4,439,609
9
.
the compounds.
'
'
’
a.
1'0.
talliyne solid. Recrystallisation __from methanol/ether
(1:3,), yielded 2-_chloromethyl=4-dimethylaminometliylr
the route of administration and the relative potency of
"
pyridine hydrochloride (20.04 g) as‘ an orange solid mp.
The invention is illustrated by the following Prepara
tions and Examples. Temperatures are given in degrees
202F204,‘
.
,
_ v
_.
,
I,
., _
,9.‘
Centigrade.
PREPARATION-4
PREPARATION l
‘
.
_
s A
i'r:
Cysteamine hydrochloride.(3.75 g) was added to a
stirred solution of sodium ethox‘ide: (preparedv from 2.83
g sodium) in ethanol’ (200 m1)‘ and“, the mixture 'was
(a) A mixture of4~cyanopyridine (31.2 g), ammonium
persulphate (136.8 g), methanol (450 ml), concentrated
sulphuric acid (16.2 ml), and water (210 ml) was "heated
0
under re?ux for 24 hours, and the methanol waslre
moved by distillation. Crushed ice (450 g) was added
cooled], to less than 10°. '2-Chloromethyl-4-dimei
thylaminome‘t‘hylpyridine dihydrochloride (7.3 g’) was
added p'oi'tionwise and the solution was stirred for l
hour‘.‘Wa,ter;.(200 ml) was added, the pH was adjusted "to
ca. 1.4 with hydrochloric acid and the volume was're‘l
duced to ca‘. 100 ml. The solution was extracted with‘
chloroform, the aqueous phase‘ was basi?ed to pH,\12
and"'“extr"actéd with‘ chloroform to give 2-(4-‘dir'ne
and the mixture was adjusted ‘to pH 12 with 10 M so
dium hydroxide and extracted with chloroform.»The
chloroform extracts were combined and evaporated
and the residue was puri?ed by elution from a silicagel
column with methanol-chloroform (7.5% v/v)\to give
4-cyano-2-hydroxymethylpyridine . (18.5 g, ‘46%)’ mp
thylaminomethyl-2-pyridylmethylthio)ethylamine (4.7
920-94?‘
g) as an oil.
~
’
P
‘
i
_-
.
(b) A solution of 4-cyano-2-hydroxymethylpyridine
20
(0.5 g) in tetrahydrofuran (25 ml) was added dropwise
ium hydride (0.25 g) in tetrahydrofuran (30 ml) and the
of 1d,; l; 7.36, 3-pyridyl proton, d, 1.1; 8.49, ‘é-“py'ridyl
mixture was stirred at room temperature for Zhours.
25
proton,_d,,_l.l. r
I
the mixture was ?ltered. The ?ltrate wasevaporated _to
give crude 4-aminomethyl~2~hydroxyrnethylpyridine
(0.28g).,
r
'
p
7
8.4, 6-pyridyl proton, d, l.
, j
.
.
.7-
I‘
'_
PREPARATION 5
' - =
’
(a) Ammonium persulphate (54.8 g) water (150 ml)
and 4-'cyanobutyri_c acid (68 g) inwater (300ml) were
,_
NMR (CDC13); p.p.m., assignment, multiplicity, inte
gral;;l3_.87, CHZNHZ, s,‘ 1.7; 4.61, vCHZOH, s,‘ 2'; 7.11,
S-pyridyl proton, d of d, 1; 7.30, 3-pyridyl proton, d‘, 1';
'
sQHZCH‘ZNHZ, m2, 4.2; 3.46, ,CH2SCH2CH'2NH'2, 's,
_2;1‘;,3.86,'CI_—1‘2N(CH3)2,s, 21,1717, 5,-‘pyridyl proton,d
over 20 minutes to a stirred mixture of lithium alumin
Wet tetrahydrofuran followed by 0.35 ml of 1.6% ‘w/w
aqueous sodium hydroxide and water were added and
__
NMR(CDC13) p.p.m., assignment, multiplicity, inte
gryal: 13,51, NHZ, s, 2.2; 2.28, N(CH3)2, ‘s, 6;, 2.65 +2.85,
30
added separately and simultaneously over 30 m'inutesit‘o
a mixture'of4-dimethylarninomethylpyridine (‘16.32 g),
silver nitrate (4g). water (200ml) and ‘concentrated
sulphuric acid (25 ml) stirred atv 80°. The reaction mix
‘
(c) A solution of 4-aminomethyl-2-hydroxymethyl
ture was stirred at 80° for..-1.-5 hours, cooled, poured
pyridine (1.38 g) in aqueous formaldehyde (25% w/w,
onto crushed ice (400 g), and. aqueous ammonia (28%
12 ml)‘ was hydrogenated at 344 kPa and, 30°,for 23
hours with 10% palladium on charcoal catalyst. .The
w/w, 200ml). The'solutivon wasvextracted'with chloro
form (900'ml)\and_t,he chloroform extracts were v\gifashied
withldilut'e sodium hydroxide, dried over magnesium
mixture was ?ltered and the ?ltrate was extra'ct'ed‘with
sulphate, and concentrated in vvacuo to give 2-(3-cyano
water at pH 5 and this aqueous extract was adjusted to 40 propyl)-4-dimethylaminomethylpyridine (9 g) as a clear
.chlorolform'fThe chloroform phase was extracted with
pH 12 and extracted with chloroform. This ‘chloroform
extract was evaporated to give 4-dimethylaminometh
yl-2-hydroxymethylpyridine (0.47 g) as an oil.
oil-b.p.. 110°—1l_2°/0.1 rnm Hg.
'1
'l
I i
_ NMR v(CDC13): p.p.m., assignment,‘ multiplicity, ‘in'te
gral;
.
'. 2.l5+2.23_+;2.40,
NMR (CDCl3):'p.p.m., assignment, multiplicity, inte
gral; 2.26, N(CH3)2, s,- 5.5; 3.42, CH2N(CH3)2, s, 2; 3.75,
45
OH, broad, 1.3; 4.78, 'CH2OH, s, 2; 7‘.l9_+7.28', v5+3
pyridyl'protonsfd of d+d, 2.1; 8.49, 6-pyridyl proton,
PREPARATION 2
Ammonium persulphate (102.7 g) in water (200ml)
m+s+m, 10; 2.92, CH CH2Cl-I2CN, t,‘ 2; 3.41,
CH2N(CH3)2, s, 2; 7.1, 5+3pyridyl protons,m, 2; ‘8.46,
6-pyridyl proton, d, 1..
'
‘
'
I
'
'
'
.
(b) 2-(3-Cyanopropyl)-4-dimethylaminomethylpyri
dine (l g) in diethyl ether (15 ml)>was added dropwise
50 to a rapidly stirred suspension of lithium aluminium
was added over 40_ minutes to a-re?uxing solution of
4-dimethylaminomethylpyridine (40.86‘ g), - methanol
(450 ml), water (210 ml) and concentrated sulphuric
acid (30ml). The resulting solution was re?uxed for 2 55
hours, water (300 ml) was added and the methanol was
distilled off.‘ The cooled solutionv was basi?edrand'ex
‘hydride (0.76 g) in ether (45 ml). The solution_.,was
stirred for 2.5 hours. Wet'tetrahydrofuran, followed by
16%, sodium ,liyd‘roxide (1 ml) and then water was
added and the mixture wasu?ltered. The’ ?ltrate ‘was
evaporated to “give. 4-(4-dimethyIaminomethyI-Z
pyridyl)b,utylamine'(11.'02g) vvas a clear oil;
I '
NMR(CDC13)E p.p.m., assignment, multiplicity, inte
tracted with chloroform to give 4-dimethylaminometh
gral; l.64+ 1.70, NH2+CH2(CH2‘)2CH2NH2, s+m, 6.3;
yl-2-hydroxymethylpyridine
2.23, N(CH3)2, S, 6; ca 2.75, CH2(CH2)2CH2NH2, m,
92°—l20°/0.06 mm Hg.
U
>_
(19-.65 .. . g)
-
PREPARATION 3'
b.p.
3.9; v3.39, .CHzN(CH3)2, s, 2;_7.l,y5+3 pyridyl protons,
l v
I V
4-Dimethylaminomethyl-Z-hydroxymethylpyridine
(13.45 g) in dichloromethane (200 ml) was added drop- .
wise to a stirred solution of thionyl chloride ‘(30 ml) in
dichloromethane (150 ml). The resulting red mixture
was stirred for 1 hour then concentratedin vacuo. The
residue was treated with ether (300 ml) ‘to yield a crys
_
v
I,
M
-
‘EXAMPLE
T
,
..
, A} solution of, 2-(4-dimetl7iylaminométhyl-2ipyridyl
methylthio)ethylamine (0.5 g) and 2'-nitroami‘n'o-H5-(6
_ methyl-3-pyrid_ylmethyl)-4-pyrimidone (0.7‘iig) in‘i'pyri
dine (3 fril) was heatedunderyre?uirfor 3.5 hours and
evaporated 'to dryness. The residtlé ‘was puri?ed by
1
4,439,610
2
-continued
(IV)
R1
PROCESS FOR PREPARING TRIARYLMETHANE
l
Rs
DERIVATIVES
R1
N
R6
This is a division of application Ser. No. 699,584 ?led
June 24, 1976 now us. Pat. No. 4,045,458.
’
10
BACKGROUND OF THE INVENTION
This invention relates to a process for preparing co
lourless chromogenic compounds which form coloured
markings upon contact with acidic materials by electron
wherein each of R1 and R2 is at least one of hydrogen,
donor-acceptor colour-forming reaction.
group, amino group, substituted amino group, hydroxyl
halogen, nitro group, alkyl group, substituted alkyl
group, substituted hydroxyl group, thiohydroxyl group,
Particularly, this invention relates to a novel process 20 or substituted thiohydroxyl group; each of R3 and R4 is
hydrogen, substituted or unsubstituted alkyl group,
cycloalkyl group, substituted or unsubstituted aralkyl
for preparing triarylmethane derivatives represented by
the following general formulae (1), (II), (III) and (IV):
group, substituted or unsubstituted aryl group, or sub
stituted or unsubstituted unsaturated alkyl group, or one
25
or both of R3 and R4 together with the adjacent nitro
gen atom may form a heterocyclic ring; R5 is at least
one of hydrogen, halogen, alkyl group, nitro group,
substituted or unsubstituted amino group, substituted or
30
unsubstituted hydroxyl group, substituted or unsubsti
tuted thiohydroxyl group; R6 is at least one of hydro
gen, halogen, lower alkyl group, lower alkoxyl group,
amino group, lower alkylamino group, nitro group,
phenyl group or phenoxy group; R7 is hydrogen, alkyl
35
group, aralkyl group or phenyl group; and R3 is lower
alkyl group or substituted or unsubstituted phenyl
group.
There are known several methods for preparing triar
ylmethane derivatives represented by the general for
mula (I), for example, U.S. Pat. No. Re. 23,024 discloses
a method in which the triarylmethane derivative is
prepared from m-dimethylamino-benzoic acid and Mi
chler’s hydrol by condensation reaction. Another
method for preparing triarylmethane derivative by con
45 densation reaction of dimethylaniline with o
phthalaldehydric acid is described in “Beilsteins Hand
buch der Organische Chemie”, Vol. 14, page 549. How
ever, these methods give triarylmethane derivative in
low yields because a large amount of by-products is
50
produced. Furthermore, these methods give only lim
ited compound having a symmetrical structure.
The triarylmethane derivatives having the general
formula (II) are novel compounds which are synthe
sized for the ?rst time by this invention.
55
The known method for preparing triarylmethane
derivatives represented by the general formula (III) and
(IV) is disclosed in U.S. Pat. Nos. 2,443,092 and
2,597,965, “Beilsteins Handbuch der Organische Che
mie”, vol. 18, page 617 and Moriga & Oda, “Kogyo
Kagaku Zasshi”, vol. 64, page 1226, (1961), in which
triarylmethane derivatives are prepared from dimethyl
aniline and phthalic anhydride by condensation. An
other method is described in U.S. Pat. Nos. 3,491,112
and 3,491,116 and in “Beilsteins Handbuch der Organis
65 che Chemie”, vol 18, pages 618-619, in which ben
zophenone-2-carboxylic acid is ?rst prepared from di
methylaniline and phthalic anhydride and then triaryl
methane derivative is prepared from the resultant ben
4,439,610
5
-continued
6
R|
c110
‘
coon
+7
LII
RIQ
-
R1
C
R2 (1X) \
'(VIII)‘
H
C
10
or CHO
COOH /
@
(V)
15
R2
(111)
~
R1
R2
(X)
20 wherein R1 and R2 are the same as described above.
R7
l
R3
As the typical compounds of 3-phenylphthalide de
rivatives represented by the above general formula (V)
7
N
R1
(XI)
.
I.
‘
R6
H
which are used in this invention, the following com
.
v
C
pounds may be exempli?ed;
,
oxidation
COOH
25
>
30
R2
(11)
.
R3
T7
N
35
I
3-[4’-(N-ethyl-N-benzyl)aminophenyl1phthalide,
3-[4’-(N-methyl-N-P-tolyl)aminophenyl]phthalide,
3-(4'-pyrrolidinophenyl)phthalide,
4-(julolidine-6'-yl)phthalide,
R1
C
. '
3-(4'-dimethylaminophenyl)phthalide,
3-(4'-dimethylamino-2'-methylphenyDphthalide, '
3-(4'—dimethylamino-2'-methoxyphenyDphthalide,
3-(4’-dimethylamino-2'-methylthiophenyl)phthalide,
3-(4’-dimethylamino-2’-chlorophenyl)phthalide,
3-(4'-dimethylarnino-2'-diethylaminophenyDphthalide,
3-(4’-diethylaminophenyl)phthalide,
3-(4’-diethylamino-2'-chlorophenyl)phthalide,
3-(4';diethylamin0-2’-methoxyphenyl)phthalide,
3-phenyl-6-dimethylaminophthalide,
3-phenyl-6-diethylaminophthalide,
'.
\0
3-[2'(or 3', or 4')-methylphenyl]-6-dimethylaminophtha
lide,
I
3-[2'(or 3', or 4’)-methoxyphenyl]-6-dimethylaminoph
co
thalide,
.
.
3-[2'(or 3', or 4')-methoxyphenyl]-6-diethylaminophtha
lide,
3-[2'-(or 3', or 4')-chlorophenyl]-6-dimethy1aminoph
R2
(IV)
thalide,
-
.
3-[2'-(or 3’, or 4')-nitrophenyl]-6-dimethylaminophtha
lide,
V
wherein R1, R2, R3, R4, R5, R6, R7 and R3 are the same 50 3-[2'-(or 3', or 4’)-nitrophenyl]-6-diethylaminophtha
as described above.
lide,
'
I
‘
3-[2', 3’(or 2', 4')-dimethylphenyl]-6-dimethylaminoph
thalide,
DETAILED DESCRIPTION OF THE
55
INVENTION
3-[2’,
‘
3’(or
thylaminophthalide,
thalide,
above described general formula (V) which is used in 60
this invention is prepared, as shown as follows, from
3-[2’,3'(or 2', 4’)-dichlorophenyl]-6-dimethylaminoph
thalide,
'
3-(2’-methyl-4'-methoxyphenyl)-6~dimethylaminoph
3-(2’-methoxy-4’-methylphenyl)-6-dimethylaminoph
thalide,
benzene derivative (VIII) and o-phthalaldehydic acid
tive (XI) by dehydration condensation:
_
3-[2’, 3’(or 2’,4')-dimethoxyphenyl]~6-diethylaminoph
3-phenylphthalide derivative represented by the
derivative (IX) by dehydration condensation, or from
benzaldehyde derivative (X) and benzoic acid deriva
4')-dimethoxyphenyl]-6-dime
2’,
'
‘
thalide,
65
'
3-[2'(or
3',
3-[2'(or
3’,
‘or
4')-dimethylaminophenyl1-6-dime
thylaminophthalide,
or
thylaminophthalide,
4’)-dimethylaminophenyl]-6-die
4,439,610
9
10
Referring to the amount of such Friedel-Crafts type
-continued
Z-methyl-S-chloroindole, Z-methyl-S-ethoxyindole,
2-methyl-7-phenylindole, Z-methyl-S-aminoindole,
1,2-dimethylindole, l-methyl-Z-phenylindole,
1.2.5-trimethylindole, l.Z-dimethyl-S-methoxyindole,
LZ-dimethyI-S-phenoxyindole,
LZ-dimethyl-S-nitroindole,
l-methyl-2-(4'-chlorophenyl)indole,
l-methyl-2-(4'-ethoxyphenyl)indole,
l-methyl-2-(4'-ethoxyphenyl)-S-dimethylaminoindole,
l-benzyl-2-methylindole, l-benzyl-2.5~dime thylindole
1-benzyl-2-methyl-S-methoxyindole,
l.2-dimethyl~7-phenylindole,
l-phenyl-2.S-dimethylindole,
catalysts, it may be controlled properly according to the
kinds of the starting materials, but it is preferable to use
them in amounts equimolar with respect to 3-phenylph
thalide derivative or more.
'
As a solvent, benzene, toluene, alkylbenzene, chloro
benzene, dichlorobenzene, bromobenzene, nitroben
zene, alkylnaphthalene, ethylene chloride, chloroform,
tetrachloromethane, tetrachloroethane, nitromethane,
nitroethane, nitropropane, carbon disul?de, kerosene,
high-boiling naphtha, etc. are preferably used. In order
to increase the rate of reaction and to minimize the
amount of catalyst, it is preferable that such a solvent
l.Z-dimethyl-5.6-dichloroindole.
should not be used or the amount of the solvent should
15 be minimized even when it is used. On the other hand,
In the practice of the invention, 3-phenylphthalide
the excess amount of solvent is preferably used for the
derivative is made to react with aniline derivative or
purpose of control of the reaction temperature, homog
indole derivative in the presence of Friedel-Crafts type
enization of reaction, extraction or the resultant prod
catalyst, if necessary, with use of a suitable solvent, at
uct, etc. Therefore, the solvent should be used as occa
the temperature of 0° to 180° C. for the period between 20 sion demands.
several minutes and several decades of hours.
In this invention, triarylmethane derivatives repre
As a Friedel-Crafts type catalyst, acidic halide Lewis
sented by the general formula (III) or (IV) are obtained
l-phenyl-2.S-diethylindole and
acid catalysts such as AlCl3, AlBl'3, BeCl2, CdClz,
by oxidation of the above obtained triarylmethane de
ZnCl2, BF3, BCl3, GaCl3, GaBrg, TiCl4, TiBr4, ZnCl4,
SnCl4, SnBr4, SbCl5, SbCl3, BiCl3, FeCl3, UCl4, PF5,
25 with use of an oxidizing agent. Triarylmethane deriva
rivatives represented by the general formula (I) or‘(II)
SbF5, AsF5 and mixed penta?uorides of Nb and Ta;
metal
alkyl
Lewis
Al2Cl3(CH3)3 + HCl,
acid
catalysts
AlCl2(C2H5),
such
as
AlCl(C2H5)1,
A1(t-C4H9)s, A1(i-C4H9)s, AuBr2C2Hs, B¢(C2Hs)2,
BRX3, MgRxz, RX2Mg.MgX2, TiCl3CH3, TiCl3(C2H5)
tive represented by the general formula (I) or (II) is
dissolved in acidic aqueous solutions such as hydrochlo
ric acid solution and sulfuric acid solution, alkaline
aqueous solutions such as caustic soda solution and
30 caustic potash solution, or organic solvents such as
alcohols, lower aliphatic carboxylic acids, ethers, ke
and Zn(C2I-I5)2, wherein Rx is alkyl group and X is
halogen; metal alkoxide Lewis acid catalysts such as
tones, aromatic hydrocarbons, and thereafter an oxidiz
ing agent is added to the solution, and then the oxida
Al(OC6H5)3, aluminum alkoxides, AlClzORx, AlCl3
tion is carried out at the temperature of 0° to 500° C. for
.Ti(ORX)4, Ti(BuO)4 and Ti(i-PrO)4, wherein Rx is
alkyl group; Brtpnsted acid catalysts such as, phos
35 the period between several minutes and several decades
of hours.
As an oxidizing agent, manganese compounds such as
per-manganates, manganates, managanese dioxide, man
ganese(III) salts and manganese acetate; chromic acid
phoric acid, polyphosphoric acid, perchloric acid,
chlorosulfonic acid, ?uosulfonic acid, alkane sulfonic
acids such as ethane sulfonic acid, p-toluenesulfonic
acid, acetic acid, chloroacetic acids, tri?uoroacetic 40 compounds such as chromic anhydride, chromic acid,
perchromates, alkyl esters of chromic acid and chromyl
acid, sulfuric acid, hydrogen halides and alkyl halides;
acidic oxide and sul?de (acidic chalcide) catalysts such
chloride; lead compounds such as PbO, PbOz and Pb(O
COCH3)4; copper compounds such as CuO, Cu(OH)2,
as alumina, Al203.CaO, Al2O3.Cr2O3, Al2O3.Fe2O3,
Al2O3.V2O3, alumino-silicates (natural), bauxite, ben
CuSO4, Cu(OCOCH3)2, CuClg and CUBI‘2; cobalt com
tonite clay, BeO, acid activated clay, chromia (with 45 pounds such as Co2(SO4)3 and C0304; cerium com
pounds such as CeOZ, Ce(SO4)2 and Ce(SO4)3; bismuth
silica-alumina), Cr2O3(synthetic), Cr2O3, Fe2O3, ?ori
din, Georgia clay, Gumbrin clay, magnesia (with silica
compounds such as Na Bi03, BiO and Bi(OCOCH3)2;
silver compounds such as AgzO, AgOCOCH3 and Ag
alumina), molybdenum oxide-alumina, M052, M083,
NO3; iron compounds such as FeClg, Fe2(SO4)3 and
MoS2.CoS, mont'morillonite clay, nickel-alumina, P205,
silica-alumina, thoria (with silica-alumina), ThO2(syn
thetic), TiOg, W03 (with silica-alumina) and zirconia
(with silica-alumina); acidic cation exchanger catalysts
50
such as performic acid, peracetic acid, perpropionic
such as sulfonated coals, sulfonated phenol-formalde
hyde resins, sulfonated divinylbenzene cross linked
polymers and exchangers with carboxyl group, phenol
potassium ferricyanate; SeO2; RuO4; 0504; inorganic
peroxides such as hydrogen peroxide, Fenton’s reagent,
persulfuric acid and salts thereof; organic peroxides
55
acid, perbutyric acid, perbenzoic acid, monoperphthalic
acid, monoperterephthalic acid, monopersuccinic acid
group or alumina-silicate skeleton; metathetic cation
and tri?uoroperacetic acid; halides such as hypochlor
forming substances such as AgAsF6, AgClO4, AgBF4,
ites, chlorates, hypobromites and bromates; oxygen;
AgNO3, AgOOCCF3, AGPO4, AgPF6, AgSbF6, Agz
ozone; ultraviolet ray; sulfoxides; amine oxides; and
chloranil are preferably used. The amount of oxidizing
agent may be controlled according to the kinds of oxi
dizing agent to be used, but it may he usually used in an
S04, AgNbF6, AgTaF6 and AgTigFg; and the mixtures
thereof may be used.
Among the above Friedel-Crafts type catalyst acidic
halide Lewis acid catalysts, Brg5nsted acid catalysts,
acidic oxide catalysts, metal alkyl Lewis acid catalysts
excess of a stoichiometric amount based on the amount
of said triarylmethane derivatives having the general
and metal alkoxide acid catalysts are preferably used
formula (I) or (II).
When the compounds having an oxidizing function
because they are highly reactive and economical. Par 65
ticularly, acidic halide Lewis acid catalysts, Brr? nsted
such as FeCl3, F6BI‘3, AgNO3, CuClg and peracetic acid
acid catalysts and acidic oxide catalysts are most prefer
able.
tion of triarylmethane derivatives represented by the
are used as a Friedel-Crafts type catalyst in the prepara
4,439,610
11
general formula (I) or (II) from 3-phenylphthalide de
rivatives and aniline derivatives or indole- derivatives,
the resultant triarylmethane derivatives represented'by
the general formula (I) or (II) are instantaneously oxi
dized to form triarylmethane derivatives represented by
the general formula (III) or (IV).
12
aluminum chloride while cooling the mixture with ice.
Then, the tetrachloroethane phase was separated with
the aid of a separatory funnel, and then stream distilled
to remove the unreacted dimethylaniline and tetrachlo
roethane. The remaining aqueous phase was neutraliz'ed
with acetic acid to obtain a pale yellow solid. The yield
‘
Namely, the reaction of a S-phenylphthalide deriva
was 42 g. This solid was recrystallized from benzene to
tive with an aniline derivative or an indole derivative to
obtain colourless crystals having a melting point (here
form a triarylmethane derivative having the general
formula (I) or (II) is immediately followed by and con
inafter referred to as m.p.) of 201° C. The obtained
crystal results in a blue colouration when it is subjected
currently occurs with the oxidizing reaction to form
to light on silica gel. This compound is triarylmethane
said triarylmethane derivative having the general for
represented by the following formula:
mula (III) or (IV). For this purpose Friedel-Crafts type
catalysts may preferably be used in an excess of the total
amount of an equimolar amount with respect to said
3-phenylphthalide derivative and a stoichiometric
CH3\
derivative having the general formula (I) or (II)
/CH3
\CH3
CH
The process of the invention for the preparation of
triarylmethane derivatives from 3-phenylphthalide de
N
CH3/
amount based on the amount of said triarylmethane
20
COOH
rivatives is a novel method which has never been de
scribed in any literature. The process of the invention
gives triarylmethane derivatives at high purities and in
extremely high yields. In addition, the process of the
N
cm/ \Cl-I3
invention makes it possible to prepare the various novel 25
triarylmethane derivatives which could not be synthe
sized by any conventional methods.
EXAMPLE 2
The triarylmethane derivatives obtained in this inven
tion form coloured markings upon contact with acidic
30
g
of 3-(p-dimethylaminophenyl)-6-dime
substances such as solid acids, e.g., acid clay, activated 30 thylaminophthalide and 17 g of N,N-diethyl-m-tolui
clay, attapulgite, zeolite, kaolin, bentonite and silicates;
dine were dissolved in 300 cc of benzene. After the
addition of 14 g of zinc chloride, the mixture was heated
and organic acidic materials such as phenol-formalde
hyde polymers, phenol-acetylene polymers, maleic acid
rosin resin, ethylene-maleic acid anhydride polymers,
at 80° C. ‘for 5 hours with stirring. After cooling, the
resultant precipitate was ?ltered and then dried. The
salicylic acid-aldehyde polymers, salicylic acid-acety
obtained precipitate was dissolved in dilute hydrochlo
lene polymers, polyvalent metal salts of those polymers
mentioned above, aromatic carboxylic acids, e.g., sali
cylic acid and salicylic acid derivatives, and polyvalent
metal salts of aromatic carboxyliclacids by an electron
donor-acceptor colour-forming reaction, therefore,
ric acid, and then the pH of the solution was adjusted at
4.0 with anaqueous solution of caustic soda to form a
yellow precipitate. This precipitate was filtered and
40 then dried. The yield was 45 g. Recrystallization from
they may be utilized as colourless chromogenic com
pounds (is. electron donor) in various ?elds which
utilize such a reaction. For example, triarylmethane
derivatives of the invention can be utilized for the pro
duction of pressure sensitive copying sheet which is
disclosed in U.S. Pat. Nos. 2,730,456 and 2,730,457 and
Japanese Pat. No. 511,757, heat sensitive copying sheet
which is disclosed in US. Pat. Nos. 3,451,338 and
V 3,539,375, hectographic copying sheet, electron beam
sensitive recording sheet, photosensitive sheet, electro
benzene gave triarylmethane represented by the follow
ing formula in the form of colourless crystals whose
m.p. was 255°—260° C. This compound turns in blue
colour upon exposure to light on TCL.
CH3\N
H3C
CH3/ O I)‘ \CZHS
CH
graphic heat sensitive recording sheet, ultrasonic re
cording sheet, toner for Xerox type copying sheet, and
leuco ink.
COOl-I
-
PREFERRED EMBODIMENT OF THE
55
INVENTION
The following examples serve to illustrate the inven
tion in more detail although the invention is not limited
to the examples.
EXAMPLE 1
30
N/czlis
of
3-(p-dimethylaminophenyl)-6-dime
thylaminophthalide and 13 g of dimethylaniline were
dissolved in 250 cc of tetrachloroethane. 14 g of anhy
N
CH3’ \cm
EXAMPLE 3
Example 1 was repeated except that 26 g of 3-(p
dimethylaminophenyl)phthalide was used instead of 30
g of 3-(p-dimethylaminophenyl)-6-dimethylaminoph
thalide to obtain 32 g of triarylmethane represented by
drous aluminum chloride was added to the solution and 65 the following formula whose m.p. was 194°—l95° C. in
the form of colourless crystals. This compound be
the resultant mixture was heated at'50" C. for 3 hours
comes bluish green upon exposure to light on silica gel.
with stirring. After the termination of reaction, 30%
aqueous solution of caustic soda was added to dissolve
4,439,610
13
CH3\N
14
N/CH3
C“ Q Q \C‘“
CH
‘ ‘0cm
H
9H1 N
5
CH
COOH
COOH
l0
EXAMPLE 4
Example 1 was repeated except that 29 g of 3-(0
/N\
CH3
CH3
methoxyphenyl)-é-dimethylaminophthalide was used 15
instead of 30 g of 3-(p-dimethylaminophenyl)-6-dime-
EXAMPLE 7
thylaminophthalide to obtain 38 g of triarylmethane
Example 1 was repeated except that 32 g of 3-(3',
represented by the following formula whose m.p. was
4’-dimethoxyphenyl)-6-dimethylaminophthalide
and
237°-238° C. in the form of colourless crystals (Recrys
tallized from acetic acid-methanol). This compound 20 13.5 g of Z-methylindole were used, respectively, in
stead of 30 g of 3-(p-dimethylaminophenyl)-6-dime
becomes bluish green upon exposure to light, on silica
gel.
thylaminophthalide and 13 g of dimethylaniline to ob
tain 33 g of triarylmethane having the following struc
0cm
N:
CH3
25
CH3
ture whose m.p. was 230°—232° C. in the form of colour
less crystals (Recrystallized from methanol). This com
pound becomes bluish violet upon exposure to light on
silica gel.
CH
30
COOH
H
CH3
N
CH:@
35
COOH
EXAMPLE 5
Example 1 was repeated except that 13.5 g of 2
methylindole was used instead of 13 g of dimethylani
line to obtain 34 g of triarylmethane having the follow
CH3
ing formula in the form of colourless crystals. This
CH3
compound becomes violet upon exposure to light on
silica gel.
-
EXAMPLE 8
45
CH3\
N
H
on;
CH3/ ‘O
N
CH
silica gel.
COOH
N
CH3/ \CH3
Example 1 was repeated except that 19.5 g of 2
phenylindole was used instead of 13 g of dimethylani
line to obtain 34 g of triarylmethane having the follow
ing structure in the form of colourless crystals. This
compound becomes blue upon exposure to light on
55
H
EXAMPLE 6
Example 1 was repeated except that 29 g of 3-(0
methoxyphenyl)-6-dimethylaminophthalide and 13.5 g
CH3/ Q CH / N
of Z-methylindole were used instead of 30 g of 3-(p
COOH
dimethylaminophenyl)-6-dimethylaminophthalide and
13 g of dimethylaniline, respectively, to obtain 29 g of
triarylmethane having the following structure whose 65
m.p. was 203°-205° C. in the form of colourless crystals
(Recrystallized from methanol). This compound be
comes blue black upon exposure to light on silica gel.
CH3
\
CH3
4,439,610
‘15
16
stead of 30 g of 3-(p-dimethylaminophenyl)-6-dime
thylaminophthalide to obtain 39 g of triarylmethane
EXAMPLE 9
Example 1 was repeated except that 32 g of 3-(2',4'
having the following structure whose m.p. was
l97°-198° C. in the form of colourless crystals. This
compound becomes bluish green upon exposure to light‘
on silica gel.
dimethoxyphenyl)-6-dimethylaminophthalide and 13.5
g of 2-methylindole were used, respectively, instead of
30
g
of
3-(p-dimethylaminophenyl)-6-dirne
thylaminophthalide and 13 g of dimethylaniline to ob
tain 27 g of triarylmethane having the following struc
CH3
CH3
)1“
CH3
ture whose m_.p. was 202°—203° C. in the form of colour
less crystals,(Recrystallized from methanol). This com 10
pound becomes bluish violet upon exposure to light on
Ni CH3
CH
_
silica gel.
CQOH
va
CH3O
0on3
CH3
N
on
20
coon
EXAMPLE 11‘
Example 1 was repeated with use of the various start
ing materials and catalysts shown in the following table
instead
of
3-(p-dimethylaminophenyl)-6-dime
thylaminophthalide, dimethylaniline and anhydrous
N
25 aluminum chloride to obtain the various triarylmethane
CH3/ \ci-n
compounds shown in the following table. The colours
formed upon exposure to light on silica gel are shown in
the following table as well.
EXAMPLE 10
Example 1 was repeated except that 30 g of '3-(p
dimethylaminophenyl)-6-ethoxyphthalide was used in
aniline or
3-phenylphthalide
derivatives
indole derivatives
C2H5
\
N
cir
2 5
/
CH
I
o
CH3
CgHs
\N’
C2H5
resultant
compounds
catalysts
ZnClZ
C2H5
C2H5
\
N
/
N
\CH
C=O
color
Blue
N
Cl/—I \©\ /©/ \c H
5
3
2 5
2
CH
COOH
N
CH3/ \cm
CH3
C4H9
\
/
Cll-lN—©—CHI
3
CH3
\N/
CH3
"
N
CH3
\
3
: ,COOH
9
CH
C4119
CI\-l3
N
CH
3
/CH3
CH
I
N
(‘3H
"
"
/
N\
C4119
Cl\-I3
CH3
N
2
"
chNn g N\cm
\C4H
o—-—c=o
CH3
N
CH3\©\ /©/ \CH3
CH
COOH
"
4,439,610
21
22
-continued
aniline or
3-phenylphthalide
indole de-
derivatives
rivatives
CH3
\
CH3
N
cil-r
/
CH
I
3
0
C2H5
CzHgy ‘
\cn
compounds
SiOz
color
CH3
\N’
N
C=o
resultant
catalysts ‘
‘
\
C2H5
N
"
/
OCH;
N
Gil-l n n \c H
3
3
CH
OCH3
2 5
COOH
N
on,’ \CH3
Cl
CH3
Cl\‘!3
,CH3
f‘
“3*
2,
C__
CH:
CH3
CH3
\N/
Clay(acid
CH3
activated)
\N
CH3
Cl SCH
Blue
’ N/
X1
3
CH50 \CH3
CH
SCH3
COOH
N
CH3’ \cH;
EXAMPLE l2
Example 1 was repeated except that 33 g of anhy
EXAMPLE 13
Example 12 was repeated ‘with use of the various
drous ferric chloride was used instead of 14 g of anhy- 3o starting materials and catalysts shown in the following
table instead of 3-(p-dimethylaminophenyl)-6-dime
drous aluminum chloride to obtain 16 g of compound
thylaminophthalide, dimethylaniline and anhydrous
having the following structure whose m.p. was 180° C.
ferric chloride to obtain the various triarylmethane
in the form of colourless crystals (Recrystallized from
compounds shown in the following table. Those com
benzene-methanol). This compound becomes blue upon
5\ pounds produce the various colours shown in the fol
contact with silica gel.
lowing table immediately upon contact with silica gel.
CH3\
N/CH3
093/
O \CH3
C\
O
i
C=0
N
CH3’ \cm
aniline or
3-phenylphthalide
indole de-
derivatives
rivatives
catalysts
compounds
C2H5\ /C2H5
FeBl'3
CH3\
CH3\
/CH3
,N-G-CH
'N\
N
‘
resultant
color
'
/CZH5
/N
Blue
N\
0-—c=o
C \
a
O
CH3
CH3
4,439,610
23
24
-cont_inued
aniline or
3-phenylphthalide
derivatives
cu,
:~—®—w
~:
ca,
indole derivatives
catalysts
resultant
compounds
C3H7\ /C3H1
ci-clz
CH3
~
color
>~
~<
o—c=o
c \
cm7
"
i
0,
C:
N
CH3’ \cm
CH3
C2H5\
/N
Czl-ls
Czl'ls
,CH3
CH
|
\N/
C2H5
FeCl3
C2l-l5
\N
CH3 CH3
CH /
N\ CH3
N
/C2H5
”
2 5 \©/\ C U \CZHS
0_ c= 0
\
CH3
(I)
c=0
CH3/ \ci-n
Cl
CH3
C2Hs\
Czl-ls
/N
/CH3
cu
|
A N03
I
CH3
N\ CH3
-
g
C2Hs\
N
/
m
CH
_
CH3
czns
-
Violet
I2 5
N
'
C \
o-—-c=o
C‘)
I
c=o
Cl
N
cnf \cm
40
C2115
\N/
C1115
/CH3
EXAMPLE
14
_
33
of
N\ CH3
45
3-(m-diethylaminophenyl)-6-dime-
C
thylaminophthalide and 13 g of dimethylaniline were
\0
dissolved in 300 cc of tetrachloroethane. 14 g of anhy-
I
drous aluminum chloride was added to the solution, and
then the mixture was heated at 50° C. for 3 hours with 50
C=o
stirring. After the termination of reaction, 30% aqueous
solution of caustic soda was added to the mixture to
dissolve aluminum chloride while cooling with ice.
/N\
Tetrachloroethane phase was steam distilled to remove
CH3
unreacted dimethylaniline and tetrachloroethane. The 55
remaining aqueous phase was neutralized with acetic
CH3
EXAMPLE 15
acid to obtain a white solid. This solid was dissolved in
600 cc of 2.5% aqueous solution of caustic soda, and
then heated at 50° C. 600 cc of 5% aqueous solution of
Example 14 was repeated except that 29 g of 3-(p
methoxyphenyl)-6-dimethylaminophthalide and 19.5 g
potassium persulfate was added dropwise to the above 60 of Z-phenylindole were used, respectively, instead of 33
solution, and then the mixture was heated at 60° C. for
g of 3-(m-diethylaminophenyl)-6-dimethylaminophtha
3 hours. After the termination of reaction, the resultant
precipitates were ?ltered and recrystallized from meth
anol to obtain 31 g of 3- m-diethylaminophenyl)-3-(p
lide and 13 g of dimethylaniline to obtain 24 g of 3-(p
dirnethylaminophenyl)-6-dimethylaminophthalide hav
ing the following structure whose m.p. was l77°—l78°
C. in the form of colourless crystals. This compound
become green on contact with silica gel.
methoxyphenyl)-3-(2-phenylindole-3-yl)-6-dime
thylaminophthalide having the following structure
65 whose m.p. was 224°—225° C. in the form of colourless
crystals (Recrystallized from benzene-methanol). This
compound becomes blue black on contact with silica
gel.
25
4,439,610
26
CHJO U OCH;
C
10
\
O
EXAMPLE 16
EXAMPLE 18
Example 14 was repeated except that 32 g of 3-(3,4
iet
dimetoxyphenyD-6-dimethylaminophthalide and 19.5 g
of 2-phenylindole were used instead of 33 g of 3-(m-die
Egg-Rail)
o
e o w
s ucture
thylaminophenyl)-6-dimethylaminophthalide and 13 g 25 géomes VIO‘iC upon contact W181 s1 1ca gel.
p
of dimethylaniline to obtain 21 g of 3-(3',4’-dimetoxy
CH2
phenyl)-3(2'-phenylindole-3'-yl)-6-dimethylaminoph
/
\
Wr ass étaztaii’zgi gem-mi, “a,” carats
(‘3H2 CH2
thalide having the following structure whose m.p. was
235°—236° C. in the form of colourless crystals (Recrys
tallized from benzene-methanol). This compound be
comes blue black upon contact with silica gel.
_
N
30
pH;
CH
CH2/
CH2\
N
C 3: : :
CH2
35
\O
l
(1:
OCH3
c1130
EXAMPLE l9
45
amm
n
nop h? e a
sagtgi . _ 1'52’- lteaglinaiig .g, alias‘?
in
t
,0
n
sructure
_
2
.1 t e or o colo r1
ta lzed fr m enzene-met no .
comes v1o et on contact wit
woe m . was
_crystals( e r s
If compoun
-
s1 1ca ge .
CH3
50
EXAMPLE 17
55
Example 14 was repeated except that 32 g of 3-(2’,4'
dimethoxyphenyl)-6-dimethylaminophthalide and 19.5
g of Z-phenylindole were used instead of 33 g of 3-(m
diethylaminophenyl)-6-dimethylaminophthalide and 13 60
g of dimethylaniline to obtain 30 g of 3-(2’,4’-dimethox
yphenyl)-3-(2'-phenylindole-3’-yl)-6-dimethylaminoph
I
c=0
EXAMPLE 20
thalide having the following structure whose m.p. was
let F no e
- et yamlélo t aide, and
239°—240° C. in the form of colourless crystals (Recrys 65 ilie
g lam In; \flaiillou _ am me or m e env tive in
stea, o, 1 et yaml e to obtam t tn gmet ane
tallized from benzene-methanol). This compound be
owmg t3. e as We
comes blue black upon contact with silica gel.