Synthesis and characterization of homologue of Irganox 1076 - Some novel observations

Article abstract of DOI:10.1081/SCC-120015701

A convenient and high yielding preparation of Irganox 1076 homologue from 2,6-di-tert-butyl phenol is reported. 2,6-Di-tert-butyl phenol on Friedel-Crafts succinoylation in the presence of aluminium chloride leads to migration and elimination of tert-butyl group without tert-butyl acceptor along with O- and C-succinoylated products.

Full text of DOI:10.1081/SCC-120015701

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Synthesis and Characterization of Homologue of
Irganox 1076—Some Novel Observations
Jigar Desai a , A. N. Misra b & K. B. Nair a c
a Department of Chemistry , Faculty of Science , M.S. University of Baroda , Baroda,
Gujarat, India
b Gujarat Alkalies and Chemicals Limited , P.O. Petrochemical, Baroda, Gujarat, India
c Department of Chemistry , Faculty of Science , M.S. University of Baroda , Baroda,
Gujarat, 390 002, India
Published online: 21 Aug 2006.
To cite this article: Jigar Desai , A. N. Misra & K. B. Nair (2003) Synthesis and Characterization of Homologue of Irganox
1076—Some Novel Observations, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 33:2, 199-205, DOI: 10.1081/SCC-120015701
To link to this article: http://dx.doi.org/10.1081/SCC-120015701
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 2, pp. 199–205, 2003
Synthesis and Characterization of Homologue of
Irganox 1076—Some Novel Observations
Jigar Desai,1 A. N. Misra,2 and K. B. Nair1,
*
1Department of Chemistry, Faculty of Science,
M.S. University of Baroda, Baroda, Gujarat, India
2Gujarat Alkalies and Chemicals Limited,
P.O. Petrochemical, Baroda, Gujarat, India
ABSTRACT
A convenient and high yielding preparation of Irganox 1076 homo-
logue from2,6-di- tert-butyl phenol is reported. 2,6-Di-tert-butyl
phenol on Friedel–Crafts succinoylation in the presence of alumi-
nium chloride leads to migration and elimination of tert-butyl
group without tert-butyl acceptor along with O- and C-succinoylated
products.
Key Words: Antioxidants; De-tert-butylation; Isomerization; Suc-
cinolyation.
Correspondence: K. B. Nair, Department of Chemistry, Faculty of Science, M.S.
University of Baroda Baroda 390 002, Gujarat, India. E-mail: jigarndesai@
rediffmail.com.
199
DOI: 10.1081/SCC-120015701
Copyright & 2003 by Marcel Dekker, Inc.
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200
Desai, Misra, and Nair
Antioxidants based on hindered phenols are of great importance
because of their multiple applications ranging from foods to fuels, plastics
as well as ultraviolet absorbing agents.[1] Among these, butylated
hydroxy toluene, tert-butyl hydroquinone and their derivatives such as
octadecyl-3-(30,50-di-tert-butyl-40-hydroxy phenyl) propionate (Irganox
1076), are of great interest because of their extensive use in food
packaging, pharmaceutical formulations, and polymer stabilization.
Scheme 1.

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Irganox 1076 Homologue
201
There are reports in literature regarding the Lewis acid catalysed
Friedel–Crafts isomerization[2] and de-tert-butylation.[3] The de-tert-
butylation is also catalysed by metal oxide[4] and mineral acids.[5] Normally
de-tert-butylation involves the treatment of tert-butyl arenes with Lewis
acid in the presence of tert-butyl acceptor.[6] De-tert-butylation of
phenolswithouttert-butylacceptorusingTFAisalsoknown,butitinvolves
harsh conditions.[7] Migration or isomerization of alkyl group from one
position in the ring to another position in the same ring is known to occur
via 1,2 shifts. Any 1,3 or 1,4 shift takes place by series of two or more
1,2 shifts.[8] The literature survey reveals that intramolecular isomeriza-
tion and de-tert-butylation without tert-butyl acceptor on a single
molecule are novel.
We report a convenient method of synthesis of homologue of
Irganox 1076 by introducing one more methylene group in the alkyl
chain. This synthesis was achieved by the application of Friedel–Crafts
succinoylation on 2,6-di-tert-butyl phenol followed by Clemmenson
reduction and subsequent esterification of the acid formed.
During the Friedel–Crafts succinoylation we observed de-tert-buty-
lation involving carbon–carbon bond rupture without tert-butyl accep-
tor, isomerization of the tert-butyl group fromthe 1,2 position in
phenol ring to the 1,4 position in the same ring along with O- and
C-succinoylation. 2,6-Di-tert-butyl phenol on Friedel–Crafts succinoyla-
tion in the presence of anhydrous AlCl3 in nitrobenzene as solvent gave
the desired C-succinoylated product 2 along with de-tert-butylated
and isomerized product 3. The reaction performed under similar experi-
mental conditions using CS2 as solvent afforded product 4 due to de-
tert-butylation, isomerization, and O-succinoylation. The keto acid 2 on
Clemmenson reduction yielded 4-(30,50-di-tert-butyl-40-hydroxy phenyl)
butanoic acid 5, which on esterification with stearyl alcohol gave
the desired octadecyl-4-(30,50-di-tert-butyl-40-hydroxy phenyl) butanoate
6 (Sch. 1).
EXPERIMENTAL
IR spectra were recorded on Perkin–Elmer IR-781 spectrophot-
ometer. 1H NMR spectra were determined on Brucker-200 MHz
(CDCl3/TMS) spectrophotometer and CMR spectra were recorded on
Bruker-50 MHz (CDCl3/TMS) spectrophotometer. Elemental analyses
were carried out on Coleman C, H analyser.

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202
Desai, Misra, and Nair
Friedel–Crafts Succinoylation on 2,6-Di-tert-butyl Phenol
To the stirring solution of 2,6-di-tert-butyl phenol (0.01 mol) and
succinic anhydride (0.015 mol) in nitrobenzene (50 mL), AlCl3
(0.02 mol) was added in parts at temperature 0–5ꢀC. The reaction mixture
was stirred for 6 h by keeping the same temperature. The mixture was
decomposed with cold water (40 mL) and HCl (10 mL). Nitrobenzene
layer was washed with water (5 Â 30 mL) and was removed using
Dean-Stark apparatus. The dark brown pasty mass was stirred with
Pet. ether (5 mL) and the solid obtained was crystallized from the mixture
of benzene and Pet. ether to get compound 2 in 55% yield. Compound 3
was isolated fromthe surface of the Dean-Stark apparatus and was
crystallized using Pet. ether in 10% yield (Path A).
The Friedel–Crafts succinoylation was performed using CS2 instead
of nitrobenzene as solvent under same experimental conditions. The mix-
ture was decomposed in cold water (40 mL) and HCl (10 mL) and carbon
disulfide was removed by simple distillation. The pasty mass obtained
was stirred with Pet. ether. The solid obtained on crystallization fromPet.
ether gave 40-tert-butyl-3-carbophenoxy propanoic acid 4 in 40% yield
(Path B).
Synthesis of 4-(30,50-Di-tert-butyl-40-hydroxyphenyl) Butanoic Acid
To a solution of keto acid 2 (0.01 mol) in toluene (25 mL), a freshly
prepared mixture of amalgamated zinc (from mossy zinc), water (20 mL)
and conc. HCl (20 mL) was added. The resulting mixture was refluxed
vigorously for 12 h with 5 mL portion of HCl being added every 4 h. After
cooling toluene layer was separated and washed with water (3 Â 30 mL).
Product obtained after removal of toluene was dried and crystallized
fromPet. ether in 90% yield.
Synthesis of Octadecyl-4-(30,50-di-tert-butyl-40-hydroxyphenyl)
Butanoate
Butanoic acid 5 (0.01 mol) was dissolved in chloroform (50 mL). To
this octadecyl alcohol (0.01 mol) was added followed by catalytic amount
of PTSA. The reaction mixture was refluxed for 6 h using Dean Stark
apparatus and the chloroformwas removed by distillation. The crude
product was chromatographed over silica gel column using Pet. ether

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Irganox 1076 Homologue
203
as eluent to isolate ester 6 as liquid in 84% yield Rf ¼ 0.81 (EtoAc–Pet.
ether, 1:9).
PHYSICAL DATA AND SPECTRAL CHARACTERIZATION
Compound 2: M.p. 164–165ꢀC (lit[9] 163–165ꢀC). Elemental analysis
(%) found for M.F. C18H26O4: C, 71.00; H, 8.09; Calcd: C, 70.59; H, 8.50.
IR (KBr) 3520, 3120, 1720, 1705, 1690 cmꢁ1. 1H NMR: ꢀH: 1.46 (18H, s,
2 Â C(CH3)3), 2.78 (2H, t, J ¼ 6.46 Hz, CH2), 3.28 (2H, t, J ¼ 6.46 Hz,
CH2), 5.73 (1H, s, OH), 7.86 (2H, s, aromatic).
Compound 3: M.p. 95–97ꢀC (lit[10] 96–98ꢀC). Elemental analysis (%)
found for M.F. C10H14O: C, 79.49; H, 8.94; Calcd: C, 80.00; H, 9.33. IR
(KBr) 3240 cmꢁ1. 1H NMR: ꢀH: 1.29 (9H, s, C(CH3)3), 4.60 (1H, s, OH),
6.75 (2H, dd, J5-6 ¼ 8.7 Hz and J2-6 ¼ 1.9 Hz, aromatic C5, C6), 7.30 (2H,
dd, J2-3 ¼ 8.7 Hz and J3-5 ¼ 2.1 Hz, aromatic C2, C3). 13C NMR: ꢀC: 154
(C1), 144 (C4), 127 (C3-5), 115.4 (C2-6), 34.76 (C(CH3)3), 32.31 (CH3).
DEPT indicates the presence of three methyl groups, two different
aromatic methine groups, two different quaternary aromatic carbon
atoms and one quaternary aliphatic carbon atom.
Compound 4: M.p. 88–90ꢀC. Elemental analysis (%) found for M.F.
C14H18O4: C, 67.6; H, 7.33; Calcd: C, 67.2; H, 7.20. IR (KBr) 3120, 1730,
.
1710, 1700 cmꢁ1 1H NMR: ꢀH: 1.30 (9H, s, C(CH3)3), 2.85 (m, 4H,
0
0
0
0
0
CH2-CH2), 7.0 (2H, dd, J5 -6 ¼ 8.7 Hz and J2 -6 ¼ 2.0 Hz, aromatic C5 ,
13
0
0
0
0
0
0
0
C6 ), 7.38 (2H, dd, J2 -3 ¼ 8.7 Hz and J3 -5 ¼ 1.9 Hz aromatic C2 , C3 ).
0
0
C NMR: ꢀC: 178.01 (CO), 170.87 (CO), 148.73 (C3 ), 148.20 (C2 ),
0
0
126.20 (C1 ), 120.71 (C4 ), 34.43 (C(CH3)3), 31.36 (CH3), 29.07 (CH2),
28.92 (CH2). DEPT indicates the presence of three methyl groups, two
methylene groups, two different carbonyl groups, two different
aromatic methine groups, two aromatic quaternary carbon atoms and
one aliphatic quaternary carbon atom.
Compound 5: M.p. 100–102ꢀC (lit[11] 119–119.5ꢀC). Elemental analy-
sis (%) found for M.F. C18H28O3: C, 74.38; H, 9.69; Calcd: C, 73.97;
.
H, 9.58. IR (KBr) 3520, 3118, 1710 cmꢁ1 1H NMR: ꢀH: 1.43 (18H,
s, C(CH3)3), 1.8 (2H, m, -CH2-CH2-CH2-), 2.3 (2H, t, -CH2-), 2.6 (2H,
t, -CH2-), 5.12 (1H, s, OH), 7.0 (2H, s, aromatic).
Compound 6: Elemental analysis (%) found for M.F. C36H64O3: C,
79.21; H, 11.56; Calcd: C, 79.41; H, 11.76. IR (KBr) 3518, 1738 cmꢁ1
.
1H NMR: ꢀH: 0.9 (3H, t, -CH2-CH3), 1.0–1.7 (50H, m, -CH2-CH2-,
including eighteen tert-butyl protons), 1.95 (2H, m, -CH2-CH2-CH2-),

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204
Desai, Misra, and Nair
2.35 (2H, t, Ph-CH2), 2.6 (2H, t, -CH2-CO-), 4.1 (2H, t, COOCH2-), 5.01
(1H, s, OH), 7.0 (2H, s, aromatic).
CONCLUSION
This new process for the synthesis of octadecyl-4-(30,50-di-tert-butyl-
40-hydroxy phenyl) butanoate is convenient, it envisages the use of
cheaper starting materials and could be implemented for large scale pre-
Scheme 2.

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Irganox 1076 Homologue
205
paration. In the presence of Lewis acid one of the tert-butyl group is
detached fromthe aromatic ring and second is isomerized from1,2 to
the 1,4 position in the same ring according to the Sch. 2. In the absence of
tert-butyl acceptor intra-molecular isomerization was observed. Here as
isomerization is fast it is reasonable to suggest that the tert-butyl group is
not completely detached from the aromatic ring but stays in the interac-
tion through ꢁ type of intermediate. Complete detachment of the tert-
butyl group in alkylation–dealkylation process would be expected to be
much slower process.
Fromthe above discussions it is reasonable to say that in case of
nitro benzene as solvent, amount of C-acylated product is more along
with some amount of 3 indicating that de-tert-butylation and isomeri-
sation is less in this solvent. The use of carbon disulfide as solvent leads to
product 4 in major quantity suggesting that extend of isomerization and
de-tert-butylation is more in this case.
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Received in the Netherlands December 10, 2001

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