IE45772B1

IE45772B1 - Process for preparing phthalide color-formers and novel substituted 5-aminobenzoic acid derivatives

Info

Publication number: IE45772B1
Application number: IE188777A
Authority: IE
Original assignee: Sterling Drug Inc
Priority date: 1976-09-24
Filing date: 1977-09-13
Publication date: 1982-11-17
Also published as: DE2742909A1; FR2368466A1; CH628922A5; GB1590915A; GB1590913A; AR224099A1; FR2371418A1; IT1198303B; FR2368486A1; GB1590914A; CA1088938A; DK422577A; LU78163A1; JPS5356224A; AU2899477A; AU517656B2; MX149663A; BR7706358A; IE771887L; BE858929A

Abstract

Compounds of formula III are prepared by condensation of the corresponding lactone (phthalide) with a compound H-Z with opening of the lactone ring. The symbols employed are explained in Claim 1. The compounds obtained can be converted by oxidation of the compound III to re-form the lactone. The compounds described are employed as colour-generating substances in a duplication system without carbon paper.

Description

This invention relates to novel 2-(a,a-aryl- and/or heteryl-disubstituted)methyl benzoic acids and to their use in a process for the'preparation of 3,‘3-aryl- and/or hefeeryl-disubstituted phthalides useful in the art of carbonless duplicating as, for example, in pressure-sensitive systems and in thermal marking systems.

Several classes of organic compounds of widely diverse structural types are known to be useful as colorless precursors for carbonless duplicating systems. Among the more important classes, there may be named phenothiazines, for examples, benzoyl leuco methylene blue; phthalides with which this invention is concerned, for example, crystal violet lactone; fluorans, for examples, 2'--anilino-S'-diethylaminofluoran and 2'-dibenzylamino-6'-diethylaminofluoran; and various other types of colorless precursors currently employed in commercially accepted carbonless copy systems. Typical of the many such systems taught in the prior art ate those described in O.S. Patents 2,712,507; 2,800,457 and 3,041,289.

The following items to date appear to constitute the most relevant prior art with regard to the present invention.

Rodionov and Fedorova in the Bulletin de I'Academie des Sciences de l'ORSS Classe des Sciences Chemie 81-8 (1940) [Chemical Abstracts 35; 2488^ (1941)] described the preparation of 3-aryl-substituted' phthalides, for example, 3-(4-dimethy1-24577 aminophenyl)-phthalide, 3-(4-diethylaminophenyl)-6,7-dimethoxyphthalide and 3-(4-ethylmethylaminophenyl)-6,7-dimethoxy phthalide by heating the appropriate Ν,Ν-dialkylaniline with the appropriate phthalaldehydic acid. The physical characteristics of the compounds are described without giving any indication as to their utility. Noland and Johnson in the Journal of the American Chemical Society 82, 5143-5147 (1960) described the preparation of 3-heteryl-substituted phthaiides, for example, 3-(1,2-dimethyl-3-indolyl)phthalide, 3-(2-methy1-3-indolyl)—6,7— dimethoxy phthalid'e and other isomers by fusing equimolar proportions of an indole and a phthalaldehydic acid. Physical data are given for the compounds and there is no Indication of their utility. Rees and Sabet in the Journal of the Chemical Society, 680-687 (1965) described the preparation and physical character15 istics of 3-(3-indolyl)phthalide. There is no indication of the utility of the compound in the reference which is prepared by the acid-catalyzed interaction of indole and phthalaldehydic acid. In the same reference, Rees and Sabet described the preparation and physical characteristics of a,α-di-(3-indolyl)20 2-methylbenzoic acid prepared by the interaction of 3-(3-indolyl)phthalide with indole in refluxing alcoholic potassium hydroxide.

No utility of the compounds is given in the reference.

U.S. Patents 2,742,483 and 3,185,709, disclose 2-(4,4 ’’-bis-(dimethylamino)benzhydryl]-5-dimethylaminobenzoic acid which Is obtained from the interaction of m-dimethylaminobenzoic acid and 4,4*-bis(dimethylamino)benzhydrol. The compound is described as the intermediate to 3,3-bis(4-dimethylaminophenyl)6-dimethylaminophthalide which according to the earlier patent, is obtained by permanganate oxidation and according to the later patent, by oxidation with molecular oxygen. The 3,3-bis(4-dimethy1 -345772 aminophenyl)-6-dimethylaminophthalide (crystal violet lactone) is well knojm as a colorless precursor for carbonless duplicating systems.

Belgian Patent. 808,535 discloses 3-[2,4-bis(dimethylamino) phenyl]-3-(4-dimethylaminophenyl)-6-dimethylaminophthalide and similar compounds which are prepared by condensing the appropriate o-(4-dialkylaminobenzoyl)benzoic acid with the appropriate Ν,Ν,Ν',N'-tetraalkyl-m-phenylenediamine. These compounds are described as being useful as colorless precursors for carbonless duplicating systems.

U.S. Patent 3,491,112 discloses 3-(4-dimethylaminophenyl)-3-(1,2-dimethyl-3-indolyl)-6-dimethylaminophthalide which is prepared by condensing 4,4'-bis-(dimethylamino)benzophenone2- carboxylic 'acid- and 1,2-dimethylindole. The compound has utility as a colorless precursor for carbonless duplicating systems U.S. Patent 3,829,322 discloses 3-(2-methyl-4-Nethyl-benzylaminophenyl)-3-(l-ethyl-2-methyl-3-indolyl)-6-dimethylaminophthalide which is prepared by interacting l-ethyl-2-methyl3- (4'-dimethylamiho-2'-carboxybenzoyl)-indole and N-benzyl-Nethyl-3-methylaniline. The compound has utility as a colorless precursor for carbonless duplicating systems.

Japanese Patent Publication No. Sho 50-124930, describes a series of compounds having the formula wherein each of Rl and Rj represents a hydrogen atom, a lower alkyl, haloalkyl, alkoxyalkyl, acyloxyalkyl, cyanoethyl, allyl, propargyl, cyelohexyl, benzyl or phenyl in which the benzene -445772 ring may be substituted by lower alkyl, halogen, nitro or lower alkoxyl radical^ or Rj_ and R2 together may form a heterocyclic ring with the adjacent nitrogen atom; R3 represents a hydrogen atom or chlorine atom; R4 represents a benzene ring or hetero5 cyclic ring which may be substituted. According to the reference, the compounds are prepared by the condensation of an appropriate aromatic aldehyde and an appropriate benzoic acid at an elevated temperature in the presence of a dehydrating agent and are described as colorless precursors in carbonless, pressure-sensi10 tive and thermal copy systems.

The overall process employed by the present invention involves three steps which comprise ii) condensing a 3-N(R)2-*4-Xbenzoic aeid with an aromatic or heterocyclic aldehyde of the formula Y-CHO in the presence of an acid condensing agent under dehydrating conditions to produce a 3-Y-5-X-6-N(R)2phthalide (Formula II); (ii) condensing said phthalide with a compound of the formula Z-H in the presence of an alkaline or an acid condensing agent to produce a 2(a-Y'«-z)methyl-4-X-5-N(R)2benzoic acid (Formula III), and (iii) oxidizing said benzoic acid to produce a 3-Y-320 Z-5-X-6-N(R)2Phthalide having the formula FORMULA I wherein each R independently represents hydrogen, non-tertiary alkyl of one to four carbon atoms, benzyl or benzyl substituted in the benzene ring by one or two of halo or alkyl of one to three carbon atoms; X represents hydrogen or halo; Y represents a mono-5' valent radical Jiavijig one of the formulae (6) (H) Z represents a monovalent 'radical having one of the formulae (A), (B) or (G) above in which represents hydrogen, nontertiary alkoxy, of one to four carbon atoms, dialkylamino or N-alkylbenzylamino in which alkyl is non-tertiary alkyl of one to four carbon atoms, R2 represents hydrogen, alkyl of one to three oarbon atoms or non-tertiary alkoxy of one to four- carbon atoms, represents hydrogen, alkyl of one to three carbon atoms, non-tertiary alkoxy of one to four carbon atoms, halo or dialkylamino in which alkyl is non-tertiary alkyl of one to four carbon atoms, R4 represents one or two of hydrogen, alkyl of one to three carbon atoms, alkoxy of one to three carbon atoms, halo or nitro, R5 represents hydrogen, non-tertiary alkyl of one to -645772 eight carbon atoms, alkenyl of two to four carbon atoms, benzyl or benzyl substituted in the benzene ring by one or two of halo or alkyl of one to.three carbon atoms, R6 represents hydrogen, alkyl of one to three carbon atoms or phenyl, and R? and R8 represent hydrogen or alkyl of one to three carbon atoms.

In accordance with the present invention there are provided novel compounds of Formula Formula III wherein R, X, Y and Z have the same respective meanings indicated in Formula I.

Following the above process one condenses a 3-N(R)2~ 4-X-benzoic acid with an aldehyde of the formula Y-CHO in the presence of an acid condensing agent under dehydrating conditions to produce a 3-Y-5-X-6-N(R)2Phthalide having the formula Formula II wherein R, X and Y have the same respective meanings indicated in Formula I.

One then condenses said phthalide of Formula II with a compound of the formula Z-H in the presence of an alkaline or an acid condensing agent to produce a 2-(a-Y-a-Z)roethyl-4X-5-N(R)jbenzoic acid of Formula III; this step is also the subject of the present invention. One then oxidizes said benzoic acid to produce a 3-Y-3-Z-5-X-6-N(R)2 phthalide of \ Formula I.

The 3-;Y-5-X-6-N(R)2phthalides of Formula II wherein R, X and Y are as defined above, which are useful as intermediates in the processes of this invention and are also useful as color precursors in carbonless duplicating and in thermal marking systems, are novel when Y is not (A) or (B). y ' I Preferred novel compounds of this type are of the Formula II wherein Y is bf the Formula (C), (D), (E)(F) or (G) wherein R, X, R7 and R® are as defined above.

The novel. 2-(a-Y-a-Z)methyl-4-X-5-N (R^bsnzoic acids of Formula III are useful as intermediates in the preparation of compounds of Formula I and are also useful as color precursors in carbonless duplicating and in thermal marking systems.

Preferred compounds of this type are of the Formula II wherein Y is of the-Formula (A) and Z is of the Formula (A), (B) or (G).

Another aspect of this invention relates to novel · classes of the compounds of Formula I. One such class of novel 3-(2-R3'-4-R1'-phenyl)-3-(2-R3-3-r2'-4-R1-phenyl)-5-X-6-N(R)220 phthalides, which are particularly useful as colorless precursors in the art of carbonless duplicating, have the formula -843772 wherein each R independently represents non-terriary alkyl of one to four carbon atoms; R^' represents hydrogen,non-tertiary alkcxy of one to four carbon atoms, N-alkylbenzylamino in whioh alkyl is non-tertiary alkyl of one to four carbon atoms or, when R3 is other than dialkylamino, dialkylamino in which alkyl is non-tertiary alkyl of one to four carbon atoms? R·'· represents dialkylamino in which 9 ί alkyl is nontertiary alkyl of one to four carbon atoms; R represents hydrogen or alkyl of one to three carbon atoms; R3 represents hydrogen, alkyl of one to three carbon atoms, non-tertiary alkoxy of one to four carbon atoms, halo or dialkylamino in which alkyl is nontertiary alkyl of one to four ο I carbon atoms; R represents hydrogen, alkyl of one to three carbon atoms, non-tertiary alkoxy of one to four carbon atoms or halo? X represents hydrogen or halo; and with the proviso that r2', r3, r3' and X cannot all be hydrogen at the same time, and are described and claimed in British Patent Specification No. 1590914.

Another such class represents the novel 3-(2-R2'-3R2-4-R1'-phenyl)-3-(l-R5-2-R6-5/G-R4-3-indolyl)-5-X-6-N(R)2phthalides of the formula X 772 (wherein each. R independently represents non-tertiary alkyl of one to fair carbon atoms; R^ represents hydrogen, non-tertiary alkoxy of one to four carbon atoms, N-alkylbenzylamino in which alkyl is nontertiary alkyl of one to four carbon atoms or, when at least one of R and RJ are other than hydrogen, dialkylamino in which alkyl is non-tertiary alkyl of one to four carbon atoms; R2 and R3'' each represent hydrogen, non-tertiary alkoxy of one to four carbon atoms or halo; R^ represents one or two of hydrogen, alkyl· of One to three carbon atoms, alkoxy or one to three carbon atoms, halo or nitro; R5 represents hydrogen, non-tertiary alkyl of one to eight carbon atoms, alkenyl of two to four carbon atoms, benzyl or benzyl substituted in the benzene ring by one or two of halo or alkyl of one to three carbon atoms; R® represents hydrogen, alkyl of one to three carbon atoms or phenyl; and X represents hydrogen or halo}, which are describedand claimed in British Patent Specification No. 1590915. -10Ai used herein, the term non-tertiary alkyl of one •to eight carbon·atoms means saturated monovalent aliphatic radicals, including branched chain radicals, for example, methyl, ethyl, propyl, isopropy'!, butyl, isobutyl, amyl, 15 methylbutyl, 3-methylbutyl, hexyl, isohexyl, heptyl, isoheptyl, octyl, isooctyl and 2-ethylhexyl.

When the terms 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 herein, there is meant saturated, acyclic groups which may' be straight or branched as exemplified by methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, and isobutoxy.

As used herein, the term alkenyl, of two to four carbon atoms means a monovalent aliphatic radical possessing a single double bond, for example, ethenyl (or vinyl), 2-propenyl (or allyl), 1-methylethenyl (or isopropenyl), 2-methyl-2-pro~ penyl, 2-methyl-l-propenyl, 2-butenyl and 3-butenyl.

When the term halo is used herein, there are included chloro, fluoro, bromo and iodo. The preferred halo sub20 stituent is chloro because the other halogens offer no particular advantages over chloro and because of the relatively low cost and ease of preparation of the required chloro intermediates. However, the other above-named halo substituents are also satisfactory, The term N-alkylbenzylamino as used herein, means an amino radical substituted by an alkyl substituent and a benzyl substituent in which the benzene ring may be unsubstituted or substituted by one or two of halo or alkyl of one to three carbon atoms. -1145772 As used herein, the term alkaline condensing agent is intended to be in'clusive of both inorganic and organic basic compounds as exemplified hereinafter.

The compounds depicted by Formula III have been 5 designated as 2-(a-Y-a-Z)methyl-4-X-5-N(R)2benzoic acids. This nomenclature defines compounds of Formula III in which the methyl group in the 2-position can bear two aromatic moieties, two heterocyclic moieties or one aromatic and one heterocyclic moiety. However, throughout this specification, wherever possible, those species defined by Formula III having two phenyl moieties attached to the 2-methyl carbon atom have been named by using the more conventional benzhydryl designation for diphenylmethyl groups.

The processes of this invention afford a novel con15 venient and economically advantageous synthetic route to a large number of both known and novel compounds as final products which are 3,3-disubstituted phthalides of the type represented by Formula I. Many species defined by Formula I are well-known to be useful as colorless precursors in carbonless duplicating systems, for example, 3,3-bis(4-dimethylaminophenyl)6-dimethylaminOphthalide or, as this compound has been more simply designated, crystal violet lactone, 3-(4-dimethylaminophenyl)-3-(1,2-dimethyl-3-indolyl)-6-dimethylaminophthalide described in U.S. Patent 3,491,112, and 3-/2,4-bis(dimethylamino)25 phenyl]-3-(4-dimethylaminophenyl)-6-dimethylaminophthalide described in Belgian Patent 808,535.

The processes of this invention also afford 3-substituted phthalides of the type represented by Formula II and 2(a,a-disubstituted)methyl benzoic acids of the type represented by Formula III. The 3-substituted phthalides of Formula II are useful as intermediates to the 2-(a,a-disubstituted)methyl-1245772 benzoic acids of Formula III which in turn are useful as intermediates to the final products depicted by Formula I. Moreover, both the 3-substituted phthalides of Formula II and the 2-(a,/xdisubstituted)methyl benzoic acids of Formula III have been found to be useful as color precursors in pressure-sensitive carbonless duplicating systems and in thermal marking systems.

The compounds represented by Formulas I, II and III above are essentially colorless in the depicted form. When the compounds of Formulas I, II and III are contacted with an acidic medium for example, silica gel or one of the types regularly employed in pressure-sensitive carbonless duplicating systems, for example, silton clay or phenolic resins, they develop a colored image of good to excellent tinctorial strength. The development of color on contact with silica gel, silton clay or a phenolic resin demonstrates that these compounds are highly suitable for use as colorless precursors, that is, color-forming substances in pressure-sensitive carbonless duplicating systems. For such application, the compounds may be incorporated in any of the commercially accepted systems known in the carbonless duplicating art. A typical technique for such application is as follows. Solutions of the colorless precursor compounds in suitable aromatic solvents are microencapsulated by well-known procedures. The microcapsules are coated on the reverse side of a transfer sheet with the aid of a suitable binder and the coated transfer sheet is then assembled in a manifold with the microcapsUle coated side in contact with a receiving sheet coated with an electron accepting substance, for example, silton clay or a phenolic resin. Application of pressure to the manifold such as that exerted by a stylus, typewriter or other form of writing or printing causes the capsules on the reverse side to rupture. The solution of the color former released from the ruptured microcapsules flows to the receiving sheet and on con-134 5 7 7 2 tact with the acidic medium thereon forms a bluish-green to reddish-purple colored image of good tinctorial strength. It is, of course, obvious that variants of this mode of application can be utilized. For example, the receiving sheet in a manifold can alternatively be coated with the subject compounds and the acidic developing agent can be contained in microcapsules applied to the reverse side of the top sheet in the manifold.

It has also been found that when the compounds of Formulas I, II and III are intimately mixed with an acidic . developer of the type generally employed in thermal papers, that is, papers which produce a colored image when contacted with a heated stylus or heated type, for'example, bisphenol A, heating of the mixture produces a colored image of varying shades from yellow to purple depending on the particular compound of thd invention employed. The·ability of the compounds of Formulas I, II and III.to form a deep color when heated in admixture with an acidic developer such as bisphenol A, makes them useful in thermal .paper marking systems, either where an original or a duplicate copy is prepared by contacting the thermal paper with a heated stylus or heated type in any of the methods Λ generally known In the art.

In view of the utility of the .compounds represented by Formulas II, III, IV and V as described above, another aspect of this invention resides in pressure-sensitive carbon25 less duplicating systems and thermal paper marking systems containing as a color-forming substance the 2- (ce - Y-a-Z)methyl-4-X5-N(R).2^®Tizoic acids depicted by Formula III, wherein R,X,Y and Z have the meanings given above. Similar systems employing the compounds of formulas IV and'V are described and claimed in og 3ritish.Patent Specification Nos. 1590914 and 1590915 respectively. -1445772 The best mode contemplated by the inventors of carrying out this invention will' now' be described as to enable any person skilled in the art to which it pertains to make and use the same.

The 3-Y-S-X-6-N(R)2phthalides of Formula II, which are produced in the first step of the present process, are obtained by interacting approximately an equimolar quantity of an appropriate aromatic or heterocyclic aldehyde with an appropriate benzoic acid in the presence of an acid condensing agent. The reaction is conveniently carried out in a dehydrating solvent which also serves as' an acid condensing agent, for example, t 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 in the range of 80 to 140°C, but more desirably, 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 nonsolvent,· 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 aminohenzoic acids required as starting materials for the first step of the instant processes in which the products of Formula II are obtained form an old and wellknown class of compounds which are either commercially available or are readily obtained by conventional procedures well known -154S77S in the art. The following compounds are exemplary of aminobenzoic acids useful in the first, step of the processes of this invention to obtain 3-Y-5-X-6-N(R)2phthalides of Formula II. 3-Aminobenzoic acid, .5 3-Amino-4-chlorobenzoic acid, 3-Dimethylaminobenzoic acid, 3-Methylaminobenzoic acid, 3-(N-Ethy1-N-methylamino)benzoic acid, 3-Ethylamino-4-l^romobenzoic acid, 3-(N-Ethyl-N-butylamino)benzoic acid, 3-Diethylaminobenzoic acid, 3-(N-Ethylbenzylamino)benzoic acid, 3-D.ibenzylaminobenzoic acid, 3-Propylamino-4-fluorobenzoic acid, 3-Diethylamino-4-iodobenzoic acid, 3-Ethylaminobenzoic acid, 3-Dimethylamin0-4-chlorobenzoic acid,· 3-[N-Butyl-N-(4-chlorobenzyl)amino]benzoic acid, and 3-[N-Methyl-N-(4-methylben'zyl)amino]benzoic acid, The aromatic and heterocyclic aldehydes required as starting materials for the first step of the instant processes in which the 3-Y-5-X-6-N(R)2phthalides of Formula II are obtained constitute an old and well-known class of compounds many of which are commercially available or are readily obtained by conventional . syntheses well known in the art. The following list of compounds exemplifies aromatic and heterocyclic aldehydes useful in carrying out the first step of the processes of this -invention leading to the compounds of Formula I.

Benzaldehyde, 2-Methylbenzaldehyde, -164S772 2-Chlorobenzaldehyde, 2- Methoxybenzaldehyde, 3- Methoxybenzaldehyde, 4- Methoxybenzaldehyde, 2-Bromobenzaldehyde, 2- Ethoxybenzaldehyde, 3- Ethoxybenzaldehyde, 4- Ethoxybenzaldehyde, 2-Fluorobenzaldehyde, 4-Isopropylbenzaldehyde, 2.3- Dimethoxybenzaldehyde, 2.4- D imethoxyben zaldehyde, 2.5- Dimethoxybenzaldehyde, 3.4- Dimethoxybenzaldehyde, 3.5- Dimethoxybenzaldehyde, 2-Butoxy-4-diethylaminobenzaldehyde, 2-Methyl-4,5-dimethoxybenzaldehyde, 2- Chloro-4-dimethylaminobenzaldehyde, 3- F. thoxy-4-methoxy benzaldehyde, 2,3,4-Trimethoxybenzaldehyde, 2-Methoxy-4-dimethylaminobenzaldehyde, 2-Methoxy-4-diethylaminobenzaldehyde, 4- Dimethylaminobenzaldehyde, 4- Benzylaminobenzaldehyde, - Methoxyindole-3-carboxaldehyde, 4-(N-Methylbenzylamino)benzaldehyde, Indole-3-carboxaldehyde, N-Methylpyrrole-2-carboxaldehyde, 2- Pyridinecarboxaldehyde, 3- Pyridinecarboxaldehyde, -174S77S 4-Pyridinecarboxaldehyde, Pyrrole-2-carboxaldehyde, 2-Thiopheneoarboxaldehyde, N-Ethyl-3-carbazolecarboxaldehyde, Piperonal, 2-Methyl-l-ji-octylindole-3-carboxaldehyde, l-r>-Butyl-2-phenylindole-3-carboxaldehyde, 9-Formyljulolidine, 4-(N-Ethylbenzylamino)benzaldehyde, 2-Methyl-4-(N-methylbenzylamino)benzaldehyde, 1,2-Dime thylindole-3-carboxaldehyde, 1- Ethyl-2-phenylindole-3-carboxaldehyde, ’ 4-D i e thy1aminoben za1dehyde, 2- Methyl-4-diethylaminobenzaldehyde, and l-Ethyl-2-methylindole-3-carboxaldehyde.

The 2-(a-Y-a-Z)methyl-4-X-5-N(R)2benzoic acids of Formula III are prepared by interacting approximately an equimolar quantity of an appropriate 3-Y-5-X-6-N(R)2Phthalide of • I Formula IX with an appropriate aromatic or heterocyclic com20 pound of the formula Z-H wherein Z is defined in the same manner as in relation to Formulas I and III. In one set of reaction conditions, the 3-substituted phthalide and the aromatic or heterocyclic compound are interacted in the presence of an alkaline condensing agent, in dilute aqueous solution at a temperature of 90-160°C. The 2-(a-Y-a-Z)methyl-4-X-5-N(R)2benzoic acid of Formula III thus formed can optionally be isolated by carefully neutralizing the alkaline or basic reaction solution with dilute aqueous acid, collecting the separated product by filtration, and drying the solid by conventional means. Alternatively, the alkaline or basic reaction solution -184 57 72 u> κ containing the 2-(u-Y~a-Z)methyl-4-X-5-N(R)2benzoic acid of Formula III in the form of a salt can be used directly in the next step of the overall processes without isolation of the product in the free-acid form.

The following basic inorganic and organic compounds are exemplary of alkaline condensing agents useful in the second step of the processes of this invention to obtain 2(a-Y-a-zlmethyl-S-NfRjjbenzoic acids of Formula III: sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, lithium carbonate, ammonium hydroxide, tetramethylammonium hydroxide, tetraethylammonium hydroxide, tetrabutylammonium hydroxide, quinuclidine, 1,4diazobicyclo[2,2,2]octane, triethanolamine, and triethylamine.

In a second set of reaction conditions, the inter15 action of an equimolar quantity of an appropriate 3-Y-5-X-5NCRjjphthalide of Formula II and an appropriate aromatic or heterocyclic compound of formula Z-H can be carried out in the presence of an acid condensing agent, for example, an organic or inorganic acid at a temperature in the range of 70-120’C.

The 2-(a-Y-a-Z)methyl-4-X-5-N(R)2benzoic acid of Formula III thus produced is then isolated by adding the reaction solution to water, chilling the resultant mixture and collecting the separated product by filtration followed by drying it by conventional methods.

The following compounds are exemplary of organic and inorganic acids useful as acid condensing agents in the second step of the processes of this invention to obtain 2-(aY-a-Z)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, 19,. . 45772 hydrobromic acid, phosphorus oxychloride, phosphorus tribromide phosphorus trichloride, and phosphorus pentachloride.

In still a third set of reaction conditions, the 2-(ay-a-Z)methyl-4-X-5-N(R)2benzoic acids of Formula III are ob5 tained by the interaction of approximately an equimolar quantity of an appropriate 3-Y-5-X-6-N(R)2phthalide of Formula II and an appropriate aromatic or heterocyclic compound of formula Z-H.

The reaction is,conveniently carried out in the presence of an acid 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, perchloroethylene, carbon tetrachloride, nitrobenzene, and so forth or optionally in the presence of an excess amount of reactant Z-H as the solvent at a temperature in the range of -10 to 110°C. When an inert organic solvent is employed, the 2-(a-Y-a-Z)methyl-4-X-5HiRJgbenzoic acid thus formed is isolated by extracting the acid condensing agent with water from the organic phase followed by extraction.of the 2-(a-Y-a-Z)methyl-4-X-5-N(R)2benzoic acid from the organic layer 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, sodium hydroxide, collecting the separated product by filtration, and drying it by conventional means. Alternatively, when excess Z-H is used as the solvent, the 2-(a-Y-a-Z)methyl-4-X-5-N(R)225 benzoic acid formed is isolated by diluting the reaction mixture with water, rendering it basic by adding a dilute aqueous solution of a base, for example, sodium hydroxide and then steam-distilling the excess Z-H away from the mixture. After the removal of excess Z-H is complete, the mixture is slightly cooled and the pH adjusted to approximately 4.9 by the addition -2045773 ‘ ' of an acid, for example, acetic acid. The separated product is collected by filtration, washed with water and dried by conventional means.

The following compounds are exemplary of Friedel-Craft 5 catalysts useful as acid condensing agents in the second step of the processes of this invention for the production of 2-(α-Υ-αZ)methyl-4-X-5-N(R)2benzoic acids of Formula III: aluminum chloride, aluminum bromide, zinc chloride, zinc bromide, boron trifluoride, boron trichloride, boron tribromide, titanium tetra10 chloride, stannic chloride, stannic bromide, antimony trichloride, ferric fluoride, ferric chloride, ferric bromide, ferric iodide, phosphorus tribromide, phosphorus trichloride, and phosphorus pentachloride.

When ferric halide salts are employed as acid condens15 ing agents in the interaction of 3-Y~5-X-6~N(R)2phthalldes with an excess of Z-H, final products, that is, 3-Y-3-Z-5-X-6-N(R)2phthalides are obtained in significant quantitites as well as the corresponding precursor intermediates, 2-(a-Y-a-Z)methyl-4X-5-N(R)2benzoic acids. It appears that a significant quantity of the 2-(a-Y-a-Z)methyl-4-X-5-N(R)2benzoic acid resulting from the condensation of the 3-Y-5-X-6-N(R)2phthalide interacted with the Z-H, is oxidized in situ to the 3-Y-3-Z-5-X-6N(R)2phthalide in the presence of the ferric halide salts.

The aromatic and heterocyclic compounds represented by the.formula Z-H, which are required for interaction with the 3-Y-5-X-6-N(R)2phthalides of Formula II to obtain the 2-(α-Υ-αZ)methyl-4-X-5-N(R)2benzoic acids of Formula III form old and well-known classes of compounds readily obtained by conventional procedures well known in the art. The following list of com30 pounds exemplifies aromatic and heterocyclic compounds falling -214S772 within the ambit of the formula Z-H which are useful in the practice of the step in the processes of this invention for producing the aforesaid benzoic acids of Formula IXI. Ν,Ν,Ν’ jN’-Tetramethyl-m-p'henylenediamine, N,N-Dibutylaniline, N,N-Diethyl-3-ethoxyaniline, N,N-Diethyl-m-anisidine, N,N-Dimethylaniline, N-Benzyl-N-ethylaniline, N,N-Diethyl-m-toluidine N,N-Diethylaniline, N-Ethyl-N-methylaniline, N-Benzyl-N-methylaniline, N-Benzyl-N-propylaniline, N,N-Dlmethyl-3-bromoaniline, Ν,Ν,N',N'-Tetraisopropyl-m-phenylenediamine, N,N-D ibu ty1-3-fluoroani1ine, N,N-Diethyl-2-methoxy-3-chloroaniline, N-Benzyl-N-methyl-3-ethylaniline, Ν,Ν,N',N'-Tetra-sec-buty1-m-phenylenediamine, N-Benzyl-N-butyl-3-iodoaniline, N,N-Diisopropyl-3-chloroaniline, N-Benzyl-N-sec-butylaniline, N.N-Di-sec-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, -224577s Ν ,Ν, Ν ’, Ν ’-Tetrabutyl-m-phenylenediamine, Ν,Ν-Dipropyl-o-anisidine, N-Isobutyl-N-ethylaniline, Ν,Ν,Ν*,N’-Tetraethyl-m-phenylenediamine, N-Propyl-N-ethylaniline, N,N-Diethyl-2-ethoxyaniline, N-Benzyl-N-sec-butyl-2-propoxyaniline, N ,N-Dimethyl-m-toludine, Indole, 1- Methy1indole, 2- Methylindole, 1.2- Dimethylindole, 1- Ethyl-2-methylindole, 2- Phenylindole, l-Propyl-2-methylindole, l-j-Benzyl-2-methylindole, l-Butyl-2-methylindole, 1- Octyl-2-methylindole, 2- Ethyl-5-methylindole, l-Benzyl-5-fluoroindole, l-Methyl-6-nitroindole, -Methoxy-l-butylindole, l-Allyl-2-methylindole, 1.2- Dimethyl-6-nitroindole, 1- (4-Chlorobenzy1)-2-methy1-5-nitroindole, 2- Ethylindole, 2-Ethyl-l-methylindole, 1- Isopropylindole, 2- Isopropylindole, l-Methyl-S-bromo-6-nitroindole, -2345772 2.5.6- Trimethylindole, l-Isobutyl-2-methylindole, 6-Bromo-2-methylindole, 1-Hexylindole, 1- (2,5-Dimethylbenzyl)-2-methylindole, 2- Propylindole, 6-Chloro-2-phenylindold, 1-(2-Ethylhexyl)-2-methylindole, 1-(2,6-Dichlorobenzyl)-2-methylindole, 1- Vinyl-2-methy1indole, 2- Ethyl-6-methylindole, -Fluoro-l-benzylindole, I 1-(4-Bromobenzy1)-2-isopropylindole, 1-(3-Chlorobenzy1)-2-ethylindole, -Chloro-l-benzylindole, l-(2-Fluorobenzyl)-2-methylindole, ’ -Iodo-l-(1-methylhexyl) indole, .6- Dimethoxyindole, 1-(2-Methylbenzyl)-2-methylindole, .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 are obtained by oxidizing the appropriate 2-(a-Y-a-Z)methyl-4-X-5NiRJj^enzoic acids of Formula III. The oxidation is conventiently carried out in aqueous alkaline solutions, for example, potassium -244 5 7 7 2 hydroxide, at a temperature in the range of 20-l60°C, but more desirably at 80-160°C. The oxidizing agent can be molecular oxygen either in the form of gaseous oxygen or.air. Alternatively, a chemical oxidizing-agent, for example, potassium per5 manganate or hydrogen peroxide may be employed. Dependent on the temperature chosen, the oxidation is carried out either at atmospheric or superatmospheric pressures. The 3-Y-3-Z-5-X6-N(R)2phthalide thus produced is separated by filtration and dried by conventional means.

Alternatively, it has been found that the 3-Y-3-Z5«X-N(R)2phthaiides of Formula I can be conveniently obtained in satisfactory yields without separate isolation and oxidation of the 2-(ct-Y-a-Z)methyl-4-X-5-N(R)2benzoic acids of Formula III by carrying out the interaction of the appropriate 3-Y-5-X-615 N(R)2phthalide with an excess of reactant Z-H in the presence of a ferric halide as the acid condensing agent and using the reaction conditions described hereinabove. The desired 3-Y-3Z-5-X-6-N(R)2phthalide obtained by this telescoped procedure is isolated by. drowning the reaction mixture in dilute aqueous solution of a strong base, for example, sodium hydroxide, steam distilling away the excess Z-H, cooling to approximately 70°C, extracting the residue with a water-insoluble organic solvent, for example, toluene,and filtering the mixture to remove any insolubles. The organic layer containing the 3-Y-3-Z-5-X-625 N(R)2phthalide is separated from the alkaline aqueous phase which contains unoxidized 2-(a-Y-cc-Z)methyl-4-X-5-N(R)2benzqic acid, generally in small amounts. The desired phthalide is then isolated by concentrating the organic layer by evaporation or distillation, collecting the solid by filtration, followed by drying by conventional means. -2545772 Trie molecular structures of the compounds of this invention were assigned on the basis of the modes of synthesis and study of their infrared, nuclear magnetic resonance, and mass spectra and elemental analysis.

' The following examples will further illustrate the invention without, however, limiting it thereto. All melting points are uncorrected. -264 57? Example 1 A. A stirred mixture of 306.0 g of acetic anhydride, 200.0 ml of glacial acetic acid, 298.0 g £-dimethylaminoben2aldehyde and 386.0 g of m-dimethylarninobenzoic acid was heated at reflux for a period of approximately four hours. The resulting mixtyre was cooled to 55°C, diluted with 700 ml of methanol an'd heated at reflux for approximately thirty minutes. The mixture was then cooled to approximately 15°C and the solid which separated was collected by filtration and washed with 700.0 ml of fresh methanol chilled to 10-15°C. The methanolwet solid was reslurried in 400 ml of fresh methanol at 10-15°C for approximately twenty minutes, separated by filtration and washed with 150 ml of chilled methanol. The solid was dried at 70°C in vacuo to yield 453.2 g of 3-(4-dimethylaminopheny1)β-dimethylaminophthalide (Formula II: R=CH3; X=H; Y=4-(CH3)2Nwhich after recrystallization from toluene was obtained as an ivory-colored solid melting at 184.5-185.5°C.

Infrared spectral analysis showed a maximum at 1745 (C=0; s) cm-^ and the nuclear magnetic resonance spectrum was consistent with the assigned structure.

A toluene solution of this product spotted on an acid Clay or an acidic resin develops a green-colored image.

B. (i). A mixture of 6.0 g of 3-(4-dimethylaminophenyl)-6dimethylaminophthalide prepared as described in part A above, 100 mlof water, 3.5 g of Ν,Ν,Ν',N'-tetramethyl-m-phenylene-. diamine and 1.8 g of flake potassium hydroxide was heated at reflux with stirrin'g for a period of approximately eighteen hours and then allowed to cool to room temperature. The resultant solution was made slightly acidic by the addition of ten percent aqueous hydrochloric acid causing a cream-colored -2745772 solid to precipitate. The solid was collected by filtration, washed with water 'and air dried at 40°C to obtain 2-Γ2,4,4>tris(dimethylamino)benzhydryl]-5-dlmethylaminobenzoic acid (Formula III: R=C&3; X=H; Y=4-(CH3)2NCgH4; Zi=2,‘4-[(CH3)2N]2CgH3) as a slightly sticky, cream-colored solid melting over the range 119-121°C.

The nuclear magnetic resonance spectrum was in accord with the assigned structure and the infrared spectral analysis had a maximum at 1700 (C=0; b) cm ./ Repetition of the above10 described procedure but substituting 5.0 g of ammonium hydroxide in one instance ahd 5\. 52 g of potassium carbonate in another for the potassium hydroxide also yielded the 2-[2,4,4'-tris(dimethylamino) benzhydryl]-5-dimethylaminobenzoic acid.

C. A solution of 29.78 g of 2-[2,4,4'-tris(dimethylamino)15 benzhydryl]-5-dimethylaminobenzoic acid prepared as described in part B above, 450.0 g of water and 16.2 g of flake potassium hydroxide was prepared and the pH adjusted to 10.0 by the gradual addition of sodium bicarbonate. The solution was then heated at approximately 75°C under an atmosphere of oxygen at 60-65 psi for approximately six hours in an agitated stainless steel autoclave. The solid which separated was collected by filtration at ambient. temperature, washed with water until alkali free when tested with Brilliant Yellow test paper and dried. The dried solid was slurried with hexane at room temperature, filtered and dried to obtain 23.6 g of 3-(2,4-bis[dimethylamino]phenyl)3-(4-dimethylaminophenyl)-6-dimethylaminophthalide (Formula I: R=CH3; X=H; Y=4-(CH3)2NCgH4; Z=2,4-[(CH3)2N]2CgH3) a pale bluecolored solid melting at 171-172°C.

The nuclear magnetic resonance spectrum was in agree30 ment with the assigned structure and a significant infrared maximum appeared at 1755 (C=O; s) cm-1. -2845772 A benzene solution of the product spotted on silica gel, an acidic clay or a phenolic resin develops a deep grapecolored image.

Example 2 5a. A stirred mixture of 35.0 ml of glacial acetic acid, .9 g of 3-(4-dimethylaminophenyl)-6-dimethylaminophthalide prepared as in Example 1, part A above, and 3.3 g of 1-ethyl2-methylindole was heated at reflux for approximately fortyfive minutes. After cooling slightly below reflux temperature, .0 ml of methanol was added and cooling was continued to ambient temperature. The resulting solution was drowned in 500.0 ml of stirred ice water and, after approximately twenty minutes, the solid which separated was collected by filtration. The solid was slurried at ambient temperature with acetone and the slurry filtered. The collected solid was dried to obtain 4.1 g of 2-[g-(4-dimethylaminophenyl)-g-(l-ethyl-2-methyl-3indolyl)]methyl-5-dimethylamlnobenzoic acid (Formula III: R=CH3j X=H; Y=4-(CH3)2NC6H4; Z=l-C-2H5-2-CH3-3-indolyl) a‘light tancolored solid-melting at 224-228°C.

Infrared spectral analysis gave a significant maxima at 1585 (C=0; s) cm-1. The nuclear magnetic resonance spectra was consistent with the assigned structure. Analysis by mass spectrum showed m/e peaks at 455(M+) and 440(M+-CH3).

B, A mixture of 4.0 g of 2-[g-(4-dimethylaminophenyl)25 g-(l-ethyl-2-methyl-3~indolyl)]methy1-5-dimethylaminobenzoic acid prepared in part A above, 1.5 g of flake potassium hydroxide and 200.0 ml of water was stirred for approximately seventeen hours at 60-70°C under an atmosphere of oxygen. -The resulting mixture was cooled to room temperature and the suspended solid was collected by filtration, washed alkali free to Brilliant Yellow test paper with water and dried to obtain 1.5 g of 3-(4dlmethylaminophenyl)-3-(l-ethyl-2-methyl-3-lndolyl)-6-dimethyl-294577g aminophthallde (Formula I:. R=CH3; X=H; Y=4-(CH3)2NCgH4; Z=l-C2Hg-2-CH3-3-i'ndolyl) as a light grape-colored solid melting over the range 104-120°C.

The infrared spectral analysis showed maxima at 1760 (C=0; vs) and 1685 (C=0; w) cm-1.

A toluene solution of this product spotted on silica gel, an acidic clay or a phenolic resin develops a dark grape color.

Example 3 A. A stirred mixture of 100 ml of water, 1.8 g of flake potassium hydroxide, 6.0 g of 3-(4-dimethylaminophenyl)-6-dimethylaminophthalide prepared in Example 1, part A above, and 2.90 g of 1,2-dimethylindole was heated'at reflux for approx> \ imately seventy-five minutes and then set aside at ambient temperature for approximately sixty-four hours. The resulting solution was .divided into two equal portions. ' One of the portions was chilled by ’adding ice and slowly made acid by adding acetic acid and dilute hydrochloric acid. A tan-colored resinous solid slowly precipitated from the solution after sufficient sodium acetate was added to saturate the solution. The solid was collected by filtration, washed and air dried at ambient temperature. After recrystallization from denatured ethanol, there was obtained 2-[a-¢4dimethylamlnophenvl) -a- (1,2-dimethyl- 3-indole)Anethvl-5-dimethvlamlnobenzoic acid (Formula III: R=CH3j X=H; Y=4-(CH3)2NCgH4; Z=l,2-(CH3)2-3-indolyl) a cream-colored solid melting over the range 192-213°C. .

The nuclear magnetic resonance spectrum was in accord with the assigned structure and the infrared spectral analysis had a maximum at 1680 (C=0; s) cm-1. -304 5 7 7 2 B. To the second portion of the alkaline aqueous solution from part A, there was added with stirring 75 ml of toluene and 0. 7 g of potassium permanganate. The solution gradually changed from green to brown and a small amount of dilute aqueous sodium hydroxide was added to keep the mixture alkaline. The toluene layer was separated and evaporated leaving a tarry residue which was triturated with denatured ethanol to obtain 3-(4-dimethylaminophenyl )-3-(1,2-dimethy1-3-indolyl)-6-dimethylaminophthalide (Formula I: R=CH3; X=H; Y=4-(CH3)2NC5H4; Z=l,2-(CH3)2~3-indolyl) . a solid melting at 184-185°C.

The infrared spectrum had a maximum at 1745 (C=O; s) cnT^ and the nuclear magnetic resonance spectral analysis was concordant with the assigned structure.

A toluene solution of the product spotted on silica ’gel) an acidic clay or phenolic resin develops a grape-colored image.

Example 4 A. ' A mixture of 600 ml of water, 10.8 g of flake potassium hydroxide, 36.0 g of 3-(4~dimethylaminophenyl)-6-dimethylamino~ phthalide prepared as in Example 1, part A above, and 20.0 g of N,N-diethyl-m-toluidine was heated with stirring in a stainless steel autoclave at 120°C for approximately seven hours and at 160°C for approximately six hours. The resulting mixture was cooled to ambient temperature and filtered to remove the insol25 ubles. The obtained aqueous solution of the potassium salt of 2-[2-methyl-4,4’-bis(dimethylamino)benzhydryl]-5-dimethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=4-(CH3)2NCgH4; Z=4(CH3>2N-2-CH3CgH3) was utilized directly in the oxidation of the next part of this example. -3145772 B. The pH of the benzoic acid-potassium salt solution obtained in part. A directly above was·adjusted to 9.5 by the addition of sodium bicarbonate, the solution was heated at 80°C for approximately seven.hours under an atmosphere of oxygen at 60-65 psi. The resulting mixture was cooled to room temperature;' the solid which separated was collected by filtration and dried at room temperature. . The. solid was dissolved in toluene, treated with decolorizing charcoal and filtered. The toluene solution was extracted with 300 ml of 3N hydrochloric acid and separated.

The aqueous acid layer was adjusted to pH 5 by the addition of sodium acetate. The solid which separated was collected by filtration, washed wi'th water and dried in vacuo at 60°C to obtain 16.5 g of 3-(4-dimethylaminophenyl)-3~(4-diethylamino-2-methyl• phenyl)-6-dimethylaminophthalide (Formula I: R=CHg} X=H; n-C6H4> Z=4-(C2H5)2N-2-CH3-CgH3) a solid melting at 183-184°C.

The' nuclear magnetic resonance spectrum was in accord with the assigned structure. Analysis by mass spectrum showed a m/e peak at 457(M+). The infrared spectral analysis had a maximum at 1763 (C=0; s) cm-\ A toluene solution of the product spotted on silica gel, an acidic clay or a phenolic resin develops a grape-colored image.

Example 5 A. To a stirred mixture of 75.0 ml of monochlorobenzene, 7.4 g of 3-(4-dimethylaminophenyl)-6-dimethylaminophthalide and 2.2 g of N-methylpyrrole maintained at 0-5°C by means of an external ice-bath, there was slowly added 6.65 g of anhydrous aluminum chloride. After stirring for approximately three hours, there was slowly added with continued cooling at 0-5°C, 100 ml of water and 100 ml of ethylene dichloride. The layers were -324S772 separated and the organic layer extracted with 150 ml of fresh water. The organic Jlayer was then extracted with 100 ml of 3N hydrochloric acid,.separated and the pH of this aqueous acid layer adjusted to 4.5 with five percent aqueous sodium hydroxide solution. The green solid which had formed was collected by filtration. After reslurrying in a mixture of acetone and methanol, the solid was filtered and dried to obtain 5.2 g of 2- Cft-(4-dlmethylaminophenyl)-a-(l-methyl-2-pyrrolyl)]methyl-5dlmethylaminobenzoic acid (Formula III: R=CHj; X=H; Y=4-(CHj)210 NC6H4’ Z=»l-CH3-2-pyrrolyl).

A significant infrared maximum appeared at 1695 *-l (C=O; w) cm .

B. A mixture of 200 ml of water, 4.8 g of the product from part A directly above and 1.5 g of flake potassium hydroxide was stirred approximately eighteen hours at 60-70°C under an atmosphere of oxygen. The solid was collected by filtration, washed with water until alkali free to Brilliant Yellow test paper and dried to' obtain 2.0 g of 3-(4-d imethylaminophenyl)3- (l-methyl-2-pyrrolyl)-6-dimethylaminophthalide (Formula I: R=CHjj X=H; Y=(CH3)2NCgH4; Z=l-CHj-2-pyrrolyl) a gray-colored solid which melted over the range 168-184°C.

The infrared spectra showed maximum at 1765 (C=O; s) cm"\ A toluene solution of the product spotted on silica gel, an acid clay or a phenolic resin develops a purple-colored image.

’ Example 6 A. Following a procedure similar to that described in Example 4, part A above, 36.0 g of 3-(4-dimethylaminophenyl)-6dimethylaminophthalide prepared as described in Example 1, part A above and 23.0 gof 3-ethoxy-N,N-diethylaniline were,interacted to obtain a solution of the potassium salt of 2-C4l-dlethylamino-332'-ethoxy-(4-dlmethylamino)benzhydryl1-5-dimethylaminobenzolc acid (Formula III:t R=CH3; X=H; Y=4-(CH3)2NCgH4; Z=4-(C2H5)2N2-C2H3O-CgH3) which was used without isolation in the next step.

B. Proceeding in a manner similar to that described in Example 1, part C above, the potassium salt solution of 2-['4'diethylamino-2*-ethoxy-(4-dimethylamino)benzhydryl]-5-dimethylaminobenzoic acid from A was oxidized to obtain 6.8 g of 3-(4diethylamino-2-ethoxyphenyl)-3-(4-dimethylaminophenyl)-6-dimethylaminophthallde (Formula I: R=CH3; X=H; Y=4-(CH3)2NCgH4; Z=4-(C2H5)2N-'2-C2H3O-CgH3) a solid melting over the range 9399°C.

The infrared spectral analysis showed a maximum at 1755 (C=O; b, s) cm1. The nuclear magnetic resonance spectrum was in accord with the assigned structure. . Mass spectral analysis 1 ' ·. . . showed a m/e peak at 487(M ).

A toluene solution of the product spotted on silica gel, an acidic clay or a phenolic resin develops a deep bluecolored image.

' Example 7 ' A, Proceeding in a manner similar to that described in Example 4, part A above, 36.0 g of 3-(4-dimethylaminophenyl)-6dimethylaminophthalide prepared as in Example 1, part A above and 15.0 g of Ν,Ν-dimethylaniline were interacted to obtain a solution of the potassium salt of 2-[4,4l-bis(dimethylamino)25 benzhydryl]-5-dimethylaminobenzoic acid (Formula III; R=GH3; X=H; Y=Z=4-(CH3).,NCgH4) which was used without isolation in the next step.

B. Employing a procedure similar to that described in Example 1, part C'above, the potassium salt solution of 2'-[4,4'30 bis(dimethylamino)henzhydryl]-5-dimethylaminobenzoic acid from 3445773 A was oxidized to obtain 3,3-bis(4-dlmethylamlnophenyl)-6-dlmethylaminophthalIde (Formula I: R=CH3; X=H; Y=Z=4-(CH3)2NCgH4) a tan-colored solid.

A significant infrared maximum appeared at 1750 -1 f (C=O; s) cm . The nuclear magnetic resonance spectra was 'concordant with the assigned structure.

A toluene solution of the product spotted on silica gel, an acidic clay or a phenolic resin develops a blue-colored image. .

Example 8 A. Following a procedure similar to that described in Example 1, part A above, 11.6 g of. 3-dimethylaminobenzoic acid and 10.6 g of 4rdiethylaminobenzaldehyde were interacted to obtain 15.3 g of 3-(4-diethylaminophenyl)-6-dimethylaminophthalide (Formula II: R=CH3; X=H; Y=(C2H5)2NCgH4) a light brown solid melting in the range 127-128.5°C.

A significant infrared maximum appeared at 1745 —1 (C=0; s) cm . Nuclear magnetic resonance analysis v/as in accord with the assigned structure.

A toluene solution of the product spotted on an acid clay develops a greenish-blue-colored image.

B. Proceeding in a manner similar to that described in Example 1, part B above, 34.4 g of 3-(4-diethylaminophenyl)-6dimethylaminophthalide prepared as described in part A above and 16.9 g of l-ethyl-2-methylindole were interacted to obtain the potassium salt of 2-[a-(4-diethylaminophenyl)-a-(1-ethy1-2methyl-3-indolyl)]methyl-5-dimethylaminobenzoic acid (Formula III: R=CH3; X=sH; Y=(C2H5)2NC6H4; Z=l-C2H5-2-CH3-3-indolyl) which was not isolated but taken directly into the next step. -35C. Employing a procedure similar to that described in Example 1, part C.above, for oxidizing the potassium salt of 2-[a-(4-diethylaminopheny1)-a-(l-ethyl-2-methy1-3-indoly1)]methyl-5-dimethylaminobenzoic acid, there was obtained 6.0 g of 3-(4-dlethylaminopheny1)-3-(l-ethyl-2-methyl-3-indolyl)-6dlmethylaminophthalld.e (Formula I: R=CH3; X=H; Y=4-(CH3)2NCgH^; Z=l-C2H5-2-CH3-3-indolyl) a light purple solid melting at 167-169°C.

·» The infrared spectrum had a maximum which appeared at 1752 (C=O; s) cm"1. The nuclear magnetic resonance spectrum was in accord with th'e assigned structure.

A toluene solution of the product spotted on silica gel, an acidic claiy or a phenolic resin.develops a purplecolored image.

Example 9 A. Following a procedure similar to that described in Example 1, part B above, 32.4 g of 3-(diethylamino)phenyl-6dimethylaminophthalide prepared as described in Example 8, part A above and 16.7 g of Ν,Ν,Ν’,N’-tetramethyl-m-phenylenediamin£ . were interacted to obtain a solution of the potassium salt of 2-C2,4-bis(dimethylamino)-4*-diethylamlnobenzhydryl]-5-dlmethylamlnobenzoic acid (Formula III: R=CH3; X=H; Y=4-(C2Hg)2NCgH4; 2=2,4.-[(CHjJgNjgCgHj) which was used without isolation in the next step.

B. Employing a procedure similar to that described in Example 1, part C above, the potassium salt of 2-[2,4~bis(dimethylamino)-4’-diethylaminobenzhydryl]-5-dimethylaminobenzoic acid from A was oxidized to obtain 11.4 g of 3-[2,4-bls(dimethyl amino)phenyl]-3-(4-diethylaminophenyl)-6-dimethylamlnophthallde (Formula I: R=CH3; X=H; Y=4-(C2H5)2NCgH4; Z=2,4-E(CH3)2N]2CgH3) as a tan solid melting at 123-125°C. -364 5 7 7 2 A significant infrared maximum appeared at 1758 (C=O; s) cm-1. The nuclear magnetic resonance spectrum was in agreement with the assigned structure.

A toluene solution of the product spotted on silica gel, an acidic clay or a phenolic resin develops a blackishpurple-colored image.

Example 10 A. Employing a procedure similar, to that described in Example 1, part A above, for interacting 7.2 g of 4-(N-ethylbenzylamino)benzaldehyde and 5.2 g pf 3-dimethylaminobenzoic acid, there was obtained 7.5 g of 3-[4~(N-ethylbenzylamlno)phenyl]-6-dimethylaminophthallde (Formula II: R=CH3; X=H; Yk(C6H5CH2,(C2H5)NC6H45 as a viscous oil· The infrared spectral analysis showed a maximum at 1760 (C=0; s) cm"1. The nuclear magnetic resonance spectrum was consistent with the assigned structure.

A toluene solution of the product spotted on silica gel develops a green-colored image.

B. Following a procedure similar to that described .in Example 2,. part A above, 4.0 g of 3-[4~(N-ethylbenzylamino)phenyl]-6-dimethylaminophthalide and 1.6 g of l-ethyl-2-methylindole were interacted to obtain 2-foc-[4-(N-ethy lbenzyl amino) phenyl]-cc-(l-ethyl-2-methyl-3-indolyl)} methyl-5-dimethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=(CgHgCH2(C2Htj)2NCgH4; Zsl-C2Hg-2-CH3-3-indolyl) which was not isolated but used in part D below.

C. Similar results were obtained when the acetic acid reaction medium was replaced with monochlorobenzene and aluminum chloride or trifluoroacetic acid. -374S772 D. Proceeding in a manner similar to that described in Example 2, part B above, 2-{a-[4-(N-ethylbenzylamino)phenyl]a-(l-ethyl-2-me thy 1-3-indolyl )}mfethyl-5-dimethylaminobt:n zoic acid from B above was oxidized to obtain 2.0 g of 3-[4-(N-ethyl5 benzylamino)phenyl]-3-(l-ethyl-2-methy1-3-indolyl)-6-dlmethylamlnophthalide (Formula X: R=CH3; X=H; Y=(CgH5CH2)(C2H5)NCgH4; Z=lC2H5-2-CH3-3-indolyl) as a pink solid melting over the range 66-95°C with decomposition.

Significant infrared maximum appeared at 1760 (C=O; s) cm1.

A toluene solution of the product spotted on an acidic resin develops a deep blue-colored, image.

Example 11 A. Proceeding in a manner similar to Example 1, part A above, 18.3 g of 4-dimethylamino-2-chlorobenzaldehyde and 16.5 g of 3-dlmethylaminobenzoic acid were interacted to obtain 20.5 g of 3-(4-dlmethylam'ino-2-chlorophenyl)-6-dimethylaminophthalide (Formula II: R=CH3; X=H; Y=2-Cl-4-(CH3)2NCgH3) a red-colored ‘ '· solid melting at 159.5-160.5°C.

A toluene solution of the product spotted on an acid clay develops a pale green-colored image.

B. Following the procedure described in Example 1, part B above, but substituting triethylamine for potassium hydroxide as the condensing agent, 3-(4-dimethylamino-2-chlorophenyl)-625 dimethylaminophthalide from A is interacted with 5-nitro-l-(4chlorobenzyl)-2-methylindole to obtain 2-{a-[5-nltro-l-^-chlorobenzyl ) -2-methy 1-3- indo lyl] -tx-(2-chloro-4-dimethy laminophenyl )1 methyl-5-dlmethylarnlnobenzoic acid (Formula III: R=CH3; X=H; Y=2Cl-4-(CH3)2NCgH3; Z=5-N02-l-(4-ClCgH4CH2)-2-CH3-3-indolyl). -384 S 7 7 2 C. Employing a procedure similar to that described in Example 1, part C above, 2-{a-[5-nitro-l-(4-chlorobenzyl)-2methyl-3-indolylJ-a-(2-chloro-4-dimethylaminophenyl} methyl-5dimethylaminobenzoic acid from B is oxidized to obtain 3-[55 η!tro-1-(4-chlorobenzyl)-2-methy1-3-indolyD-3-(2-chloro-4dimethylaminophenyl)-6-dimethylaminophthaIlde (Formula I: . R=CH3; XeH; Y=2-Cl-4-(CH3)2NCgH3; Z=5-NO2-l-(4-ClCgH4CH2)-2CH3-3-indolyl). s Example 12 ' A. Employing a procedure similar to that described in Example 1, part A above, for interacting 8.2 g of j>-anisaldehyde and 11.6 g of 3-dimethylaminobenzoic acid utilizing acetic anhydride alone as the reaction medium there was obtained 9.4 g of 3-(4-methoxyphenyl)-6-dimethy1amlnophthalide (Formula II: R=CH3; X=H; Y=4-CH3OCgH4) as a white solid melting at 169-170°C.

The infrarad spectral analysis showed a' maximum at 1755 (C=O; s) cm"^J The nuclear magnetic resonance spectrum • was concordaht with the assigned structure.

A toluene solution of the product spotted on an acid clay develops a blue-colored image.

B. Proceeding in a manner similar to that described in Example 1, part B above, but substituting lithium carbonate for potassium hydroxide as the condensing agent, 3-(4-methoxyphenyl)-6-dimethylaminophthalide from A is interacted with 125 butyl-2-metbylindoie to obtain 2-Γα-(l-butyl-2-methyl-3-indolyl)α-( 4-methoxyphenyl)]methy1-5-dimethylaminobenzolc acid (Formu1a III: R=CH3; X=H; Y=4-CH30CgH4; Z=l-C4Hg-2-CH3-3-indolyl)..

C. Following the procedure described in Example 1, part C above, 2-[a-(1-buty1-2-methy1-3-indoly1)-a-(4-methoxyphenyl)]30 methyl-5-dimethylaminobenzoic acid from B is oxidized to obtain •39** . ' 3-(1-butyl-2-methy lr-3-3 ndolyl)-3-(4-methoxyphenyl)-6-dimethylaminophthalide (Formula I: R=CH3; X=H; Y=4-CH3OCgH4; Z-l-C^Hg2-CH3-3-indolyl).· D. Employing a procedure similar to that described in Example 1, part B above, 3-(4-methoxyphenyl)-6-dimethylaminophthalide, prepared as described in part A above, was interacted with Ν,Ν,Ν’,Ν'-tetramethyl-m-phenylenediamine to obtain / the potassium salt of 2-f2,4-bis(dimethylamino)-4'-methoxybenzhydryl]-5-dimethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=4-CH3OCgH4; Z=2,4-f(CH^gNjgCgHj) which was employed in the oxidation step without prior isolation from its alkaline aqueous preparation medium.

E. Proceeding in a manner similar to that described in Example 1, part C above, for oxidizing the potassium salt of 2-f2,4-bis(dimethylamino)-4*-methoxybenzhydryl]-5-dimethylaminobenzoic acid, there was obtained 10.4 g of 3-f2,4-bis(dimethylamino) pheny 1)-3-( 4-methoxyphenyl )-6-dimethylaminophthallde (Formula I: R=CH3; X=H; Y=4-CH30CgH4; Z=2,4-f(CH3)2N]CgH3), an orange-tan-colored solid which melted at 90-94°C.

The infrared spectrum showed a maximum at 1762 (C=0; s) cm-\ The nuclear magnetic resonance spectrum was consistent with the assigned structure.

A toluene solution of the product spotted on phenolic resin develops a black-colored image.

Example.13 A. Proceeding in a manner similar to Example 1, part A above, 11.6 g of 3-dimethylaminobenzoic acid and 8.2 g of oanisaldehyde were interacted using acetic anhydride alone as the reaction medium to obtain 11.7 g of 3-(2-methoxyphenyl)-630 dlmethylaminophthalide (Formula II: R=CH3; X=H; Y=2-CH'3OCgH4) as an orange solid melting at 165-166.5°C. -4045772 A significant infrared maximum appeared at 1760 (C«=0; s) cm1. The nuclear magnetic resonance spectra was concordant with the assigned structure.

A toluene solution of the product spotted on an acid 5 clay develops a pale yellow-colored image.

B. Following the procedure described in Example 1, part B above, 3-(2-methoxyphenyl)-6-dimethylaminophthalide from A' is interacted with W,N,N',Ν’-tetrabutyl-m-phenylenediamine to obtain 2-[2,4-bis(dibutylamino)-(21-methoxy)benzhydryl]-5-di10 methylaminobenzoic acid (Formula III: R=CH3; X=H; Y=2-CH3OCgH4; Zn2,4-[(C4H9)2N]2CgH3).

C. Employing a procedure similar to that described in Example 1, part C above, 2-[2,4-bis(dibutylamino)-(2'-methoxyphenyl)benzhydryl]-5-dimethylaminobenzoic acid from B is oxidized to obtain 3-[2,4-bls(dibutylamino)phenyl3-3-(2-methoxyphenyl)-6'dlmethylamlnophthalide (Formula I: R=CH3; X=H; Y=2-CH3OCgH4; 2=2,4-[(C4H?)2N]2CgH3).

Example 14 A. Following a procedure similar to that described in Example 1, part A above, 11.6 g of 3-dimethylaminobenzoic acid ahd 9.0 g of 4-ethoxybenzaldehyde·were interacted in acetic anhydride to obtain 2*6 g of 3-(4-ethoxyphenyl)-6-dimethylaminophthalide (Formula II: R=CH3; X=H; Y=4-C2HgOCgH4) as a white solid melting at 115.5-118°C. / .

Infrared spectral analysis showed a maximum at 1750 (CaO; s) cm . The nuclear magnetic resonance analysis was in accord with the assigned structure.

A toluene solution of the product spotted on an acid clay develops a green-colored image. -4145772 B. Employing a procedure similar to that described in Example 1, part B above, 3-(4-ethoxyphenyl)-6-dimethylaminophthalide from A is interacted with N,N-dimethy1-m-toludine to obtain 2-(4-dimethylamino-2-methyl-4,-ethoxybenzhydryl)-55 dimethylaminobenzoic acid (Formula XII: R=CH3; X=H; Y=4-C2Hg0CgH Z=4-(CH3)2N-2-CH3C6H3).

C. · ' Proceeding in a manner similar, to that described in # Example 1, part C above, 2-(4-dimethylamino-2-methyl-4’-ethoxybenzhydryl)-5-dimethylaminobenzoic acid from part B above is oxidized to obtain 3-(4-dimethylamino-2-methylphenyl)-3-(4ethoxyphenyl)-6-dlmethylaminophthalide (Formula I: R=CH3; Χ=Η;Υ*= 4-C2H5OC6H4; Z=4-(CH3)2N-2-CH3C6H3).

Example 15 A. Employing a procedure similar to that described in Example 1, part A above, for interacting 11.6 g of 3-dimethylaminobenZoic acid and 10.6 g of 3,4-dimethoxybenzaldehyde. in acetic anhydride'there was obtained 0.75 g of 3-(3,4-dimethoxyphenyl )-6-dimethylaminophthalide (Formula II: R=CH3; X=H; Y=3,4(CH3O)2CgH3) a lightxyellow-colored solid melting at 148-150dC.

A significant infrared maximum appeared at 1765 (C=O; s) cm-1.

A toluene solution of the product spotted on an acid claydevelops a pale yellow-colored image.

B. Proceeding in a manner similar to that described in Example 1, part B above, but substituting quinuclidine for potassium hydroxide as the condensing agent, 3-(3,4-dimethoxyphenyl) -6-dimethylaminophthalide from A is interacted with 1octyl-2-methylindole to obtain 2-Ca-(l-octyl-2-methyl-3-indolyl)g-(3,4-dlmethoxyphenyl)]methyl-5-dimethylatninobenzoic acid (Formula III: R=CH3; X=H; Y=3,4-(CH3O)2CgH3; Z=l-CgH17-2-CH33-indolyl). -424 5 7 7 2 C, Following the procedure described in Example 2, part B above, 2-[a-(l-octyl-2-methyl-3-indolyl)-a-(3,4-dimethoxyphenyl )]methyl-5-dimethyl aminohenzoic acid from B is oxidized to obtain 3-(1-octyl-2-methyl-3-indolyi)-3-(3,4-dimethoxy5 phenyl)-6-dimethylaminophthalide (Formula I: R=CH3; X=H; Y=3,4-(CH3O)2CgH3; Z=l-C8H17-2-GH3-3-indolyl).

Example 16 A. Proceeding in a manner similar to Example 1, part A above, 14.35 g of 4-diethylamino-2-methylbenzaldehyde and 12.37 g of 3-dimethylaminobenzoic acid were interacted in acetic anhydride to obtain 5.3 g of. 3-(4-diethylamino-2-methylphenyl)-6-diroethylaminophthalide (Formula II: R=CH3; X=H; Y=4-(C2H5)2N-2-CH3C6H3) a solid melting at 135-136.5°C.

The infrared spectral analysis showed a. maximum at 1750 (C=0; s) cm-1. The nuclear magnetic resonance spectra was in.accord with the assigned structure.

A toluene solution of the product spotted on an acid clay develops a blulsh-green-colored image.

B. Following the procedure described in Example 1, part B above, but substituting lithium hydroxide for potassium hydroxide as the condensing agent, 3-(4-diethylamino-2-methylphenyl)6-dimethylaminophthalide from A is interacted with 1-(2,5-dimethylbenzyl ) -2-methylindole to obtain 2-{g-[l-(2,5-dirnethylbenzyl)-2methyl-3-indolyl]-a-(4-diethylamino-2-methylphenyl)} methy1-5-di25 methylaminobenzoic acid (Formula III: R=CH3; X=H; Y=4-(C2H5)2N-2CH3C6H3; Z=l-[2,5-(CH3)2C6H3CH2]-2-CH3-3-indolyl).

Example 17 A. Employing a procedure similar to that described in Example 1, part A above, for interacting 11.6 g of 3-dimethyl30 aminohenzoic acid and 12.4 g of 89 percent 3-ethoxy-4-methoxy.+345772 benzaldehyde in acetic anhydride, there was obtained 3-(3ethoxy-4-methoxyphenyl)-6-dimethylaminophthalide (Formula II: R=CH3; X=H; Y=3-CgHgQ-4-CH3O-CgH’3) a solid which had an infrared spectrum maximum at 1760 (C=O; s) cm1, B. Proceeding in a manner similar to that described in Example 1, part Babove, 3-(3-ethoxy-4-methoxyphenyl)-6-dimethyl aminophthalide from A is interacted with Ν,Ν,Ν',N’-tetrasec-butyl-m-phenylenediamlne to obtain 2-[2,4-bis(di-secbutylamino)-31-ethoxy-4'-methoxybenzhydrylj-S-dlmethylamino10 benzoic acid (Formula III: R=CH3; X=H; Y=3-C2H5O-4-CH3OCgH3; Ze2,4-[(s-C4H9)2N)2CgH3).

C. Following the procedure described in Example 1, part C above, 2-[2.4-bls(dl-sec-butylamino)-31-ethoxy-41-methoxvbenzhydryl]-5-dimethylaminobenzoic acid from B is oxidized to obtain 3-[2,4-bis(di-sec-butylamlno? phenyl]-3-(3-ethoxy-4methoxyphenyl)-6-dlmethylaminophthalide (Formula I: R=CH3; X=H; Y=3-C2H5O-4-CH3OCgH35 Z=2,4-[(s-C4H9)2N]2CgH3).

Example 18 A. Proceeding in a manner similar to Example 1, part A above, 11.6 g of 3-dimethylaminobenzoic acid and 10.0 g of 2,4dimethoxybensaldehyde were interacted in acetic .anhydride to obtain 14.0 g of 2-(2,4-dimethoxypheny1)-6-dimethylaminophthalide (Formula II: R=CH3; X=H; Y=2,4-(CH3O)2CgH3) as a yellow-colored solid melting at 123-125°C.

A significant infrared maximum appeared at 1750 (C=O; s). cm-1.

B. Following the procedure described in Example 1, part B above, but substituting tetraethylammonium hydroxide for po-444577 tassium hydroxide as the condensing agent, 3-(2,4-dimethoxyphenyl )-6-dimethylaniinophthalide from A is interacted with 5iodo-l-(l-methylhexyl)indole to obtain 2-/rt-[5-iodo-l-'l-methylhexyl)-3-indolyl]-«.-(2,4-dimethoxyphenyl)} methyl-5-d.imethyl5 aminobenzoic acid (Formula III: R=CH3; X=H; Y=2,4-(CH3O)2CgH3; Z=5-I-l-[1-CH3(CgH12)]-3-indolyl).

C. Employing a procedure similar to that described in Example 2, part B above, 2-{a-[5-iodo-l-(l-methylhexyl)-3indolyl)-a-(2,4-dimethoxyphenyl)} methy1-5-dimethylaminobenzoic acid from B is oxidized to obtain 3-[5-iodo-l-(l-methylhexyl)3-indolyl1-3-(2,4-dimethoxyphenyl)-6-dimethylaminophthalide (Formula I: R=CH3; X=H; Y=2,4-(CH3O)2CgH3; Z=5-I-1-[1-CH3(CgHj2)]-3-indolyl).

D. Proceeding in a manner similar to that described in Example 1, part B above, 25.1 g of 3-(2,4-dimethoxyphenyl)-6dimethylaminophthalide prepared as described in part A above and 13.4 g of Ν,Ν,Ν',N'-tetramethyl-m-phenylenediamine were interacted to obtain the potassium salt of 2-[2,4-dlmethoxy21,41-bi s(d i methy1ami no)ben zhyd ry1]-5-d i methy1ami noben 201c acid (Formula 1X1: R=CH3; X=H; Y=2,4-(CH3O)2CgH3; z=2,4[(CH3)2N]2CgH3) which was employed in the oxidation step without prior isolation from its aqueous preparation medium.

E. Following the procedure described in Example 1, part C above, for oxidizing the potassium salt of 2-[2,4-dimethoxy25 2',4'-bis (dimethylamino)benzhydryl]-5-dirnethylaminobenzoic acid, there was' obtained 9.0 g of 3-(2,4-dimethoxyphenyl.) -3Γ 2,4-bis(dimethylami no)pheny1]-6-dimethylaminophthalide (Formu1a I: R=CH3; X=H; Y=2,4-(CH3O)2CgH3; Z=2,4-[(CH3)2Nl2CgH3) a reddish broWn-colored solid which melted over the range 153-160°C. 45A significant infrared maximum appeared at 1760 (C=O; s) cm-1. The nuclear magnetic resonance, spectrum was consistent with the assigned structure.

A toluene solution of the product spotted on a 5 phenolic resin develops a reddish-brown-colored image.

F. Employing a procedure similar to that described in Example 1, part B above, 25.1 g of 3-(2,4-dimethoxyphenyl)-6dimethylaminophthalide prepared as described in part A above, and 15.5 g of l-etfoyl-2-methylindole' were interacted to obtain the potassium salt of 2-Γα-(2.4-dimethoxyphenyl·)-oc-(l-ethyl-2methyl-3-indolyl)]methyl-5-dimethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=2,4-(CH3O)2CgH3; Z=l-C2H5-2-CH3-3-indolyl) which was used in the oxidation step without prior isolation from its aqueous preparation medium.

G. Proceeding in a manner similar to that described in Example 1, part C above, for oxidizing the potassium salt of 2-[a-(2,4-dimethoxyphenyl)-a-(l-ethyl-2-methy1-3-indolyl)]methyl-5-dimethylaminobenzoic acid, there was obtained 1.6 g of 3-(2,4-dimethoxyphenyl)-3-(l-ethyl-2-methyl-3-iridolyl)-620 dimethylaminophthalide (Formula I: R=CH3; X=H; Y=2,4-(CH3O)2CgH3; Z=l-C2Hg-2-CH3-3-indolyl) an off-white solid which melted at 215-217°C.

A significant infrared maximum appeared at 1764 (C=0; s) cm-1. The nuclear magnetic resonance spectrum was in accord with ’the assigned structure.

A toluene solution of the product spotted on silica gel develops a grape-colored image. -464 5 7 7 2 Example 19 A. 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-carbazolcarboxaldehyde were interacted in acetic anhydride to obtain 6.33 g of 3-(9-ethy1-3-carbazolyl)6-dimethylaminophthalide (Formula II: R=CH3; X=H; Y=9-C2Hg-3carbazolyl) as a light brown solid melting over the range 142145°C.

.A significant infrared maximum appeared at 1760 (C=O; s) cm1’.

B. Employing a procedure similar to that described in Example 1, part B above, 3-'(9-ethy 1-3-carbazolyl)-6-dimethyl15 aminophthalide from A is interacted with Ν,Ν,Ν’,N’-tetrabutylm-phenylenediamine, to obtain 2-[a- (9-ethyl-3-carbazolyl).]-a[2,4-bls(dlbutylamino)phenyl]methyl-5-dlmethylamlnobenzolc acid (Formula III: R=CH3; X=H; Y=9-C2H5-3-carbazolyl; Z=2,4tlC4H9^2N^2C6H3^.

C. Proceeding in a manner similar to that described in Example 1, part C above, 2-[a-(9-ethyl-3-carbazolyl)]-a-[2,4bis(dibutylamino)phenyl]methyl-5-dimethylaminobenzoic acid from B is oxidized to obtain 3-(9-ethyl-3-carbazoly1)-3-C2,4-bis(dihutylamino)phenyl]-6-dimethylaminophthalide (Formula I: R=CH3J X=H; Y=9-C2H5-3-carbazolyl; z=2,4-[(c4H9)2N]2CgH3).

Example 20 A. Proceeding in a manner similar to Example 1, part A above, 5.0 g of 9-formyljulolidine and 4.6 g of 3-dimethylaminobenzoic acid were interacted to obtain 5.0 g of 3-(9-julolidinyl)3C 6-dimethylaminophthalide (Formula II: R=CH3; X=H; Y=9-julolidinyl) -474577 8 In the Infpared spectral analysis, a maximum was observed at 1760 (C.=0; s) cm \ A toluene solution of the product spotted on an acid clay develops a green-colored image. ,Β. Following the procedure described in Example 1, part B above, but substituting sodium carbonate for potassium hydroxide as the condensing agent, 3-(9-julolidinyl)-6-dimethylaminophthalide from A is interacted with 5-methoxy-l-butylindole to obtain 2-[a-(5-methoxyl-l-butyl-3-indolyl)-a-(9-julolidinyl)]methyl-5-dlmethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=9-julolidinyl; Z=5-CH3O-l-C4Hg-3-indolyl).

Example 21 A. Following a procedure similar to that described in Example 1, part A above, 7.5 g of 3,4-(methylenedioxy)benzaldehyde and 9.1 g of 3-dimethylaminobenzoic acid were interacted in acetic anhydride to obtain 0.9 g of 3-(3,4-methylenedioxyphenyl)-6-dimethylaminophthalide (Formula II: R=CH3; X=H; Y=l-[3,4-(0CH2O)CgH3]) a light yellow solid melting over the range 134-143°C.

A significant infrared maximum appeared at 1750 (C=0; s) cm-1. The nuclear magnetic resonance spectra was concordant with the assigned structure. Analysis by mass spectrum showed a m/e peak at 297(M+).

A toluene solution of the product spotted on an- acid clay develops a green-colored image.

B. Employing a.procedure similar to that described in. Example 1, part,B above, but substituting ammonium hydroxide for potassium hydroxide as the condensing agent, 3-(3,4-methylenedioxyphenyl)-6-dimethylaminophthalide from A is interacted with \ I 2-isopropylindole to obtain 2-[a-(2-lsopropyl-3-indolyl)-g-(3,4_4845772 methylenedioxypheny1)lrnethyI-5-dlfflethylaminobenzoic acid (Formula III: R=CH'3; X=H; Y=l-[3,4(OCH2O)CgH3]; Z=2-i.~C3H7-3indolyl).

C. Proceeding in a manner similar to that described in Example 1, part C above, 2-[a-(2-isopropyl-3-indolyl)-a-(3,4methylenedioxyphenyl)Jmethyl-5-dimethylaminobenzoic acid from B is oxidized to obtain 3-(2-isopropyl-3-indolyl)-3-(3,4methylenedioxyphenyl)-6-dimethylaminophthalide (Formula I: R=CH3; X=H; Y=l-[3,4(OCH2O)CgH3] ; Z=2-_i-C3H7-3-indolyl).

‘ Example 22 A. Proceeding in a manner similar to Example 1, part A above, 5.6 g of 2-thiophenecarboxaldehyde and 9.1. g of 3-dimethylaminobenzoic acid were interacted in acetic anhydride to obtain 0.92 g of 3-(2-thienyl)-6-dimethylaminophthalide (Formula II·. R=CH35 X=H; Y=2-thienyl) as an oily white-colored solid.

The infrared spectral analysis showed a maximum at 1763 (C=O; s) cm1. The nuclear magnetic resonance spectrum was concordant with the assigned structure.

A toluene solution of the product spotted on an acid 20 clay develops a yellow-colored image.

B. Following the procedure described in Example 1, part B above, 3-(2-thienyl)-6-dimethylaminophthalide from A is interacted with Ν,Ν,Ν·,Ν’-tetraethyl-m-phenylenediamine to obtain 2-£g-(2-thienyl)-g-£2,4-bis(diethylaminojphenyl]} methyl-525 dimethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=2-thienyl; •Z=2,4-t2H5)2N]2CgH3).

C. Employing a procedure similar to that described in Example 1, part C above, 2-£a-(2-thienyl)-g-[2,4-bis(diethylamlno)phenyl]} methyl-5-dimethylaminobenzoic acid from B is oxidized to obtain 3-(2-thlenyl)-3-[2,4-bls(diethylamino)-4945778 phenyl]-6-dimethylaminophthallde (Formula I: R=CH3; X=H; Y=2-thienyl’; Ζ=ί2,4-[(C^g) 2N] 2CgH3).

Example 23 A. Following a procedure similar to that described in Example 1, part A above, 7.7 g of 3-dimethylaminobenzoic acid and 4.4 g of N-methylpyrrole-2-carboxaldehyde were interacted in acetic anhydride to obtain 3-(1-methy1-2-pyrrolyl)-6-dimethylaminophthalide (Formula XI: R=CH3; X=H; Y=1-CH3~2pyrrolyl).

The significant infrared maximum appeared at 1760 (C=O; s) cm-1.

A toluene solution of the product spotted on an acid clay develops a purple-colored image.

B. Employing a procedure similar to that described in Example 2, part A above, 3-(1-methy1-2-pyrrolyl)-6-dimethylaminophthallde \from A is interacted with l-vinyl-2-methylindole to obtain ·2-[(χ-(l-vinyl-2-methy1-3-indolyl)-g-(1-methyl 2- pyrrolyl)]methyl-5-dimethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=l-CH3-2-pyrrolyl; Z=l-CH2=CH-2-CH3-3-indolyl).

C. Proceeding in a manner similar to that described in Example 1, part C above, 2-[a-(l-vinyl-2-methyl-3-indolyl)-(x(l-methyl-2-pyrrolyl)]methyl-5-dimethylaminobenzoic acid from part B above is oxidized to obtain 3-(l-vinyl-2-methy1-3indolyl ) -3-(1-methy1-2-pyrrolyl)-6-dimethylaminophthalide (Formula I: R=CH3; X=H; Y=l-CH3-2-pyrrolyl; Z=l-CH2=CH-2-CK33- lndolyl).

Example 24 • A. Employing a procedure similar to that described in Example 1, part A above, for interacting 4.6 g. of 3-dimethyl30 aminobenzoic acid and 4.6 g of l-ethyl-2-methylindole-3-carbox aldehyde in acetic anhydride to obtain 2.6 g of 3-(l-ethyl-2methyl-3-lndolyl)-6-dimethylaminophthalide (Formula II: R=CH3; X=H; y=l-C2Hg-2-CH3-3-indolyl) a light brown solid melting at 177-180°C.

A significant infrared maximum appeared at 1747 (C=0; s) cm-}·. The nuclear magnetic resonance spectrum was in accord with the assigned structure.

B. Proceeding in a manner similar to that described in Example 5, part A above, 3-(l-ethyl-2-methyl-3-indolyl)-6-dimethylaminophthalide from A is interacted with l-ethyl-2-methylindole to obtain 2-[g,g-bis(l-ethyl-2-methyl-3-lndolyl)]methyl5-dlmethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=Z=1C2H5-2-CH3-3-indolyl).

Example 25 A. Following a procedure similar to that described in Example 1, part A above, l,2-dimethylindole-3-carboxaldehyde and 3-dimethylaminobenzoic acid are interacted to form 3-(1,2dlmethyl-3-lndolyl)-6-dimethylaminophthalide (Formula II: R=CH3; X=H{ Y=l,2-(CH3)2-3-indolyl) which melts at 234-236°C.

B. Employing a procedure similar to that described in Example 1, part B above, 3-(1,2-dimethy1-3-indolyl)-6-dimethylaminophthalide from A is interacted with Ν,Ν,Ν*,N*~tetraethylm-phenylenediamine to obtain 2-fa-(1,2-dimethyl-3-indolyl)-g[2,4-bis(dimethylamino)]pheny 1^ methy1-5-dimethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=l,2-(CH3)2-3-indolyl; Z=2,4bis[(CH3)2N]2C6H3). -5145773 Example 26 , V · A. A .stirred mixture of 98.0 ml of Ν,Ν-dimethylaniline and 20.9 g of 3-(4-dimethylaminophenyl)-6-dimethylamir. iphthalide prepared as in Example 1, part A above, was warmed to approximately 75°C to form a clear solution which was then cooled by means of a cold water bath to 20°C. Over a period of ten minutes, 9.5 g of anhydrous zinc chloride was slowly added to the solution while allowing the temperature to rise to approximately 24°C.

After stirring for approximately thirty minutes at a temperature in the range of 25 to 30°C, the reaction mixture was heated to approximately 50°C and maintained in the range of 50-55°C for two hours during which time two charges of 1.9 g each of anhydrous zinc chloride were added to the reaction mixture. Then 150.0 ml of hot tap water and 20 g of 50 percent aqueous sodium hydroxide were slowly added and the resulting mixture was set aside at ambient temperature overnight. The excess Ν,Ν-dimethylaniline was steam-distilled from the reaction mixture. · After cooling to approximately 75°C, diatomaceous earth was added, the resultant mixture filtered and the filter cake washed with 40.0 ml of warm water. The wash was combined with the alkaline filtrate and the whole solution slowly dripped into a mixture of 35.0 ml of water and 18.0 ml of acetic acid with vigorous stirring The pH of the resulting slurry was adjusted to 4.9 by .the addition of ten percent aqueous sodium hydroxide. After cooling to 25°C the light blue solid was collected by filtration, washed with water and dried in vacuo to obtain 25.0 g of 2-(4,4’-bis(dimethylamino) -benzhydryl] -5-dimethylaminobenzoic acid (Formula III: R= CH3; X=H; Y=Z=4-(CH3)2NCgH4) a light gray solid which melted at 208-211°C.

The infrared spectral analysis showed a maximum at 1655 (C=0; s) cm-1. -524 5 7 7 2 B. Employing a procedure similar to that described in Example 1, part C above, 2-[4,4'-bis(dimethylamino)-benzhydryl]5-dimethylaminobenzoic acid prepared as described in part A above was oxidized to obtain 3,3-bis(4-dimethylaminophenyl)-6-dimethylaminophthalide (Formula 1: R=CH3; X=H; Y=Z=4-(CH3)2NCgH4), a tancolored solid which melted at 173.5-178.5°C.

A significant infrared maximum appeared at 1750 (C=0; s) cm-1. The nuclear magnetic resonance spectrum was consistent with the assigned structure, A toluene solution of the product spotted on silica gel, an acidic clay or a phenolic resin develops a blue-colored image.

C. Following a procedure similar to that described in part A above, but substituting 18.2 g of anhydrous stannic chloride for the anhydrous zinc chloride, 70.0 ml of Ν,Ν-dimethylaniline and 14.9 g of 3-(4-dimethylaminophenyl)-6-dimethylamlnophthalide prepared as described in Example 1, part A above were interacted to obtain 15.0 g of 2-C4,4*-bis(dimethylamino)-benzhydryl]-5-dimethylaminobenzoic acid Vhich melted at 208-212°C.

A significant infrared maximum appeared at 1705 (C=0; s) cm1.

D. ‘ Proceeding in a manner similar to that described in part A above, but replacing the anhydrous zinc chloride with 9.3 g of anhydrous aluminum chloride, 70.0 ml of Ν,Ν-dimethylaniline. and 14.9 g of 3-(4-dimethylaminophenyl)-6-dimethylaminophthalide, prepared as described in Example 1, part A above were interacted to Obtain 16.1 g of 2-[4,4'-bis (dimethylamino)-benzhydryl]-5-dimethylamlnobenzoic acid, a light blue powder which melted at 209-213°C.

A significant infrared maximum appeared at 1705 (C=O; s) cm-1. The nuclear magnetic resonance spectrum is consistent with the assigned structure. -5345773 E. Following the procedure described in part A directly above, 70.0 ml of Ν,Ν-dimethylaniline and 14.9 g of 3-(4-dimethylaminophenyl)-(j-dimethylaminophthalide, were interacted in the presence of 15.0 g of anhydrous ferric chloride. The reaction mixture was drowned in water and subjected to steam-distillation to remove the excess Ν,Ν-dimethylaniline. Then there was added to the remaining aqueous mixture 120.0 ml of toluene, .0 ml of water and diatomaceous earth. The resulting mixture was stirred at 75-80°C, filtered and the filter cake washed twice with 25.0 ml portions of hot toluene. The washes were combined with the filtrate, the aqueous layer separated and cooled to-approximately 40°C. The pH was adjusted to 4.9 by the addition of acetic acid. The solid that formed was collected by filtration, washed with water and dried to obtain 0.2 g pf somewhat impure 2-[4,4'-bis(dimethylamino)benzhydryl]-5-dimethy1amlnobenzoic acid (Formula III: R^CH^; X=H; Y=Z=4-(CH3)^CgH^), a pale blue-colored solid which melted at 187.5-193°C.

A'significant infrared maximum appeared-at 1710 (C=0; s) cm-1.

The remaining toluene layer from above was evaporated to dryness to obtain 26.0 g of a sticky pale blue-colored solid.

A ten gram aliquot of the solid was slurried in 50.0 ml of hot toluene, the undissolved solid collected by filtration after cooling to room temperature and washed with 10.0 ml of toluene and dried in vacuo to obtain 5.8 g of an iron complex of 2-[4,4’bis(dimethylamino)benzhydryl]-5-dimethylaminobenzoic acid as a gray-colored solid. The thus obtained iron complex was slurried in water and rendered alkaline to phenolphthalein test paper by the addition of five percent aqueous sodium hydroxide, heated to approximately 90°C, cooled to approximately 30°C and filtered •5445772 twice through diatomaceous earth. The slightly hazy filtrate was slowly made acid to approximately pH 5 by the addition of dilute aqueous acetic acid. The solid which separated was collected by filtration, washed with water and air dried to obtain 2-(4,41-bis(dimethylamino)benzhydryl1-5-dimethylaminobenzoic acid (Formula III: R=CH3; X=Hj Y=Z=4-(CH3)2NC6H4) as a light gray-colored solid which melted over the range 203-210°C.

The infrared spectrum had a significant maximum at 1710 (C=0; s) cm-1. The nuclear magnetic resonance spectrum was concordant with the assigned structure.

The combined toluene filtrate and wash from above was evaporated to obtain 4.4 g of 3,3-bis(4-dimethylaminophenyl)-6dimethylaminophthalide (Formula I: R=CH3; X=H; Y=Z=4-(CH3)2NCgH4), a dark blue-colored solid.

A significant infrared maximum appeared at 1759 (C=O; s) cm-1. The nuclear magnetic resonance spectrum was consistent with the assigned structure.

A toluene solution of the product spotted on silica gel develops a blue-colored image.

F. Proceeding in a manner similar to that described in part E above, 0.3 g of 3-(2,4-dimethoxyphenyl)-6-dimethylaminophthalide, prepared in a manner similar to Example 18, part A above, was interacted with 3.0 ml of Ν,Ν-dimethylaniline in the presence of 0. 3 g of anhydrous ferric chloride to obtain significant amounts of 2-Γ(2,4-dimethoxy-4'~ditnethylamino-benzhydryl]5-dimethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=2,4(CH3O)2CgH3; Z=4-(CH3)2NCgH4) and 3-(4-dimethylaminophenyl)-3(2,4-dlmethoxyphenyl)-6-dimethylaminophthalide (Formula I: R=CH3; X=H; Y=2,4-(CH3O)2C6H3; Z=4-(CH3)2NCgH4).

G. Employing a procedure similar to that described in part E above, 0.3 g of 3-(4-dimethylaminophenyl)-6-dimethylarninophthalide 5545772 prepared as described in Example 1, part A above was interacted with 3.0 ml of l-ethyl-2-methylindole in the presence of 0. 32 g of anhydrous ferric chloride to obtain significant amc ints of 2-(g-(4-dimethylaminopheny1)-g-(l-ethyl-2-methy1-3-indolyl)15 methy1-5-dimethylaminobenzolc acid (Formula III: R=CH3; X=H; Y= 4-(CH,)„NC,H.; Z=l-C.H^-2-CH^-3-indolyl) and 3-(4-dimethylaminoD tL O 4 c. □ D < t phenyl )-3-(1-ethyl-2-methy1-3-indolyl)-6-dimethylaminophthalide (Formula I: R=CH3; X=H; Y=4-(CH3)2NCgH4; Z=l-C2H5-2-CH3-3-indolyl) Example 27 A. Following the procedure described in Example 26, part A, 9.9 g of 3-(4-methoxyphenyl)-6-dimethylaminophthalide, prepared as described in Example 12, part A above, and 89.0 ml df Ν,Ν-dimethylaniline were interacted in the presence of 9.5 g of anhydrous zinc chloride at room temperature to Obtain 13.7 g of 2-(4-dimethy1amino-41-methoxybenzhydryl)-5-d imethylaminobenzoic acid as an off-white colored solid melting at 185-190°C.

B. A stirred mixture of 8.1 g of 2-(4-dimethylamino-4'methoxybenzhydryl) "•5-dimethylaminobenzoic acid from part A above, 40.0 ml of water, 1.6 g of 50 percent aqueous sodium hydroxide and 2. 7 ml of isopropyl alcohol' was maintained at a temperature in the range of 85-96°C while 20.3 g of ten percent aqueous hydrogen peroxide was added over a period of approximately six hours. The reaction mixture was set aside at ambient temperature overnight. The solid was collected by filtration, washed free of alkali with water and dried in vacuo to obtain 5.5 g of 3-(4dimethylaminopheny1)-3-(4-methoxyphenyl)-6-dimethylaminophthalide, a yellow-colored solid which melted at 156-161°C.

A significant infrared maximum appeared at 1754 (C=O; s) cm-1. The nuclear magnetic resonance spectrum was consistent with the assigned structure. -5645772 A toluene solution of the product spotted on an acid clay or an acidic resin develops a green-colored image.

Example 28 A. Proceeding in a manner similar to that described in Example 26, part A above, 10.7 g of 3-(4-dimethylaminophenyl)6-dimethylaminophth3li.de, prepared as described in Example 1, part A above and 50.0 ml of N-methylaniline were interacted in the presence of anhydrous zinc chloride at room temperature to obtain 13.8 g of 2-Γ(4-dimethylamino-41-methylaminoIbenzhydryll5-dimethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=4-(CH3)2~ NCgH^; Z=4-CH3NHCgH4) as a tan-colored solid softening at 118°C and melting at 128-130°C.

A significant infrared maximum appeared at 1691 (C=O; s) cm-1. The nuclear magnetic resonance spectrum was in accord with the assigned structure.

B. Following a procedure similar to that described in Example 27, part B ,above, 6.0 g of 2-[(4-dimethylamino-4'-methylamino)benzhydryl]-5-dimethylaminobenzoic acid from part A above was oxidized to obtain 2.38 g of 3-dimethylaminophenyl-3-methylaminophenyl-6-dimethylaminophthalide (Formula I: R=CH3; X=H; Y= 4-(CH3)2NCgH4; Z=4-CH3NHCgH4) as a tan-colored solid melting over the range 126-135°C.

The infrared spectral analysis showed a maximum at 1751 (C=0; s) cm-1. The nuclear magnetic resonance spectrum was concordant with the assigned structure.

A toluene solution of the product spotted on silica gel, an acidic clay or a phenolic resin develops a reddish-blue-colored image. 374-577 2 Example 29 A. Employing a procedure similar, to that described in Example 26, part Λ above, 5.4 g of 3-(4-dimethylaminophenyl)5-dimethylaminophthalide, prepared as described in Example 1, ’ ή part Λ above and 57 g of N,N-diethyl-m-toluidine were interacted in the presence of anhydrous zinc chloride at 100 to 110°C to obtain 4.5 g of 2-f(2-methyl-4-diethylamino-41-dimethylamino)benzhydryl]-5-ditnefehylaminobenzoic acid (Formula III: R=CH3; X-H; Y=4-(CH3)2NCgH3; Z=2-CH3-4-(C2H5)NCgH4) as a brownish-pink colored solid which melted over the range 105-115°C. ' r A significant infrared maximum appeared at 1700 (C=0; s) cm"\ The nuclear magnetic resonance spectrum was in accord with the assigned structure.

B. Proceeding in a manner similar to that described in Example 27, part B above, 3.7 g of 2-[(2-methyl-4-diethylamino4'-dimethylamino)benzhydryl]-5-dimethylaminobenzoic acid from part A above was oxidized to obtain 1.8 g of 3-(2-methyl-4-diethylaminophenyl)-3-(4-dimethy1aminophenyl)-6-dlmethylamlnophthallde (Formula I: R=CH3; X=H; Y=4-(CH3)2NCgH4; Z=2-CH3~4(C2H5)2NCgH3) as a brown solid which melted at 190-195°C.

A significant infrared maximum appeared at 1760 (C=0; s) cm1. The nuclear magnetic resonance spectrum was in accord with the assigned structure.

A toluene solution of the product when spotted on silica gel or a phenolic resin develops a purple-colored image.

Example 30 A. Following a procedure similar to that described above in Example 1, part A, 36.6 g of 2-chloro-4-dimethylaminobenzaldehyde and 33.0 g of 4-dimethylaminobenzoic acid were interacted in acetic anhydride to obtain 52.1 g of 3-(2-chloro-4-dimethylaminophenyl)-6-dimethylaminophthalide (Formula I: R=CH3; X=Z=H; Y=2-Cl-4-(CH3).,NCgH3) as a red crystalline solid which melted at 159-160°C. -5848772 A significant infrared maximum appeared at 1770 (C=O; s) cm-1.

B. Employing a procedure similar to that described in Example 26, part A above, 6.5 g of 3-(2-chloro-4-dimethylaminophenyl)-6-dimethylphthalide from part A above and 30.0 ml of Ν,Νdimethylaniline were interacted in the presence of 5.3 g of anhydrous zinc chlqridq to obtain 8.0 g of 2-[2-chloro-4,41-dimethylamino ) benzhydryl] -5-dimethyl aminobenzoic acid (Formula III: R=CH3; X=H; Y=2-Cl-4-(CH3)2NC6H3; Z=4-(CH3)2NCgH4) as a pink powder which melted over the range 180-190°C.

The infrared spectrum showed a maximum at 1610 (C=0; s, b) cm-1. The nuclear magnetic resonance was concordant with the assigned structure.

C. Proceeding in a manner similar to that described in Example 27, part B above, 5.4 g of 2-[2-chloro-4,4'-bis(dimethylamino)benzhydryl]-5-dimethylaminobenzoic acid was oxidized to obtain 2.9 g of 3-(2-chloro-4-dimethylaminophenyl)-3-(4-dimethylaminophenyl?-6-dimethylaminophthallde (Formula I: R=CH3; X=H; Y=2-Cl-4-(CH3)2NCgH3; Z=4-(CH3)2NCgH4), a pale bluish-graycolored solid which melted at 233-234°C.

A significant infrared maximum appeared at 1760 (C=0; s) _i > cm . The nuclear magentic resonance spectrum was concordant with the assigned structure.

A toluenfe solution of the product spotted on silica gel develops a bluish-purple-colored image.

Example 31 A. Employing a procedure similar to that described in Example 26, part A above, 7.0 g of 3-(2,4-dimethoxyphenyl)-6dimethylaminophthalide, prepared as described in Example 18, part A above and 31.0 ml of Ν,Ν-dimethylaniline were interacted in the -5945772 presence of zinc chloride at room temperature to obtain 10.9 g of 2-(2,4-dimethoxyb41-dimethylaminobenzhydryI)-5-dimethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=2,4-(CH3O)2CgH3; Z=4(CH3)2NCgH4), a whijfce solid which melted over the range 105135°C. ι 1 The infrared spectrum had a significant maximum at 1696 (C=0; s) cm-1. The nuclear magnetic resonance spectrum was consistent with the assigned structure.

B. Following a procedure similar to that described in Example 27, part ,B above, 6.5 g of 2-(2,4-dimethoxy-4'-dimethylaminobenzhydryl)-5-dimethylaminobenzoic acid was oxidized to obtain 2.2 g of 3-(2,4-dimethoxyphenyl)-3-(4-dimethylaminophenyl)6-dimethylaminophthalide (Formula I: R=CH3; X=H; Y=2,4-(CH30)2~ CgH3; Z=4-(CH3)2NCgH4), a pale yellow-colored solid which melted at 191. 5-193.5°C.

A significant infrared meximum appeared at 1758 (C=O; s) cm-1. The nuclear magnetic resonance spectrum was in accord with the assigned structure.

A toluene solution of the product spotted on a phenolic resin develops a light blue-colored image.

Example 32 A. Proceeding in a manner similar 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 Ν,Ν-dimethylaniline were interacted in the presence of zinc chloride at room temperature to obtain 14.3 g of 2-(2methoxy-4tr-dimethylaminobenzhydryl)-5-dimethylaminobenzoic acid (Formula III: R=CH,3; X=H; Y=2-CH3OCgH4; Z=4-(CH3)2NCgH4), a light yellow solid which melted over the range 229-234°C.

The infrared spectrum had a significant maximum at 1690 (C=O; s) cm-1. The nuclear magnetic resonance spectrum was consistent with the assigned structure.

B. Employing ρ procedure similar to that described in Example 27, part B above, 6.1 g of 2-(2-methoxy-4'-dimethylaminobenzhydryl)-5-dimethylaminobenzoic acid was oxidized with hydrogen peroxide to obtain 1.05 g of 3-(2-methoxyphenyI )-3-(4dimethylaminophenyl)-6-dimethylaminophthalide (Formula I: R =CH 3; ΧχΗ; Y=2--CH30CgH4; Z=4-(CH3)2NCgH4), a light yellow-colored solid which melted at 215-216°C.

A significant infrared maximum appeared at 1750 (C=0; s) cm-1. The nuclear magnetic resonance spectrum was consistent with the assigned structure.

A toluene solution of the product spotted on silica gel develops a light blue-colored image and spotted on a phenolic resin develops a light green-colored image.

Example 33 A. Following the procedure described above in Example 26, part A, 14.2 g of 3-(4-methoxyphenyl)-6.-dimethylaminophthalide prepared as described in Example 12, part A above and 35.0 ml of l-ethyl-2-methylindole were interacted in the presence of anhydrous zinc chloride at a temperature in the range of 90 to llO^C to obtain 15.5 g of 2-[κ-(4-methoxyphenyl )’-o> (l-efchyl-2-methyl3-lndolyl)1methyl-5-dimethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=4-CH3OCgH4; Z=1 - C2H5~2-CH3-3-indolyl, a light grey-coloured solid which melted over the range 115-126°C.

The infrared spectrum had a significant maximum at 1683 (C=0; s) cm1. The nuclear magnetic resonance spectrum was consistent with the assigned structure,.

B. Proceeding in a manner similar to that described in Example 1, part C above, 2-[a-(4-methoxyphenyl)-a-(l-ethyl-2methyl-3-indolyl)]methyl-5-dimethylaminobenzoic acid is oxidized to obtain 3-(4-methoxyphenyl)-3-(l-ethyl-2-methyl-3-indolyl)-6dlmethylaminophthalide (Formula I: R=CH3; X=H; Y=4-CH3oCgH4; Z=l-C2H5-2-CH3-3-indolyl). -6j_ 4S772 ν Example 34 A. Employing a procedure similar to that described in Example 1, part A gbove, 13.3 g of 2-butoxy-4-diethylaminobenzaldehyde and 9. 7 g of m-dimethylaminobenzoic acid were refluxed in acetic anhydride to obtain 3-(2-butoxy-4-diethylaminOphenyl)6-dimethylaminophthalide (Formula I: R=CH3; X=Z=H; Y=2-C4HgO-4(C2Hg)2NCgH3) as a tarry residue.

The infrared spectrum had a significant maximum which appeared at 1760 (C=O; s) cm1. The nuclear magnetic resonance spectrum was in accord with the assigned structure.

B. Proceeding in a manner similar to Example 26, part A above, 3-(2-butoxy-4-diethylaminophenyl)-6-dimethylaminophthalide from part A above is interacted with l-octyl-2-ethylindole to obtain 2-(g-(2-butoxy-4-diethylaminophenyl)-a-(l-octyl-2-ethyl-315 indolyl)]methyl-5-dimethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=2-C4HgO-4-(C2H5)2NCgH3; Z=l-CgH17-2-C2H5-3-indolyl).

C. . Following the procedure described in Example 2, part B above, 2-(g-(2-butoxy-4-diethylaminophenyl)-g-(l-octyl-2-ethyl-3indolyl)]methyl-5-dimethylaminobenzoic acid from B above is oxi20 dized to obtain 3-(2-butoxy-4-diethylaminophenyl)-3-(l-octyl-2ethyl-3-lndolyl)-6-dimethylaminophthalide (Formula I: R=CH3; X=H; Y=2-C4HgO-4-(C2H5)2NCgH3; Z=l-CgH17-2-C2H5-3-indolyl).

Example 35 A. Proceeding in a manner similar to that described in Example 5, part A above, 7.4 g of 3-(4-dimethylaminophenyl)-6dimethylaminophthalide, prepared as described in Example 1, part A above and 3.0 g of Ν,Ν-dimethylaniline were interacted In 40 g of ethylene dichloride in the presence of 6.65 g of anhydrous aluminum chloride at reflux to obtain 2.7 g of 2-(4,4'-bis(di30 methylamino)benzhydryl]-5-dimethylaminobenzoic acid '(Formula III: R=CH3; X=H; Y=Z=4-(CH3)2NCgH4), a pale blue solid. „62" A significant infrared maximum appeared at 1700 (C-O; s, b) cm-1. The nuclear magnetic resonance spectrum was consistent with the assigned structure.

B. Following the procedure similar to that described in Example 1, part C above, 2-[4,4,-bis(dimethylamino)benzhydryl]5-dimethylaminobenzoic acid is oxidized to obtain 3,3-bis(4-dimethylaminophenyl)-6-dimethylaminophthalide (Formula I: R=CH3; X=H; YsZ=4-(CH3)2NCgH4).

It is contemplated that by following the procedure described in Example 1, part A, but using in place of ja-dimethylaminobenzaldehyde and m-dimethylaminobenzoic acid approximately molar equivalent quantities of the appropriate Y-CHO and 3-N(R)24-X-benzoic acid the compounds of Examples 36-50 are obtained.

Example 36 3-(2-Methylphenyl)-6-[N-methyl-N-(4-methylbenzyl)]aminophthalide using 2-methylbenzaldehyde and 3-[N-methyl-N• (4-methylbenzyllamino]benzoic acid.

Example 37 3-(l-Ethyl-2-phenyl-3~indolyl)-5-iodo-6-diethylaminophthalide using l-ethyl-2-phenylindole-3-carboxaldehyde and 3-diethylamino-4-iodobenzoic acid.

' Example 38 3_(4-Pyridinyl)-6-dibenzylaminophthalide using 4pyridinecarboxaldehyde and 3-dibenzylaminobenzoic acid.

Example 39 3-(2,3-Dimethoxyphenyl)~6-diethylaminophthalide using 2,3-dimethoxybenzaldehyde and 3-diethylaminobenzoic acid.

Example 40 3-(2-Methyl-l-ri-octyl-3-indolyl)-5-chloro-6-aminophthalide using 2-methyl-l-ri-octylindole-3-carboxaldehyde and 3-amino-4-chlorobenzoic acid. -6345772 Example 41 • 3-(5-Methoxy-3-indolyl)-6-(N-ethylbenzylamino)phthalide using 5-methoxyindole-3-carboxaldehyde and 3-(N-ethylbenzylamino)benzoic acid.

Example 42 3-(2,3,4-Trimethoxypheny1)-6-(N-ethy1-M-butylamino)phthalide using· 2,3,4-trimethoxybenzaldehyde and 3-(N-ethyl-Nt butylamino)benzoic acid.

Example 43 3-(2-Pyridinyl)-5-chloro-6-dimethylaminophthalide using 2-pyridinecarboxaldehyde and 3-dimethylamino-4-chlorobenzoic acid.

Example 44 3-(2-Bromophenyl)-6-(N-methyl-N-(4-chlorobenzyl)amino]phthalide using 2-bromobenzaldehyde and 3-[N-methyl-N(4-chlorobenzyllamino]benzoic acid.

Example 45 . 3-[2-Methyl-4-(N-methylbenzylamino)phenyl]-5-bromo6-ethylaminophthalide using 2-methyl-4-(N-methylbenzylamino)benzaldehyde and 3-ethylamino-4-bromobenzoic acid.

Example 46 3-(2-Fluorophenyl)-6-(N-ethyl-N-methylamino)phthalide using 2-fluorobenzaldehyde and 3-(N-ethyl-N-methylamino)benzoic acid.

Example 47 3-(2-Pyrroly1)-5-fluoro-6-propylaminophthalide using 4-pyrrole-2-carboxaldehyde and 3-propylamino-4-fluorobenzoic acid. 6445772 Example 48 3_(l_n_Butyl-2-phenyl-3-indolyl)-6-ethylaminophthalide using l-£-butyl-2-phenylindole-3-carboxaldehyde and 3-ethylaminobenzoic acid.

Example 49 . . 3_(2-Methoxy-4-diethylaminophenyl)-6-methylaminophthalide using 2-methoxy-4-diethylaminobenzaldehyde and 3methylaminobenzoic acid.

Example 50 3-(3-Etho'xyphenyl)-6-aminophthalide using 3-ethoxybenzaldehyde and 3-aminobenzoic acid.

It is contemplated that by following a procedure selected from those described in Example 1, part B, Example 2, part B, Example 5, part A, or Example 26, part A for interacting approximately molar equivalent quantities of the appropriate 3_Y-5_X_6-N(R)2Phthalide and Z-H in the presence of the indicated condensing agent, 'the compounds of Examples 51-65 are obtained.

Example 51 2—CP—(3-Isopropyl-4-diethylamino-2'-methyl)benzhydryl]5-[N-methyl-N-(4-methylbenzyl)amino]benzoic acid using 3-(2methylphenyl)-6-[N-methyl-N-(4-methylbenzyl)aminophthalide and N,N-diethyl-3-isopropylaniline in the presence of oxalic acid after Example 2, part B.

Example 52 2-{a-(l-Ethyl-2-phenyl-3-indolyl)-a~[4-(N-isobutylN-ethylamino)phenyl]} methyl-4-iodo-5-diethylaminobenzoic acid using 3-(l-ethyl-2-phenyl-3-indolyl)-5-iodo-6-diethylaminophthalide and N-isobutyl-N-ethylaniline in the presence of lithium carbonate after Example 1, part A. •65 _ Example 53 2-[a.-(4-Pyridinyl)-a-(4~diethylamino-2-propoxyphenyl)]methyl-5-dibenzylaminobenzoic acid using 3-(4-pyridiny’)-6-dibenzylaminophthalide and N,Nrdiethyl-2-propoxyaniline in the presence of phosphorus trichloride after Example 26, part A.

Example 54 2- {a-[1-(4-Bromobenzyl)-2-isopropyl-3-indolyl]-a-(2,3dimethoxyphenyl)) methyl-5-diethylaminobenzoie acid using 3-(2,3dimethoxyphenyl)-6-diethylaminophthalide and l-(4-bromobenzyl)10 2-isopropylindole in the presence of methanesulfonic acid after Example 2, part A.

Example 55 2-[a-(2-Methyl-l-jT-octyl-3-indoly1)-a-(N-isopropyl-3pyrrolyl)]methyl-4-chloro-5-aminobenzoic acid using 3-(2-methyl15 i-£-octyl-3-indolyl)-5-chloro-6-aminophthalide and N-isopropylpyrrole in the presence of diethanolmethylamine after Example 1, part B.

Example 56 2-fa-[(2-Ethoxy-4-diethylamino)phenyl]-a-(5-methoxy20 3-indolyl)} methyl~5-(N-ethylbenzylamino)benzoic acid using 3-(5methoxy-3-indolyl)-6-(N-ethylbenzylamino)phthalide and N,N-diethyl-2-ethoxyaniline in the presence of lithium hydroxide after Example 1, part B.

Example 57 2-[a-(2,3,4-Trimethoxypheny1)-q-(l-isoamyl-3-indoly1)]methyl-5-(N-ethyl-N-butylamino)benzoic acid using 2-(2,3,4-trimethoxyphenyl)-6-(N-ethyl-N-butylamino)phthalide and 1-isoamylindole in the presence of triethanolamine after Example 1, part B -66457 Example 58 2-[a-(2-Metboxy-3-chloro-4-diethylaminophenyl)-a-(2pyridinyl)]methyl-4-chloro-5-dimethylaminobenzoic acid using 3-(2-pyridinyl)-5-chloro-6-dimethylaminopthalide and N,N-d.i5 ethyl-2-methoxy-3-chloroaniline in the presence of citric acid after Example 2, part A.

Example 59 2-[2-Bromo~2',4'-bis-(diisopropylamino)]benzhydry1-5[N-methyl-N-(4-chlorobenzyl)amino]benzoic acid using 3-(2-bromo10 phenyl)-6-[N-methyl-N-(4-chlorobenzyl)amino]phthalide and Ν,Ν,Ν', tetraisopropyl-m-phenylenediamine in the presence of 1,4-diazabicyclo[2,2,2]octane after Example 1, part B.

Example 60 2-[(2-Methyl-2-fluoro-4-N-methylbenzylamino-4'-di15 butylamino)benzhydryl]-4-bromo-5-ethylaminobenzoic acid using 3-[2-methy1-4-(N-methylbenzylamino)phenyl]-5-bromo-6-ethylaminophthalide and N,N-dibutyl-3-fluoroaniline in the presence of phosphoric acid after Example 2, part A.

Example 61 2-[(2 *-Pluoro-3-propoxy-4-N-sec-butyIben zy1amino)benzhydryl]-5-(N-ethyl-N-methylamino)benzoic acid using 3-(2fluorophenyl)-6-(N-ethyl-N-methyl)aminophthalide and N-benzylN-sec-butyl-2-propoxyaniline in the presence of boron trifluoride after Example 26, part A.

Example 62 2-[a-(3-Indolyl)-a-(2-pheny1-5,6-dichloro-3-indoly1)]methyl-4-fluoro-5-(N-propylJaminobenzoic acid using 3-(3-indolyl) -fluoro-6-propylaminophthalide and 5,6-dichloro-2-phenylindole in the presence of glycolic acid after Example 2, part A. -67• 45773 Example 63 2-[κ-(2-Iodo-4-N-n-bu tylbenzylaminophenyl)-a-(1-ributyl-2-phenyl-3-indolyl)]methy1-5-N-ethylaminobenzoic acid using 3-(l-jn-buty1-2-pheny1-3-indoly1)-6-ethylaminophthalide and N-benzyl-N-butyl-3-iodoaniline in the presence of hydro- . chloric acid after Example 2, part A.

Example 64 2-[a-(2-Methoxy-4-diethylaminophenyl)-a-(l-methyl6-nitro-3-indolyl)]methyl-5-N-methylaminobenzoic acid using 3-(2-methoxy-4-diethylaminophenyl)-6-methylaminophthalide and 1- methyl-6-nitroindole in the presence of toluenesulfonic acid after Example 2, part A.

Example 65 2- [a-(3-Butoxyphenyl)-a-(2-isopropyl-3-indolyl) ] - . methyl-5-aminoben.zoie acid using 3-(3-butoxyphenyl)-6-aminophthalide and 2-isopropylindole in the presence of phosphorus oxychloride after Example 2, part B.

It is contemplated that by following an oxidation procedure selected 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-(a-Y-a-Z)methyl-4-X-5-N(R) benzoic acid the compounds of Examples 66-80 are obtained.

Example 86 3- (2-Methylphenyl)-3-(3-isopropy1-4-diethylaminopheny1)-6-[N-methyl-N-(4-methylbertzyl)]aminophthalide using 2- [(3-isopropyl-4-d'iethylamino-2'-methyl)benzhydryl]-5-[Nmethy1-N-{4-methylbenzyl)amino]benzoic acid.

Example 67 3-(1-Ethyl-2-phenyl-3-indoly1)-3-[4-(N-isobutyl-Nethylamino)phenyl]-5-iodo-6-diethylaminaphthalide using 2-{ct(l-ethyl-2-phenyl-3-indolyl)-a-[4-(N-isobutyl-N-ethylamino)phenyl]J methyi-4-iodo-5-diethylaminobenzoic acid. _684 S 7 7 2 Example 68 3-(4-Pyridinyl)-3-(4-diethylamino-2-propoxyphenyl)6-dibenzylaminophthalide using 2-(a-(4-pyridinyl)-a-(4-diethylam5no-2-propoxyphenyl)]methyl-5-dibenzylaminobenzoic acid.

Example 69 3-(1-(4-Bromobenzyl)-2-isopropyl-3-indolyl]-3-(2,3dimethoxypheriyl)-6-diethylaminophthalide using 2-{a-[l-(4~ bromobenzyl)-2-isopropyl-3-indolyl]-a-(2,3-dimethoxyphenyl )J methyl-5-diethylaminobenzoic acid.

Example 70 3-(2-Methyl-l-£-octyl-3-indolyl)-3-(N-isopropyl-3pyrrolyl)-5-chloro-6-aminophthalide using 2-[a-(2-methyl-l£-octyl-3-indolyl)-a-(N-isopropyl-3-pyrrolyl)]methyl-4-chloro~ - ami'nobenzoic acid.

Example 71 3-(2-Ethoxy-4-diethylaminopheny1)-3-(5-methoxy-3indolyl)-6-(N-ethylbenzylamino)phthalide using 2-{a-[(2-ethoxy4-diethylamino)phenyl)-a-(5-methoxy-3-indolyl)^ methyl-5-(Nethylbenzylamino)benzoic acid.

, Example 72 3-(2,3,4-Trimethoxypheny1)-3-(l-isoamyl-3-indolyl)6— (N-ethyl-N-butylamino)phthalide using 2-[a-(2,3,4-trimethoxyphenyl) -a-(1-isoamy1-3-indolyl)]methyl-5-(N-ethyl-N-butylamino)benzoic acid.

Example 73 3-(2-Methoxy-3-chloro-4-diethylaminophenyl)-3-(2pyridinyl)-5-chlorp-6-dimethylaminophthalide using 2-[a-(2methoxy-3-chloro-4-diethylaminophenyl)-a-(2-pyridinyl)jmethyl4-chloro-5-dimethylaminobenzoic acid. -69.43778 Example 74 3-(2-Bromopheny1)-3-[2,4-bis(diisopropylaminolphenyl]6_[N_methyl-N{4-chlorobenzyl)amino]phthalide using 2-{[2-bromo2',4’-bis(diisopropylamino)]benzhydryl}~5-[N-methyl-N-(4-chlorobenzyl lamino] benzoic acid.

Example 75 3- C2-Methyl-4-N-methylbenzylaminophenyl)-3-(2-fluoro4- dibutylaminophenyl)-5-bromo-6-ethylaminophthalide using 2[(2-methyl-2'-fluoro-4-N-methylbenzylamino-4’-dibutylaminp)benzhydryl]-4-bromo-5-ethylaminobenzoic acid.

Example 76 3_(2-Fluorpphenyl1-3-[3-propoxy-4(N-sec-butylbenzylamino)phenyl]-6-(N-ethyl-N-methyl)aminophthalide using 2-[(2'fluoro-3-propoxy-4-N-sec-butylbenzylamino)benzhydryl]-5-(Nethyl-N-methyl)aminobanzoic acid.

Example 77 3-(3-Indoly1)-3-(2-pheny1-5,6-dichloro-3-indoly1)5- fluoro-6-(N-propyl)aminophthalide using 2-£a-(3-indolyl)-a(2-phenyl-5,6-dichloro-3-indolyl)]methyl-4-fluoro-5-(N-propyl)aminobenzoic acid.

Example 78 3-[ 2-Iodo-4- (N-£-butylbenzy lamino) phenyl] -3- (1-in-butyl2-phenyl-3-indolyl)-6-N-ethylaminophthalide using 2-{a-[2-iodo4-(N-n.-butylbenzylamino)phenyl]-a-(l-£-butyl-2-phenyl-3-indolyl)} methyl-5-N-ethylaminobenzoic acid.

Example 79 3-(2-Methoxy-4-diethylaminopheny1)-3-(1-methy1-6nitro-3-indolyl)-6-N-methylaminophthalide using 2-[a-(2-methoxy4-diethylaminophenyl)-a-(l-methyl-6-nitro-3-indolyl)]methyl-5N-methylaminobenzoic acid. -7045772 Example R0 3-(3-Bu ^oxyphenyl )-3-(2-isopropyl-3-indolyl)-6-aminophthalide using 2-[qc-(3-butoxypheny1)-α.-2-isopropy 1-3-indolyl)]methyl-5-aminobenzoic acid.

Example 81 The use of the compounds of Formulas X through XII and' described in Examples 1 through 80 as color forming components in pressure-sensitive microencapsulated copying systems is illustrated with reference to the product of Example 1, part C.

A, A mixture of 196 ml of distilled water and 15.0 g of pigskin gelatin was stirred at approximately 50°C for approximately 45 minutes. There was then added to the mixture a warmed (approximately 50°C) solution of 49.0 g of alkylated biphenyls and 1.0 g of 3-[2,4-bis(dimethylamino)phenyl]-3-(4-dimethylaminophenyl)-6-dimethylaminophthalide (Formula I: R=CH3; X=H; Y=4(CH3)2NCgH4; Z=2,4-[(CH3)2N]2CgH3), prepared as described above in Example 1, part C. The resulting solution was stirred for approximately fifteen minutes. A second solution of 81.0 ml of distilled water and 10.0 g of gum arabic was then prepared and warmed to approximately 50°C for approximately one hour.

B. · The two solutions, the first containing water, gelatin, alkylated biphenyls and the product, and the second containing water and gum arabic were mixed and the pH adjusted to 9 by the addition of approximately 0.7 ml of 20 percent aqueous sodium hydroxide. The resulting mixture was transferred to a larger reactor equipped with a variable speed one-half horsepower Eppenbach Homo-Mixer (Gifford-Wood Co., Hudson, N.Y.) and' there was added over a period of two to three minutes 650 ml of distilled water which had been heated to 50°C. With the stirrer running at an applied voltage of between 20 to 25 volts, there was slowly added sufficient ten percent aqueous acetic acid to -71457 72 set the pH at 4.5, this being the point where coacervation was initiated. The stirrer speed was increased by raising the applied voltage to approximately thirty volts and approximately four drops of 2-ethylhexanol were added to suppress foaming.

After approximately twenty minutes, a sample of the suspension was examined microscopically and found to have stabilized in the range of 20 to 25 microns particle size whereupon an external ice/water bath was immediately placed around the reactor con-!· taining the suspension. At approximately 20°C, the agitation speed was reduced by decreasing the applied voltage to the range of 20 to 25 volts. Cooling was continued and at approximately 15°C, 10.0 ml of glutaraldehyde was added over a period of five minutes. When the internal temperature reached 10°C; the agitation speed was further reduced by lowering the applied voltage to approximately 20 volts and these conditions maintained for approximately thirty minutes. At this time, the Eppenbach I Homo-Mixer was replaced'with a conventional blade type laboratory 'agitator and the suspension was stirred an additional three * hours during which period the temperature was allowed to warm to room temperature. The microencapsulated product was isolated by pouring the slurry through an ASTM #18 stainless steel sieve to remove any large agglomerates and then collecting the capsules by filtration. .· The collected capsules were washed successively with four 100 ml portions of distilled water each and stored as a water-wet pulp. A sample of the pulp analyzed by drying in vacuo at 80°C was found to consist of 37.5 percent solids.

C. To 125 ml of distilled water, 10.6 g of oxidized corn starch was added over a period of ten to fifteen minutes with stirring. This mixture was heated to a temperature''in the range of ,70"80°C and maintained until all the starch dissolved. The starch solution was cooled to ambient temperature and there was -724 5 7 7 2 added 100 g of the capsule-containing water-wet pulp from part B above and 43.0 ml of distilled water. The capsules and starch solution were mixed at room temperature using an Eppenbach HomoMixer set at an applied voltage of 25 volts for five minutes and then at an applied voltage of 30 volts for an additional five minutes to complete the suspension of the capsules in the starch solution.

D. The stock starch-microcapsule suspension prepared in part C above was coated on paper sheets to a thickness of approx10 imately 0.0015 inch and the coated paper air dried. The paper thus coated with the microencapsulated colorless precursor was assembled as the top sheet in a manifold system by positioning the coated side in contact with the coated side of a commercially available receiving sheet coated with a color developer of the electron accepting type. More specifically, papers coated with a phenolic resin and with an acidic clay were employed in this test; An image was then drawn with a stylus on the top sheet bearing the microencapsulated colorless precursor on its reverse side causing the affected microcapsules to rupture thus allowing the solution of the colorless precursor held by said microcapsules to flow into contact with the color developing substance on the receiving sheet.whereupon a deep blue-colored image promptly formed.

When evaluated in a duplicating 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-C2H5O-4-(C2H5)2NCgH3; Z=4-(CH3)2NCgH4), produced a blue-colored developed image; the product of Example 10, part D, 3-[4-(N-ethylbensylamino)phenyl]30 3-(l-ethyl-2-methy1-3-indolyl)-6-dimethylaminophthalide (Formula I: R=CH3; X=H; ¥=4-(CgH5CH2)(C2H5)NCgH4; Z=l-C2H5~2-CH3-3-7345772 indolyl), produced a^ purple-colored developed image; the product of Example 24,, part A, 3-(l-ethyl-2-methyl-3-indolyl)-6dimethylaminophthalide (Formula II: R=CH3; X=H; Y=l-C2Hg-2-CH33-indolyl), produced a light-red-colored developed image; the product of Example 10, part A, 3-[4-(N-ethylbenzylamino)phenyl]6-dimethylaminophthalide (Formula II: R=CH3; X=H; Y=4-(CgHgCH2)(CgHglNCgH^), produced a green-colored developed image; the produce of Example 8, ^art A, 3-(4-diethylaminophenyl)-6-dimethylaminophthalide (Formula II: R=CH3; X=H; Y=4-(C2H5)2'NCgH4), produced a green-colored developed image; the product of Example 2,. part A, 2-[a-(l-ethyl-2-methyl-3-indolyl)-a-(4-dimethylaminophenyl)]methyl-5-dimethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=4-(CH3)2NCgH4; Z=l-C2H5-2-CH3-3-indolyl), produced a purple-colored developed image; the product of Example 1, part B, 2-[2,4,4’-tris(dimethylamino)benzhydryl]-5-dimefnylaminobenzoic acid (Formula III: R=CH3; X=H; Y=4-(CH3)2NCgH4; Z=2,4[(CH3)2N]2CgH3), produced a bluish-purple-colored developed image.

Example 82 The utility of the compounds of Formulas I through III whose preparations are described in the foregoing examples as color forming components in thermal marking systems is illustrated by the incorporation.and testing of the compound of Example 1, part C, 3-[2,4-bIs(dimethylamino)phenyl]~3-(4-dimethylaminophenyl)-6-dimethylaminophthalide (Formula I: RsCH3; X=H; Y=4-(CH3)2NCgH4; Z=2,4-[(CH3)2N]2CgH3) In a thermal sensitive marking paper. The test paper was prepared by a procedure similar to that, described in U.S. Patent 3,539,375.

A. A mixture of 2.0 g of 3-[2,4-bis(dimethylamino)phenyl]3-(4-dimethylaminophenyl)-6-dimethylaminophthalide,‘8.6 g of a ten percent aqueous solution of polyvinyl alcohol (approximately -7445772 percent hydrolyzed), 3.7 g of water and 31.6 g of 1/16 inch diameter zirconium grinding beads which was charged into a container which was placed in a mechanical shaker. Shaking was effected for one hour. The zirconium beads were then removed by straining the mixture through a No. 40 sieve.

B. Similarly, a mixture of 9.8 g of 4,4'-isopropyli’dine diphenol (Bisphenol A), 42.0 g of a ten percent aqueous polyvinyl alcohol solution (approximately 99 percent hydrolyzed), 18.2 g of water and 221.2 g of 1/16 inch diameter zirconium grinding beads was charged into a container which was placed in a mechanical shaker. After shaking was effected for one hour, the zirconium beads were removed by straining through a No. 40 sieve.

C. A coating composition was prepared by mixing 2.1 g of the slurry from A and 47.9 g of the slurry from B. The mixture was then uniformly coated on sheets of paper at thicknesses of approximately 0.003 inch and the coated sheets airdrie’d. The coated paper was tested by tracing a design on the coated side of the paper placed on a smooth flat surface With a stylus heated to'approximately 130°C. A deep purple-colored image corresponding to the traced design promptly developed.

When evaluated in a thermal marking system by heating in admixture with Bisphenol A, the product of Example 6, part B, 3-(2-ethoxy-4-diethylaminopheny1)’-3-(4-dimethylaminophenyl)-6dimethylphthalide (Formula.!: R=CH3; X=H; Y=2-C2H5O-4-(C2H5)2NCgH3; Z=4-(CH3>2NCgH4), produced a blue-colored developed image; the product of Example 10, part D, 3-[4-(N-ethylbenzylamino)phenyl]3-(1-ethy1-2-methy1-3-indolyl)-6-dimethylaminophthalide (Formula X: R=CH3; X=H; Y=4-(CgH5CH2)(C2H5)NCgH4; Z=l-C2H5-2-?H3-3-indolyl), produced a dark blue-colored developed image; the product of Example 24, part A, 3-(l-ethyl-2-methyl-3-indolyl)-6-dimethyl-7545772 \ aminophthalide (Formula II: R=CH3; X=H; Y=l-C2Hg-2-CH3-3-indolyl), produced a purple-colored developed image; the product of Example 10, part A, 3-[4-(N-ethylbenzylamino)phenyl]-6-dimethylaminophthalide (Formula'll: R=CH3; X=H; Y=4-(CgH5CH2)(C2H5)NCgH4), produced a green-colored developed image; the product of Example 12, part A, 3-(4-methoxyphenyl)-6-dimethylaminophthalide (Formula II: R=CH3; X=H; Y=4-CH30CgH4), produced a yellow-colored developed image; the product of Example 14, part A, 3-(4-ethoxyphenyl)-6dimethylaminophthalide (Formula II: R=CH3; X=H; Y=4-C2HgOCgH4), produced a yellow-colored developed image; the product of Example 21, part A, 3-[1-(3,4-methylenedioxylphenyl]-6-dimethylaminophthalide (Formula II: R=CH3; X=H; Y=l-(3,4-OCH2OCgH3), produced a yellowish-brown-colored developed image; the product of Example 1, part B, 2-(2,4,4’-tris(dimethylamino)benzhydryl]15 5-dimethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=4(CH3)2NC6H4; Z=2,4-[(CH3)2i)]2CgH3), produced a blue-colored developed image; the .product of Example 2, part A, 2-[a-(4dimethylaminophenyl)-a-(1-ethy1-2-methy1-3-indolyl)-methy1-5dimethylaminobenzoic acid (Formula III: R=CH3; X=H; Y=420 . (CH3)2NCgH4; Z=l-C2Hg-2-CH3-3-indolyl), produced a purplecolored developed image.

Claims

1. CLAIMS : 1A compound of the Formula III (herein) «herein each R independently represents hydrogen, non-tertiary alkyl of one to four carbon atoms, benzyl or benzyl substituted in the benzene ring by one 5 or two of halo or alkyl of one to three carbon atoms; X represents hydrogen or halo; Y represents a monovalent radical having one of the Formulas (A) through (H) (herein); and Z represents a monovalent radical having the Formula (A), (B) or (G) (herein) in whioh R^ represents hydrogen, non-tertiary alkoxy of one to 10 four carbon atoms, dialkylamino or N-alkylbenzylamino in which

2. Alkyl is non-tertiary alkyl of one to four carbon atoms; R represents hydrogen, alkyl of one to three carbon atoms or non

3. Tertiary alkoxy of one to four carbon atoms; R represents hydrogen, alkyl of one to three carbon atoms, non-tertiary alkoxy of 15 one to four carbon atoms, halo or dialkylamino in which alkyl is 4 non-tertiary alkyl of one to four carbon atoms; R represents one or two of hydrogen, alkyl of one to three carbon atoms, alkoxy of one to three carbon atoms, halo or nitro; R 5 represents hydrogen, non-tejrtiary alkyl of one to eight carbon atoms, 20 alkenyl of two to four carbon atoms, benzyl or benzyl substituted in the benzene ring by one or two of halo or alkyl of one to three carbon atoms; R® represents hydrogen, alkyl of One to three 7 8 carbon atoms or phenyl; and R and R represent hydrogen or alkyl of one to three carbon atoms. 25 2. A compound according to claim 1, wherein Y and Z are each the radical (A). -773. 2-(2,4,4 1 -Tris(dimethylamino)benzhydryl]-5-dimethy1aminobenzoic acid.

4. 2-12'-Methyl-4,4'-bis (dimethylamino)benzhydryl]-5-dimethylaninobenzoic acid.

5. 2- (2 1 -Ethoxy-4-dimethylamino-4 1 -diethylaminobenzhydryl) 5-dimethylaminobenzoic acid.

6. 2-(2,4-Bis(dimethylamino)-4’-diethylaminobenzhydryl]5-dimethylaminobenzoic acid.

7. 2-(4-Methoxy-4 *-dimethylaminobenzhydryl)-5-dimethylaminobenzoic acid.

8. 2-[4-Methoxy-2' ,4 1 -bis(dimethylamino)benzhydryl]-5-dimethylaminobenzoie acid.

9. A compound according to claim 1, wherein Y is the radical (A) and Z is the radical (B) or (G).

10. 2-[a-(4-Dimethylaminophenyl)-a-(1-ethyl-2-methyl-3indolyl)]methyl-5-dimethylaminobenzoic acid.

11. 2-[a-(4-Dimethylaminophenyl)-a-(l,2-dimethyl-3-indolyl)]methyl-5-dimethylaminobenzoic acid.

12. 2-[a-(4-Diethylaminophenyl)-a-(l-ethyl-2-methyl-3indolyl)]methyl-5-dimethylaminobenzoic aeid.

13. 2-ία-(4-(N-Ethylbenzylamino)phenyl]-a-(l-ethyl-2-methyl-3-indolyl)}methyl-5-dimethylaminobenzoic acid.

14. 2-(a-(2,4-Dimethoxyphenyl)-a-(1-ethyl-2-methyl-3indolyl)]methyl-5-dimethylamihobenzoic acid.

15. 2-[a-(4-Dimethylaminophenyl)-a-(l-methyl-2-pyrrolyl)]methyl-5-dimethylaminobenzoic acid. 12 3

16. A compound according to claim 1, wherein R , R or R when alkoxy has 1 to 3 carbon atoms and R^ is not alkenyl of 2 to 4 carbon atoms. 12 3

17. A compound according to claim 1, wherein R , R or R -78is alkoxy of 1 to 4 carbon atoms or R® is alkenyl of 2 to 4 carbon atoms.

18. A process for preparing a compound according to any one of claims 1 to 17, which comprises condensing a com5 pound of the Formula II (herein) with a compound of the formula Z-H wherein Z is as defined in claim 1, in the presence of an alkaline or an acid condensing agent.

19. A process according to claim 18, wherein the compound of Formula II is obtained by condensing a 3-N(Rj)10 4-X-benzoic acid with an aldehyde of the formula Y-CHO wherein Y is as defined in claim 1, in the presence of an acid condensing agent under dehydrating conditions.

20. A process for preparing a compound of the Formula I (herein) which comprises oxidizing a compound 15 as claimed in any one of claims 1 to 17.

21. A pressure-sensitive carbonless duplicating system or thermal paper marking system containing as a color-forming substance a compound according to any one of claims 1 to 17, or produced by the process according 20 to any one' of claims 18 to 20.

22. A compound according to claim 1, substantially as herein described with reference to the Examples.

23. A process according to claim 18, substantially as herein described with reference to the Examples.

24. 25 24. A product when prepared by the process according to any one of claims 18 to 20 and 23. 25. A pressure-sensitive carbonless duplicating system or thermal paper making system, as claimed in claim 21 and substantially as herein described with

25. 30 reference to the Examples.