Note: Descriptions are shown in the official language in which they were submitted.
93
DERIVATIVES OF 2-OXAZOLINES USEFUL AS INTERMEDIATES
IN THE PREPARATTON O~ ANTIOXIDANTS
_
BACKGROUND OF THE INVENTION
The present invention relates to derivatives o:~ 2-oxazo-
lines useful as in-termediates in the preparation of antioxidants.
Such antioxidan-ts are disclosed in U.S. Pa-tent No. 4,145,556 issued
March 20, 1979.
SUMM~RY OF THE INVE:NTION
The presen-t invention relates to compounds of -the formula
V 0 B
l 11 . I
X--C ---C-OCH2--C K
W_ n D
where in K is NH2 or -NH2. HL and L is a halide anion :Eor ex-
ample, chloride, bromide or iodide, wherein B is hydros~en, Cl to
C4 alkyl, -CH2OH or -CH2OC-Y; Y is hydrogen, C1 -to C30 alkyl,
C4 to C8 cycloalkyl, C6 to C10 aryl, substituted aryl or A, wherein
A is
R~
H0 .~ ~ CH2-CH2-, II
R~
-
wherein R and R1 may be the same or different and are C1 to C12
alkyl or C8 -to C10 aralkyl; D is hydrogen, Cl -to C4 al~l, -CH2OH
o
or CH2OC-Z, wherein Z is hydrogen, C1 to C30 alkyl, C4 to C8
cycloalkyl~ C6 to C10 aryl~ C6 to C10 substituted aryl, A, wherein
.~
-2~ 7B1;~3
A is as de:fined above, or Z is a divalent group connecting -two
esteramine moieties; n is an inteyer equal to O or 1; with the pro-
viso -tha t when n is 0, X is hydrogen, Cl to C30 alkyl, C~ to C8
cycloalkyl, C6 to C10 aryl, subs titu ted aryl, A, wherein A is as
defined above, or
O B
Il I
-Q-C-o-CH2--C ~K
wherein Q is C~ to C8 alkylene, thiodie thylene or phenylene, with
the proviso that Q and Z cannot bo-th be divalent at the same -time
and -tha-t either X must be the radical A, or if X is not -the radical
o
A, then B must be the radical E, wherein E is -CH2-0-C-A, and
when n is 1, W is -CH20H or E, wherein E is defined above, V is
C1 to Ca~ alkyl, -CH20H or E, wherein E is as defined above, X is
C1 to C30 alkyl, C~ to C8 cycloalkyl, C6 to C~O aryl, substitu ted
aryl, the radicals
R W o s
HO --~,~ CH2 or -Q--V --COCH2C--K
wherein R and R1 are defined above, Q is C2 to C6 alkylene,
thiodimethylene or phenylene, with the provisio that Q and Z cannot
be divalent at the same time and that either X must be a radical of
the formula II or B or W mus-t be E, wherein E is as defined above.
The terms alkyl and alkylene comprise linear and
branched moieties and the term cycloalkyl includes bridged and
non-bridged groups.
~, Y!
The compounds of the present inven-tion are use~ul as
intermediates for -the preparation of antioxidants for protecting
organic materials that are normally subject -to oxidative de0rada-tion.
Examples of such antioxidants are disclosed in U . S .
Patent No. 4,145,556 -to Hirsch et al, issued March 20, 1979. An
intermecliate compound of this invention may be used to prepare
(N, Nl-bis [2- (3, 5-di--t-butyl -4-hydroxyphenyl)propionyloxye-thyl)
oxamide (hereinafter called "BPEO") which is an an-tioxidan-t dis-
closed in the above mentioned Hirsch e-t al patent (example 1). The
antioxidant properties of BPEO and the o-ther antioxidants disclosed
in the Hirsch et al patent are set forth at column 5 lines 16-59 and
Examples IX-XIV of said pa-tent.
The process by which these compounds of the invention
may be converted into antioxidants includes, for example in -the
case of BPEO, condensing (3, 5-di--t-C4Hg-4-C6H2OH)CH2CH2
COOCH2 CH2NH2 with oxalic acid or acid chloride using well known
amidation conditions.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In the compounds of the present invention E~ and R1 are
preferably C~ to C12 alkyl and are mos-t preferably tertiary butyl.
Aryl or phenyl groups of the compounds of the present invention
are preferably substituted with one or more hydroxy, halogen (e.g.
fluorine, chlorine, bromine or iodine), C1 to C12 alkyl, amino, or
nitro groups. The substituents on the aryl group may be the same
or different. Preferred divalent groups connecting two esteramine
moieties are ca:rbon-carbon bonds, C1 to C8 alkylene, thiodiethylene
and phenylene.
The ammonium sal-ts of the presen-t invention may be
prepared by hydrolysis of oxazoline of the Formula II
, . ~ . ~ . .
.
-3a-
7~ ~3
o _
V / I I I
N--D
wherein ~, V, W, B, D, and n are defined as above.
The amines of Formula I wherein K is -NH2, of the pre-
sent inven-tion are prepared by neu-traliza-tion of the ammonium salts
of Formula I wherein K is -N~12. HL and L is as defined above.
The hydrolysis is carried ou-t by reac-ting the oxazoline of
formula III with a stoichiometric amount of a mineral acid and a
stoichiome-tric amount of wa-ter in the presence of a sui-table solvent.
The neutralization is carried out by adding an aqueous
solution of a base to a cool solution of the amine hydrohalide of that
formula I until the solution is slightly basic.
Exan~ples of suitable acids that may be used in this hy-
drolysis are hydrochloric, hydrobromic, hydroiodic, phosphoric,
nitiric and sulfuric.
Examples of sui table slovents that may be used in this
invention are diethylether, methylene chloride, dichloroethane,
chlorobenzene, chloroform, hexane, petroleum either, benzene,
toluene, xylene, di-n-propylether, di-n-bu-tyle ther, diphenylether,
tetrahydrofuran, me-thanol, ehtanol, n-propanol, isopropanol, n-
butanol, -t-butanol, cyclohexanol, hexanol, dimethyl formamide and
dimethylsulfoxide .
Examples of the suitable bases that may be used in the
execution of this invention are ammonium hydroxide, li-thium hy-
droxide, magnesium hydroxide, sodium bicarbonate, sodium car-
bonate, potassium carbonate and potassium bicarbonate.
The foregoing list of mineral acids, bases and solvents is
representative of materials used in the execution of the invention
and is by no means exhaustive.
~....
~'713 ~
The followin~ list of compounds is representative
of compounds of the present inventi.on and is by no means ex-
haustive.
2-Aminopropyl 3-13,5-di-t-butyl-4-hydroxyphenyl)~
propionate
2-Aminopropyl 3-(3,5-di-t:-butyl-4-hydroxyphenyl~-
propionate hydrochloride
2-Amino-3-methylpentyl[3-(3,5-di-t-butyl-4-hydroxy-
phenyl)propionate]
2-Amino-3-methylpentyl[3-(3,5-di-t-butyl-4-hydroxy-
phenyl)propionate]hydrobromide
2-Amino-2-methylpropyl[3-(3,5-di-t-butyl-4-hydroxy-
phenyl)propionate]
2-Amino-2-methylpropyl[3-(3,5-di-t-butyl-4-hydroxy-
phenyl)propionate]hydroiodide
2-Amino-2-(hydroxymethyl)propyl[3-(3,5-di-t-butyl-
4-hydroxyphenyl)propionate]
2-Amino-2-(acetoxymethyl)propyl[3-(3,5-di-t-butyl-
4-hydroxyphenyl)propionate]
2-Amino(acetoxymethyl)propyl[3-(3,5-di-t-butyl-4-
hydroxyphenyl)propionate~hydrochloride
2-Amino-2-(hexanoyloxymethyl)propyl[3-(3,5~di-t
butyl-4-hydroxyphenyl)propionate]
2-Amino-2-(dodecanoyloxymethyl)propyl[3~(3,5-di-t-
butyl-4-hydroxyphenyl)propionate]
2-Amino-2-(stearoyloxymethyl)propyl[3-(3,5-di-t-
butyl-4-hydroxyphenyl)propionate]
2-Amino-2-(benzoxymethyl)propyl[3-(3,5-di-t-butyl-4-
hydroxyphenyl)propionate]
2-Amino-2-methyltrimethylene bis~3-(3,5-di-t-butyl-
4-hy~roxyphenyl)propionate]
,;
2-Amino-2-(hydroxymethyl~butyl[3-(3,5-di-t-butyl-4-
hydroxyphenyl)propionate]
2-Amino-2-(Acetoxy methy:l.)butyl[3-(3,5-di-t-butyl-
4-hydroxyphenyl)propionate]
2-Amino-2-(hexanoyloxy methyl)butyl[3-(3,5-di-t-
butyl-4-hydroxyphenyl)propionate]
2-Amino-2-(dodecanoyloxy methyl)butyl[3-(3,5-di~t-
butyl-4-hydroxyphenyl)propionate]
2-Amino-2-(stearoyloxy methyl)butyl[3-(3,5-di-t-butyl-
4-hydroxyphenyl)propionate]
2-Amino-2-(benzoxymethyl) butyl[3-(3,5~di-t-butyl-4-
hydroxyphenyl)propionate]
2-Amino-2-ethyl trimethylenebis[3-(3,5-di-t-butyl-4-
hydroxyphenyl)propionate]
2-Amino-2-(hydroxymethyl)-3-hydroxypropyl[3-(3,5-di-
t-butyl-4-hydroxyphenyl)propionate]
2-Amino-2-(acetoxy methyl)-3-hydroxypropyl[3-(3,5-di-
t-butyl-4-hydroxyphenyl)propionate]
2-Amino-2-(hexanoyloxy methyl)-3-hydroxypropyl[3-
(3,5-di-t-butyl-4-hydroxyphenyllpropionate]
2-Amino-2-(dodecanoyloxy methyl)-3-hydroxypropyl[3-
(3,5-di-t-butyl-4-hydroxyphenyl)propionate~
2-Amino-2-(stearoyloxy methyl)-3-hydroxypropyl E 3~(3,5-
di-t-butyl-4-hydroxyphenyl)propionate]
2-Amino-2-(benzoxy methyl)-3-hydroxypropyl[3-(3,5-di-
t-butyl-4-hydroxyphenyl)propionate]
2-Amino-2-(hydroxymethyl)trimethylene bis[3-~3,5-di-
t-butyl-4-hydroxyphenyl)propionate]
~L~L t~
2-Amino-2-(acetoxy)methyltrimethylenebis[3-~3,5-di-
t~butyl-4-hydroxyphenyl)propionate]
.2-Amino-2-(hexanoyloxy)methyltrlmethylenebis[3-~3,5-
di-t-butyl-4-hydroxyphenyl)propionate]
2-Amino-2-(dodecanoyloxy)methyltrimethylenebis~3-
(3,5-di-t-butyl-4-hydroxyphenyl)propionate]
2-Amino-2-(stearoyloxy)methyltrimethylenebis[3-(3,5-
di-t-butyl-4-hydroxyphenyl)propionate]
2-Amino-2-(benzoxy)methyltrimethylenebis[3-(3,5-di-
t-butyl-4-hydroxyphenyl)propionate]
2-Amino-isobutanetriyltris[3-(3,5-di-t-butyl-4-
hydroxyphenyl)propionate]
2-Amino-2-isobutanetriyltris[3-(3,5-di-t-butyl-4-
hydroxyphenyl)propionate]hydrochloride
2-Amino-2-[3-(3,5-di-t-butyl-4~hydroxyphenyl)propion-
oyloxy]methyltrimethylene diacetate
2-Amino-2-[3-(3,5-di-t-butyl-4-hydroxyphenyl)propion-
oyloxy]methyltrimethylene dihexanoate
2-Amino-2-[3-(3,5-di-t-butyl-4-hydroxyphenyl)propion-
oyloxy]methyltrimethylene didecanoate
2-Amino-2-[3-(3,5-di-t-butyl-4-hydroxyphenyl)propion-
oyloxy]methyltrimethylene distearate
2-Amino-2-13-(3,5-di-t-butyl-~-hydroxyphenyl)propion-
oyloxy]methyltrimethylene dibenzoate
Example 1
2-Amino-2-methylpropyl[3-(3,5-di-t- utyl-4-hyd oxy-
~henyl)propionate].
In a 1 liter, three-neck, round-bottom flask equipped with a
thermometer, stirrer and condenser were placed 66.2 g (0.2
moles) 2-[3-~3,5-di-t-butyl-4-hydroxyphenyl)ethyl]-4,4-dimethyl-
'7~
--7--
2-oxazoline, 400 ml isopropanol and 33 ml 6N hydrochloric acid.
The mixture was heated to 45C for 2 hours and then cooled.
To this stirred solution was added 250 ml of water and 33 ml of
6N sodium hydroxide. The product was removed by filtration and
dried. The title compound, thus obtained, melted at 97-99C
Example 2
2-Amino isobutanetriyl tris~3-(3,5-d_-t-butyl-4-
_~_roxyphenyl)propionate]
to 44.2g (0.05 moles) of 2-[3-(3,5-di-t-butyl-4-
hydroxyphenyl)ethyl]-2-oxazoline-4,4-dimethyl bis~3-(3,5-
di-t-butyl-4-hydroxyphenyl)propionate] in 200 ml of toluene was
added 8.2 ml of 6N hydrochloric acid. After the mixture was
stirred for 3 hours, 6 g of sodium carbonate were added. The
mixture was stirred for 15 minutes and the layers were separated.
The amine was not isolated; it was used as is in subsequent re-
actions.
Example 3
2-Amino-2-ethyltrimethylene bis[3-(3,5-di-t-butyl-4-
hydroxyphenyl)pro~ionatelhydrochloride.
In a 2 liter, three-neck, round-bottom flask equipped
with a therm~ter, stirrer and condenser were placed 298g (0.48
moles) of 2-[3-(3,5-di-t-butyl-4-hydroxyphenyl~ethyl]-4-ethyl-
2-oxazoline-4-methyl[3-(3/5-di-t-butyl-4-hydroxyphenyl)propion-
ate], 800 ml of :isopropanol and 90 ml of 6N hydrochloric acid.
The mixture was refluxed for 4 hours. The isopropanol was re-
moved and the residue was refluxed in a 2:1 mixture of hexane-
toluene to remove the residual water. On cooling the product
crystallized. It was removed by filtration and dried. The
melting point was 144~150C.
.X
7~f~
Example 4
2-Amino-2-methyltrimethylene b~sE3-~3,s-di-t-butyl-4-
hydroxyphenvl)~ropionate]hydrochloride.
The title compound was prepared as described in Ex-
ample 3 except that 451 g ~0.743 mo:Les~ of 2-E2-(3,5-di-t-butyl-
4-hydroxyphenyl)ethyl]-4-methyl-2-oxazoline-4-methyl[3-(3,5-di-
t-butyl-4-hydroxyphenyl)propionate] were used instead of 0.48
moles of 2-[2-(3,5-di~t-butyl-4-hydroxyphenyl)ethyl]-4-ethyl-
2-oxazoline-4-methyl[3-(3,5-di-t-butyl-4-hydroxyphenyl)propion-
ate]. The title compound melted at 161-166C.
,X
