Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
This inv:ention relates to colorants. More particularly, it
concerns a family of red colorants which find special application as red
colorants for edibles.
FD~C Red #2, a monoazo dye of the formula
HO SO3Na
N 03 ~ N = ~
S03Na
commonly known as Amaranth, was among the most widely used colors in foods,
drugs and cosmetics. In 1975 these uses were prohibited in the United States
when the Food and Drug Administration ruled that the dye's safety was
questionable. The removal from commerce of this compound has left a great
need. Edibles such as cherry, raspberry, and strawberry-flavored gelatin
desserts, beverages, candies and jams, and nonedibles such as inks and dyes
were formulated around the particular tint and hue of this color. Several
replacement colors have been proposed but have not been fully acceptable.
For example, FD~C Red #40, another monoazo dye which has the formula
OCH3 HO
NaO3S~ ~ O ~ N = N
H3C
S03Na
2 !~
and which is d~sclosed in United States Patent 3764a,733,
issued February 8, 1972 to Rast et al, is now being used as a
replacement. This material has a brownish cast which interferes
with many uses. Natural colors, such as are extracted from
~eets, have ~een suggested as well but have low coloring power~
and thus unaccepta~ly high costs in use. The present lnventlon
seeks to provide a replacement for now-delisted azo color Red #2,
This invention discloses a l~mited family Or new anthraquinone
~ colorants which are excellent color matches for Red #2. The
; lO colorants of this inventlon can take on two forms. They can
he monomeric, as have been all food colors approved for use
I heretofore. Preferably, however, these new colors are in
polymeric ~orm. As is disclosed ln`United States Patent
3,920,855, issued November 18, 1975 to Dawson et al~ ha~ing
colors in polymeric ~orm can be advantageous. ~Jhen polymer~c
colors are used in edibles, if the s~ze o~ the molecules of
polymeric color exceeds a certain limit - usually a molecular
size of from about laO0 to 2aoo Daltons ~ and if the color
compounds do not break down and khus mainta~n this size, the
polymeric colors are not absorbed through the walls of the ~as~
trointestinal tract. This means that ~hen such mater~als are
eaten, they essent~ally pass dlrectly through the gastrointest~
inal tract. They are not taken into the body or its systemic
circulation and thus any risk of poss~le systemic toxicity is-
ellminated.
According to the invention, there is provided a compound of
the formula
O X
~ NH 3
~/0
R2
wherein Rl and R2 are independently selected rom the group of hydrogen,
halos of atomic number g through 53, inclusive, lower alkyls and lower
alkoxies of from l to 3 carbon atoms, nitros, and sulfonates and wherein X
is a halo of atomic number 17J through 53 inclusive or -NR3R~, wherein R3
and R4 are each independently hydrogen, lower alkyl of 1 to 4 carbon atoms
or lower alkyl sulfonate of l to 4 carbon atoms.
Preferred colors of this invention are those in which R3 is
hydrogen and R~ is hydrogen, alkyl or alkyl sulfonate.
This application is a divisional of our copending application
Serial No. 293J227~ filed December 16, 1977, which relates to polymeric
; colorants having the formula
\ / n
wherein Rl and R are independently selected from the group of hydrogen,
halos of atomic number 9 througk 53 inclusiveJ lower alkyls and lower
alkoxies of from 1 to 3 carbon atoms, nitro, and~ sui~onate; R3 is hydrogen
or a lower alkyl oE 1 to 3 carbon atoms, B is an organic polymeric backbone
attached to N by a covalent bond and characterized as having essentially
no crosslinks and containing only covalent bonds stable under the acidic,
basic and enzymatic conditions o:E the mammalian gastrointestinal tract; and
n is a number from 10 to 4000.
The remaining three positions on khe pendant non-
fused aromatic ring to which Rl and R2 are co~alently
bonded carry hydrogens. Rl and R2 preferably are separately
attached to the ring at the 2, 4 or 6 positions. Preferably,
~ Rl is hydrogen and R2 is selected from the class of sub-
3 stituents set forth hereinabove. More preferably, Rl is
~ hydrogen and R2 is hydrogen, chIoro or methoxy.
s~ .
' In a most preferred color Rl and R2 are both
;, hydrogen. This is an excellent red. Surprisingly, the
presence of the diverse range of other Rl and R2 substituents,
varying from strongly electron withdrawing nitro groups to
strongly electron donating alkoxy groups makes only minor
differences in the shade of these colors. A group of pre-
ferred colors having a single nonhydrogen substituent on
the nonfused ring is shown in Table I.
'
`~ TABLE I
- . _
. : .
5ubstituent Rin~ Position
Cl 2 or 4
Br 2 or 4
SO ~ M+ 4
NO2 2 or 4
_o-CH3 2 or 4
C2~5 2 or 4
- 6 -
Preferred backbones in the polymeric colors are carbon~oxygen
ether backbones and essentially linear alkyl carbon-carbon backbones
containing pendant primary and lower alkyl secondary amines in acetylated
or unacetylated form, with or without additional covalently attached
pendant groups such as sulfonates, phosphonates, carboxyls and the like.
Examples of these preferred backbones and the resulting polymeric colors
are given in Table II.
2~
P-176
~ABLE II
Back~one Polymeric Color
-- _.
polyvinylamine ~CH - CH2 ~ EI - CH2t
NH N~I2
1. *
Chrom.
.~ n = 10 ~o 4000, preferab].y 100-2000
~ m = 0.3 to 5n
.
S polyvinylamine ~C~-CH2~CH-CH2t
with acetylated l~ n¦ m
residual amines NH N~c
Chrom~
copoly(vinylamine/ ~&H-CH2~H-CH2~CH~CH2t
vinylsulfonate) ~ n ~ P ¦ m
(sho~ in sodium fo~n) NH SO3+Na NH2
: (other alkaline metals 1.
will work) Chrom.
~amine can be l. to 3
caxbon N-alkyl amine n ~ 10 to 2000
as well) m = 0.3 to 5n
p ~ 0.3 to 2 ~n~m)
.
copoly(vi~ylamine~vinyl ~CH-CH~CH-CH2~CE-CH2~
sulfonate) with acetylated ¦ n t - P 1 m
residual amines. INH SO3 ~Na N~IAc
Chrom.
poly N methylvinylamine ~cH-c~2)(cH-cH2t
(other n-lower alkyl ~~ n I m
amines can be used as N-CH3 N-CE3
well)
~' Chrom.
.,
~ Chr~m. equals '
39
.
~a-
~ ' ~
2~2~
P~176
T~BLE II (Cont'd)
Backbone Polymeric Color
copoly(vinylamine/
~ acrylic acid) tCH-CI~H~C~CH-CH~
(amines can be ¦ n ¦ m ¦ P
acetylated as well) NH NH2 COOH
Chrom.
.
sulfonated polyvinylamine ~CH-CH2 ~ H CH2~- fH-C~I2)p
N-methylvinylamine ~R NR NR
or the like I J
ChromO . H ~Q3~ Na
R = lower alkyl
of l to 3 carbons
or hydrogen
(secondary alkyl and
` 15 primary amines can be
acetyl~ted)
aminated poly(epichloro- -~ÇH-CH~-o~ 4~H CH2 O~ CH-CH~-O)
hydrin) (with added l n ~ m I ~ P
sulfamates ~H ~H~ ~H
~- ~hxom. ~O3'' ~Na
.. .
. .
aminated and acetylated
poly(epichlorohydrin) ~CIH-CH~-O)n (~H~CH2-O~m
NH ~HAc
lhromr
Among backbones~ polyvinylamine and copoly~vinylamine/
vinylsul~onate), either acetylated or unacetylated, are pre~
ferred. These preferred backbones preferably have molecular
weights o~ about 10,000 to about 150,000 Daltons and, in the
case of the copolymer, an amine to sulfonate ratio of from
1:1 to 3:1O A polyvinylamine ~leeting this weight range has
from about 200 to about 3000 units, a copolymer -- from
about 60 to about 1800 amine unitsO The choice among back-
bones often depends upon the degree of water solubility
required of the final polymer colorant product. Polar groups
such as carboxyls, phosphonates and especially sulonat~s are
required in the pol~meric colorant to impart good water solu-
bility properties. ~hen the color unit itself contains sul-
fonates, i.e., when Rl and/or R2 axe sulfonates or alkyl sul-
fonates, it-is not necessary to have these polar groups attached
to the backbone as wellO When the color unit does not contain
sulonate Rlls or R2's, good water solubilities, i.e., solubility
in p~ 7 room temperature water of at least 1000 ppm, are achiPved
only when a backbone containing polar groups -- such as the
29 copolymer backbones -- is employed.
The colors of this invention may be prepared by the
following two routes. These routes are presented as exemplaxy
methods and are not to be construed as limiting the scope of
this invention.
The first route begins with l~amino-2-methyl-4-bromo-
anthraquinone, a material marketed by Sandoz Color and Chemical
~ r~
- ~ under the tradc~e AMBAX, or made as in Example I.
~ C1~3
--10--
r
2.~
~-176
This material is reacted with a benzylic acid chloride~
CH2-COCl
~ 2
. ..
corresponding to the nonfused pendant aromatic ring desired
in the colorant as follows:
fl Br CH2 - COCl
S ~ C~3+
. ~ .
~ a3
.:_ , Y
~2 ~1
,
This reaction is carried out in li~uid pha~e in a reactior-
solvent. Suitable solvents include aprotic organic liqul~s
especially cyclic and acyclic olefinically saturated aromatic
or aliphatic hydrocarbons such as benzene, toluene, xylene,
hexane, cyclohexane, heptane, C6-Cg hydrocarbon mixed sol-
vents, cyclic and acyclic ethers such as dimethoxyethane,
P-~76
1,4 dioxane, diglyme, and the like~ This reaction is carried
out at elevated temperatures such as from 50C to 150C with
temperatures of ~rom 75C to 130C being preferred. In our
work the atmospheric reflux temperature of the solvent has
S been used. The reaction could be carried out under pressure
to obtain higher temperatures if desiredO Reac ion time is
inversely proportional to temperature. Reaction times of
from a ~ew (3-5~ minutes to about 24 ~ours generally are
employed. The following examples will aid in selecting times
- and temperatures. At 50-80C, times of about 10-2~ hours
are usually adequate~ At 110-115C, the re~ction appears
complete in about 20-30 minutes with tiTnes of from 20 minutes
to three hours being used; at 150C, 3 to 5 minutes are
adequate. Generally, a slight molar excess of the 2cid halide
is employed since it is the less expensive reactant. AMBAX/
acid halide ratios of 1:1 to 1:2.0 are generally preferred
with ratio of 1:1.1 to 1:1.3 being most preferred.
This AMBAX addition product is then c~clized with baseO
CH ~OH ) ~ ~ CH + H~o
- 3 - ~ 1 3
2~ ~I ~ C~ ~ H
R2 Rl !; R2 R
-12-
The base employed is not critical, any strong inorganic base such as NaOH,
KOH or the like will work. From 0.5 to 2 equivalents ~basis colorant) of
base may be used. This step is generally carried out at elevated
temperatures such as 90C to 250C with temperatures of 90C to 200C being
preferred. This step can immediately follow the acid halide addition step
by adding base to the crude halide addition product and heating for from
about five minutes to about 24 hours. At S0C 24 hours is a good reaction
time, at 110-120C, 15 minutes to one hour are employed. At 175-200C,
five minutes are employed. Otherwise, the halide addition product can be
isolated by evaporation of solvent and crystallization and dissolved in
fresh inert aprotic solvent such as those used for the addition and then
treated with base. This more complicated method offers some yield
advan~ages. Both methods yield the new colors
O Br
C~13
~<~ ~
R2 Rl
wherein Rl and R2 are as already defined. It will be appreciated that the
Br substituent is present principally because the AMBAX starting material
is a bromo compound. Other halo leaving groups (i.e., Cl , I ) are
-13-
essentially equivalent. The examples which follow will show the preparation
of such equivalent materials. This color may be urther reacted at this
stage to introduce or change the Rl and R2 substituen~s. Particularly,
sulfonate Rl's or R2's may be introduced at this stage by liquid phase
contact with 100% H2S04 at 80-150C for 0.5 to 2 hours, or by treatment
with 15-30% oleum at room temperature (18C~ to 50C for 0.5 to 5 hours.
The color is next coupled to an amine. This may be a R3-N-R4
monomeric amine as has been defined or it may be an amine group-containing
polymer backbone as has been described above in connection with the invention
of the parent application Serial No. 293,227. In this step the amine
displaces the halo leaving group on the anthraquinone ring as follows:
Backbone + ll CH3
Nl - R3
R2 Rl
R4 or Ba~Gkbone
0 N-R
¦ CH3 + HBr
NH
R2 Rl
-14-
~2~
! P 176
This step is carried out in liquid phase as well,
generally in a water or mixed water/organic solvent and ~ase
and with a copper catalyst. This amine displacement is an
adaption of the classic Ullmann reactionO
Water, and water containing up to abou-t ~5~ of a
water-miscible organic, such as an alkanol or glycol (methanol,
ethanol, ethylene glycol and the like) 9 mono and dialkyl ethers
cf ethylene glycols such as the materials marketed by Union
Carbide undex the trademark Cellosolv~ , and liguid organic
bases such as pyridine may be used a- solvent~ Water and water
containing up to about 20~ pyridine are preferred solvents.
The copper catalyst useful for this coupling may be copper
metal, a copper (preerably cuprousl salt or an oxide of
copper, for example ~inely divided copper metal, Cu~C12, and
Cu2O suppoxted on carbon black. A catalytically effeative
amount of catalyst is employed. Such an amount oan ranye ~rom
about 0.0I to about 0.5 equivalents (preferanly 0.05 to 0.4
; equivalents) o copper per equivalent of reactive amine.
Base, especially a strong inorganic base such as NaOH or KOEI~
should be present in an amount in excess of the molar amount
of chromophore being coupled. Preferably ~rom 0.5 to 5
equivalents ~basis-frQe amine) of base is present with amounts
from 1 to 3 (especially about 2) equivalents giving best
results. The coupling is effected at a temperature o~ from
about 60C to about 200C, prefQrab]y 80C to about 150C,
and a tim~ of from about 0.2 hoursto about 24 hours, preferably
0.5 hours to about 8 hours, dependlng upon the temperature.
-lS-
This yields the coupled product
R4 or ~ackbone
O N-R
;` ~ ~
ll N~ 3
R2 Rl
as a crude reaction mixture~ The desired product can be freed of catalyst
and impurities as desired. It may also be subjected to post treatments such
as acetylation or the like as desired.
The second preparative route is similar to the first. rrhe acid
chloride is attached to the AMBAX in the same way. Then, however, instead
of separately cyclizing the AMBAX addition product, the uncyclized addition
product is coupled to the amine or amine-containing backbone with the
conditions of the coupling also effecting cyclization. Economies of produc-
tion may favor the second route, but yields and product purities are often
somewhat higher with the longer process.
The products of this invention and that of the par~nt application
;~; are excellent red colors. Those containing polar groups in their chromo-
~ phores or attached to their amines (i.e., when R4 or the backbone contains
:
;'
~'
-16-
a polar group) are water soluble. As solutions they present clear, brigh-t
intense reds. When added in coloring amounts such as from 10 to 10,000
ppm wt, they bond to and dye fibers and other substrates.
The polymeric dyes present especially advantageous utilities
as colorants for edibles. The polymer compounds wherein Rl and R2 are
hydrogen are especially useful in this application as these materials are
virtually a direct match in hue for now-banned Red #2. Ihe other
polymeric members of this colorant family are good reds for foods~ blending
well with yellows and blues to give the range of oranges, reds and grapes
desired by the food industry.
For food use the colorants may be polymeric and of molecular
weight above about 1000 Daltons, preferably above about 2000 Daltons so as
to preclude their absorption through the walls o the G.I. tract.
In edible applications the polymeric colors are dissolved in
beverages and syrups, dry mixed into powdered drink mix and cake mix, and
otherwise conventionally admixed with foods~ beverages, pharmaceuticals and
cosmetics. The amount of color used in these applications will range between
about 10 ppm wt and about 1000 ppm wt, basis inished foocl, beverage, or
pharmaceutical. Cosmetic uses may requ:ire higher use levels.
3~
The invention is urther illustrated by the ollowin~ ~xarnples,
some of which are included for re~erence purposes. These are intended solely
to exemplify the invention and are not to be construed as limiting the
scope of the inven~ion which is instead defined solely by the appended
claims.
-18-
'
2~L
~-176
EX~MPLE I
Preparation of
~ H
wherein ~l and R2-are hydrogen.
, :
A. l-amino-2-methylanthraquinone (~0 g) is slurried wi.th
1500 ml of HOAc in a 5-liter ~lask. The tempera~ure is raised
to 40C. Neat bromine (405 g) .is added over 2-l/2 houxs wikh
stirring at ~0-50Co The mixture is stirred for 20 addikiunal
minutes and filt~red. The solids so recovered are washed with
HOAc and water and sucked dry with an aspirator and tran~:Eerred.
to a reaction flask along with 150 g of NaHSO3 and~l.5 li.ters
o water. The mixture is gradually heated to 90C (over two
hours) with stirring to give l-amino-2~methyl~~-bromoant.hra~
quinone as a solid which is recovered frorn the reaction mixture
by filtration in 90% yield, rinsed with water and dried over-
night at 155C and 1 r~m Hg absolute vacu~m.
It will be appreciated that chlorine or iodine could
be substituted for bromine in this reaction if desired.
-19
'
P~17~
B. ~ ~ ~Cl C6H~CH3 ~ ~c~3
Wt used 15.8 g ~.5 ~ 21.7 g (theory)
Moles used 0.050 0O055
Ratio l.0 lol
A 250 ml flask e~uipped with ov~xhead stirrer, water-cooled
condenser, and ~r inlei is charged with the bromoanthraquinone
of part A and 120 ml of toluene. To the red slurry is added
the phenylacetyl chloride and the mixture is heated to reflux.
The xea~tion is followed by thin~layer ~hromatography. After
one hour most of the starting material is gone. After three
hours, the reaction appears to be over, althouyh some starting
' material still remains.
After 3.5 hours total refluxing, the reaction i~ cooled
to ca~ 80 and filtered. The dark yellow filtrate is con-
centrated to ca. 30 ml on a rotor~ evaporator and co~led~ A
large amount of dar~ solid forms which is isolated and washed
with ether unti~ a yellow (dark) solid is obtained. The solid
is oven dried at 70Q, < 1 mm, for four hours ~o afford 1G .5 g
~57.6%) of yellow-green solid productO
-20
. ~ f
'
P-176
C ~'J:1~' CH3~\/OH ~J~
~3 AqO KO~I > ~ ~ ~ ~I3
.
Wt used 4.56 g 0.45 g 4.37 g (theory)
Moles used lO.S mmole 800 mg - f.w~
,
.~ A 100 ml 3-necked flask is equipped with water-cooled
~5 condenser, overhead stirrer, thermowell, and Ar inlet. The
flask .is charged with the phenylacetyl product of Part B,
and 30 ml methyl cellosolve. The conten~s are heated to 122
- and the KOH in 0.6 ml H20 is added drop~ise over o~le minute.
: The reaction is stirred at 120 for on~ hour.
The.reaction mixtuxe is cooled to about 5C. Isolation
of a solid precipitate, followed by washing, affords 1.71 g
(39~1%) of hright~ shining gold solid.
The darkl yellow filtrate is concentrated via rotary
evaporator to dryness and the dark solid is recrystallized
from 170 ml of HOAc to afford 2.3 g {52.6%) of a dull, golden
colored powder. Total yield is 4.01 g (91.8%).
-21-
~ 9~ P-17~
EXAMæ~E II
Pxeparation of a monomeric colorant from the product o~
Example I NaO~
Aqueous ~ ~
CH3 + + NaO~ C~zCl2 ~ ~ ~3
. 5 ~ ~* used 1.:0 g O.306 g 7.2 ml of 1
; Moles used 2.4 mmole 2.2 mmole 7~2 mequiv.
' ' ' .
A 25 ml flask is charged with the product of Example I, sulfo-
propylamine, aqueous sodiu~ hydroxide, 3 7 6 ml H20, l.Z ml pyridine,
and 40 mg cuprous chloride. The flask is equipped with a
. lO magnetic stirrer, thermowell, and reflux conde.nser. ~fter flush-
ing the system with argon and de-a~rating, the contents are
heated to reflux ~95-100) for 3.3 hr. The reaction mix~uxe
is then cool.ed to room temperature, diluted with dilute sodlum
hydroxide solution, and carefully filtered to remove solids~
The solution is then concentrated to dryness under reduced
pressurè, and the resultant solid dissolved back into wate.r.
The pure, monomeric dye can be isolated by preparative thin
layer chromatography,-preparative high pressure liquid chromatograp.~y~
or by recrystallization.
-~2-
P-176
EXAMPLE III
To 2304 g of acetamide ttechnical3 in a 1~ liter
xeaction flask is added 62.2 ml o~ 6M aqueous sulfuric acid
followed immediately by 661 g of acetaldehyde (99 ~). This
mixture is stirred and ~eated until the internal temperature
reaches 78C tll minutes) at which point the cléar solution
spontaneously crystallizes, causing a temperature rise to
95C. The reaction product, ethy1idene-~is-acetamide, is ~
not separated. ~eating and stirring are ~continued for another
five minutes to a temperàture of 107C and a mixture of 150 g
calcium carbonate (precipitated chalk) and 150 g of Celite~
diatomaceous earth powder is added. A ~irst distilla~e
fraction of water and acetamide is remo~ed. The remaininy
materials are cracked at 35 mm Hg and 185~C. A fraction made
up of vinylacetamide and acetamide is taken overhead, analyzed
by NMR and ~ound to CGntain 720 g of vinylacetamide and 306 ~
of acet~mide. A portion of this pooled material is dissolved
in isopropanol, cooled, and filtered to yield a stock solution:
This stock solution is analyzed and found to be 4.1 molar in
vinylacetamideO
Into a five liter flask is added 505 ml ~272 g) of a
. ; , .
vinylacetamide solution obtained by stripping isopropanol from
900 ml of the above stock solutio~ (containing 3.6g moles of
~inylacetamide)O ~IBN (15 g) in 1500 ml o~ water is added
followed by 1279 g of 25% W sodium vinyls~lfonate in water
(Research Organic Corporation) and a liter o water. This is
two equivalents of sulfonate per three equivalents of vinyl-
acetamide. Followiny deoxygenation, the mix~ure is heated to
-~3-
; ~ ~ ~ ~ P~17~
65C and there maintained with stirring ~or three hours~ This
reaction mixture is then reduced to 2/3 volume, solid AIBN
is removed and the liquid added to eight gallons of isopropanol.
The copolymer precipitate is collected and ~ried in VaCtlUm to
yield 865 g of solid copolvmer (MW 6~6 x 104). Whenever an
experimental molecular weight is given in this specification,
it is derived by gel permeation techniques. In the primary
technique, a silanized porous glass support is used with a
O.01 M LiBr in D~F eluent. Detection is by refractometer with
standardization being based on suitable purchased poly(styxene)
or poly~styrene sulfonatej standards.
. .
Into a two liter flask is added 863 g of t~e just-noted
solid product, 2.5 liters of water and a liter of concentrated
hydrochloric acid. The mixtur~ is refluxed ~99-110C) ~or
about 24 hours and cooled, the solid precipitate is washed,
and dissolved in three liters of 10~ NaOEI. This mixture is
added to about 12 liters of methanol to give 400 g of ine
solid copolymer precipitate~
-24-
323l
P-176
EX ~ PLE IV
O Br
H3 1 d~O/pyridLne Fo1~ic
NH ~ vlnylsulfonate CU2C12' NaO~ c3lorant.
copol~mer
(Example I) (~xample III)
Wt. used 0.-958 g 0.500 g 0.~77 g
Moles used 2.30 mmol ~.835 me~ 0.39 mg - f.w.
Ratio 0.60 1.0 0.20 equiv. Cu*
. .
A 50 ml two~necked flask is charged wit~l ~he copolymer,
~lI.5 ml l N MaOH, 1 ml o pyrid~ne and 4 ml H2O. The system is
: de~aera~ed.... The polymer dissolves and the anthraquinone and
10Cu2C12 are added an~ the mixture is heated to 97~ Af~er 2 1~2
hr~ the mixture is cooled and diluted with 40 ml water at pH 11.
~ he diluted mixture is filtered to afford 100 ml of a
red solution. The solution is ultrafiltered using 10~ pyri.dine
in water at pH 11 and later pH 7 water as mak.eup.
l~The red solution i5 l~ophîlized to afford 0.850 g of
red solid which is determined to be
-25-
P~17 6
~CH-CH2) A ~CH_CH2~H-CH~
CH3
IH
~herein A ~ B ~ D equals about 900.
A -- ~ 180
B ~ _, 360
. D ~ ~ 360.
,. . .
-26
2~23L
P-176
EXAMPLE V
Preparation o~ an acetylated version of the colorant
of Example IV.
The product of Example IV (255 mg) is dissol~ed in 12 ml
of water and cooled to 5~O Fifty percent NaOH is added to pH 12
followed by 0.2 g of ace-tic anhydride. The pH adjustment to 12
and 2cetic anhydride addition are repeated twice. The red solu-
tion is fil~ered, ultrafiltered and lyophilized to yield a
soli~ product of Example IV whexein about 95% of the free backbone
amines are converted to HN-~O groups. This red ~olid is ~n
H3
excell~nt colorant. It is very good replacement for existing
red food colors. Virtually identical colors would result when
the ~ollowing changes are made.
1. The backbone amine to sulon~te ratio is varied from
1.5:1 to ~.0:1.
2. The backbone peak molecular weight is varied froM
35,000 to 80,0~0.
3. The fraction of total bac]sbone amines substituted with
chromophores is variéd from 25% to 40%.
4. The degree of acetyla~ion is varied between 80% to
98% of the total amines.
~-~7~
~2~Zl P- L75
E~XAMPLÆ VI
_ ._
Preparation of
O Br
CH3
~ ~ ~NH
Cl
A C1 C1
1~0) + SOC12
~ I : 24 hr ~
: ` COO~ ~ OCl
Wt. used 17.06 y 11.90 g 18.9 y (theory)
M~les used 0.100 0.100
A 50 ml flask is charged with the oryanic acid and
the SOC12. A sinyle boiling chip is added and the flask
fitted with air condenser and drying tube. Heating in a
45 oil bath is begun. The reaction is cooled after 23
hours.
To the solution is added 5 ml of benzene. Volatlle
material is pumped o~f at room temperature at 0.5 mm Hg.
The product is then dis-tilled through a short path vacuum
distillation apparatus as a water white product, b.p. 63-64
at 0.10 mm Hy. The yield of distilled product is 12.3 g
(65%).
-28-
~2S~
O Br toluene ~
l3 ~ ~ ~ C~3
Wt. used 15~8 g 10.87 g 120 ml 23.4 g (theory)
~oles used 0.050 0.0575
Ratio 1.0 1.15
The procedure of Example II, Part B, is repeated using the above
materials to afford the abo~e product.
C.
O Br O Br
`CH 3 KO~I ~ ~ c~l3
~ ~ Cl~ ~
Wt. used 9.85 g 0.88 g 9.46 g (theory)
Moles used 0.021 0.0157 g
Ratio 1.0 0.75
rme product of P æ t B and 60 ml of Cellosolve are added to 1 250 ml
flask. r~ne slurry is heated to 123 . The KOH is dissolved in 1.0 ml H2O
and added over one minute. The reaction is cooled afber heating at 115 for
35 minutes. The mixture is allowed to cool slowly to ro~m temperature and
then oooled to 5 &. A solid precipitate is isolated and washed to afford
3.32 g of glittering, ~rowni~sh/golden crystals.
-29-
'1~
The dark filtrate is concentrated to dryness and the resul-tant
dark solid recrystallized frcm 675 ml boiling HOAc. The greenish~yellcw
needles are isolated and washed. Drying at 85, < 1 mm for four hours
affords 3.8 g of a golden solid.
-30-
r
~.
P-176
EXAMPI.E VII
If the preparation of Example VI is repeated using the
chloro or iodo anthraquinones shown in Example I in place of the
brorno anthraquinone, the correspondin~ chloro or iodo products
would result.
~ Similaxly, use o~ the 2f 4-dîchloro, the 2-chloro, the
: bromo or the iodo equivalents of the 4~chloro acid in place
of the 4-chloro acid in step A of E~ample VI would result
in the 2,4-dichloro, the 2-chloro, the bromo or the iodo-substituted
products.
.
-31~
'
~2~1
P~176
EXAMPLE VIII_
Attachment of the pr~duct of Example VI to the polymer of
Example III.
.: .
~opolymer pyridine/H2o Polymeric
of III CU2C12' NaOH Colorant
. ,~
Cl
W~. used 1.037 g ~.500 0~077 g ~u2C12
Mm~les used 2,30 3.835 m~q 0039 n~ of Cu2Cl~
11.5 mmol~ Orr
~atio 0.6 1.0 0.2 equiv Cu~
3.0 Q~UiV. o~r
. ..
The copol~ner is dissolved in 11.5 ml lN NaOH and 4 mI H20
The solution is de~aerated (3 tirnes, ~7ith Ar) and the anthra-
pyridon~ derivative, Cu2Cl~, and pyridine ~1.5 ml) are added.
The reaction i5 stirred at 96-97 for two hours and ~0 minutes,
then cooled and diluted with dilute aqueous sodium hydroxideO
The dilute mixture i5 filtered to afford 115 ml of a dar}c
red dye solution. ITltrafiltr~tion is ca~ried out with 10%
pyridine--pH 11 waterO Then, the product is divided into two
portions.
One psrtion is acetylated and the other is lyophilized to
afford 490 mg of red solid in accord with E~ample V~
-32-
(- ~
~ 2~
,,
P-176
The unacetylated product has the ormula
C~ H~CH2 ) m ~H-C~I
H NH2SO3Na+
n ~ m ~ P = ~900
n - 180
~ ~ NH m - 360
Cl p ~ -360
The acetylated version differ~ only in that the residual NH~'s
on the backbone are present ~5 NHAc~so Both are excellent
red colorants...
Substitution of the products of Example VII for the product
o~ EY.ample VI as feedstock for this Example would yield their
poly.mer product counterparts.
. .
-33-
~-176
EXAMPLE IX
Preparation of
~C~:13
~ "NH
NH + o
The product o E ample I, ~
0.6 g and ~.4 g of 20% olewm are stirred together at room
., temperature. After one-hal~ hour, it appears that reaction ha~
occurred. The stirring is continued for a total of five hours.
The reaction mixture is poured over ice and water and a solid
precipitate forms and is collected. The solid is dissolved
in a liter of 2 M NEl~OX, filtered and the solution is evaporated
to dryness. The solid which results is extracted with methanol.
The methanol i~ evaporated to afford 0.775 g of ~he desired
sulfonate product.
3~-
~Z~32~
EX~MPJ~E X
Formation of a homopolymeric polyamlnoethylene backbone for coupl-
ing colors into polymeric form
A red~brown solution of 460 g of vinylaoetamide, 557 y acetamide,
and 123 g ethylidene-bis-a oe ta~ide, (one-half of five combined vinyl-
acetamide preparations essentially in accord with Example III) in 570 ml
methanol is filtered through 250 g of Pmberlite ~IRC-50 ion exchange resin
over an eight-hour period. The column is rinsed with 1000 ml methanol. m e
combined column eluent is stripped to its original volume of 1,667 ml,
treated with 7.75 g of AI~N polymerization catalyst (1 mole %), deoxygenated,
and stirred under Argon at 65 & for 15 hours to polymerize. Solid polymer
is precipitated from the resulting very thick solution by addition to 15
liters of acetone. m e polymer is collected by filtration, washed with aoe-
tone and dried in a vacuum oven (80 &) for two days to afford 459 g of crude
poly(vinylacetamide) contaminated with aoetamide as a yellow, s~igranular
solid having molecular weight of 2 x 104 as determined by Gel Permeation
Chromatographyl using dimethylformamide as eluenk and polystyrene as stand-
ards.
~e crude poly(vinylaoe tamide) (459 g) is dissolved in 1000 ml
water with heating. Concentrated hydrochloric acid (1000 ml) is added and
the resulting dark brown soluticn is stirred and heated at a gentle reflux
~97-106C) for 19 hours. A precipitate forms and is redissolved by addition
of 200 ml water. Reflux is co~tinued and over the next eight hours
-35-
3~
P-176
1000 ml water is added in several portions to maintain solu-
bility of the polymer D After a total of 27 hours at re~lux,
the polymer is preclpi-tated by the addition of 1000 ml con-
centrated hydrochloric acid. The mixt~lre i5 cooled to 18C
and the thick polymeric gum isolated by decantation and
dried under vacuum at 50-75C with occasional p lverizaticn
for 40 hours to give 332 g of poly(vinylamine hydrochloride)
as a brown granular solid i77~ yield from vinylacetamide, 59%
from acetaldehyde)~
.
.. .
-3~-
P~176
EXAMPLE XI
Formation of a polymeric colorant from the anthraquinone
product of Example IX and the pol~mer product of Example X.
Following the procedures of Examples IY, 0.754 g of the
anthraquinone product of Example IX is coupled to 0.200 g or
the polyaminoethylene product of Example XO Copper catalyst
(0.021 g) and NaOH ~three equivalents hasis polymer) are used.
The reaction is carried out for one houx at 97C. The reacti~n
mixture is diluted and filtered and ultrafiltered. The retentate
of the ultrafiltration is divided into two portions. One i5
lyophilized to afford the following product
H-C~2 ~ ~ CH~)n
NH NH
(~
~ ~ ~ m ~ 260
.. ~CH3 n ~ 200
, ~IH
Na~ O3S ~ ~
The other portion is acetylated in accord with th~ general
procedure of Example V to give a product wherein the residual
lS backbone amines are acetylatedq In this and in all acetylations
in this disclosure, conversion of amines to amides is usually
not quantitative. Usual conversions are 80~8% of the amine
being converted.
-37
f ~ ~z~
P-176
EXA~?LE XI I
NO C 2 5 hrs Q35 ~ ~2
02H COCl
Wt. Used 18.11 g 12.0 lg.9 (theory)
Moles Used 0.100 OolOl
The reagents are weighed into a flask and allowed
to stand at room temperature (~ 21) overnight. ~ stirring
bar is added and the reaction driven to completion by war~in~
at 35 until no solid is visible (.five additional hours). To
the red solution i5 added 5 mls ben~ene and -the volatile
material is removed with vacuum.
B. The 2-nitro acid chloride of Part A is reacted l~ith ~MBAX
and the ring is closed to give the product
~ 2
The general reactions of Example I are used. The reaction of
this acid chloride with ~MB~X is more facile and requires only
three hours at re~lux.
-38-
~J~ - f
~2~21
. P-17
C. - ~he product of Paxt B is attached to the polymer
of Example III using the method of Example IV~ This product
is divided into two portivns r one of which is acetylated.
. .
~39-
~2~ 2~
P-176
E~AMPLE ~
A. OCH3 OCH3
~3 + SOC12 r240hrten p. ~ [~
~ COOH COCl
Wt. Used 16.16 g- 11.90 g18.4 g (theory)
Moles Used 0.100 0.100
A flask is charged with the carboxylic acid and
thionyl chloride and allowed to stand at room temperature
with occasional swirling for 24 hours. The endothermic
reaction begins immediately and proceeds at a very good
rate, generating an orange solution.
After 24 hours, nearly all gas evolution has ceased.
Six ml benzene is added and the volatile material i5 removed
with vacuu~. The product is purified hy distillation.
B. A flask is charged wi-th 15.8 g AMBAX and 115 ml
toluene. Then r the acid chloride, 10:1 g, is added. The
lS red slurry is heated to reflux for 2.0 hours.
The hot mixture is filtered and a black res;due
washed with three portions of hot toluene. The toluene is
stripped off afording a solid ~hich is washed with ether.
The product is dried overnight at 70, ~ 1 mm to afford
19.48 g of dull green powder.
-40-
~ 9~1 P-17~
This product i5 treated with base i~- accord with the
procedures of Example 1, Part C, to 1~ield
~ ~ CH
C. q'he prod~ct o~ Part B i~ coupled ~o the polymer o~
Example III to afford a polymeric dye o~ the structure
. ~ ,
~CII - CH2-~C~I - CEI2-~H - CH2t---
2 ---
m = ~360
H3C ~ ~-' p = ~360
:
~Z~l
~-176
EXP~PLE XIV
This exa~.ple illustrates an alterative preparation of the
;
compound of this invention.
Br
~r diglY~e~ ~ 0
1. 100-113 ~ ~
C~3 ~ ~ c~3
Wt. used 1.897 kg 1.113 kg 370 g
Moles used 6.0 ~ 702
r Ratio 1.0 1.2
.~ .
; - A~22~1iter resin };ettle iS ch~ryed ~7ith the a~thraqu~none
and 13.8 liter of dig].yme. The reactox is fitted with a ~-necked
s~ 10 head which is equipped ~7ith overhead stirrer, thermocouple, argon
outl~t~reflux conclenser, and an argon inlet to sweep the system.
~ The reaction mixture is then heated to 111-113 and the acid
ti chloride is added quickly. After 30 minutes at 111~117~ a p~
probe is inserted into the reaction mixture in place of the
1~ argon inlet. A solution of 370 g of potassi~n hydroxide in
346 ml of water is then carefully added portionwise while th~
pH of the system i5 monitored. By the end of the hydroxide
addition, the pH meter should give a readlng of ca. 10.3.
Product soon begins to drop out and after a total reaction time
of 90 minutes ~including 30 minUte acetylation time) the heating
mantle is turned of.
-~2-
,,
Z~3Z~L
P-176
Next the system is cooled re~lu~ively by gradually reducin~
the internal pressure using a water aspirator. When the pressure
reaches 27-inch ~Ig of vacu~n, the internal temperature is 55.
The vacuum is released and 3 liter or methanol are added. The
resultant slurry is then filtered via a cer~nic filter~ng crcck
and sucked dry. The filter cake is washed with one 4~1iter
portion of methanol, sucked dry at a large watex aspirator, and
finall~ vacuum oven dried overnight at 80, 0.4 mm Hg. The yield
of yellow--green product is 1.904 kg (76~)o
.
- .
, .
.
-43-
P-176
EXAMPLE XV
This example shows a one-step closing and attachment
to a backbone.
Br
Copolymer H Op~ridine Polymeric
of Example 2 ~ C~lorant
H
~2
Wt. Used ~1.0 g 2.4 g 0.076 y
Moles Uscd 2.3 mmo1e 3.S4 meq 0.39 mmole
CU;~C12
Ratio 0.6 1.0 n. 20 e~. Cu~
, .
.
A 25 ml flask.is char~ed with the anthra~uinone
derivative, the copolymer backbone, 11.5 mls lN NaOH solution,
1.3 mls pyridine, and the cuprous chloriae. The ~lask is
equipped ~lith reflux condenser, magnetic stirrer, and thermo-
couplc. The s~stem is then de-aerated and ~lushed with argon.
The reaction mixture next is stirred and heated at ~6-100C
for 3.5 hours, a~ter which time the reaction mixture is
cooled, diluted, filtered, and ultra~iltered~ The resultant
dye is then acetylclted as in ~xample V and ~orked up as in
E~:ample ~ to afford a red dye which is indistinyuishable from
the dye prepared accordin~ to Example V.
-~4-
