CA1110244A - Synthesis of chromogenic indolylphenyldihydrofuropyridin-one compounds - Google Patents

Synthesis of chromogenic indolylphenyldihydrofuropyridin-one compounds

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Publication number
CA1110244A
CA1110244A CA 294539 CA294539A CA1110244A CA 1110244 A CA1110244 A CA 1110244A CA 294539 CA294539 CA 294539 CA 294539 A CA294539 A CA 294539A CA 1110244 A CA1110244 A CA 1110244A
Authority
CA
Grant status
Grant
Patent type
Prior art keywords
pyridine
reaction
compounds
anhydride
mixture
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
CA 294539
Other languages
French (fr)
Inventor
Troy E. Hoover
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Appvion Inc
Original Assignee
Appvion Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Grant date

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04Ortho-condensed systems
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B41PRINTING; LINING MACHINES; TYPEWRITERS; STAMPS
    • B41MPRINTING, DUPLICATING, MARKING, OR COPYING PROCESSES; COLOUR PRINTING
    • B41M5/00Duplicating or marking methods; Sheet materials for use therein
    • B41M5/124Duplicating or marking methods; Sheet materials for use therein using pressure to make a masked colour visible, e.g. to make a coloured support visible, to create an opaque or transparent pattern, or to form colour by uniting colour-forming components
    • B41M5/132Chemical colour-forming components; Additives or binders therefor
    • B41M5/136Organic colour formers, e.g. leuco dyes
    • B41M5/145Organic colour formers, e.g. leuco dyes with a lactone or lactam ring
    • CCHEMISTRY; METALLURGY
    • C09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; MISCELLANEOUS COMPOSITIONS; MISCELLANEOUS APPLICATIONS OF MATERIALS
    • C09BORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B11/00Diaryl- or thriarylmethane dyes
    • C09B11/04Diaryl- or thriarylmethane dyes derived from triarylmethanes, i.e. central C-atom is substituted by amino, cyano, alkyl
    • C09B11/26Triarylmethane dyes in which at least one of the aromatic nuclei is heterocyclic

Abstract

SYNTHESIS OF CHROMOGENIC

INDOLYLPHENYLDIHYDROFUROPYRIDIN-ONE COMPOUNDS

ABSTRACT OF THE DISCLOSURE
Chromogenic pyridine compounds having the formula:

Description

l~f~Z9~
This invention relates to a one-vessel process for the synthesis of chromogenic pyridine compounds.
More particularly, the invention relates to a method for the preparation of chormogenic lactone compounds derived from pyridine-carboxylic acid which does not involve the isolation of any intermediates.
Chromogenic pyridine compounds of the nature synthesized in accordance with the present invention are known in the art and are described in, for 10 example, U.S. Patents 3,775,424 and 3,853,869 to Farber, issued on November 27, 1973 and December 10, 1974, respectively. The compounds described therein are colorless materials which are capable -~ of forming a color when contacted with an appropriate acidic substance. Hence, they find utility in pressure-senstive record material and mark-forming manifold systems.
Processes for the preparation of said chromo-genic pyridine compounds as known in the art generally comprise three separate steps. In one typical method, quinolinic acid is converted to the anhydride:

-o ~COOH acetic ¢ ~ ~ anhydride > ¢ \ X C\ ll The resulting quinolinic anhydride is next reacted with an indole to yield a keto acid:

- 2 -}24~

,~ 111 . 12 R2 The keto acid is then condensed with an aromatic amine to yield a pyridine compound:

- R3~ R4 ¢~COOU ~3 ~ N ~R5 R~ N /~

N~l- C=O
. ~ .

: In the above formulae, Rl, R2, R3 and R4 are each hydrogen, an alkyl radical having l to 4 carbon - atoms, or a phenyl radical, preferably methyl or ^ - 3 -, . ,~

ethyl, and R5 is a hydrogen atom, an alkyl radical having 1 to 4 carbon atoms, or an alkoxy radical having 1 to 4 carbon atoms, preferably methyl, methoxy or ethoxy.
; 5 Alternatively, the keto acid has been formed by the reaction of quinolinic anhydride with an aromatic amine:

,'`

O
R3 Friedel-~ \O ~ ~ N \ catalyst .- R5 ., .
I IVI

F~3 ~C

This keto acid is then condensed with an indole to yield the same pyridine compound;

2~
~R3 ¢~ ~ ~R~

:'~ lVI
: ~3 C
2 I `o~;
~_o N ~
''' W

n Rl, R2, R3, R4 and R5 have the same signi-ficance as described above.
The overall yield of these typical procedures is about 48% from the pyridine-2,3-dicarobxylic acid. :
In accordance with the present invention, it has now been discovered that these types of compounds can be synthesized in a one-vessel process . 10 without isolation of any intermediate. In addition to reducing the complexity of the process by elimin-ating isolation steps, there is the unexpected advantage of an increase in overall yield from the acid to approximately 75~.
Accordingly, one of the objects of the present invention is to provide a one-vessel, continuous process for the preparation of chromogenic pyridine compounds.

~. .

. -- 5 --2~14 :.
Another object of the present invention is to provide a more convenient procedure for the preparation of : chromogenic lactone compounds derived from pyridine-carboxylic . acid in a reduced amount of reaction time.
A further object of the invention is to obtain a considerably improved overall yield of said chromogenic pyridine compounds.
Accordingly, the invention provides a continuous, one-vessel process ~or the preparation of isomeric chromogenic pyridine compounds having the formulae:

N ~ _r and . R3 R / ~ ¦ ¦ ~ N
: ~ C=O 1 R2 '' wherein Rl, R2, R3 and R4 are each hydrogen, an alkyl group having 1 to 4 carbon atoms, o~ phenyl, and R5 is hydrogen, an alkyl group having 1 to 4 carbon atoms or an alkoxy group having 1 to 4 carbon atoms, which comprises reacting pyridine-2,3-~ .

^` 1~1~2~

~ dicarboxylic acid with acetic anhydride at a temperature of ¦~
: about 120 to 130C, cooling to give pyridine-2,3-dicarboxylic anhydride, purifying, adding an indole compound having the formula:

, ~
~ W (II) Rl wherein Rl and R2 are as defined above, to the reaction mixture, heating to about 65 to 75C for about 3 hours to form the iso-meric keto acids having the formulae:

COO~

7 Rl ~ (III) : ~2 and ,..

~ 11 ~J , .
Rl wherein Rl and R2 are as defined aboye, purif~ing and then adding to the reaction mixture an amino compound having the - 6a -Z~4 ':
formula:
. R~ R4 :. N
.. I (IV) ,' ~

wherein R3, R4 and R5 are as defined above, heating to about 45 to 55C, adJusting the pH of the reaction mixture to at least about 8 and separating said chromogenic pyridine compound from the reaction mixture.
The general one-vessel reaction sequence, as depict-ed below, may be considered to consist of three states:
STAGE I
-- .
-:
:,. O

l0 ~ + 2(C 3CO)2O l0mC ~ ~ ~ +

:. O

(CH3CO)2O + CH3COOH
a. The pyridine-2,3~dicarboxylic anhydride precipitates on . . .
cooling~
b. The acetic anhydride and acetic acid are removed with a CC14 siphon wash, c. The quinolinic anhydride remaining in the reaction vessel is used in the next stage.

t 1.8 1 ~ 3 hrs.
. I

~ ~ /COOH ~ ,~

C~

a. The excess indole and bis-indolyl pyridyl dye may be removed by siphon extraction with chlorobenzene.
b. From this chlorobenzene extract the indole may be recovered and the useful by-product, the bis-indolylpyridyl dye, - isolated, if desired.
c. The isomeric keto acids remaining in the reaction vessel are used in the next stage.

,~

2~
`' ' : 1 STAGE 3 1 3\

e I 1 ~cH~rn~o (mixed isomers)

3\ _~C --~
N ~--C=O R2 .' ~

' 3~ N {~ C R1 N~
~C=O R2 - ~N

+NaOCOCH3 a. The reaction mixture is diluted with water. Sodium hydroxide solution is added to hydrolyze the acetic anhydride and to permit the dye lactone to form (pH ~ 8) b. The precipitated solid dye products are filtered to remove the sodium acetate.
- c. An appropriate hydrocarbon wash, in which the dyes are insoluble can be used to remove any unreacted substituted aniline.
d. A final aqueous alcohol wash of appropri-ate proportions is used to remove highly colored undesired side products. The alcohol used may be an alkanol such as methanol, ethanol or isopropanol. The proportions used are suitably 30-50~0 in water; however, any proportion may be used so long as it is capable of remov-ing colored by-products without dissolving excessive amounts of dye compounds.
Rl, R2, R3 and R4 are each hydrogen, an alkyl radical having l to 4 carbon atoms, or a phenyl radical, and R5 is hydrogen, an alkyl radical having . 1 to 4 carbon atoms or an alkoxy radical having 1 to 4 carbon atoms. Preferably Rl, R2, R3 and R4 are each methyl or ethyl, and R5 is preferably methyl, methoxy or ethoxy.
Experimentally, it has been found that when ; Rl, R3 and R4 are each ethyl, R2 is methyl and R5 is ethoxy, the yield of homogenous compounds ! formed is about 74%. The yields determined for each stage in this case were as follows:

Stage l: 86%
Stage 2: 92%
Stage 3: 93%
, .
In addition, the isolated yield of the bis-indolyl-pyridyl dye compound is about 7-8%. This compound is a red color reactant dye and can be useful for blending with the major color reactant dyes. Thus, the useful overall yield from 2,3-pyridine-dicarboxylic acid may be as high as 82% in accor-dance with the procedure of this invention.

.

' ~ _ g _ Z~

The first stage of the reaction procedure is conducted at a temperature of about 120 to 130C. The reaction of the pyridine-2,3-dicarboxylic acid does not proceed at a sufficient rate below 120C. The upper limit is determined by the boiling point of acetic anhydride, which is 140C. Thus, an upper limit of about 130C
is quite satisfactory for the reaction.
The pyridine-2,3-dicarboxylic anhydride formed in the first stage of the procedure is reacted with the alkyl indole compound in the second stage at a temperature of about 65 to 75C. Below 65C., a two phase mixture occurs, whereas above about 65C a solution within which the reaction readily proceeds is obtained. A disadvantageous amount of by-products is obtained above the upper limit of about 75C.
The third stage of the process is conducted at a temperature of about 45 to 55C. Below 45C., the reaction rate is too slow. The upper limit of about 55C is suitably employed during this stage of the procedure since the keto acids start to break down to form undesirable side products above this temperature.
The desired chromogenic compound then forms after adjustment of the pH of the resultant reaction mixture to the alkaline side, preferably at a pH
of about 8 o~ higher.
As noted above, the homogenous pyridine com-3 pounds prepared in accordance with the invention are useful, usually as a mixture of the obtained isomers, as dye-forming components in carbonless copy paper. Such formulations are well known in the art, for example, as disclosed in U.S. Patents 3,775,424 and 3,853,869, cited above, or in U.S.
Patent 3,627,581, which issued to Phillips on December 14, 1971, and the compounds synthesized in accordance with the present invention may be used as the colorless chromogenic compound in such

4 formulations as the color reactant material.

, The following example is given merely as illus-trative of the present invention and is not to be considered as limiting. Unless otherwise noted, the percentages therein and throughout the applica-tion are by weight.

EXAMPLE
In a 100-ml round bottom flask are placed

5.01 g. (0.03 mole) of 2,3-pyridinedicarboxylic acid and 9 ml. (o.o6 mole) of acetic anhydride.
- 10 A clear solution results upon heating at 120-130C
for 20 minutes. On cooling, as soon as crystalliza-tion starts, 60 ml. of CC14 is added. The mixture of CC14, acetic anhydride and acetic acid is siphoned off. Three additional CC14 (10 ml. each) washes are made.
Added to the solid in the reaction flask is

6.88 g. (0.0433 mole) of 1-ethyl-2-methylindole.
The mixture is maintained at 65-70C for 3 hours.
! A solid-liquid stirable mixture is present during this time. To the cooled reaction mixture is added 50 ml. of benzene (or chlorobenzene). The benzene and soluble components are siphoned off and two additional 15 ml. washes are made.
To the keto acids remaining in the reaction flask are added 4.63 g. (0.0240 mole) of N,N-diethyl-m-phenetidine and 32 ml. of acetic anhydride.
After 4 hours at 55C, the reaction slurry is poured into 28 g. of sodium hydroxide in 250 ml. of water.
The precipitated product is stirred for one hour at 50C. The product is filtered and then washed several times with water, 20 ml. of 30% methanol-water and finally with 15 ml. of petroleum ether (60-110C). The overall yield of the isomeric chromogenic compounds, (7-(1-ethyl-2-methylindol-3-yl)-7-(4-dimethyl-amino-3-ethoxyphenyl)-5,7-dihydro-35 furo[3,4-b]-pyridine-5-one and 5-(1-ethyl-2-.' ~

t-~za~9t methylindol-3-yl)-5-(4-dimethylamino-3-ethoxyphenyl)-5,7-dihydrofuro[3,4-b]-pyridine-7-one, is 74% based on the amount of starting pyridine-2, 3-dicarboxylic acid. The ratio of said isomers in the product is about 20 to 1, respectively.
- The invention being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be considered - as a departure from the spirit and scope of the invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims.

:, ~3

Claims (7)

1. A continuous, one-vessel process for the preparation of isomeric chromogenic pyridine compounds having the formulae:

(I) and wherein R1, R2, R3 and R4 are each hydrogen, an alkyl group having 1 to 4 carbon atoms, or phenyl, and R5 is hydrogen, an alkyl group having 1 to 4 carbon atoms or an alkoxy group having 1 to 4 carbon atoms, which comprises reacting pyridine-2,3-dicarboxylic acid with acetic anhydride at a temperature of about 120° to 130°C, cooling to give pyridine-2,3-dicarboxylic anhydride, purifying, adding an indole compound having the formula:

(II) ,wherein R1 and R2 are as defined above, to the reaction mixture, heating to about 65° to 75° C for about 3 hours to form the isomeric keto acids having the formulae:

(III) and ,wherein Rl and R2 are as defined above, purifying and then adding to the reaction mixture an amino compound having the formula:

(IV) ,wherein R3, R4 and R5 are as defined above, heating to about 45° to 55°C, adjusting the pH of the reaction mixture to at least about 8 and separating said chromogenic pyridine compound from the reaction mixture.
2. A process in accordance with claim 1, wherein R1, R2, R3 and R4 are each methyl or ethyl and R5 is methyl, methoxy or ethoxy.
3. A process in accordance with claim 1, wherein the pH of the reaction mixture is adjusted during the last step of the procedure with sodium hydroxide.
4. A process in accordance with claim 1, wherein acetic anhydride and acetic acid are removed with a CC14 wash after the formation of said pyridine-2,3-dicarboxylic anhydride,
5. A process in accordance with claim 1, wherein the resultant chromogenic pyridine compound comprises an isomeric mixture thereof.
6. A process in accordance with claim 1, wherein the resultant chromogenic pyridine compound is isolated from the reaction mixture and washed in a suitable solvent,
7. The isomeric chromogenic compounds 7-(1-ethyl-2-methyl-indol-3-yl)-7-(4-diethylamino-2-ethoxyphenyl)-5,7-di-hydrofuro[3,4-b]pyridin-5-one and 5-(1-ethyl-2-methylindol-3-yl)-5-(4-diethylamino-2-ethoxyphenyl)-5,7-dihydrofuro[3,4-b]-pyridin-7-one.
CA 294539 1977-09-29 1978-01-09 Synthesis of chromogenic indolylphenyldihydrofuropyridin-one compounds Expired CA1110244A (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US83786777 true 1977-09-29 1977-09-29
US837,867 1977-09-29

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Country Status (5)

Country Link
JP (1) JPS5452095A (en)
CA (1) CA1110244A (en)
DE (1) DE2842263C2 (en)
FR (1) FR2408609B1 (en)
GB (2) GB2006248B (en)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK536979A (en) * 1978-12-29 1980-06-30 Appleton Paper Inc Chromogenic material and process for its preparation
CA1139942A (en) * 1978-12-29 1983-01-25 Bruce W. Brockett Pressure-sensitive record material
US4275905A (en) * 1978-12-29 1981-06-30 Appleton Papers Inc. Pressure-sensitive record material
US4246318A (en) * 1979-04-09 1981-01-20 Appleton Papers Inc. Thermally-responsive record material
JPS56151597A (en) * 1980-04-28 1981-11-24 Yamamoto Kagaku Gosei Kk Recording material
US4668790A (en) * 1981-12-23 1987-05-26 Ciba-Geigy Corporation Chromogenic dihydrofuropyridinones
US4508897A (en) * 1981-12-23 1985-04-02 Ciba Geigy Corporation Preparation of chromogenic azaphthalides
FI76342C (en) * 1983-04-07 1988-10-10 Ciba Geigy Ag Foerfarande Foer framstaellning of 4-azaftalidfoereningar.
US4587343A (en) * 1983-05-09 1986-05-06 Ciba-Geigy Corporation Chromogenic 3,3-bisindolyl-4-azaphthalides
EP0140833B1 (en) * 1983-09-15 1988-03-02 Ciba-Geigy Ag 5- and 6-azaphthalides, their mixture of isomers, process for their production and their use in recording materials which are sensitive to pressure and heat
JPS6085986A (en) * 1983-10-18 1985-05-15 Yamada Kagaku Kogyo Kk Color forming recording material
US4675407A (en) * 1985-01-15 1987-06-23 Ciba-Geigy Corporation Ring-substituted 4-azaphthalides

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE791898A (en) * 1971-11-26 1973-05-24 Ciba Geigy Ag Process for the preparation of chromogenic substances from indoles and anhydrides of vicinal dicarboxylic acids, aromatic or heteroaromatic, new chromogenic this category, and their use
BE791793A (en) * 1971-12-06 1973-03-16 Ncr Co chromogenic compounds
JPS503426A (en) * 1973-05-16 1975-01-14
DE2429871C3 (en) * 1974-06-21 1981-05-14 Cmb Colonia Management- Und Beratungsgesellschaft Mbh & Co Kg, 5000 Koeln, De

Also Published As

Publication number Publication date Type
DE2842263A1 (en) 1979-04-05 application
GB2006248A (en) 1979-05-02 application
FR2408609A1 (en) 1979-06-08 application
FR2408609B1 (en) 1983-01-28 grant
GB2006248B (en) 1982-04-28 grant
DE2842263C2 (en) 1989-02-16 grant
GB2031934B (en) 1982-11-10 grant
GB2031934A (en) 1980-04-30 application
CA1110244A1 (en) grant
JPS5452095A (en) 1979-04-24 application

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