

Z represents a monovalent radical of formula (A), (B) or (G)

3

628,922

in which R represents a non-tertiary alkyl group of 1 to 4 carbon atoms; R1 'represents a hydrogen atom or a non-tertiary alkoxy group of 1 to 3 carbon atoms, N-alkylbenzylamino where the alkyl group is a non-tertiary alkyl group of 1 to 4 carbon atoms, or when R3 is other than 'a dialkylamino group, R1' represents a dialkylamino group in which the alkyl group is a non-tertiary alkyl group of 1 to 4 carbon atoms; R1 "represents a dialkylamino group in which the alkyl groups are non-tertiary and have from 1 to 4 carbon atoms; R2 'represents a hydrogen atom or an alkyl group of 1 to 3 carbon atoms; R3 represents a atom hydrogen or an alkyl group of 1 to 3 carbon atoms, non-tertiary alkoxy of 1 to 4 carbon atoms, a halogen atom or a dialkylamino group in which the alkyl groups are non-tertiary and hence have 4 atoms carbon; R3 'represents a hydrogen atom or an alkyl group of 1 to 3 carbon atoms, non-tertiary alkoxy of 1 to 4 carbon atoms or a halogen atom; X represents a hydrogen atom or halogen; and provided that R2 ', R3, R3' and X cannot all be hydrogen at the same time; characterized in that the process of claim 1 is carried out and that the corresponding compound of formula is then oxidized III thus obtained 25 3. Process for the preparation of a compound of formula V

gene, characterized in that the process of claim 1 is carried out and that the corresponding compound of formula III thus obtained is then oxidized.

4. The method of claim 1, wherein Y and Z are each the radical A.

5. Use of a compound of formula III, obtained by the process of claim 1, in a duplication system without pressure-sensitive carbon paper, or thermal paper marking system, containing as a color-generating substance a compound of formula III.

6. Use of a compound of formula IV, obtained by the process of claim 2, in a duplication system without pressure-sensitive carbon paper, or thermal paper marking system, containing as a color-generating substance a compound of formula IV.

7. Use of a compound of formula V, obtained by the method of claim 3, in a duplication system without pressure-sensitive carbon paper, or thermal paper marking system, containing as a color-generating substance a compound of formula V.

in which R represents a non-tertiary alkyl group of 1 to 4 carbon atoms; R1 'represents a hydrogen atom or a non-tertiary alkoxy group of 1 to 4 carbon atoms, N-alkylbenzylamino in which the alkyl group is a non-tertiary alkyl group of 1 to 4 carbon atoms or, when at least 1 one of R2 and R3 "is other than a hydrogen atom, a dialkyl-55 amino group in which the alkyl groups are non-tertiary and have from 1 to 4 carbon atoms; R2" and R3 "each represent an atom hydrogen, an alkoxy group of 1 to 3 carbon atoms or a hylogen atom; R4 represents one or two hydrogen radicals, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, halogen or nitro; R5 represents a hydrogen atom or a non-tertiary alkyl group of 1 to 8 carbon atoms, alkenyl of 2 to 4 carbon atoms, benzyl or benzyl substituted on the benzene ring by one or two halogen or alkyl radicals of 65 1 to 3 carbon atoms; R6 represents a hydrogen atom or an alkyl group 1 to 3 carbon atoms or phenyl; and X represents a hydrogen or halo atomProcess for the preparation of 2- (di-subst. methyl) -5-aminobenzoic acids and their phthalides, and use of these substances.

The present invention relates to a process for the preparation of 3,3-aryl- and / or heteryl-phthalides used in the field of reproduction without carbon paper such as, for example, in pressure-sensitive systems and thermal marking systems; and the preparation of new 3-aryl- or heteryl-phthalides.

It is known that several categories of organic compounds with very diverse structures can be used as colorless precursors for reproduction systems without carbon paper. Among the most important categories, phenothiazines can be named, for example benzoyl-leuco-methylene blue; the phthalides that this invention relates to, for example the lactone of crystallized violet; fluoranes, for example 2'-anilino-6'-diethylaminofluorane and 2'-diben-zylamino-6'-diethylaminofluorane; and various other types of colorless precursors commonly used in commercially used carbonless duplicate systems. Typical examples of these systems described in the prior art are those of U.S. patents. No. 2.712.507, 2.800.457 and 3.041.289.

The following articles appear to be the most relevant prior art for the present invention at this time. Rodionov and Fedorova in the Bulletin of the Academy of Sciences of the USSR, Class of Chemical Sciences 81-8 (1940) (Chemical Abstracts 35: 24884 [1941]) describe the preparation of 3-aryl-phthalides, for example the 3- (4-dimethylaminophenyl) -phthalide, 3- (4-diethylamino-phenyl) -6,7-dimethoxy-phthalide and 3- (4-ethylamino-phenyl) -6,7-dimethoxy-phthalide, by heating suitable N, N-dialkylaniline with appropriate phthalaldehyde acid. The physical characteristics of the compounds are described without any indication as to their usefulness.

Noland and Johnson in the Journal of the American Chemical Society 82, 5143-5147 (1960) describe the preparation of 3-heterylphthalides, for example 3- (1,2-dimethyl-3-indolyl) phthalide, 3- (2 -methyl-3-indolyl) -6,7-dimethoxy-phthalide and other isomers, by fusion of equi-molar proportions of an indole and a phthalaldehyde acid. The physical characteristics of these compounds are given but there is no indication of their usefulness. Rees and Sabet in the Journal of the Chemical Society, 680-687 (1965)

628,922

describe the preparation and physical characteristics of 3- (3-indolyl) phthalide. There is no indication of the usefulness of the compound in the reference, which compound is prepared by acid catalyzed interaction of indole and phthalaldehyde. In the same reference, Rees and Sabet describe the preparation and the physical characteristics of a, a-di- (3-indolyl) -2-methylbenzoic acid by interaction of 3- (3-indolyl) phthalide with indole in alcoholic potassium hydroxide at reflux. No utility for the compounds is given in the reference.

U.S. patents No. 2.742.483 and 3.185.709 describe 2- [4,4 '-bis- (dimethylamino) benzhydryl] -5-dimethyl-aminobenzoic acid which is obtained by interaction of m-dimethylaminobenzoic acid and 4, 4'-bis (dimethyl-amino) benzhydrol. The compound is described as being an intermediate leading to 3,3-bis (4-dimethylamino-phenyl) -6-dimethylaminophthalide which, according to the oldest patent, is obtained by oxidation with permanganate and according to the most recent patent by oxidation by molecular oxygen. 3,3-bis (4-dimethyl-aminophenyl) -6-dimethylaminophthalide (crystalline violet lactone) is well known as a colorless precursor for reproduction systems without carbon paper.

Belgian Patent No. 808,535 describes 3- [2,4-bis (dimethyl-amino) phenyl] -3- (4-dimethylaminophenyl) -6-dimethylami-nophthalide and similar compounds which are prepared by condensing the o- (4-diaIkylaminobenzoyl) benzoic acid suitable with the appropriate N, N, N ', N'-tetra-alkyl-m-phenylenedia-mine. These compounds are described as being useful as colorless precursors for carbonless paperless reproduction systems.

The U.S. Patent No. 3,491,112 describes 3- (4-dimethyl-aminophenyl) -3- (1,2-dimethyl-3-indolyl) -6-dimethylami-nophthalide which is prepared by condensing the acid 4,4 ' -bis- (dimethylamino) benzophenone-2-carboxylic and 1,2-dimethylindole. The compound has utility as a colorless precursor in carbonless reproduction systems.

The U.S. Patent No. 3.629.322 describes 3- (2-methyl-4-N-ethyl-benzylaminophenyl) -3- (1 -ethyl-2-methyl-3-indolyl) -6-dimethylaminophthalide which is prepared by interaction of l-ethyl-2-methyl-3- (4'-dimethylamino-2'-carboxy-benzoyl) -indole and N-benzyl-N-ethyl-3-methylaniline. The compound has utility as a colorless precursor in carbonless reproduction systems.

Japanese patent publication No. Sho 50-124930 describes a series of compounds of formula

in which each of R 1 and R 2 represents a hydrogen atom or a lower alkyl, haloalkyl, alkoxyalkyl, acyloxyalkyl, cyanoethyl, allyl, propargyl, cyclohexyl, benzyl or phenyl group in which the benzene ring may be substituted by a lower alkyl, halogen radical , nitro or lower alkoxy; or Ri and R2 together form a heterocyclic ring with the adjacent nitrogen atom; R3 represents a hydrogen or chlorine atom; R4 represents a benzene ring or a heterocyclic ring which can be substituted. According to the reference, the compounds are prepared by condensation of a suitable aromatic aldehyde and a suitable benzoic acid, at a high temperature, in the presence of a dehydrating agent, and the compounds are described as colorless precursors in s reproduction without carbon paper, in pressure-sensitive systems and in thermal reproduction systems.

The overall process preferably used comprises three steps which consist in: condensing a 3-N (R) 2-4-X-ben-10 zoic acid with an aromatic or heterocyclic aldehyde of formula Y-CHO in the presence of a acid condensation under dehydration conditions, to obtain a 3-Y-5-X-6-N (R) 2-phthalide (Formula II); condensing said compound, according to the invention, with a compound of formula ZH îs in the presence of an alkaline or acidic condensation in order to obtain an acid 2 (cc-Y-aZ) methyl-4-X-5-N (R) 2 benzoic (formula III); and optionally oxidizing said benzoic acid to obtain a 3-Y-3-Z-5-X-6-N (R) 2phthalide of formula

\

20

25

In which R represents a hydrogen atom or a non-tertiary alkyl group of one to four carbon atoms, benzyl or benzyl substituted on the benzene ring by one or two halogen atoms or alkyl groups having from one to three atoms carbon; X represents a hydrogen or halogen atom; Y represents a monovalent radical having one of the formulas

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(AT)

(B)

(VS)

(D)

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(F)

(E)

or

R

8

and

(G) (H)

Z represents a monovalent radical having one of the formulas (A), (B) or (G) above, where R1 represents a hydrogen atom or a non-tertiary alkoxy group of one to four carbon atoms, dialkylamino or N- alkylbenzylamino where the alkyl groups are non-tertiary alkyl groups of one to four carbon atoms, R2 represents a hydrogen atom or an alkyl group of one to three carbon atoms or non-tertiary alkoxy of one to four carbon atoms, R3 represents a hydrogen atom or an alkyl group of one to three carbon atoms, non-tertiary alkoxy of one to four carbon atoms, a halogen atom or a dialkylamino group where the alkyl group is a non-tertiary alkyl group of one with four carbon atoms; R4 represents one or two hydrogen atoms or alkyl group of one to three carbon atoms, alkoxy of one to three carbon atoms, halogen atoms or nitro groups, R5 represents a hydrogen atom or a non-tertiary alkyl group from one to eight carbon atoms, alkenyl from two to four carbon atoms, benzyl or benzyl substituted on the benzene ring by one or two halogen atoms or alkyl groups having from one to three carbon atoms, R6 represents a d atom hydrogen or an alkyl group of one to three carbon atoms or phenyl, and R7 and R8 represent hydrogen atoms or alkyl groups of one to three carbon atoms.

According to the present invention, there are provided new compounds of formula

COOK

Y

in which R, X, Y and Z have the same meanings as in formula I.

According to the preceding method, a 3-N (R) 2-4-X-benzoic acid is condensed with an aldehyde of formula Y-CHO, in the presence of an acidic condensing agent, under dehydration conditions, to obtain a 3-Y-5-X-6-N (R): phthalide of formula

0

in which R, X and Y have the same meanings as in formula I.

Said phthalide of formula II is then condensed with a compound of formula Z-H in the presence of an alkaline or acidic condensing agent to obtain an acid.

2- (a-Y-cc-Z) methyl-4-X-5-N (R) 2-benzoic acid of formula III. The said benzoic acid is then oxidized to obtain a 3-Y-

3-Z-5-X-6-N (R) 2phthalide of formula 1.

The 3-Y-5-X-6-N (R) 2phthalides of formula II in which, io X and Y are as defined above, which are useful as intermediates in the processes of this invention and which are also usable as precursors stained in carbonless paper reproduction systems and in thermal marking systems, are new when Y is neither a group (A) nor a group (B).

The preferred new compounds of this type are those of formula II in which Y has the formula (C), (D), (E), (F) or (G) where R, X, R7 and R8 are as defined above .

The new 2- (aYaZ) methyl-4-X-5-N (R) 2 ben-20 zoic acids of formula III can be used as intermediates in the preparation of compounds of formula I and can also be used as colored precursors in systems reproduction without carbon paper and in thermal marking systems.

Preferred compounds of this type are those of formula II in which Y has the formula (A) and Z has the formula (A), (B) or (G).

Another aspect of this invention relates to new categories of compounds of formula I. Such a category of new 3- (2-R3'-4-Rl'-phenyl) -3- (2-R3-3-R2'- 4-R1 "-phenyl) -5-X-6-N (R) 2-phthalides, which are particularly useful as colorless precursors in the field of reproduction without carbon paper, have the formula

35

FORM IV

in which R represents a non-tertiary alkyl group of one to four carbon atoms, R1 'represents a hydrogen atom or a non-tertiary alkoxy group having from one to four carbon atoms, N-alkylbenzylamino where the alkyl group is a non-tertiary alkyl group of one to four carbon atoms or, when R3 is other than a dialkylamino group, dialkylamino in which the alkyl groups are non-tertiary alkyl groups having from one to four carbon atoms; R1 "represents a dialkylamino group in which the group

628922

alkyl is non-tertiary and has from one to four carbon atoms; R2 'represents a hydrogen atom or an alkyl group of one to three carbon atoms; R3 represents a hydrogen atom or an alkyl group having from one to three carbon atoms, non-tertiary alkoxy from one to four carbon atoms, a halogen atom or a dialkylamino group in which the alkyl groups are non-tertiary and have from one to four carbon atoms; R3 "represents a hydrogen atom or an alkyl group having from one to three carbon atoms, non-tertiary alkoxy having from one to four carbon atoms or a halogen atom; X represents a hydrogen or halogen atom ; and provided that R2 ', R3, R3' and X cannot all be hydrogen atoms at the same time.

Another similar category includes the new 3- (2-R3 "-3-R2" -4-R1'-phenyl) -3- (1-R5-2-R6-5 / 6-R4-3-indolyl) - 5-X-6-N (R) 2-phthalides, which are particularly useful as colorless precursors in the field of reproduction without carbon paper and which have the formula

—R

FORM V

in which R represents a non-tertiary alkyl group of one to four carbon atoms; R1 'represents a hydrogen atom or a non-tertiary alkoxy group of one to four carbon atoms, N-alkylbenzylamino in which the alkyl group is non-tertiary and has from one to four carbon atoms, or when at least one of R2 "and R3 'is other than hydrogen, a dialkylamino group in which the alkyl group is non-tertiary and has from one to four carbon atoms; R2" and R3 "each represent a hydrogen atom or an alkoxy group non-tertiary of one to four carbon atoms or a halogen atom; R4 represents one or two hydrogen radicals, alkyl of one to three carbon atoms, alkoxy of one to three carbon atoms, halogen or nitro; R5 represents one atom hydrogen or a non-tertiary alkyl group of one to eight carbon atoms, alkenyl of two to four carbon atoms, benzyl or benzyl substituted on the benzene ring by one or two halogen or alkyl radicals of one to three carbon atoms; R6 represents a hydrog atom ene or an alkyl group of one to three carbon atoms or phenyl; and X represents a hydrogen or halogen atom.

As used herein, the term "non-tertiary alkyl of one to eight carbon atoms" refers to saturated monovalent aliphatic radicals including branched chain radicals, for example methyl, ethyl, propyl, isopropyl, butyl, amyl , 1-methylbutyl, 3-methylbutyl, hexyl, isohexyl, heptyle, isoheptyl, octyl, isooctyle and

2-ethylhexyl.

When the expressions “alkyl of one to three carbon atoms”, “alkoxy of one to three carbon atoms” and “non-tertiary alkoxy of one to four carbon atoms” are used here, they denote saturated acyclic groups which may be linear or branched, for example methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, s-butoxy and isobutoxy groups.

As used herein, the term "alkenyl of two to four carbon atoms" means a monovalent aliphatic radical having a single double bond, for example, ethe-nyl (or vinyl), 2-propenyl (or allyl), 1 -methylethenyl (or isopropenyl), 2-methyl-2-propenyl, 2-methyl-1-propene-nyl, 2-butenyl and 3-butenyl.

When the term halogen is used here, it includes chlorine, fluorine, bromine and iodine. The preferred halo substituent is chlorine because the other halogens do not have any particular advantages over chlorine and because of the relatively low price and the ease of preparation of the necessary chlorine intermediates. However, the other halogenated substituents mentioned above are also satisfactory.

The expression "N-alkylbenzylamino" as used herein denotes an amino radical substituted by an alkyl substituent and a benzyl substituent where the benzene ring can be unsubstituted or substituted by one or two halogen atoms or alkyl groups from one to three carbon atoms.

As used herein, the term "alkaline condensing agent" includes basic inorganic and organic compounds as will be found in the examples below.

The compounds represented by formula III have been called 2- (a-Y-a-Z) methyl-4-X-5-N (R) 2 benzoic acids. This nomenclature defines compounds of formula III in which the methyl group in position 2 can carry two aromatic rings, two heterocyclic rings or an aromatic ring and a heterocyclic ring. However, in this description, whenever possible, the compounds defined by formula III having two phenyl groups attached to the carbon atom of the methyl group in position 2 have been named using the more conventional designation "benzhydryl" for diphenylmethyl groups.

The methods of this invention provide a new, convenient and economically advantageous synthetic route to obtain a large number of known and new compounds, as end products, which are 3,3-disubstituted phthalides of the type represented by formula I. Many species defined by formula I are well known as colorless precursors in reproductive systems without carbon paper, for example 3,3-bis (4-dimethylaminophenyl) -6-dimethylaminophthalide, even more simply called violet lactone crystallized, the

3- (4-dimethylaminophenyl) -3- (1,2-dimethyl-3-indolyl) -6-dimethylaminophthalide described in the US patent. 3,491,112, 3- [2,4-bis (dimethylamino) -phenyl] -3- (4-dimethylaminophenyl) -6-dimethylaminophthalide described in Belgian Patent No. 808,535, etc.

Methods described below make it possible to prepare 3-substituted phthalides of the type represented by formula II. The 3-substituted phthalides of formula II are intermediates leading to the 2-methylbenzoic acids cc, a-disubstituted of formula III which in turn are useful as intermediates for the production of the final products represented by formula I. In addition, phthalides 3 -substituted kills of formula II and 2-methylbenzoic acids

6

s

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7

628,922

a, a-disubstitutes of formula III have been found to be usable as color precursors in pressure-sensitive carbonless reproduction systems and in thermal marking systems.

The new compounds represented by formulas I, II and III above are essentially colorless in the form described. When the compounds of formulas I, II and III are brought into contact with an acid medium, for example silica gel or one of the types commonly used in pressure-sensitive carbonless reproduction systems, for example silt clay or phenolic resins, they give a colored image having a good to excellent color intensity. The appearance of a color on contact with silica gel, clay loam or a phenolic resin shows that these compounds are entirely suitable for use as colorless precursors, that is to say as color-generating substances. in pressure-sensitive carbonless reproduction systems. For such an application, the compounds can be incorporated into any of the commonly accepted systems known in the art of carbonless reproduction. A typical technique for such an application is as follows: microencapsulation is carried out, by well known procedures, of solutions of the colorless precursors in suitable aromatic solvents. The microcapsules are coated on the back of a transfer sheet using an appropriate binder and then the coated transfer sheet is assembled in a bundle, the coated side of the microcapsules being in contact with a receiving sheet coated with a electron accepting substance, for example clay loam or phenolic resin. The application of pressure to the bundle like that exerted by a stylus, a typewriter or any other form of writing or printing, causes that the capsules deposited on the back break. The solution of the color-generating agent released from the broken microcapsules flows to the receiving sheet and, in contact with the acid medium which this sheet carries, quickly forms a green-bluish to reddish purple colored image of good intensity. color. It is of course obvious that variants of this mode of application can be used. For example, the receiving sheet in a bundle can conversely be coated with the compounds in question and the acid developing agent can be contained in microcapsules applied to the back of the upper sheet of the bundle.

It has also been found that when the compounds of formulas I, II and II are intimately mixed with an acid developer of the type generally used in thermal papers, that is to say in papers which produce a colored image when puts them in contact with a heated stylus or a heated character, for example bisphenol A, heating the mixture produces a colored image of varied shades ranging from yellow to purple depending on the particular compound of the invention used. The ability of the compounds of formulas I, II and III to form a dark color when heated in admixture with an acid developer such as bisphenol A makes them useful in thermal labeling systems on paper, which are prepared original or a copy by contacting the thermal paper with a heated stylus or heated character by any of the methods well known in the art.

In view of the usefulness of the new compounds represented by formulas II, III, IV and V as described above, the following are described pressure-free carbonless reproduction systems and paper thermal marking systems, containing as a color-generating substance one of the 3-Y-5-X-6-N (R) 2-phthalides described by formula II; 2- (a-Y-a-Z) methyl-4-X-5-N (R) 2benzoic acids described by formula III; of

2- (2-R3'-4-Rl'-phenyl) -3- (2-R3-3-R2'-4-R1 "-phenyl) -5-X-6-N (R) 2phthalides described by formula IV; and

3- (2-R3 "-3-R2" -4-R '' - phenyl) -3- (l-R5-2-R6-5 / 6-R4 -3-indolyl) -5-X-6- N (R) 2-phthalides described by the formula V where R, R1, R1 ', R' ", R2, R2 ', R2", R3, R3', R3 ", R4, R5, R6, X, Y and Z have the same meanings as in formulas II, III, IV and V.

The best embodiment considered for the implementation of this invention will now be described to allow those skilled in the art to implement it.

The 3-Y-5-X-6-N (R) 2phthalides of formula II can be obtained by reacting approximately equi-molar amounts of a suitable aromatic or heterocyclic aldehyde with a suitable benzoic acid in the presence of a acid condensing agent. The reaction is conveniently carried out in a dehydrating solvent which also serves as an acidic condensing agent, for example acetic anhydride, a mixture of acetic anhydride and acetic acid, an acid chloride such as phosphorus oxychloride, or in a mineral acid, preferably concentrated hydrochloric acid, at a temperature of 80 to 140 ° C but preferably at the reflux temperature of the solvent. The 3-Y-5-X-6-N (R) 2phthalide thus obtained can generally be isolated by filtration from the reaction medium. Alternatively, a miscible non-solvent, for example a short chain aliphatic alcohol, can be added to the reaction medium before filtration. The isolated product is dried by conventional means.

The various aminobenzoic acids necessary as starting substances corresponding to formula II constitute an old well-known category of compounds which are available commercially or which are easily obtained by conventional methods well known in the art. The following compounds are examples of the aminobenzoic acids which can be used to obtain 3-Y-5-X-6-N (R) 2phthalides of formula II.

3-aminobenzoic acid 3-amino-4-chlorobenzoic acid 3-dimethylaminobenzoic acid 3-methylaminobenzoic acid 3- (N-ethyl-N-methylamino) benzoic acid 3 - (N-ethyl-N-butylamino) benzoic acid 3-ethylamino -4-bromobenzoic acid 3-diethylaminobenzoic acid 3- (N-ethylbenzylamino) benzoic acid 3-dibenzylaminobenzoic acid 3-propylamino-4-fluorobenzoic acid 3-diethylamino-4-iodobenzoic acid 3-ethylaminobenzoic acid 3-dimethylamino acid 3- [N-butyl-N- (4-chlorobenzyl) amino] benzoic acid and 3- [N-methyl-N- (4-methylbenzyl) amino] benzoic acid.

The aromatic and heterocyclic aldehydes necessary as a starting material to obtain the 3-Y-5-X-6-N (R) 2phthalides of formula II constitute an old well-known category of compounds, many of which are commercially available or are easily obtained by conventional syntheses well known in the art. The following list of compounds gives examples of the aromatic and heterocyclic aldehydes leading to the compounds of formula I.

Benzaldehyde,

2-methylbenzaldehyde

2-Chlorobenzaldehyde,

2-Methoxybenzaldehyde,

3-Methoxybenzaldehyde,

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1 "

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4-Methoxybenzaldehyde,

2-Bromobenzaldehyde,

2-Ethoxybenzaldehyde,

3-Ethoxybenzaldehyde,.

4-Ethoxybenzaldehyde,

2-Fluorobenzaldehyde,

4-IsopropylbenzaIdehyde,

2.3-Dimethoxybenzaldehyde,

2.4-Dimethoxybenzaldehyde,

2.5-DimethoxybenzaIdehyde,

3.4-Dimethoxybenzaldehyde,

3.5-DimethoxybenzaIdehyde, 2-Butoxy-4-diethylaminobenzaldehyde, 2-Methyl-4,5-dimethoxybenzaldehyde,

2-Chloro-4-dimethylaminobenzaldehyde,

3-Ethoxy-4-methoxybenzaldehyde, 2,3,4-Trimethoxybenzaldehyde, 2-Methoxy-4-dimethylaminobenzaldehyde, 2-Methoxy-4-diethyaminobenzaldehyde,

4-Dimethylaminobenzaldehyde,

4-Benzylaminobenzaldehyde,

5-Methoxyindole-3-carboxaldehyde, 4- (N-Methylbenzylamino) benzaldehyde, Indole-3-carboxaldehyde, N-Methylpyrrole-2-carboxaldehyde,

2-Pyridinecarboxaldehyde,

3-Pyridinecarboxaldehyde,

4-PyridinecarboxaIdehyde,

PyrroIe2-carboxaldehyde,

2-Thionphenecarboxaldehyde, N-Ethyl-3-carbazolecarboxaldehyde,

Piperonal,

2-Methyl-1-n-octylindole-3-carboxaldehyde,

1-n-ButyI-2-phenylindole-3-carboxaldehyde, 9-Formyljulolidine,

4- (N-Ethylbenzylamino) benzaldehyde,

2-Methyl-4- (N-methylbenzylamino) benzaldehyde, 1,2-Dimethylindole-3-carboxaldehyde,

1-Ethyl-2-phenylindole-3-carboxaldehyde, 4-Diethylaminobenzaldehyde,

2-Methyl-4-diethylaminobenzaldehyde and 1-Ethyl-2-methylindole-3-carboxaldehyde.

The 2- (aYaZ) methyl-4-X-5-N (R) 2 benzoic acids of formula III are prepared by reacting approximately equimolar amounts of a 3-Y-5-X-6-N (R ) Appropriate 2 phthalide of formula II with an appropriate aromatic or heterocyclic compound of formula ZH in which Z is defined in the same manner as for formulas I and III. Under a series of reaction conditions, the 3-substituted phthalide and the aromatic or heterocyclic compound are reacted in the presence of an alkaline condensing agent, in dilute aqueous solution at a temperature of 90-160 ° C. The 2- (aYaZ) -methyl-4-X-5-N (R) 2 benzoic acid of formula III thus obtained can optionally be isolated by carefully neutralizing the alkaline or basic reaction solution with dilute aqueous acid, by collecting the product which separates by filtration, and drying the solid by conventional means. Alternatively, the reaction or basic solution containing 2- (aYaZ) methyl-4-X-5-N 'R' benzoic acid of formula III in the form of a salt can be used directly in the next step of the process overall without isolation of the product in the free acid form.

The following basic organic and inorganic compounds are examples of the "alkaline condensing agents" used in the second step of the processes of this invention to obtain 2- (aYaZ) methyl-5-N (R) 2benzoic acids of formula III : sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, lithium carbonate, ammonium hydroxide, tetramethylammonium hydroxide, tetraethylammonium hydroxide, tetrabutylammonium ammonium hydroxide, quinuclidine, l, 4 -diazabicyclo [2,2,2] octane, triethanol-amine and triethylamine.

In a second series of reaction conditions, it is possible to carry out the reaction of an equimolar amount of an appropriate 3-Y-5-X-6-N (R) 2 phthalide of formula II and of an aromatic compound or heterocyclic suitable of formula ZH in the presence of an acidic condensing agent, for example an organic or mineral acid at a temperature of 70 to 120 ° C. The 2- (aYaZ) methyl-4-X-5-N (R) 2benzoic acid of formula III thus obtained is then isolated by adding the reaction solution to water, cooling the resulting mixture and collecting by filtration the product which separates then by drying it by conventional methods.

The following compounds are examples of the organic and mineral acids usable as "acid condensing agents" in the second step of the methods of this invention to obtain 2- (aYaZ) methyl-5-benzoic acids of formula III : formic acid, acetic acid, propionic acid, glycolic acid, oxalic acid, citric acid, methanesulfonic acid, toluenesulfonic acid, phosphoric acid, polyphosphoric acid, hydrofluoric acid, hydrochloric acid, hydrobromic acid, phosphorus oxychloride, phosphorus trimbromide, trichloride phosphorus and phosphorus pentachloride.

In a third series of reaction conditions, the 2- (aYaZ) methyl-4-X-5-N (R) 2benzoic acids of formula III are obtained by interaction of an approximately equimolar amount of a 3-Y -5-X-6-N (R) 2phthalide suitable for formula II and an aromatic or heterocyclic compound suitable for formula ZH. The reaction is conveniently carried out in the presence of an acidic condensing agent of the type generally defined as a Friedel-Craft catalyst, in the presence of an inert organic solvent, for example monochlorobenzene, ethylene dichloride, perchlorethylene, carbon tetrachloride, nitroben-40 zene, etc., or possibly in the presence of an excess of the reagent ZH as solvent, at a temperature of -10 to + 110 ° C. When an inert organic solvent is used, the 2- (aYaZ) methyl-4-X-5-N (R) 2 benzoic acid thus formed is isolated by extracting the acidic condensing agent with water from water. of the organic phase, then extracting 2- (aY-cc-Z) methyl-4-X-5-N (R) 2ben-zoic acid in the organic phase with dilute aqueous hydrochloric acid. The product is obtained by neutralizing the aqueous acid solution with a dilute aqueous solution of a base, for example so sodium hydroxide, by collecting the separated product by filtration and drying it by conventional means. Or, when an excess of the reactant ZH is used as solvent, the 2- (aYaZ) methyl-4-X-5-N (R) 2benzoic acid formed is isolated by diluting the reaction mixture with water, al-55 calinizing by adding a dilute aqueous solution of a base, for example sodium hydroxide, and by distilling off by excess steam the mixture of ZH. Once the removal of excess Z-H is complete, the mixture is slightly cooled and the pH is adjusted to about 4.9 by addition of an acid, for example acetic acid. The product which separates is collected by filtration; it is washed with water and dried by conventional means.

The following compounds are examples of the Friedel-Craft catalysts which are used as acid condensers in the second step of the processes of this invention for the production of 2- (aYaZ) methyl-4-X- acids 5-N (R) 2benzoic acid of formula III: aluminum chloride, aluminum bromide, zinc chloride, zinc bromide, tri-

boron fluoride, boron trichloride, boron tribromide, titanium tetrachloride, stannic chloride, stannic bromide, antimony trichloride, ferric fluoride, ferric chloride, ferric bromide, ferric iodide, phosphorus tribromide, phosphorus trichloride and pentachloride phosphorus.

When ferric halides are used as acidic condensing agents in the reaction of 3-Y-5-X-6-N (R) 2phtaIides with an excess of the reactant ZH, the final products are obtained, i.e. 3-Y-3-Z-5-X-6-N (R) 2phta-lides in significant quality as well as the corresponding intermediate precursors, 2- (aYaZ) methyl-4-X-5-N (R ) 2benzoic. It seems that a significant amount of 2- (cc-Y-aZ) methyl-4-X-5-N (R) 2benzoic acid, resulting from the condensation of 3-Y-5-X-6-N (R) 2phthalide with the reagent ZH, or oxidized in situ to 3-Y-3-Z-5-X-6-N (R) 2phta-lide in the presence of ferric halides.

The aromatic and heterocyclic compounds represented by the formula ZH, which are necessary for the reaction with the 3-Y-5-X-6-N (R) 2phthalides of formula II to obtain the acids 2- (aYaZ) -methyl-4 -X-5-N (R) 2benzoic acid of formula III, constitute old categories of compounds easily obtained by conventional methods known in the art. The following list of compounds gives examples of aromatic and heterocyclic compounds belonging to the field of formula ZH and which can be used in the implementation of the stage of the methods of this invention making it possible to obtain the aforementioned benzoic acids. of formula III:

N, N, N ', N' -Tetramethyl-m-phenylenediamine, N, N-Dibutylaniline,

N, N-Diethyl-3-ethoxyaniline,

N, N-Diethyl-m-anisidine,

N, N-Dimethylaniline,

N -Benzy 1-N-ethylaniline,

N, N-Diethyl-m-toluidine N, N-Diethylaniline,

N-Ethyl-N-methylaniline,

N-Benzyl-N-methylaniline,

N-Benzyl-N-propylaniline,

N, N-Dimethyl-3-bromoaniline, N, N, N ', N'-Tetraisopropyl-m-phenylenediamine, N, N-Dibutyl-3-fluoroaniline, N, N-Diethyl-2-methoxy-3-chloroaniline, N-Benzyl-N-methyl-3-ethylaniline, N, N, N ', N'-Tetra-s-butyl-m-phenylenediamine, N-Benzyl-N-butyl-3-iodoaniline, N, N-Diisopropyl- 3-chloroaniline, N-Benzyl-Ns-butylaniline,

N, N-Di-s-butylaniline,

N, N-Diethyl-3-isopropylaniline,

N, N-Diisobutylaniline,

N, N-Diethyl-2-propoxyaniline,

N, N-Dipropylaniline,

N-Isopropyl-N-methylaniline,

N-Methyl-N-propylaniline,

N, N, N ', N' -T etrabutyl-m-phenylenediamine, N, N-Dipropyl-o-anisidine,

N-Isobutyl-N-ethylaniline,

N, N, N ', N' -Tetraethyl-m-phenylenediamine, N-Propyl-N-ethylaniline,

N, N-Diethyl-2-ethoxyaniline, N-BenzyI-N-s-butyI-2-propoxyaniline, N, N-Dimethyl-m-toludine,

Indole,

1-Methylindole,

2-Methylindole,

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1,2-Dimethylindole,

1-Ethyl-2-methylindole,

2-Phenylindole,

1-Propyl-2-methylindole,

1-Benzyl-2-methylindole,

1 -Butyl-2-methylindole,

1-Octyl-3-methylindole,

2-Ethyl-5-methylindole,

1 -Benzyl-5-fluoroindole,

l-Methyl-6-nitroindole,

5-Methoxy-1-butylindole,

1 -Allyl-2-methylindole,

1,2-Dimethyl-6-nitroindole,

1- (4-Chlorobenzyl) -2-methyl-5-nitroindole,

2-Ethylindole,

2-Ethyl-1-methylindole,

1-Isopropylindole,

2-Isopropylindole,

1 -Methyl-5-bromo-6-nitroindole,

2,5,6-Trimethylindole,

1 -Isobutyl-2-methylindole,

6-Bromo-2-methylindole,

1-Hexylindole,

1- (2,5-Dimethylbenzyl) -2-methylindole,

2-Propylindole,

6-Chloro-2-phenylindole,

l- (2-Ethylhexyl) -2-methylindole,

1- (2,6-DichIorobenzyl) -2-methyl! Indole, 1 -Vinyl-2-methylindole,

2-Ethyl-6-methylindole,

6-Fluoro-1 -benzylindole, l- (4-Bromobenzyl) -2-isopropylindole, l- (3-Chlorobenzyl) -2-ethylindole,

5-Chloro-1 -benzylindole,

l- (2-Fluorobenzyl) -2-methylindole,

5-Iodo-1 - (1-methylhexyl) indole,

5,6-Dimethoxyindole,

l- (2-Methylbenzyl) -2-methylindole, 5,6-Dichloro-2-phenylindole,

1-Isoamylindole,

1 - [3- (2-Methyl) -1 -propenyl] -2-methylindole,

Pyrrole,

N-Methylpyrrole,

N-Ethylpyrrole,

N-Propylpyrrole and N-Isopropylpyrrole.

The 3-Y-3-Z-5-X-6-N (R) 2phthalides of formula I can be obtained by oxidizing 2- (aYaZ) methyl-4-X-5-N (R) 2benzoic acids of formula III. The oxidation can be carried out in conventional manner in aqueous alkaline solutions, for example potassium hydroxide, at a temperature of 20 to 160 ° C, but preferably from 80 to 160 ° C. The oxidizing agent can be molecular oxygen in the form of gaseous oxygen or air. Alternatively, a chemical oxidizing agent, for example potassium permanganate or hydrogen peroxide, can be used. Depending on the temperature chosen, the oxidation is carried out at atmospheric pressure or at a higher pressure. The filter is separated

3-Y-3-Z-5-X-6-N (R) 2phthalide thus obtained and it is dried by conventional means.

Alternatively, it has been found that 3-Y-3-Z-5-XN (R) 2phthalides of formula I can be conveniently obtained with satisfactory yields without isolation and separate oxidation of 2- (aYaZ) methyl acids -4-X-5-N (R) 2benzoic acid of formula III, by carrying out the reaction of the appropriate 3-Y-5-X-6-N (R) 2phta-lide with an excess of reagent ZH, in the presence of a ferric halide as an acidic condensing agent and

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using the reaction conditions described above. The desired 3-Y-3-Z-5-X-6-N (R) 2phthalide, obtained by this “telescoped” procedure, is isolated by immersing the reaction medium in a dilute aqueous solution of a strong base, for example sodium hydroxide, by distilling off the excess ZH by distillation at the water value, cooling to approximately 70 ° C., extracting the residue with an organic solvent which is insoluble in water, for example toluene , and filtering the mixture to remove all insoluble matter.

The organic layer containing 3-Y-3-Z-5-X-6-N (R) 2 phthalide is separated from the aqueous alkaline phase which contains 2- (aYaZ) methyl-4-X-5- acid. N (R) 2 non-oxidized benzoic acid, generally in small quantities. The desired phthalide is then isolated by concentrating the organic layer by evaporation or distillation, by collecting the solid by filtration and then drying it by conventional means.

The molecular structures of the compounds of this invention have been assigned on the basis of the mode of synthesis and the study of their infrared spectrum, their magnetic resonance spectrum, their mass spectrum and their elemental analysis.

The following examples better illustrate the invention without however limiting it. All melting points are given uncorrected.

Example 1

A. A stirred mixture of 306.0 g of acetic anhydride, 200.0 ml of glacial acetic acid, 298.0 g of p-dimethylaminoben-zaldehyde and 386.0 is heated to reflux for approximately 4 hours. g of m-dimethylaminobenzoic acid. The resulting mixture is cooled to 55 ° C, diluted with 700 ml of methanol and heated to reflux for about 30 minutes. The mixture is then cooled to approximately 15 ° C. and the solid which separates is collected by filtration and washed with 700.0 ml of methanol which has not yet been used, cooled to

10-15 ° C. The wet methanol solid is again diluted in 400 ml of unused methanol at 10-15 ° C for about 20 minutes, separated by filtration and washed with 150 ml of cooled methanol. The solid is dried at 70 ° C. under vacuum, which gives 453.2 g of 3- (4-dimethylamino-phenyl) -6-dimethylaminophthalide (formula II: R = CH3; X = H; Y = 4- (CH3 ) 2N-CeH4) which, after recrystallization from toluene, forms an ivory-colored solid melting at 184.5-185.5 ° C.

The infrared spectral analysis presents a maximum at 1745 cm-1 (C = 0; strong) and the nuclear magnetic resonance spectrum is compatible with the assigned structure.

A toluene solution of this product, deposited in the form of spots on an acid resin or an acid clay,

gives an image of green color.

B. (1) A reflux mixture of 6.0 (3- (4-dimethylamino-phenyl) -6-dimethylaminophthalide, prepared as described in part A above, of 100 ml is heated to reflux for approximately 18 hours. water, 3.5 g of N, N, N ', N'-tetramethyl-m-phenylenediamine and 1.8 g of potassium hydroxide flakes, then allowed to cool to room temperature . The resulting solution is slightly acidified by the addition of 10% aqueous hydrochloric acid, which causes a cream-colored solid to precipitate. The solid is collected by filtration, washed with water and dried in air at 40 ° C, and the acid 2- [2-, 4,4'-tris (dimethylamino) is obtained benzyhydryl] -5-dimethylami-nobenzoic acid (formula III: R = CH3; X = H;

Y = 4- (CH3) 2NC &H4; Z = 2.4 - [(CH3) 2N] 2C6H3) in the form of a slightly sticky cream-colored solid melting in the range from 119 to 121 ° C.

The nuclear magnetic resonance spectrum is in agreement with the assigned structure and the infrared spectral analysis presents a maximum at 1700 cm-1 (C = 0; wide).

B. (2) The repetition of the preceding procedure, but by replacing potassium hydroxide with 5.0 g of ammonium hydroxide in one case and 5.52 g of potassium carbonate in the other, also provides 2- [2,4,4'-tris (dimethyl-amino) benzhydryl] -5-dimethylaminobenzoic acid.

C. A solution of 29.78 g of the acid is prepared

2- [2,4,4 '- tris (dimethylamino) benzhydryl] -5-dimethylamino-benzoic prepared as described in part B above, 450.0 g of water and 16.2 g of flakes of potassium hydroxide and the pH is adjusted to 10.0 by progressive addition of sodium bicarbonate. The solution is then heated to about 75 ° C under an oxygen atmosphere at 4.2-4.55 kg / cm2 for about 6 hours in a stirred stainless steel autoclave. The separating solid is collected by filtration at room temperature, washed with water until it is free of base when tested with a bright yellow test paper, and the dryer. The dried solid is diluted with hexane at room temperature, filtered and dried, which gives 23.6 g of 3- (2,4-bis [dimethylamino] phenyl) -3- (4-dimethylaminophenyl ) -6-dimethylaminophtaIide (formula I: R = CH3; X = H; Y = 4- (CH3) 2NCeH4; 25 Z = 2.4 - [(CH3) 2N] 2CôH3) a pale blue solid melting at 171- 172 ° C.

The nuclear magnetic resonance spectrum is in agreement with the assigned structure and a significant infrared maximum appears at 1755 cnr1 (C = O; strong). A solution in the benzene of the product, deposited on silica gel, an acid clay or a phenolic resin, gives an image of a forced grape color.

Example 2

35 A. A stirred mixture of 35.0 ml of glacial acetic acid and 5.9 g of 3- (4-dimethylaminophenyl) -6-dimethylaminophthaide prepared as in Example 1 is heated at reflux for approximately 45 minutes. part A above, and 3.3 g of 1-ethyl-2-methyl-indole. After cooling slightly below the reflux temperature, 20.0 ml of methanol are added and the cooling is continued to room temperature. The resulting solution is poured into 500.0 ml of stirred ice water and, after approximately 20 minutes, the solid which has separated is collected by filtration. The solid is diluted at room temperature in acetone and the suspension is filtered. The solid collected is dried and 4.1 g of 2- [a- (4-dimethylaminophenyl) -a- (1 -ethyl-2-methyl-3-indolyl) methyl-5-dimethylaminobenzoic acid (formula III: R = CH3; X = H; Y = 4- (CH3) 2NCeH4; Z = I-C2H5-2-CH3-50 3-indolyl), a light brown yellow solid melting at 224-228 ° C.

The infrared spectral analysis presents a significant maximum at 1685 cm- '(C = 0; strong). The nuclear magnetic resonance spectrum is compatible with the attri-55 fogging structure. Mass spectrum analysis shows peaks m / e at 455 (M +) and 440 (M + -CH3).

B. A mixture of 4.0 g of 2- [a- (4-dimethylaminophenyl) -a- (1-ethyl-2-methyl) acid is stirred for approximately 17 hours at 60-70 ° C under an oxygen atmosphere. -3-60 indolyl) methyl-5-dimethylaminobenzoic acid prepared in part A above, 1.5 g of potassium hydroxide flakes and 200.0 ml of water. The resulting mixture is cooled to room temperature and then the suspended solid is collected by filtration, washed with water until it is freed from the base in bright yellow test paper, and dried to give 1.5 g of 3- (4-dimethylamin-phenyl) -3- (1-ethyl-2-methyl-3-indolyl) -6-dimethylamino-phthalide (formula I: R = CH3 ; X = H; Y = 4- (CH3) 2NCsH4;

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Z = 1 -C2H5-2-CH3-3-indolyl), in the form of a light grape-colored solid melting between 104 and 120 ° C.

Infrared spectral analysis presents maxima at 1760 (C = 0; very strong) and 1685 (C = 0; weak) cm- '.

A toluene solution of this product, deposited on silica gel, an acid clay or a phenolic resin, gives a dark grape color.

Example 3

A. A stirred mixture of 100 ml of water, 1.8 g of potassium hydroxide flakes, 6.0 g of 3- (4-dimethylamino-phenyl) -6 is heated to reflux for approximately 75 minutes. -dimethylaminophthalide, prepared in Example 1 part A above, and 2.90 g of 1,2-dimethylindole and then allowed to stand at room temperature for about 64 hours. The resulting solution is divided into two equal portions.

One of the portions is cooled by adding ice, and it is slowly acidified by adding acetic acid and dilute hydrochloric acid. A yellowish brown resinous solid slowly precipitates out of the solution after sufficient sodium acetate has been added to saturate the solution. The solid is collected by filtration, washed and air dried at room temperature. After recrystallization from denatured ethanol, 2- [a- (4-dimethyl laminophenyl) -a- (1,2-dimethylin-dole)] methyl-5-dimethylaminobenzoic acid is obtained (formula III: R = CHs; X = H; Y = 4- (CH3) 2NC6H4; Z =

1,2- (CH3) 2-3-indolyl), cream-colored solid melting between 192 and 213 ° C.

The nuclear magnetic resonance spectrum is in agreement with the assigned structure and the infrared spectral analysis presents a maximum at 1680 cm- '(C = 0; strong).

B. 75 ml of toluene and 0.7 g of potassium permanganate are added to the second portion of the alkaline aqueous solution in part A. The solution gradually changes from green to brown and a small amount of dilute aqueous sodium hydroxide is added to obtain the alkaline mixture. The toluene layer is separated and evaporated, which leaves a gummy residue which is triturated with denatured ethanol to obtain 3- (4-dimethylamino-phenyl) -3- (1,2-dimethyl- 3-indolyl) -6-dimethylaminophthalide (formula I: R = CH3; X = H; Y = 4- (CH3) 2NC6H4; Z = 1,2, (CH3) 2-3-indoIyl), solid melting at 184- 185 ° C.

The infrared spectrum has a maximum at 1745 cm- '(C = 0; strong) and the spectral analysis by nuclear magnetic resonance is in agreement with the assigned structure.

A toluene solution of the product deposited on silica gel, an acid clay or a phenolic resin gives a grape color image.

Example 4

A. A mixture of 600 ml of water, 10.8 g of hydroxide flakes is heated by stirring in a stainless steel autoclave at 120 ° C for about 7 hours, at 160 ° C for about 6 hours. potassium, 36.0 g of 3- (4-dimethyl-aminophenyl) -6-dimethylaminophthalide prepared as in Example 1, part A above, and 20.0 g of N, N-di-ethyl- m-toluidine. The resulting mixture is cooled to room temperature and filtered to remove insolubles. The aqueous solution obtained from the potassium salt of 2- [2-methyl-4,4'-bis (dimethyl-amino) benzhydryl] -5-dimethylaminobenzoic acid is used directly in the oxidation of the following part of this example. (formula III: R = CH3; X = H; Y = 4- (CH3) 2NC6H4; Z = 4- (CH3) 2N-2-CH3C6H3).

B. The pH of the potassium salt solution of benzoic acid obtained in part A above is adjusted to 9.5 by addition of sodium bicarbonate, the solution is heated to 80 ° C. for about 7 hours under atmosphere oxygen, at 4.2-4.55 kg / cm2. The resulting mixture is cooled to room temperature; the solid which separates is collected by filtration and dried at room temperature. The solid is dissolved in toluene, treated with bleaching charcoal and filtered. The toluene solution is extracted with 300 ml of 3N hydrochloric acid and separated. The pH of the aqueous acid layer is adjusted to 5 by addition of sodium acetate. The solid which separates is collected by filtration, washed with water and dried under vacuum at 60 ° C., and 16.5 g of 3- (4-dimethylaminophenyl) -3- are obtained (4 -diethylamino-2-methyl-phenyl) -6-dimethylaminophthalide (formula I: R = CH3; X = H; Y = 4- (CH3) 2-N-CÔH4; Z = 4- (C2H5) 2N-2-CH3 -C6H3), solid melting at 183-184 ° C.

The nuclear magnetic resonance spectrum is in agreement with the assigned structure. Mass spectrum analysis indicates a peak m / e at 457 (M +). Infrared spectral analysis has a maximum at 1763 cm-1 (C = 0; strong).

A solution in toluene of the product deposited on silica gel, an acid clay or a phenolic resin gives a grape color image.

Example 5

A. To a stirred mixture of 75.0 ml of monochlorobenzene, 7.4 g of 3- (4-dimethylaminophenyl) -6-dimethylamino-phthalide and 2.2 g of N-methylpyrrole, kept at 0-5 ° C using an external ice bath, 6.65 g of anhydrous aluminum chloride are slowly added. After approximately 3 hours of stirring, 100 ml of water and 100 ml of ethylene dichloride are added slowly, continuing to cool to 0-5 ° C. The layers are separated and the organic layer is extracted with 150 ml of fresh water. Then the organic layer is extracted with 100 ml of 3N hydrochloric acid, separated and the pH of this aqueous acid layer is adjusted to 4.5 with a 5% aqueous solution of sodium hydroxide. The green solid which has formed is collected by filtration. After resuspension in a mixture of acetone and methanol, the solid is filtered and dried, which gives 5.2 g of 2- [a- (4-dimethylaminophenyl) -a- (1 -methyl-2-pyrrolyl)] - methyl-5-dimethylaminobenzoic acid (formula III: R = CH3; X = H; Y = 4- (CH3) 2-NC6H4; Z = 1-CH2-2-pyrrolyl).

A significant infrared maximum appears at 1695 cm- '(C = 0; weak).

B. A mixture of 200 ml of water, 4.8 g of the product from part A above and 1.5 g of potassium hydroxide flakes.

The solid is collected by filtration, washed with water until it is free of base with bright yellow test paper and dried, which gives 2.0 g of 3- (4-dimethylamino -phenyl) -3- (1-methyl-2-pyrrolyl) -6-dimethylaminophthalide (formula I: R = CH3; X = H; Y = (CH3) 2NC6H4; Z = I-CH3-

2-pyrrolyl), gray solid which melts between 168 and 184 ° C.

The infrared spectrum has a maximum at 1765 cm- '(C = 0; strong). A toluene solution of the product deposited on silica gel, an acid clay or a phenolic resin, gives an image of purple color.

Example 6

A. By following a procedure similar to that described in example 4, part A above, 36.0 g of

3- (4-dimethylaminophenyl) -6-dimethylaminophthalide prepared as described in Example 1, part A above, and 23.0 g of 3-ethoxy-N, N-diethylaniline, to obtain a solution of the potassium salt 2- [4 '-diethyl-amino-2'-ethoxy- (4-dimethylamino) benzhydryl] -5-dimethyl- acid

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aminobenzoic acid (formula III: R = CH3; X = H; Y = 4- (CH3) 2NC6H4; Z = 4- (C2H5) 2N-2-C2HsO-C6H3),

which is used without separation in the next step.

B. Proceeding in a similar manner to that described in Example 1, part C above, the potassium salt solution of 2- [4'-diethylamino-2'-ethoxy- ( 4-dimethylamino) -benzhydryl] -5-dimethyl-amino-benzoic from part A, to obtain 6.8 g of 3- (4-diethyl-amino-2-ethoxyphenyl) -3- (4-dimethylaminophenyl) -6 -dimethylaminophthalide (formula I: R = CH3; X = H; Y = 4- (CH3J2NCÔH4; Z = 4- (C2HS) 2N-2-C2H5-0-C6H3), solid melting over the interval from 93 to 99 ° vs.

The infrared spectral analysis presents a maximum at 1755 cm- '(C = 0; broad, strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure. Mass spectroscopy analysis shows a peak m / e at 487 (M +).

A toluene solution of the product deposited on silica gel, an acid clay or a phenolic resin gives a dark blue image.

Example 7

A. By proceeding in a similar manner to that described in example 4, part A above, 36.0 g of

3- (4-dimethylaminophenyl) -6-dimethylaminophthalide prepared as in Example 1, part A above, and 15.0 g of N, N-dimethylaniline, to obtain a solution of the potassium salt of acid 2 - [4,4'-bis (dimethylamino) -benzhy-dryl] -5-dimethylaminobenzoic acid (formula III: R = CH3; X = H; Y = Z = 4- (CH3) 2NCeH4), which is used without separation in the next step.

B. Using a procedure similar to that described in example 1, part C above, the potassium salt solution of 2- [4,4'-bis (dimethylamino) benz-hydryl acid is oxidized. ] -5-dimethylaminobenzoic acid from part A, to obtain 3,3-bis (4-dimethylaminophenyl) -6-dimethylami-nophthalide (formula I: R = CH3; X = H; Y = Z =

4- (CH3) 2NCfiH4), yellow-brown solid.

A significant infrared maximum appears at 1750 cm-1 (C = 0; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

A toluene solution of the product deposited on silica gel, an acid clay or a phenolic resin gives a blue color image.

Example 8

A. Following a procedure to that described in Example 1, part A above, 11.6 g of 3-dimethylaminobenzoic acid and 10.6 g of 4-diethylaminoben-zaldehyde are reacted and obtains 15.3 g of 3- (4-diethylamino-phenyl) -6-dimethylaminophtaIide (formula II: R = CH3; X = H; Y = (C2H5) 2NCôH4), light brown solid melting between 127 and 128.5 ° vs.

A significant infrared maximum appears at 1745 cm-1 (C = 0; strong). The nuclear magnetic resonance analysis is in agreement with the assigned structure.

A toluene solution deposited on an acid clay gives an image of greenish blue color.

B. By proceeding in a similar manner to that described in example 1, part B above, 34.4 g of 3- (4-diethylaminophenyl) -6-dimethylaminophthalide prepared as described in part A are reacted. above, and 16.9 g of 1-ethyl-2-methylindole and the potassium salt of 2- [a- (4-diethylaminophenyl) -a- (1 -ethyl-2-) acid is obtained methyl-3-indo! yl] methyl-5-dimethylaminobenzoic acid (formula III: R = CH3: X = H; Y = (C2H5) 2NCÔH4; Z = I-C2H5-2-CH3-3-indolyl), it is not isolated but used directly in the next step.

C. Using a procedure similar to that described in example 1, part C above, to oxidize the potassium salt of 2- [a- (4-diethylamino-phenyl) -a- (1 -ethyl-2-methyl-3-indolyl)] - methyl-5-dimethylamino-benzoic, 6.0 g of 3- (4-diethylaminophenyl) -3- (1-ethyl-2-methyl-3-indolyl) are obtained ) -6-dimethylaminophthalide (formula I: R = CH3; X = H; Y = 4- (CH3) 2NCeH4; Z = 1-C2H5-2-CH3-3-indolyl, light purple solid melting at 167-169 ° C .

The infrared spectrum has a maximum which appears at 1752 cnr1 (C = 0; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

A toluene solution of the product deposited on silica gel, an acid clay or a phenolic resin gives a purple color image.

Example 9

A. By following a procedure similar to that described in example 1, part B above, 32.4 g of 3- (diethylamino) phenyl-6-dimethylaminophthalide prepared as described in example 8 are reacted, part A above, and 16.7 g of N, N, N ', N'-tetramethyl-m-phenylenediamine to obtain a solution of the potassium salt of the acid

2- [2,4-bis (dimethylamino) -4'-diethylaminobenzhy-dryl] -5-dimethylaminobenzoic acid (formula III: R = CH3; X = H; Y = 4- (C2Hs) 2NC6H4; Z = 2,4- (CH3) 2N2C6H3, which is used without isolation in the next step.

B. Using a procedure similar to that described in example 1, part C above, the potassium salt of 2- [2,4-bis (dimethylamino) -4'-diethylamino- acid is oxidized. benzhydryl] -5-dimethylaminobenzoic acid to obtain 11.4 g of 3- [2,4-bis (dimethylamino) phenyl] -3- (4-diethylamino-phenyl) -6-dimethylaminophthalide {formula I: R = CH3; X = H; Y = 4- (C2H5) 2NC6H4; Z = 2.4 - [(CH3) 2N] 2-CeH3, in the form of a yellow-brown solid melting at 123-125 ° C.

A significant infrared maximum appears at 1758 cm- '(C = 0; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

A toluene solution of the product deposited on silica gel, an acid clay or a phenolic resin gives an image of blackish purple color.

Example 10

A. Using a procedure similar to that described in Example 1, part A above, and reacting 7.2 g of 4- (N-ethylenzenzamino) benzaldehyde and 5.2 g of acid

3-dimethylaminobenzoic acid, 7.5 g of 3- [4- (N-ethylbenzylamino) -phenyl] -6-dimethylaminophta-lide are obtained (formula II: R = CHs; X = H; Y = (C6H5CH2) (C2H5) N-CôH4, in the form of a viscous oil.

Infrared spectral analysis presents a maximum at 1760 cm- '(C = 0; strong). The nuclear magnetic resonance spectrum is compatible with the assigned structure.

A toluene solution of the product deposited on silica gel gives an image of green color.

B. Using a procedure similar to that described in example 2, part A above, 4.0 g of 3- [4- (N-ethylbenzylamino) -phenyl] -6-dimethylaminophta-lide are reacted. and 1.6 g of 1-ethyl-2-methylindole and the acid is obtained

2- (a- [4- (N-ethylbenzylamino) -phenyl] -a- (l-ethyl-2-methyl-

3-indolyl)] methyl-5-dimethylaminobenzoic acid (formula III: R = CH3; X = H; Y = (C6HsCH2) (C2HS) 2NC6H4; Z = 1-C2H5-2-CH3-3-indolyl), we do not isolate but we use in part D below.

C. Similar results are obtained when the acetic acid used as reaction medium is replaced by monochlorobenzene and aluminum chloride or trifluoroacetic acid.

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D. By proceeding in a similar manner to that described in example 2, part B above, the acid is oxidized.

2- {a- [4- (N-ethylbenzylamino) phenyl) -a- (1 -ethyl-2-methyl-3-indolyl) | methyl-5-dimethylbenzoic acid from part B above, and we obtain 2.0 g of 3- [4- (N-ethylbenzylamino) phenyl] -

3- (1 -ethyl-2-methyl-3-indolyl) -6-dimethylaminophthalide (formula I: R = CH3; X = H; Y = (C6H5CH2) (C2H5) NC6H4; Z = 1-C2H5-2-CH3 -3-indolyl), in the form of a pink solid melting over the interval from 66 to 95 ° C with decomposition.

A significant infrared maximum appears at 1760 cm- '(C

- 0; strong). A toluene solution of the product deposited on an acid resin gives a dark blue image.

Example 11

A. By proceeding in a similar manner to that of Example 1, part A above, 18.3 g of

4-dimethylamino-2-chlorobenzaldehyde and 16.5 g of 3-dimethylaminobenzoic acid and 20.5 g of

3- (4-dimethylamino-2-chlorophenyl) -6-dimethylaminophta-lide (formula II: R = CH3; X = H; Y = 2-Cl-4- (CH3) 2NC6H3), red solid melting at 159 -160.5 ° C.

A toluene solution of the product deposited on an acid clay gives a pale green image.

B. Following the procedure described in example 1, part B above, but by substituting triethylamine for potassium hydroxide as condensing agent, the 3- (4-dimethylamino-2-chlorophenyl) is reacted. ) -6-dimé-thylaminophtalide from part A above, with the

5-nitro-2- (4-chlorobenzyl) -2-methylindole to obtain 2- [a- [5-nitro-1 - (4-chlorobenzyl) -2-methyl-3-indolyl] -a- ( 2-chloro-4-dimethylaminophenyl)] - methyl-5-dimethylaminobenzoic acid (formula III: R = CH3; X = H; Y

- 2-Cl-4- (CH3) 2NC6H3; Z = 5-NO2-1- (4-ClC6H4CH2) -2-CH3-3-indolyl).

C. Using a procedure similar to that described in example 1, part C above, the acid is oxidized

1 - | a- [5-nitro-1 - (4-chlorobenzyl) -2-methyl-3-indolyl] -a- (2-chloro-4-dimethylaminophenyl) methyl-5-dimethyl-aminobenzoic acid from part B for get 3- [5-nitro-

1- (4-chlorobenzyl) -2-methyl-3-indolyl] -3- (2-chloro-

4-dimethylaminophenyl) -6-dimethylaminophthalide (formula I: R = CH3; X = H; Y = 2-Cl-4- (CH3) 2NC6H3; Z = 5-N02-1- (4-ClH4CH2) -2-CH3 -3-indolyl).

Example 12

A. Using a procedure similar to that described in Example 1, part A above, and reacting 8.2 g of p-anisaldehyde and 11.6 g of 3-dimethylaminobenzoic acid, using anhydride alone as reaction medium, 9.4 g of 3- (4-methoxyphenyl) -6-dimethyl-aminophthalide (formula II: R = CH3; X = H; Y = 4-CH3OC6H4) are obtained of a white solid melting at 169-170 ° C.

The infrared spectral analysis presents a maximum at 1755 cm- '(C = 0; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

A toluene solution of the product deposited on an acid clay gives a blue color image.

B. By proceeding in a similar manner to that described in example 1, part B above, but by substituting lithium carbonate for potassium hydroxide as condensing agent, the 3- (4 -methoxy-phenyl) -6-dimethylaminophthalide from part A above with 1-butyl-2-methylindole to obtain the acid

2- {a- (1 -butyl-2-methyl-3-indolyl) -a- (4-methoxy-phenyl)] methyl-5-dimethylaminobenzoic acid (formula III: RCH3; X = H; Y = 4-CH3OC6H4;

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Z = I-C4H9-2-CH3-3- indolyl).

C. Following the procedure described in example 1, part C above, the 2- [a- (1-butyl-2-methyl-3-indolyl) -a- (4-methoxyphenyl) acid is oxidized. )] - methyl-5-dimethylaminobenzoic from part B, to obtain 3- (1-butyl-2-methyl-3-indolyl) -3- (4-methoxyphenyl) -6-dimethyl-aminophthalide (formula I : R - CH3; X = H; Y = 4-CH3OC6H4; Z =

1-C4H9-2-C H3-3-indolyl).

D. Using a procedure similar to that described in example 1, part B above, the 3- (4-methoxyphenyl) -5-dimethylaminophthalide prepared as described in part A above is reacted with N, N, N ', N'-tetramethyl-m-phenylenediamine to obtain the potassium salt of 2- [2,4-bis (dimethyl-amino) -4'-methoxybenzhydryl] -5-dimethylaminobenzoic acid ( formula III: R = CH3; X = H; Y = 4-CH3OC6H4; Z = 2.4 - [(CH3) 2N] 2C6H3) which is used in the oxidation step without prior isolation from its alkaline aqueous preparation medium.

E. Using a procedure similar to that described in example 1, part C above, to oxidize the potassium salt of 2- [2,4-bis (dimethylamino) -4'-methoxy acid -benzhydryl] -5-dimethylaminobenzoic acid, 10.4 g of 3- [2,4-bis (dimethylamino) -phenyl] -3- (4-methoxy-phenyl) -6-dimethylaminophthalide are obtained (formula I: R = CH3; X = H; Y = 4-CH3OC6H4; Z = 2.4 - [(CH3) 2N] 2C6H3), an orange-brown yellow solid which melts at 90-94 ° C.

The infrared spectrum has a maximum at 1762 cm −1 (C = 0; s). The nuclear magnetic resonance spectrum is compatible with the assigned structure.

A toluene solution of the product deposited on a phenolic resin gives a black image.

Example 13

A. By proceeding in a similar manner to that described in Example 1, part A above, 11.6 g of 3-dimethylaminobenzoic acid and 8.2 g of o-anisaldehyde are reacted using acetic anhydrous alone as reaction medium, and 11.7 g of 3- (2-methoxy-phenyl) -6-dimethylaminophthalide are obtained (formula II: R = CH3; X = H; Y = CH3OC6H4) as an orange solid, melting at 165-166.5 ° C.

A significant infrared maximum appears at 1760 cm-1 (C = 0; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

A toluene solution of the product deposited on an acid clay gives a pale yellow image.

B. Following the procedure described in example 1, part B above, the 3- (2-methoxy-phenyl) -6-dimethylaminophthalide of part A is reacted with N, N, N ', N'-tetrabutyl-m-phenylenediamine to obtain 2- [2,4-bis (dibutylamino) - (2 '-methoxy) -benzhy-dryl] -5-dimethylaminobenzoic acid (formula III: R = CH3; X = H; Y = 2-CH3OC6H4; Z = 2.4 - [(C4H9) 2N3] 2CeH3.

C. Using a procedure similar to that described in example 1, part C above, the acid is oxidized

2- [2,4-bis (dibutylamino) - (2'-methoxyphenyl) benzhy-dryl] -5-dimethylaminobenzoic acid from part B to obtain le3- [2,4-bis (dibutylamino) phenyl] -3- (2 -methoxy-phenyl) -6-dimethylaminophthalide (formula I: R = CH3; X = H; Z = 2-CH3OC6H4; Z = 2,4 - [(C4H9) 2N] C6H3.

Example 14

A. Following the procedure similar to that described in example 1, part A above, 11.6 g of 3-dimethylaminobenzoic acid and 9.0 g of ethoxybenzaldehyde are reacted in the anhydride. acetic and 2.6 g of

3- (4-ethoxyphenyl) -6-dimethylaminophthalide (formula II: R

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= CH3; X = H; Y = 4-C2H5OC6H4), in the form of a white solid, melting at 115.5-118 ° C.

Infrared spectral analysis indicates a maximum at 1750 cm- '(C = 0; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure. A toluene solution of the product deposited on an acid clay gives an image of green color.

B. Using the procedure similar to that described in example 1, part B above, the 3- (4-ethoxyphenyl) -6-dimethylaminophthalide of A is reacted with N, N-dimethyl-m -toludine to obtain 2- (4-dimethyl-amino-2-methyl-4'-ethoxybenzhydryI) -5-dimethylamino-benzoic acid (formula III: R = CH3; X = H;

Y = 4-C2H5OC6H4; Z = 4- (CH3) 2N-2-CH3C6H3).

C. By proceeding in a similar manner to that described in example 1 part C above, the acid is oxidized

2- (4-dimethylamino-2-methyl-4'-ethoxybenzhydryl) -5-dimé-thylaminobenzoic from part B above to obtain the

3- (4-dimethylamino-2-methylphenyl) -3- (4-ethoxy-phenyl) -6-dimethylaminophthalide (formula I: R = CH3; X = H; Y = C2H5OC6H4; Z - 4- (CH3) 2N- 2-CH3C6H3).

Example 15

A. Using a procedure similar to that described in example 1, part A above, and reacting 11.6 g of 3-dimethylaminobenzoic acid and 10.6 g of 3,4-dimé-thoxybenzaldehyde in acetic anhydride, 0.75 g of 3- (3,4-dimethoxyphenyl) -6-dimethylaminophthalide is obtained (formula II = R = CH3; X = H; Y = 3.4- (CH3) 2C6H3) , light yellow solid melting at 148-150 ° C.

A significant infrared maximum appears at 1765 cm-1 (C = 0; strong).

A toluene solution of the product deposited on an acid clay gives a pale yellow image.

B. By proceeding in a similar manner to that described in example 1, part B above but by substituting quinuclidine for potassium hydroxide as condensing agent, the 3- (3,4- dimethoxy-phenyl) -6-dimethylaminophthalide A with l-octyl-2-methyl-indole to obtain l- [a- (l-octyl-2-methyl-3-indolyl) -a- (3,4 -dimethoxyphenyl)] methyl-5-dimethylamino-benzoic (formula III: R = CH3; X = H; Y = 3.4- (CH30) 2C6H3; Z = 1- C8Hi7-2-CH3-3-indolyl).

C. Following the procedure described in example 2, part B above, the 2- [a- (1-octyl-2-methyl-3-indolyl) -a- (3,4 -dimethoxyphenyl)] methyl-5-dimethylamino-benzoic from B to obtain 3- (1-octyl-2-methyl-3-indolyl) -3- (3,4-dimethoxyphenyl) -6-dimethylaminophthalide (formula I: R = CHa; X = H; Y = 3,4- (CH30) 2C6H3; Z =

1-CsHn-2-CH3-3-indolyl).

Example 16

A. By proceeding in a similar manner to Example 1, part A above, reacting 14.35 g of 4-diethylamino-

2-methylbenzaldehyde and 12.37 g of 3-dimethylaminobenzoic acid in acetic anhydride to obtain 5.3 g of

3- (4-diethylamino-2-methylphenyl) -6-dimethylaminophta-lide (formula II: R = CH3; X = H; Y = 4- (C2Hs) 2N-2-CH3C6H3), solid melting at 135-136, 5 ° C.

The infrared spectral analysis presents a maximum at 1750 cm- '(C = 0; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

A toluene solution of the product deposited on an acid clay ■ gives a bluish green color image.

B. Following the procedure described in example 1, part B above, but by substituting lithium hydroxide for potassium hydroxide as condensing agent, the 3- (4-diethylamino) is reacted. 2-methylphenyl) -6-dimen-

thylaminophthalide of A with 1- (2,5-dimethylbenzyl) -2-methylindole to obtain 2- [a- [1- (2,5-di-methybenzyI) -2-methyl-3-indoIyl] - a- (4-diethylamino-2-methylphenyl)) methyl-5-dimethylaminobenzoic s (formula III: R = CHs; X = H; Y = 4- (C2H5) 2N-2-CH3C6H3; Z = 1- [2, 5- (CH3) 2C6H3CH2] 2-2-CH3-3-indoIyl).

Example 17

A. Using a procedure similar to that described in Example 1, part A above, to react 11.6 g of 3-dimethylaminobenzoic acid and 12.4 g of 3-ethoxy-4-methoxybenzaldehyde at 89%, in acetic anhydride, 3- (3-ethoxy-4-methoxyphenyl) -6-dimethylami-nophthalide is obtained (formula II: R = CH3; X = H; Y = 3-C2H5O-4 ■ îs -CH3O-C6H3), solid which has a maximum in the infrared spectrum at 1760 cm-1 (C = O; strong.)

B. By proceeding in a similar manner to that described in example 1, part B above, the 3- (3-ethoxy-4-methoxyphenyl) -6-dimethylaminophthalide is reacted.

20 A with N, N, N ', N'-tetra-s-butyl-m-phenylenediamine and 2- [2,4-bis (di-s-butylamino) -3'- acid is obtained ethoxy-4'-methoxybenzhydryl] -5-dimethylamino-benzoic acid (formula III: R = CH3; X = H; Y = 3-C2H5O-4-CH3OC6H3; Z = 2,4 - [(s-C4H9) 2N] 2C6H3 ).

2s C. Following the procedure described in example 1, part B above, the 2- [2,4-bis (di-s-butyl-amino-3 '-ethoxy-4') acid is oxidized. -methoxybenzhydry] -5-dimethylamino-Ipenzoic acid from B to obtain 3- [2,4-bis (di-s-butyl-amino) phenyl] -3- (3-ethoxy-4-methoxyphenyl) -6-dimethyl- Aminophthalide (formula I: R = CH3; X = H;

Y = 3-C2H5O-4-CH3OC6H3;

Z - 2,4 - [(s-C4H9) 2N] 2C6H3).

Example 18

A. Proceeding in a similar manner to that of Example 1, part A above, 11.6 g of 3-dimethylaminobenzoic acid and 10.0 g of 2,4-dimethoxyben-zaldehyde are reacted in acetic anhydride and 14.0 g of 2- (2,4-dimethoxyphenyl) -6-dimethylaminophthalide (formula 40 II: R = CH3; X = H; Y = 2.4- (CH30) 2C6H3 are obtained ), in the form of a, yellow solid, melting at 123-125 ° C.

A significant infrared maximum appears at 1750 cm-1 (C = 0; strong).

A toluene solution of the product deposited on a 4s acid clay gives a blue color image.

B. Following the procedure described in Example 1, Part B above, but substituting tetraethylammonium hydroxide for potassium hydroxide as a | condensation, react 3- (2,4-dimethoxy-

50 phenyl) -6-dimethylaminophthalide from A with 5-iodo-1 - (1-methylhexyl) indole to obtain 2- (a- [5-iodo-l- (l-methylhexyl) -3-indolyl] acid -a- (2,4-dimethoxy-phenyl)) - methyl-5-dimethylaminobenzoic acid (formula III; R. = CH3; X = H; Y = 2,4- (CH30) 2CöH3; Z = 5-Il- [ 1-CH3-55 (C6Hi2)] - 3-indolyl).

C. Using a procedure similar to that described in Example 2, part B above, the acid obtained in B above is oxidized and 3- [5-iodo-1- ( 1-methyl- | hexyl) -3-indolyl] -3- (2,4-dimethoxyphenyl) -6-dimethylami-

60 nophthalide (formula I: R = CH3; X = H;

Y = 2,4- (CH30) 2C6H3; Z = 5-I-1- [1-CH3- (C6Hi2)] - 3-indolyl).

D. By proceeding in a similar manner to that described

. in Example 1, part B above, 25.1 g of 65 3- (2,4-dimethoxyphenyl) -6-dimethylaminophthalide prepared as described in part A above, and 13.4 g are reacted N, N, N ', N' -tetramethyl-m-phenylenediamine to obtain the potassium salt of 2- [2,4-dimethoxy-2 ', 4' -bis

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(dimethylamino) benzyhydryl] -5-dimethylaminobenzoic acid (formula III: R = CHs; X = H; Z = 2,4- (CH30) 2C6H3; Z = 2,4- (CH3) N) 2C6H3). used in the oxidation step without prior isolation from the aqueous preparation medium.

E. Following the procedure described in Example 1, part C above to oxidize the potassium salt of the acid

2- [2,4-dimethoxy-2 ', 4' -bis (dimethylamino-benz-hydryl] -5-dimethylaminobenzoic acid, 9.0 g of

3- (2,4-dimethoxyphenyl) -3- [2,4-bis (dimethyl-amino) phenyl] -6-dimethylaminophthalide (formula I: R = CHs; X = H; Y = 2,4- (CH30) 2C6H3; Z = 2.4 - [(CH3) 2N] 2-CóH3, reddish brown solid which melts over the range of 153 to 160 ° C.

A significant infrared maximum appears at 1760 cm- '(C = O; strong). The nuclear magnetic resonance spectrum is compatible with the assigned structure.

A toluene solution of the product deposited on a phenolic resin gives an image of reddish brown color.

F. Using a procedure similar to that described in example 1, part B above, 25.1 g of 3- (2,4-dimethoxyphenyl) -6-dimethylaminophthalide prepared as described in part are reacted A above and 15.5 g of 1-ethyl-2-methylindole to obtain the potassium salt of 2- [a- (2,4-dimethoxyphenyl) -a- (1 -ethyl-2-methyl) acid -3-indolyl)] methyl-5-dimethylaminobenzoic acid (formula III:

R = CHs; X = H; Y = 2,4- (CH30) 2CeH3; Z = I-C2H5-2-CH3-3-indolyl), which is used in the oxidation step without prior isolation from its aqueous preparation medium.

G. By proceeding in a similar manner to that described in Example 1, part C above, to oxidize the potassium salt of 2- [a- (2,4-dimethoxyphenyl) -a- ( l-ethyl-

2-methyl-3-indolyl] -methyl-5-dimethylaminobenzoic acid, 1.6 g of 3- (2,4-dimethoxyphenyl) -3- (1-ethyl-2-methyl-3-indolyl) -6- are obtained dimethylaminophthalide (formula I: R = CH3; X = H; Y = 2,4- (CH30) 2-C6H3; Z = 1-C2Hs-2-CH3-3 indolyl), dirty white solid which melts at 215-217 ° vs.

A significant infrared maximum appears at 1764 cm- '(C = O; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

A toluene solution of the product deposited on silica gel gives a grape-colored image.

Example 19

A. By following a procedure similar to that described in Example 1, part A above, 7.8 g of 3-dimethylaminobenzoic acid and 8.9 g of 9-ethyl-3-car- are reacted. bazolcarboxaldehyde in acetic anhydride and 6.33 g of 3- (9-ethyl-3-carbazolyl) -6-dimethylami-nophthalide are obtained (formula II: R = CH3; X = H; Y = 9- C2Hs-3-car-bazolyl), as a light brown solid melting in the range of 142 to 145 ° C.

A significant infrared maximum appears at 1760 cm- '(C = O; strong).

A toluene solution of the product deposited on an acid clay gives an image of greenish blue color.

B. Using a procedure similar to that described in example 1, part B above, the product of A above is reacted with N, N, N ', N'-tetrabutyl-m-phenylene -diamine and 2- [a- (9-ethyl-3-carbazolyl)] - a- [2,4-bis (dibutylamino) phenyl] methyl-5-dimethylamino-benzoic acid (formula III: R = CH3; X = H; Y = 9-C2H5-

3-carbazolyl; Z = 2.4 - [(C4H9) 2] N2C6H3).

C. By proceeding in a similar manner to that described in example 1, part C above, the acid of paragraph B above is oxidized to obtain 3- (9-ethyl-3-carba-zolyl ) -3- [2,4-bis (dibutylamino) phenyl] -6-dimethylamino-phthalide (formula I: R = CH3; X - H; Y = 9-C2H5-

3-carbazolyl; Z = 2.4 - [(C4H9) 2N] 2C6H3).

Example 20

A. By proceeding in a similar manner to that of Example 1, part A above, 5.0 g of 9-for-myljulolidine and 4.6 g of 3-dimethylaminobenzoic acid are reacted to obtain 5.0 g of 3- (9-juIolidinyl) -6-dimethylaminophta-lide (formula II: R = CEb; X = H; Y = 9-julolidinyl).

In the infrared spectrum, we observe a maximum at 1760

10 cm- '(C = O; strong).

A toluene solution of the product deposited on an acid clay gives an image of green color.

B. Following the procedure described in Example 1, part B above, but substituting potassium carbonate-

is sium with potassium hydroxide as a condensing agent, the product of A is reacted with 5-methoxy-1-buty-lindole, and the acid 2- [a- (5-methoxy) is obtained -1-butyl-3-indolyl) -a- (9-julolidinyl) -methyl-5-dimethylaminobenzoic acid (formula III: R = CHs; X = H; Y = 9-julolidinyl;

Z = 5-CH30-1-C4H9-3-indolyl).

Example 21

A. By following a procedure similar to that described in example 1, part A above, the reaction is carried out in the an-

25 acetic hydride 7.5 g of 3,4- (methylenedioxy) benzaldehyde and 9.1 g of 3-dimethylaminobenzoic acid and 0.9 g of 3- (3,4-methylenedioxyphenyl) -6-dimethylaminophta are obtained -Iide (formula II: R = CH3; X = H;

Y = l- [3,4- (0CH20) CfiH3])

30 light yellow solid melting at 134-143 ° C.

A significant infrared maximum appears at 1750 cm- '(C = O; strong). The magnetic resonance spectrum is in agreement with the assigned structure. Mass spectrum analysis indicates a peak m / e at 297 (M +).

A toluene solution of the product deposited on an acid clay gives an image of green color.

B. Using a procedure similar to that described in example 1, part B above, but by substituting ammonium hydroxide for potassium hydroxide

40 as a condensing agent, the product of A is reacted with 2-isopropylindole and the 2- [a- (2-iso-propyl-3-indolyl) -a- (3,4- methylenedioxyphenyl)] methyl-5-dimethylaminobenzoic acid (formula III: R = CH3; X = H;

Y = 1- [3.4 (0CH20) C6H3]; Z = 2-i-C3H7-3-indolyl).

45 C. By proceeding in a similar manner to that described in example 1, part C above, the acid of B is oxidized above, to obtain 3- (2-isopropyl) -3-indolyl ) -3- (3,4-methylenedioxyphenyl) -6-dimethylaminophthalide (formula I: R = CHs; X = H; Y = 1- - [3,4 (0CH20) CeH3]; Z =

50 2-i-C3H7-3-indolyl).

Example 22

A. By proceeding in a similar manner to that of Example I, part A above, 5.6 g of 2-thio-

55 phenecarboxaldehyde and 9, 1 g of 3-dimethylaminobenzoic acid in acetic anhydride and 0.92 g of 3- (2-thienyl) -6-dimethylaminophthalide are obtained (formula II: R = CH3; X = H; Y = 2-thienyl), in the form of a white oily solid.

60 The infrared spectrum has a maximum at 1763 cm- '(C = O; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

A toluene solution of the product deposited on an acid clay gives an image of yellow color.

65 B. Using the procedure described in example 1 part B above, the product of A is reacted with N, N, N ', N'-tetraethyl-m-phenylenediamine to obtain acid 2 - | cc- (2-thienyl) -a- [2,4-bis (diethylamino) -

628,922

phenyl] | methyl-5-dimethylaminobenzoic acid (formula III: R = CH3; X = H; Y = 2-thienyl; Z = 2,4 - [(C2H5) 2N] 2C6H3).

C. Using the procedure similar to that described in example 1, part C above, the acid obtained is oxidized at B to obtain 3- (2-thényl) -3- [2,4-bis (diethyl-amino) -phenyl] -6-dimethylaminophthalide (formula I: R = CHj; X = H; Y = 2-thienyl; Z = 2,4 - [(C2H5) 2N] 2CöH3).

Example 23

A. Following the procedure similar to that described in Example 1, part A above, 7.7 g of 3-dimethylaminobenzoic acid and 4.4 g of N-methylpyr-role-2- are reacted. carboxaldehyde in acetic anhydride and 3- (1-methyl-2-pyrrolyl) -6-dimethylaminophthalide is obtained (formula II: R = CH3; X = H; Y = 1-CH3-2-pyrrolyl) .

A significant infrared maximum appears at 1768 cm- '(C = O; strong).

A toluene solution of the product deposited on an acid clay gives an image of purple color.

B. Using a procedure similar to that described in example 2, part A above, the product of A is reacted with 1-vinyl-2-methylindole and the acid is obtained.

2- [a- (1 -vinyl-2-methyl-3-indolyl) -a- (l -methyl-2-pyrrolyl)] - methyl-5-dimethylaminobenzoic acid (formula III: R = CH3; X = H; Y = 1-CH3-2-pyrrolyI; Z = 1-CH2 = CH-2-CH3-3-indolyl).

C. By proceeding in a similar manner to that described in Example 1, part C above, the acid from the preceding part B is oxidized to obtain 3- (1-vinyl-2-methyl-3- indolyl) -3- (1-methyl-2-pyrrolyl-6-dimethylaminophthalide (formula I: R = CH3; X = H; Y = 1-CH3-2-pyrrolyl; Z =

1-CH2 = CH-2-CH-3-indolyl).

Example 24

A. Using a procedure similar to that described in Example 1, part A above, to react 4.6 g of 2-dimethylaminobenzoic acid and 4.6 g of 1-ethyl-2-methylindole- 3-carboxaldehyde of acetic anhydride, 2.6 g of 3- (1-ethyl-2-methyl-3-indolyl) -6-dimethyl-aminophthalide are obtained (formula II: R = CH3; X = H; Y = I-C2H5-2-CH3-3-indolyl), yellow brown solid melting at 177-180 ° C.

A significant infrared maximum appears at 1747 cm- '(C = O; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

A toluene solution of the product deposited on an acid clay gives an image of purple color.

B. By proceeding in a similar manner to that described in example 5, part A above, the reaction is reacted.

3- (1-ethyl-2-methyl-3-indolyl) -6-dimethylaminophthalide of A with 1-ethyl-2-methylindole and the acid is obtained

2- [a, a-bis (1 -ethyl-2-methyl-3-indolyl)] methyl-5-dimethyl aminobenzoic acid (formula III: R = CH3; X = H; Y = Z = 1-C2Hs-CH3- 3-indolyl).

Example 25

A. Using a procedure similar to that described in example 1, part A above, the reaction is reacted.

1,2-dimethylindole-3-carboxaldehyde and 3-dimethylaminobenzoic acid, to form 3- (1,2-dimethyl-3-indolyl) -6-dimethylaminophthalide (formula II: R = CH3; X = H; Y = 1.2, (CH3) 2-3-indolyl), which melts at 234-236 ° C.

B. Using a procedure similar to that described in example 1, part B above, the compound of A is reacted with N, N, N ', N' -tetraethyl-m-phenylenediamine to obtain 1 2- [a- (1,2-dimethyl-3-indolyl) -a- [2,4-bis (dimethylamino)] - phenyl] methyl-5-dimethyl-aminobenzoic acid (formula III: R = CH3; X = H; Y = 1.2, (CH3) 2-3-indolyl; Z = 2,4-bis [(CH3) 2N] 2CoH3).

Example 26

A. A stirred mixture of 98.0 ml of N, N-dimethylaniline and 20.9 g of 3- (4-dimethylamino-phenyl) -6-dimethylaminophthalide prepared as in Example 1 is heated to approximately 75 ° C. , part A, to obtain a clear solution which is then cooled to 20 ° C using a cold water bath. Over 10 minutes, 9.5 g of anhydrous zinc chloride are added slowly to the solution while allowing the temperature to rise to approximately 24 ° C. After approximately 30 minutes of stirring at a temperature between 25 and 30 ° C, the reaction mixture is heated to about 50 ° C and maintained between 50 and 55 ° C for 2 hours, during which time it is added to the reaction mixture two charges of 1.9 g each of anhydrous zinc chloride. Then 150.0 ml of hot tap water and 20 g of 50% aqueous sodium hydroxide are added slowly and the resulting mixture is left to stand at room temperature overnight. The excess N, N-dimethylaniline is distilled off by entrainment in water vapor. After cooling to about 75 ° C, diatomaceous earth is added, the resulting mixture is filtered, and the filter cake is washed with 40.0 ml of hot water. The wash water is combined with the alkaline filtrate and the whole solution is slowly poured into a mixture of 35.0 ml of water and 18.0 ml of acetic acid, with vigorous stirring. The pH of the resulting suspension is adjusted to 4.9 by the addition of 10% aqueous sodium hydroxide. After cooling to 25%, the light blue solid is collected by filtration, washed and dried under vacuum, which gives 25.0 g of 2- [4,4'-bis (dimethylamino) -benzhy- acid. dryl] -5-dimethylaminobenzoic acid (formula III: R = CH3; X = H; Y = Z = 4- (CH3) 2NHôH4), light gray solid which melts at 208-211 ° C.

The infrared spectral analysis presents a maximum at 1655 cm- '(C = O; strong).

B. Using a procedure similar to that described in example 1, part C above, the 2- [4,4'-bis (dimethylamino) -benzhydryl] -5-dimethylamino-benzoic acid is oxidized as described in the previous part A to obtain 3,3-bis (4-dimethylaminophenyl) -6-dimethyl-aminophthalide (formula I: R = CH3; X = H; Y = Z = 4- (CH3) 2NCeH4), solid yellow brown that melts at

173.5-178.5 ° C.

A significant infrared maximum appears at 1750 cm- '(C = O; strong). The nuclear magnetic resonance spectrum is compatible with the assigned structure.

A toluene solution of the product deposited on silica gel, an acid clay or a phenolic resin gives a blue image.

C. By following a procedure similar to that described in part A above, but by substituting 18.2 g of anhydrous stannic chloride for anhydrous zinc chloride, 70.0 ml of N, N-dimethylaniline are reacted and 14.9 g of 3- (4-dimé-thylaminophényl) -6-diméthylaminophtalide prepared as described in example 1, part A and one obtains 15,0g of acid

2- [4,4-bis (dimethylamino) -benzhydryl] -5-dimethylamino-benzoic which melts at 208-212 ° C. A significant infrared maximum appears at 1705 cm- '(C = O; strong).

D. By proceeding in a similar manner to that described in part A above, but by replacing the anhydrous zinc chloride with 9.3 g of anhydrous aluminum chloride, 70.0 ml of N are reacted, N-dimethylaniline and 14.9 g of

3- (4-dimethylaminophenyl-6-dimethylaminophthalide, prepared as described in example 1 part A, and 16.1 g of 2- [4,4-bis (dimethylamino) -benzhydryl] -5 acid are obtained -dimethylaminobenzoic acid, light blue powder that melts

at 209-213PC.

A significant infrared maximum appears at 1705 cm-1 (C = O; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

16

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65

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E. Following the procedure described in section A just above, 70.0 ml of N, N-dimethylani-line and 14.9 g of 3- (4-dimethylaminophenyl) -6-dimethylami-nophthalide are reacted. in the presence of 15.0 g of anhydrous ferric chloride. The reaction mixture is immersed in water and subjected to distillation by entrainment in steam to remove the excess N, N-dimethylaniline. Then 120.0 ml of toluene, 25.0 ml of water and diatomaceous earth are added to the resulting aqueous mixture. The resulting mixture was stirred at 75-80 ° C, filtered, and the filtration cake washed twice with 25.0 ml portions of hot toluene. The detergents are combined with the filtrate, the aqueous layer is separated and cooled to about 40 ° C. The pH is adjusted to 4.9 by addition of acetic acid. The solid which forms is collected by filtration, washed with water and dried to give 0.2 g of 2- [4,4'-bis (dimethyl-amino) benzhydryl] acid. -5-somewhat impure dimethylaminobenzoic acid, (formula III: R = CHs; X = H; Y = Z =

4- (CH3) 2C6H4), pale blue solid which melts at 187.5-193 ° C. 20

A significant infrared maximum appears at 1710 cm-1 (C = O; strong).

The toluene layer resulting from the preceding treatment is evaporated to dryness and 26.0 g of a sticky pale blue solid are obtained. 10 g of the solid are diluted in 50.0 ml of hot toluene, the undissolved solid is collected by filtration, after cooling to room temperature, and washed with 10.0 ml of toluene and dried under vacuum, and 5.8 g of an iron complex of 2- [4,4'-bis (dimethyl-amino) benzhydryl] -5-dimethylaminobenzoic acid are obtained in the form of a gray solid. The iron complex thus obtained is diluted in water and made alkaline with phenolphthalein test paper, by adding 5% aqueous sodium hydroxide, heating to approximately 90 ° C., cooling to approximately 30 °. C and filtered twice on diatomaceous earth. The slightly cloudy filtrate is slowly acidified to about pH 5 by addition of dilute aqueous acetic acid. The solid which separates is collected by filtration, washed with water and dried in air and the acid is obtained

2- [4,4 '-bis (dimethylamino) benzhydryl] -5-dimethylamino-40 benzoic (formula III: R = CH3; X = H; Y = Z = 4- (CH3) 2NC6H4) gray solid which melts between 203 and 210 ° C.

The infrared spectrum has a significant maximum at 1710 cm-1 (C = O; strong). The nuclear magnetic resonance spectrum 45 is in agreement with the assigned structure.

The toluene filtrate and the washing liquids combined from the previous operation are evaporated and 4.4 g of 3.3-bis (4-dimethylaminophenyl) -6-dimethylaminophthalide are obtained (formula I: R = CHs; X = H; Y = Z = 4- (CHs) 2NC6H4), 50 dark blue solid.

A significant infrared maximum appears at 1759 cnr1 (C »O; strong). The nuclear magnetic resonance spectrum is compatible with the assigned structure.

A toluene solution of the product deposited on silica gel55 gives a blue color image.

F. Proceeding in a manner similar to that described in part E above, 0.3 g of 3- (2,4-di-methoxyphenyl) -6-dimethylaminophthalide, prepared in a similar manner, is reacted. to that of Example 18, part A, above, 60 with 3.0 ml of N, N-dimethylaniline in the presence of 0.3 g of anhydrous ferric chloride and significant amounts of acid 2 are obtained - [(2,4-dimethoxy-4'-dimethylamino-benzhy-dryl] -5-dimethylaminobenzoic acid (formula III: R = CH3; X = H; Y = 2,4- (CH30) 2CôH3; Z = 4- ( CH3) 2NCeH4) and 65

3- (4-dimethylaminophenyl) -3- (2,4-dimethoxyphenyl) -6-dimethylaminophthalide (formula I: R = CH3; X = H; Y = 2,4- (CH3) 02C6H3; Z = 4- (CH3 ) 2NC6H4).

G. Using a procedure similar to that described by the preceding part E, 0.3 g of 3- (4-dimé-thylaminophényI) -6-dimethylaminophtaIide prepared as described in example 1, part A is reacted above with 3.0 ml of

1-ethyl-2-methylindole, in the presence of 0.32 g of anhydrous ferric chloride and significant amounts of 2- [a- (4-dimethylaminophenyl) -a- (1 -ethyl-2- methyl-

3-indolyl)] - methyl-5-dimethylaminobenzoic acid (formula III: R = CH3; X = H; Y = 4- (CH3) 2NC6H4; Z = I-C2H5-2-CH3-

2-indolyl) and 3- (4-dimethylaminophenyl) -3- (1-ethyl-2-methyl-3-indolyl) -6-dimethylaminophthalide (formula I: R = CH3; X = H; Y = 4- ( CHa) 2NC6H4; Z = 1-C2Hs-2-CH3-3-indolyl).

Example 27

A. Following the procedure described in Example 26, part A, react 9.9 g of 3- (4-methoxyphenyl) -6-dimé-thylaminophtalide, prepared as described in Example 12, part A above, and 89.0 ml of N, N-dimethylaniline, in the presence of 9.5 g of anhydrous zinc chloride, at room temperature, and 13.7 g of 2- ( 4-dimethyl-amino-4'-methoxybenzhydryl) -5-dimethylaminobenzoic acid in the form of a dirty white solid melting at 185-190 ° C.

B. Maintained at a temperature of 85-96 ° C, a stirred mixture of 8.1 g of the acid from part A above, 40.0 ml of water, 1.6 g of 50% aqueous sodium hydroxide and 2.7 ml isopropyl alcohol, while adding in approximately 6 hours 20.3 g of aqueous hydrogen peroxide to

10%. The reaction mixture is allowed to stand at room temperature overnight. The solid is collected by filtration, washed with water until it is free of base and it is dried under vacuum, which gives 5.5 g of 3- (4-dimethyl-aminophenyl) - 3- (4-methoxyphenyl) -5-dimethylaminophta-lide, yellow solid which melts at 156-161 ° C.

A significant infrared maximum appears at 1754 cm- '(C = O; strong). The nuclear magnetic resonance spectrum is compatible with the assigned structure.

A toluene solution of the product deposited on an acid clay or on an acid resin gives an image of green color.

Example 28

A. By proceeding in a similar manner to that described in example 26, part A above, 10.7 g of

3- (4-dimethylaminophenyl) -6-dimethylaminophtaIide, prepared as in Example 1, part A above, and 50.0 ml of N-methylaniline, in the presence of anhydrous zinc chloride at room temperature, and l '13.8 g of 2 - [(4-dimethylamino-4'-methylamino) -benzhydryl] -5-dimé-thylaminobenzoic acid (formula III: R = CH3; X = H; Z =

4- (CH3) 2-NC &H4; Z = 4-CH3NHC6H4), in the form of a yellow-brown solid softening at 118 ° C and melting at 128-130 ° C.

A significant infrared maximum appears at 1691 cm- '(C = O; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

B. Following a procedure similar to that described in Example 27, part B above, the acid from the preceding part A is oxidized to obtain 2.38 g of 3-dimethylamino-phenyl-3-methylaminophenyl- 5-dimethylaminophthalide (formula I: R = CH3; X = H; Y = 4- (CH3) 2NC6H4; Z =

4-CH3NHCöH4), in the form of a brown-yellow solid, melting in the range 126-135 ° C.

Infrared spectral analysis presents a maximum at 1751 cm- '(C = O; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

A toluene solution of the product deposited on silica gel, an acid clay or a phenolic resin gives an image of reddish blue color.

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Example 29

A. Using a procedure similar to that described in example 26, part A above, react 5.4 g of 3- (4-dimethylaminophenyl) -5-dimethylaminophtaIide, prepared as described in example 1, part A above, and 57 μg of N, N-diethyl-m-toluidine, in the presence of anhydrous zinc chloride, at 100-110 ° C. and 4.5 g of acid are obtained

2 - [(2-methyl-4-diethylamino-4'-dimethylamino) -benzhy-dryl] -5-dimethylaminobenzoic acid (formula III: R = CH3; X = H: Y = 4- (CH3) 2NC6H4; Z = 2 -CH3-4- (C2Hs) NC6H4), as a brownish pink solid which melts in the range 105-115 ° C.

A significant infrared maximum appears at 1700 cm-1 (C = O; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

B. By proceeding in a similar manner to that described in Example 27, part B above, 3.7 g of the acid from the preceding part A are oxidized, to obtain 1.8 g of

3- (2-methyl-4-diethylaminophenyl) -3- (4-dimethylamino-phenyl) -6-dimethylaminophthalide (formula I: R = CH3; X: H; Y = 4- (CH3) 2NC6H4; Z = 2- CH3-4- (C2H5) 2NCfiH3, in the form of a brown solid which melts at 190-195 ° C.

A significant infrared maximum appears at 1760 cm * 1 (C = O: strong). A nuclear magnetic resonance spectrum is in agreement with the assigned structure. 25

A toluene solution of the product deposited on a silica gel or on a phenolic resin gives an image of purple color.

Example 30 30

A. Following the procedure similar to that described in example 1, part A, 36.6 g of 2-chloro are reacted.

4-dimethylaminobenzaldehyde and 33.0 g of 4-dimethyl-aminobenzoic acid in acetic anhydride to obtain

52.1 g of 3- (2-chloro-4-dimethylaminophenyl) -6-dimethyl-aminophthalide (formula I: R = CH3; X = Z = H; Y = 2-Cl-4- (CH3) 2NC6H3) , in the form of a red crystalline solid which melts at 159-160 ° C.

A significant infrared maximum appears at 1770 cm- '(C = O; strong). 40

B. Using a procedure similar to that described in example 26, part A, 6.5 g of the product of the preceding part A and 30.0 ml of N, N-dimethylaniline are reacted, in the presence of 5 , 3 g of anhydrous zinc chloride to obtain

8.0 g of 2- [2-chloro-4,4 '-bis (dimethylamino) benzhy- 45 dryI] -5-dimethylaminobenzoic acid (formula III: R = CH3; X = H; Y = 2-Cl- 4- (CH3) 2NC6H3; Z = 4- (CH3) 2NCeH4), in the form of a pink powder, which melts in the range of 180-190 ° C.

The infrared spectrum has a maximum at 1610 cm-1 (C so = O; strong, broad). The nuclear magnetic resonance spectrum agrees with the assigned structure.

C. By proceeding in a similar manner to that described in Example 27, part B above, 5.4 g of the preceding acid are oxidized to obtain 2.9 g of 3- (2-chloro-4 -dimethyl- ss aminophenyl) -3- (4-dimethylaminophenyl) -6-dimethyl-aminophthalide (formula I: R = CH3; X = H; Y = 2-Cl-4- (CH3) 2NC6H3; Z = 4- ( CH3) 2NC6H4), in the form of a pale bluish gray solid which melts at 233-234 ° C.

A significant infrared maximum appears at 1760 cm * 1 60 (C = O; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

A toluene solution of the product deposited on silica gel gives an image of bluish purple color.

65

Example 31

A. Using a procedure similar to that described in example 26, part A above, 7.0 g of 3- (2,4-dimethoxyphenyl) -6-dimethylaminophthalide, prepared as in Example 18, part A above, and 31.0 ml of N, N-dimethylaniline in the presence of zinc chloride at room temperature, and 10.9 g of 2- (2,4- dimethoxy-4'-dimethylaminobenzhydryl) -5-dimethyl-aminobenzoic acid (formula III: R = CH3; X = H; Y = 2,4- (CH30) iC6H3; Z = 4- (CH3) 2NCôH4), white solid which melts in the range 105-135 ° C.

The infrared spectrum has a significant maximum at 1696 cm- '(C = O; strong). The nuclear magnetic resonance spectrum is compatible with the assigned structure.

B. Following the procedure similar to that described in example 27, part B, 10.5 g of acid are oxidized

2- (2,4-dimethoxy-4'-dimethylaminobenzhydryl-5-dimethylaminobenzoic acid to obtain 2.2 g of 3- (2,4-dimé-thoxyphenyl) -

3- (4-dimethylaminophenyl) -6-dimethylaminophthalide (formula I: R = CH3; X = H; Y = 2,4- (CH30) 2-C6H3; Z = 4-

(CH3) 2 NCôHU, pale yellow solid which melts at 191.5-193.5 ° C.

A significant infrared maximum appears at 1758 cm-1 (C = O; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

A toluene solution of the product deposited on a phenolic resin gives a light blue image.

Example 32

A. By proceeding in a similar manner to that described in example 26, part A above, 9.9 g of 3- (2-methoxyphenyl) -6-dimethylaminophthalide, prepared as described in Example 13, part A above, and 49.0 ml of N, N-dimethylaniline, in the presence of zinc chloride at room temperature, and 14.3 g of 2- (2-methoxy acid) are obtained -4'-dimethylaminobenzhydryl) -5-dimethylami-nobenzoic acid (formula III: R = CH3; X = H; Y = 2-CH3OC6H4; Z = 4- (CH3) îNC6H4), light yellow solid, which melts in the meantime 229-234 ° C.

The infrared spectrum has a significant maximum at 1690 cm * 1 (C = O; strong). The nuclear magnetic resonance spectrum is compatible with the assigned structure.

B. Using a procedure similar to that described in example 27, part B, above, 6.1 g of the acid of A above are oxidized with hydrogen peroxide and obtains 1.05 g of 3- (2-methoxyphenyl) -3- (4-dimethylamino-phenyl) -6-dimethylaminophthalide (formula I: R = CH3; X = H; Y = 2-CH3OC6H4; Z = 4- ( CH3) 2NCeH4), light yellow solid which melts at 215-216 ° C.

A significant infrared maximum appears at 1750 cm-1 (C = O; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

A toluene solution of the product deposited on silica gel gives a light blue color image, and deposited on a phenolic resin gives a light green color image.

Example 33

A. Following the procedure described above in example 26, part A, react 14.2 g of 3- (4-methoxy-phenyl) -6-dimethylaminophthalide prepared as described in example 12, part A above, and 35.0 ml of 1-ethyl-2-methylindole, in the presence of anhydrous zinc chloride at a temperature of 90 to 110 ° C., and 15.5 g of 2- (2) acid are obtained. a- (4-methoxyphenyl) -a- (1-ethyl-2-methyl-3-indolyl)] methyl-5-dimethylaminobenzoic acid (formula III: R = CH3; X = H; Y = 4-CH3OC6H4; Z = 4 - (CH3) 2NC6H4), light gray solid which melts in the range 115-126 ° C.

The infrared spectrum presents a significant maximum at

1683 cm- '(C = O; strong). The nuclear magnetic resonance spectrum is compatible with the assigned structure.

B. By proceeding in a similar manner to that described in example 1, part C above, the acid obtained in A above is oxidized, which gives 3- (4-methoxyphenyl) -

3- (1 -ethyl-2-methyl-3-indolyl) -6-dimethylaminophthalide (formula I: R = CH3; X = H; Y = 4-CH3OC6H4; Z =

4- (CH3): NC4H4).

Example 34

A. Using a procedure similar to that described in example 1, part A above, 13.3 g of 2-butoxy-4-diethylaminoben-zaldehyde and 9.7 are refluxed in acetic anhydride. g of m-dimethylaminobenzoic acid, and 3- (2-butoxy-4-diethylaminophenyl) -6-dime-thylaminophthalide is obtained (formula I: R = CH3; X = H; Y =

2-C4H90-4- (C2H5) 2NC6H3), in the form of a tarry residue.

The infrared spectrum presents a significant maximum which appears at 1760 cnr1 (C = O; strong). The nuclear magnetic resonance spectrum is in agreement with the assigned structure.

B. By proceeding in a similar manner to that of example 26, part A above, the product of the preceding part A is reacted with l-octyl-2-ethylindole to obtain 2- [ a- (2-butoxy-4-diethylamino-phenyl) -cc- (1 -octyl-2-ethyl-3-indolyl)] - methyl-5-dimethylaminobenzoic acid (formula III: R

= CHs; X = H; Y = 2-C4H "0-4- (C2H5) 2NC6H 3; Z = 1-C8Hi7-2-C2H5-3-indolyl).

C. Following the procedure described in example 2, part B above, the acid of the preceding paragraph B is oxidized, to obtain 3- (2-butoxy-4-diethylamino-phenyl) -3- ( l-octyl-2-ethylI-3-indolyl) -6-dimethylaminophta-lide (formula I: R = CH3; X = H; Y = 2-C4HoO-4- (C2H5) 2-NCöH3; Z = 1-C8Hi7 -2-C2H5-3-indolyl).

Example 35

A. By proceeding in a similar manner to that described in example 5, part A above, 7.4 g of

3- (4-dimethylaminophenyl-6-dimethylaminophthalide, prepared as described in Example 1, part A above, and 3.0 g of N, N-dimethylaniline in 40 g of ethylene dichloride in the presence of 6.65 g of anhydrous aluminum chloride, at reflux, and 2.7 g of 2- [4,4'-bis (dimethyl-amino-benzhydryI] -5-dimethylaminobenzoic acid (formula III: R = Ch3; X = H; Y = Z = 4- (CH3) 2NC6H4), pale blue solid.

A significant infrared maximum appears at 1700 cm- '(C = 0; strong, wide). The nuclear magnetic resonance spectrum is compatible with the assigned structure.

Following the procedure similar to that described in example 1, part C above, 2- [4,4'-bis (dimethylaminobenzhydryl)] - 5-dimethylamino-benzoic acid is oxidized to obtain 3, 3-bis (4-dimethylamino-phenyl) -6-dimethylaminophthalide (formula I: R = CH3; X = H; Y = Z = 4- (CH3) 2NC6H4).

It will be seen that by following the procedure described in Example 1, part A, but using instead of p-dimethylaminobenzaldehyde and m-dimethylaminobenzoic acid approximately equivalent molar amounts of the aldehyde Y- Appropriate CHO and suitable 3-N (R) 2-4-X benzoic acid, the compounds of Examples 36 to 50 are obtained.

Example 36

3- (2-Methylphenyl) -6- [N-methyl-N- (4-methyl-benzyI)] - aminophthalide from 2-methylbenzaldehyde and 3- [N-methyl-N- (4- methylbenzyl) amino] benzoic.

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Example 37

3- (1-Ethyl-2-phenyl-3-indolyl) -5-iodo-6-diethyl-amino-phtaiide from l-ethyl-2-phenylindole-3-car-boxaldehyde and 3- diethylamino-4-iodobenzoic acid.

Example 38

3- (4-Pyridinyl) -6-dibenzylaminophthalide from pyri-dinecarboxaldehyde and 3-dibenzylaminobenzoic acid.

Example 39

3- (2,3-Dimethoxyphenyl) -6-diethylaminophthalide from 2,3-dimethoxybenzaldehyde and 3-diethylamino-benzoic acid.

Example 40

3- (2-Methyl-1-n-octayl-3-indolyl) -5-chloro-6-aminophta-lide from 2-methyl-1-n-octylindole and 3-amino-4-chlorobenzoic acid.

Example 41

3- (5-Methoxy-4-indolyl) -6- (N-ethylbenzylamino) phthalide from 5-methoxyindole-3-carboxaldehyde and acid

3- (N-ethylbenzylamino) -benzoic.

Example 42

3- (2,3,4-Trimethoxyphenyl) -6- (N-ethyl-N-butyl-amino) phtaIide from 2,3,4-trimethoxybenzaldehyde and 3- (N-ethyl-N- butylamino) benzoic.

Example 43

3- (2-PyridinyI) -5-chloro-6-dimethylaminophthalide from 2-pyridinecarboxaldehyde and 3-dimethylamino acid-

4-chlorobenzoic acid.

Example 44

3- (2-Bromophenyl) -6- [N-methyl-N- (4-chloro-benzyl) -amino] phthalide from 2-bromobenzaIdehyde and 3- [N-methyl-N- (4 -chlorobenzyl) amino] benzoic.

Example 45

3- [2-Methyl-4- (N-methylbenzylamino) phenyl] -5-bromo-6-ethyl-aminophthalide from 2-methyl-4- (N-methylben-zylamino) benzaldehyde and 3- ethylamino-4-bromo-benzoic.

Example 46

3- (2-Fluorophenyl) -6- (N-ethyl-N-methylamino) phthalide from 2-fluorobenzaldehyde and 3- (N-ethyl-N-methylamino) benzoic acid.

Example 47

3- (2-Pyrrolyl) -5-fluoro-6-propylaminophthalide from 4-pyrrole-2-carboxaldehyde and 3-propylamino-4-fluorobenzoic acid.

Example 48

3- (1 -n-Butyl-2-phenyl-3-indolyl) -6-ethylaminophthalide from l-n-butyl-2-phenylindole -3-carboxaldehyde and 3-ethylaminobenzoic acid.

Example 49

3- (2-Methoxy-4-diethylaminophenyl) -6-methyl-aminophthalide from 2-methoxy-4-diethylaminobenzaldehyde and 3-methylaminobenzoic acid.

Example 50

3- (3-Ethoxyphenyl) -6-aminophthalide from 3-ethoxy-benzaIdehyde and 3-aminobenzoic acid.

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It will be seen that by following an operating mode chosen from those described in example 1, part B; Example 2, Part B; Example 5, part A; or Example 26, part A, to react approximately equivalent amounts of the appropriate 3-Y-5-X-6-N (R) 2phthalide and ZH in the presence of the indicated condensing agent, the compounds are obtained examples 51 to 65.

Example 51

2- [ß- (3-isopropyl-4-di-ethylamino-2 '-methyl) benzhy-dryl] -5- [N-methyl-N- (4-methylbenzyl) amino] benzoic acid from 3- (2-methylphenyl ) -6- [N-methyl-N- (4-methyl-benzyl)] aminophthalide and N, N-diethyl-3-isopropylani-line in the presence of oxalic acid according to Example 2, part B .

Example 52

2-ja- (1-ethyl-2-phenyl-3-indolyl) -a- [4- (N-isobutyl-N-ethylamino) phenyl)} methyl-4-iodo-5-diethylaminobenzoic acid from 3- (1-ethyl-2-phenyl-3-indolyl) -5-iodo-6-diethylaminophthalide and N-isobutyl-N-ethylaniline in the presence of lithium carbonate according to Example 1, part A.

Example 53

2- [a- (4-pyridinyl) -a- (4-diethylamino-2-propoxy-phenyl)] - methyl-5-dibenzylaminobenzoic acid from 3- (4-pyridinyl) -6-dibenzylaminophthalide and N , N-di-ethyl-2-propoxyaniline in the presence of phosphorus trichloride, according to Example 26, part A.

Example 54

2- (a- [1- (4-bromobenzyl) -2-isopropyl-3-indolyl] -a- (2,3-dimethoxyphenyl) Jmethyl-5-diethylamino-benzoic acid from 3- (2,3- dimethoxyphenyl) -6-diethylami-nophthalide and 1- (4-bromobenzyl) -2-isopropylindile in the presence of methanesulfonic acid according to Example 2, part A.

Example 55

2- [a- (2-methyl-ln-octyl-3-indolyl) -a- (N-iso-propyl-3-pyrrolyl)] acid methyl-4-chloro-5-aminobenzoic acid from 3- (2- methyl-ln-octyl-3-indolyl) -5-chloro-6-ami-nophthalide and N-isopropylpyrrole in the presence of di-ethanolmethylamine according to Example 1, part B.

Example 56

Acid 2- [a - [(2-ethoxy-4-diethylamino) phenyl] a- (5-methoxy-3-indolyl)] methyl-5- (N-ethylbenzylamino) benzoic from 3- (5- methoxy-3-indolyl) -6- (N-ethylbenzyl-amino) phthalide and N, N-diethyl-2-ethoxyaniline in the presence of lithium hydroxide, according to Example 1, part B.

Example 57

2- [a- (2,3,4-trimethoxyphenyl) -a- (1-isoamyl-3-indolyl)] - methyl-5- (N-ethyl-N-butylamino) benzoic acid from 2- (2, 3,4-trimethoxyphenyl) -6- (N-ethyl-N-butyl-amino) phthalide and 1-isoamylindole in the presence of trietha-nolamine according to Example 1, part B.

Example 58

2- [a- (2-methoxy-3-chloro-4-diethylami-nophenyl) -a- (2-pyridinyl)] methyl-4-chloro-5-dimethylami-nobenzoic acid from 3- (2-pyridinyl ) -5-chloro-6-dimethyl-aminophthalide and N, N-diethyl-2-methoxy-3-chloro-aniline in the presence of citric acid, according to Example 2, part A.

Example 59

2- [2-bromo-2 ', 4' -bis- (diisopropylamino)] benzhy-dryl-5- [N-methyl-N- (4-chlorobenzyl) amino] benzoic acid from 3- (2-bromophenyl) -6- [N-methyl-N- (4-chloro-benzyl) -amino] phthalide and N, N, N ', N'-tetraisopropyl-m-phenylenediamine in the presence of 1,4-diazabi-cyclo [ 2,2,2] octane, according to Example 1, part B.

Example 60

2 - [(2-methyl-2-fluoro-4-N-methylben-zylamino-4'-dibutylamino) -4-bromo-5-ethylaminoben-zoic acid from 3- [2-methyl-4- (N -methylbenzyl-amino) phenyl] -5-bromo-6-ethylaminophthalide and N, N-dibutyl-3-fluoroaniline in the presence of phosphoric acid according to Example 2, part A.

Example 61

2 - [(2 '-hioro-3-propoxy-4-Ns-butyl-benzylamino) -benzhydryl] -5- (N-ethyl-N-methylamino) benzoic acid from 3- (2-fluorophenyl) -6- (N-ethyl-N-methyl) aminophthalide and N-benzyl-Ns-butyl-2-pro-poxyaniline in the presence of boron trifluoro according to Example 26, part A.

Example 62

2- [a- (3-indolyl) -ct- (2-phenyl-5,6-dichloro-3-indolyl)] - methyl-4-fluoro-5- (N-propyl) aminobenzoic acid from 3- ( 3-indolyl) -5-fluoro-6-propylaminophthalide and 5,6-dichloro-2-phenylindole in the presence of glycolic acid according to Example 2, part A.

Example 63

Acid 2- [a- (2-iodo-4-Nn-butylbenzylaminophenyl) -a- (ln-butyl-2-phenyl-3-indolyl)] methyl-5-N-ethyl-aminobenzoic acid from 3- (ln -butyl-2-phenyl-3-indolyl) -6-ethylaminophthalide and N-benzyl-N-butyl-3-iodoaniline in the presence of hydrochloric acid according to Example 2, part A.

Example 64

2- [a- (2-methoxy-4-diethylaminophenyl) -a- (1-methyl-6-nitro-3-indolyl)] methyl-5-N-methyl-aminobenzoic acid from 3- (2-methoxy -4-diethylamino-phenyl) -6-methylaminophthalide and 1-methyl-6-nitroindole in the presence of toluenesulfonic acid, according to Example 2, part A.

Example 65

2- [a- (3-butoxyphenyl) -a- (2-isopropyl-3-indolyl)] - methyl-5-aminobenzoic acid from 3- (3-butoxy-phenyl) -6-aminophthalide and 2- isopropylindole in the presence of phosphorus oxychloride, according to Example 2, part B.

We will see that if we follow an oxidation procedure chosen from those described in Example 1, part C; example 2, part B, example 3, part B or example 27, part B, for oxidizing the appropriate 2- (aYaZ) methyl-4-X-5-N (R2) -benzoic acid, the compounds of Examples 66 to 80 are obtained.

Example 66

3- (2-Methylphenyl) -3- (3-isopropyl-4-diethylamino-phenyl) -6- [N-methyl-N- (4-methylbenzyl)] aminophthalide from acid 2 - [(3-isopropyl -4-diethylamino-2'-methyl) benzhydryl] -5- [N-methyl-N- (4-methyl-benzyl) amino] benzoic.

Example 67

3- (1-Ethyl-2-phenyl-3-indolyl) -3- [4- (N-isobutyl-N-ethyl-

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amino) -phenyl] -5-iodo-6-diethylaminophtaIide from acid 2- [a- (1 -ethyl-2-phenyl-3-indolyl) -a- [4- (N-isobutyl-N- ethylamino) -phenyl)) methyl-4-iodo-5-diethylamino-benzoic.

Example 68

3- (4-Pyridinyl) -3- (4-diethylamino-2-propoxy-phenyl) -6-dibenzylaminphthalide from acid 2- [a- (4-pyridinyl) -ct- (4-diethyl-amino -2-propoxy-phenyl)) methyl-5-dibenzylaminobenzoic acid.

Example 69

3- [1 - (4-Bromobenzyl) -2-isopropyl-3-indolyl] -3- (2,3-dime-thoxyphenyl) -6-diethylaminophthalide from 2- | a- [l- ( 4-bromobenzyI) -2-isopropyl-3-indolyl] -cc- (2,3-dime-thoxyphenyl) | -methyl-5-diethylaminobenzoic acid.

Example 70

3- (2-Methyl-1 -n-octyl-3-indolyl) -3- (N-isopropyl-3-pyr-rolyl) -5-chloro-6-aminophthalide from acid 2- [a- (2-methyl-1 -n-octyl-3-indolyl) -a- (N-isopropyl-3-pyr-rolyl)] methyl-4-chloro-5-aminobenzoic acid.

Example 71

3- (2-Ethoxy-4-diethylaminophenyl) -3- (5-methoxy-3-indolyl) -6- (N-ethylbenzylamino) phthalide from 2- (a- [2-ethoxy-4- diethylamino) phenyl] -a- (5-methoxy-3-indolyl)} methyl-5- (N-ethylbenzylamino) benzoic.

Example 72 3- (2,3,4-Trimethoxyphenyl) -3- (1 -isoamyl-3-indolyl) -5- (N-ethyl-N-butylamino) phthalide from 2- [a- ( 2,3,4-trimethoxyphenyl) -a- (1-isoamyl-3-indolyl)] methyl-5- (N-methyl-N-butylamino) benzoic.

Example 73

3- (2-Methoxy-3-chloro-4-diethylaminophenyl) -3- (2-pyri-dinyl) -5-chloro-6-dimethylaminphthalide from 2- [a- (2-methoxy-3) acid -chloro-4-diethylaminophenyl) -a- (2-pyri-dinyl)] methyl-4-chloro-5-dimethylaminobenzoic acid.

Example 74

3- (2-Bromophenyl) -3- [2,4-bis (diisopropylamino) -phenyl] -6- [N-methyl-N- (4-chlorobenzyl) amino] phthalide from acid 2 - {(2 -bromo-2 ', 4' -bis (diisopropyl-amino)] benzhydryl) -5- [N-methyl-N- (4-chlorobenzyl) amino] -benzoic acid.

Example 75

3- (2-Methyl-4-N-methylbenzylaminophenyl) -3- (2-fluoro-4-dibutylaminophenyl) -5-bromo-6-ethylaminophthalide from acid [(2-methyl-2'-fluoro-4 -N-methylbenzyl-amino-4'-dibutylamino) -benzhydryl] -4-bromo-5-ethylami-nobenzoic acid.

Example 76

3- (2-Fluorophenyl) -3- [3-propoxy-4- (Ns-butylbenzyl-amino) phenyl] -6- (N-ethyl-N-methyl) aminophthalide from acid 2 - [(2 '-fluoro-3-propoxy-4-Ns-butylbenzylamino) -benzhydryl] -5- (N-ethyl-N-methyl) aminobenzoic acid.

Example 77

3- (3-Indolyl) -3- (2-phenyl-5,6-dichloro-3-indolyl) -5-fluoro-6- (N-propyl) aminophthalide from 2- [a- ( 3-indolyl) -a- (2-phenyl-5,6-dichloro-3-indolyl)] methyl-4-fluoro-5- (N-propyl) -aminobenzoic acid.

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Example 78

3- [2-Iodo-4- (Nn-butylbenzylamino) phenyl] -3- (ln-butyl-2-phenyl-3-indolyl) -6-N-ethylaminophthalide from 2- (a- [ 2-iodo-4- (Nn-butylbenzylamino) -s phenyl] -a- (l -n-butyl-2-phenyl-3-indolyl)) - methyl-5-N-ethyl-aminobenzoic acid.

Example 79

3- (2-Methoxy-4-diethylaminophenyl) -3- (1-methyl-6-nitro-3-indolyl) -5-N-methylaminophthalide from 2- [a- (2-methoxy- 4-diethylaminophenyl) -a- (1-methyl-6-nitro-3-indoIyl)] methyl-5-N-methylaminobenzoic acid.

Example 80

is 3- (3-Butoxyphenyl) -3- (2-isopropyl-3-indolyl) -6-amino-phthalide from 2- [a- (3-butoxyphenyl) -a-2-iso-propyl acid -3-indolyl)] - methyl-5-aminobenzoic acid.

Example 81

The use of the compounds of formula I to III and of the compounds described in Examples 1 to 80, as color generating components in microencapsulated pressure-sensitive reproduction systems, is illustrated with reference to the product of Example 1 , part C.

A. Stirred at about 50 ° C for about 45 minutes, a mixture of 196 ml of distilled water and 15.0 g of pigskin gelatin. A heated solution (about 50 ° C) of 49.0 g of alkylated biphenyls and 1.0 g of 3- [2,4-bis (dimethylamino) phenyl] -3- (4-dimethyl- Aminophenyl) -6-dimethylaminophthalide (formula I: R = CHs; X = H; Y = 4- (CH3) 2NC6H4; Z = 2.4 - [(CH3) 2N] 2C6H3, prepared as described above in the example 1,

Part C. The resulting solution is stirred for about 15 minutes. Then a second solution of 81.0 ml of distilled water and 10.0 g of gum arabic is prepared and heated to about 50 ° C for about 1 hour.

B. The two solutions are mixed, the first containing water gelatin, alkylated biphenyls and the product, and the second containing water and gum arabic, and the pH is adjusted to 9 by adding approximately 0 , 7 ml of 20% aqueous sodium hydroxide. The resulting mixture is transferred to a larger reactor equipped with a variable speed mixer [Eppenbach Homo-Mixer (Gifford-Wood Co. Hudson, NY)] with a power of 0.37 kW, and is added in two at 45 minutes 650 ml of distilled water which was heated to 50 ° C. While the agitator is running at an applied voltage between 20 and 25 V, enough 10% aqueous acetic acid is slowly added to bring the pH to 4.5, this being the point at which coacervation begins. The speed of the agitator is increased by increasing the applied voltage to approximately 30 V and approximately 4 drops of 2-ethyl-hexanol are added to suppress foaming. After approximately 20 minutes, the sample of the suspension is examined under a microscope and it is found to be stabilized at a particle size between 20 and 25 microns, and an external bath is then immediately placed around the reactor containing the suspension. water and ice. At about 20 ° C, the stirring speed is reduced by reducing the applied voltage between 20 and 25 V. The cooling is continued and at about 15 ° C 60 10.0 ml of glutaraldehyde are added in 5 minutes. When the internal temperature reaches 10 ° C., the stirring speed is further reduced by lowering the applied voltage to approximately 20 V and these conditions are maintained for approximately 30 minutes. At this point, the mixer is replaced by a laboratory stirrer of the conventional paddle type and the suspension is stirred for an additional 3 hours, during which time the temperature is allowed to return to ambient temperature. The microencapsulated product is isolated by pouring the suspension into

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through a 1 mm stainless sieve, to remove all large agglomerates and the capsules are collected by filtration. The capsules collected are then washed with four 100 ml portions of distilled water and stored as a wet paste of water. A sample of the pulp analyzed by drying under vacuum at 80 ° C. appears to contain 37.5% solids.

C. To 125 ml of distilled water, 10.6 g of oxidized corn starch are added over 10 to 15 minutes, with stirring. This mixture is heated to a temperature of 70 to 80 ° C and held there until all of the starch dissolves. The starch solution is cooled to room temperature and then 100 g of wet water paste containing the capsules from the previous part B and 43.0 ml of distilled water are added. The capsules and the starch solution are mixed at room temperature using an Eppenbach Homo-Mixer, at an applied voltage of 25 V for 5 minutes and then at an applied voltage at 30 V for an additional 5 minutes to complete suspending the capsules in the starch solution.

D. The starch and microcapsule suspension prepared in part C above is coated on sheets of paper, to a thickness of about 40 microns and dried to

look the coated paper. The coated paper is assembled with the colorless microencapsulated precursor as the top sheet of a bundle, placing the coated side in contact with the coated side of a commercially available receiving sheet coated with a color developer. electron acceptor type. More particularly, in this test, papers coated with a phenolic resin or an acid clay are used. An image is then drawn with a stylus on the upper sheet carrying on the back the colorless microencapsulated precursor, which causes the microcapsules concerned to rupture, thus allowing the colorless precursor solution contained by said microcapsules to flow and come in contact with the color developing substance on the receiving sheet, which enables a dark blue color image to be quickly formed.

When evaluated in a duplication system prepared and tested as described above, the product of Example 6, part B, 3- (2-ethoxy-4-diethylaminophenyl) -3- (4-dimethylaminophenyl ) -6-dimethylphthalide (formula I: R = CH3; X = H; Y = 2-C2H50-4- (C2H5) 2NCÔH3; Z = 4- (CH3) 2NCÔH4), produces a developed image of blue color; the product of Example 10, part B, 3- [4- (N-ethylbenzylamino) phenyl] -3- (1-ethyl-2-methyl-3-indolyl) -6-dimethylaminophthalide 45 (formula I: R = CH3; X = H; Y = 4- (C6HsCH2) - (C2H5) NC6H4; Z = 1-C2H5-2-CH3-3-indolyl), produces a developed purple image;

the product of Example 24, part A, 3- (1-ethyl-2-methyl-3-indolyl) -6-dimethylaminophthalide so

(formula II: R = CHs; X = H; Y = 1-C2Hî-2-CH3-3-indolyl), gives a developed image of light red color; the product of Example 10, part A, 3- [4- (N-ethylbenzyl-amino) phenyl] -6-dimethylaminophthalide (formula II:

R = CHs; X = H; Y = 4- (C6H5CH2) - (C2H5) NC6H 4, ss gives a developed image of green color; the product of Example 8, part A, 3- (4-diethylaminophenyl) -6-dimethylaminophthalide (formula II:

R = CHs; X = H; Y = 4- (C2Hs) 2NC6H4, gives a developed image of green color; the product of Example 2, 60 part A, 2- [a- (1-ethyl-2-methyl-3-indolyl) -a- (4-dime-thylaminophenyl)] methyl-5-dimethylaminobenzoic acid ( formula III: R = CHs; X = H; Y = 4- (CH3) 2NC6H4; Z = 1-C2Hs -2-CH3-3-indolyl), gives a developed image of purple color; the product of Example 1, part B, acid 65

2- [2,4,4 '-tris (dimethyl amino) benzhydryl] -5-dimethylaminobenzoic acid (formula III:

R = OHs; X = H; Y = 4- (CH3) 2NC "H4; Z = 2.4 - [(CH3) 2N] 2C6-

H4, gives a developed image of bluish purple color.

Example 82

The usefulness of the compounds of formulas I to III, the preparations of which are described in the preceding examples, as color-generating components in thermal marking systems, is illustrated by the incorporation and testing of the compound of the example. 1, part C, 3- [2,4-bis (dimethyla-mino) phenyl] -3- (4-dimethylaminophenyl) -6-dimethylami-nophthalide (formula I: R = CH3; X = H; Y =

4- (CH3) 2NC6H4; Z = 2.4 - [(CH3) 2N] 2CêH3, in heat-sensitive marking paper. The test paper is prepared according to a procedure similar to that described in the US patent. No 3,539,375.

A. A mixture of 2.0 g of 3- [2,4-bis (dimethyl-amino) phenyl] -3- (4-dimethylaminophenyl) -6-dimethylami-nophthalide is introduced into a container placed in a mechanical stirrer. 8.6 g of a 10% aqueous solution of polyvinyl alcohol (about 99% hydrolyzed), 3.7 g of water and

31.6 g of 1.6 mm diameter zirconium grinding balls. Agitation is carried out for one hour. The zirconium beads are then removed by draining the mixture on a 420 micron mesh opening sieve.

B. In the same way, a mixture of 9.8 g of 4,4-isopropylidine diphenol (Bisphenol A) and 42.0 g of a 10% aqueous solution is introduced into a container placed in a mechanical stirrer. polyvinyl alcohol (approximately 99% hydrolyzed), 18.2 g of water and 221.2 g of 1.6 mm diameter zirconium grinding balls. After one hour of stirring, the zirconium beads are removed by draining on a 420 micron sieve.

C. A coating composition is prepared by mixing 2.1 g of the suspension of A and 47.9 g of the suspension of B. The mixture is then uniformly coated on sheets of paper to thicknesses of approximately 75 microns and the coated sheets are air dried. The coated paper is tested by drawing a pattern on the coated side of the paper placed on a smooth flat surface, with a stylus heated to about 130 ° C. A dark purple image quickly forms corresponding to the drawn drawing.

When evaluated in a thermal labeling system by heating with Bisphenol A, the product of Example 6, part B, 3- (3-ethoxy-4-diethylamino-phenyl) -3- (4-dimethylaminophenyl) -6-dimethylphthalide (formula I: R = CHs; X = H; Y = 2-C2HsO-4- (C2H5) 2N-C6H3; Z = 4- (CH3) 2NC6H4), gives a developed image of ■ blue color; the product of Example 10, part D, 3- [4- (N-ethylbenzylamino) phenyl] -3- (1-ethyl-2-methyl-3-indolyl) -6-dimethylaminophthalide (formula I: R = CH3; X = H; Y = 4- (C6H5CH2) (C2H5) NC "H4; Z = 1-C2Hs-2-CH3-3-indolyl), gives a developed image of dark blue color; the product of Example 24, part A, 3- (1-ethyl-2-methyl-3-indolyl) -6-dimethylami-nophthalide (formula II: R = CH3; X = H; Y = I-C2H5 -2-CH3-3-indolyl), gives a developed image of purple color; the product of Example 10, part A, 3 - [4- (N-ethylbenzylamino) - phenyl] -6-dimethylamino-phthalide (formula II: R = CH3; X =

H; Y = 4- (CeHsCH2) (C2Hs) NC6H4), gives a developed image of green color; the product of Example 12, part A, 3- (4-methoxyphenyl) -6-dimethylaminophthalide, formula II: R = CH3; X = H; Y = 4-CH3-OC6H4), gives a developed image of yellow color; the product of Example 14, part A, 3- (4-ethoxyphenyl) -6-dimethylaminophthalide (formula II: R = CH3; X = H; Y = 4-C2H50C6H4),

gives a developed yellow image; the product of Example 21, part A, 3- [1- (3,4-methyl)

Ienedioxy) phenyl] -6-dimethylaminophthalide (formula II: R = CH3; X = H; Y = 1 - (3,4-0CH20C6H3), gives a developed image of yellowish brown color; the product of Example 1, part B, 2- [2,4,4 '-tris (dimethylamino) -benzhydryl] -5-dimethylaminobenzoic acid (formula III: R = CH3; X = H; Y = 4- (CH3) 2NC6H4; Z = 2,4 - [(CH3) 2N] 2CôH3), gives an image

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developed color blue color; the product of Example 2, part A, 2- [a- (4-dimethylaminophenyl) -a- (1 -ethyl-2-methyl-3-indolyl) -methyl] -5-dimethylaminobenzoic acid (formula III :

s R = CHs; X = H; Y = 4- (CH3) 2NC6H4; Z = 1-C2H5-2-CH3-3-indolyl), gives a developed image of purple color.

b