A Safe Cost-Efficient Synthesis of 4,6-Diaminoresorcinol

Full text of DOI:10.1021/jo961675g

J . Org. Chem. 1997, 62, 8255-8256
8255
A Sa fe Cost-Efficien t Syn th esis of
,6-Dia m in or esor cin ol
Sch em e 1
4
R. Garth Pews,* Zenon Lysenko, and Paul C. Vosejpka
Central and New Businesses R&D, The Dow Chemical
Company, Midland, Michigan 48674
Received October 7, 1996 (Revised Manuscript Received
September 11, 1997 )
In tr od u ction
Recent developments in the synthesis of the high-
strength liquid crystalline polymer [p-phenylenebenzobis-
(
oxazole)] (PBO)1 require a regioselective, high-yield,
ratios of <10. Presumably, these solvents phase-sepa-
rated with the liquid ammonia-sodium hydroxide solu-
tion and the reaction, if any, was slow and nonselective.
Methylene chloride, dialkyl formamides, and dimethoxy-
methane gave VNS:NAS ratios comparable to the results
of Makosza and Sienkiewicz in tetrahydrofuran.
inexpensive synthesis of 4,6-diaminoresorcinol (DAR) as
the polymer precursor. The synthesis of DAR has been
Although 4,6-dinitro-1,2,3-trichlorobenzene (5) was
hydrolyzed to 2-chloro-4,6-dinitroresorcinol (6) in the
reported in moderate yield (30-50%) from nitration of
resorcinol diacetate.2
1
,2,3-trichlorobenzene process,3 the hydrolysis of 2,4-
This synthesis has inherent dangers due to the forma-
tion of the explosive 2,4,6-trinitroresorcinol (styphnic
acid) and suffers from low monomer yields. An alterna-
tive synthesis of DAR has been reported utilizing 1,2,3-
dinitro-5-chlorophenol (2) to 4,6-dinitroresorcinol (3) was
not successful. We found that 2 is initially converted to
3
. However, in the presence of excess sodium hydroxide,
3
3 undergoes further degradation to intractable decom-
position products.
trichlorobenzene. With limited and decreasing avail-
ability of 1,2,3-trichlorobenzene, we report a safe, cost-
efficient synthesis of DAR via hydroxylation of 2,4-
dinitrochlorobenzene.
Resu lts a n d Discu ssion
Makosza and Sienkiewicz reported on the hydroxyla-
tion of nitroarenes via vicarious nucleophilic substitution
(VNS) of hydrogen utilizing alkyl hydroperoxides and
potassium tert-butoxide in liquid ammonia with the
substrate dissolved in tetrahydrofuran.4 The product of
the VNS reaction of 2,4-dinitrochlorobenzene (1) was 2,4-
dinitro-5-chlorophenol (2), a potential precursor to DAR
(Scheme 1). By utilizing a 2:1 mole ratio of base to
hydroperoxide, a 93% yield of 2 was obtained. For the
conversion of 1 to 4 to be commercialized, inexpensive
substitutions for potassium tert-butoxide and tetrahy-
drofuran would be required, as well as the demonstration
of the hydrolysis of 2 to 3.
The effect of solvents on the selectivity of the VNS
reaction with competing nucleophilic aromatic substitu-
tion (NAS) was investigated using anhydrous cumene
5
hydroperoxide and powdered sodium hydroxide. The
product of the competing NAS reaction is 2,4-dinitrophe-
nol. Cumene, 2-propanol, N-methylmorpholine, 1-meth-
oxy-2-propanol, and 1,2-dimethoxyethane gave VNS:NAS
This problem was circumvented by conversion of 2 to
,4-dinitro-5-methoxyphenol (7) by the addition of metha-
2
nol to the liquid NH
reaction.
3
after completion of the VNS
(1) Wolfe, J . F., Synthesis Research and Process of PBZ Polymers;
The results for this “one pot” conversion of 1 to 7 are
summarized in Table 1. Methylene chloride is the
solvent of choice due to its low cost and ease of recovery.
The isolation of 7 required prior removal of the cumene
hydroperoxide byproducts, R-methylstyrene and cumyl
alcohol, from the phenate salt of 7 by extraction with
toluene. If the cumene byproducts were not separated
from the phenate salt, the recovered phenol 7 would not
final report on Contract No. AFWAL-TR-86-4025, SRI International,
Sept. 1986.
(2) Schmitt, R. J .; Ross, D. S.; Hardee, J . R.; Wolfe, J . F. J . Org.
Chem. 1988, 53, 5568-5569.
(
(
(
3) Lysenko, Z. U. S. Patent 4,766,244, Aug 13, 1988.
4) Makosza, M.; Sienkiewicz, K. J . Org. Chem. 1990, 55, 4979.
5) Reference 4 mentions the use of sodium hydroxide as a base but
also notes “differences in selectivity compared to potassium tert-
butoxide presumably due to limited solubility of NaOH in liquid
ammonia.”
S0022-3263(96)01675-1 CCC: $14.00 © 1997 American Chemical Society

8
256 J . Org. Chem., Vol. 62, No. 23, 1997
Notes
Ta ble 1. P r ep a r a tion of 2,4-Din itr o-5-m eth oxyp h en ol
reactor at 150 °C overnight, 4 was obtained in 93% yield,
as the dihydrochoride salt.
Su m m a r y
A commercially feasible process for the manufacture
of 4,6-diaminoresorcinol has been demonstrated from
inexpensive 2,4-dinitrochlorobenzene via vicarious nu-
cleophilic substitution. The novel route described pro-
vides DAR monomer for PBO and eliminates the inherent
dangers associated with nitration of diphenolic materials.
Exp er im en ta l Section
Gen er a l P r oced u r e for th e Vica r iou s Su bstitu tion Re-
a ction . 2,4-Dinitrochlorobenzene (20.2 g, 0.1 mol) and cumene
hydroperoxide (20 g, 80% 0.1 mol) were diluted with methylene
chloride (50 mL) and added dropwise to a slurry of powdered
3
NaOH (20 g, 0.5 mol) in (dry ice condenser) anhyd NH (125
mL) at -33 °C over a period of 1 h. After the addition was
substrate
C6H5C(CH3)2OOH NaOH NH3 7 (%
complete, the reaction mixture was allowed to warm to ∼ -10
(mol)
solvent
NMP
DMAC
DMF
CH2Cl2
(CH3O)2CH2
(mol)
(mol) (mL) yield)
°
C, and methanol (75 mL) (containing 1-2 g of sodium hypo-
0
0
0
0
0
.1
.1
.1
.1
.1
0.1
0.1
0.1
0.1
0.1
0.5
0.5
0.5
0.5
0.5
100
100
100
100
100
84
phosphite to destroy any residual hydroperoxide) was added
dropwise. After this addition was complete, the reaction was
allowed to warm to rt and stirred for 3-4 h (or overnight).
The reactor was equipped with a short path distillation
column and the mixture heated to recover methylene chloride
and, if desired, methanol. During the distillation, water was
added dropwise to maintain the phenate salt in a slurry. After
cooling, the contents were transferred to a separatory funnel
82
a
80
83
79
a
Product contains <10% of the impurity 2,4-dinitro-5-dimethy-
laminophenol.
2
containing 250 mL of H O, and the aqueous solution was
precipitate upon acidification. In this manner, crude
yields in excess of 80% were obtained.
extracted twice with toluene to remove cumene byproducts. After
evaporation of the toluene, 18.5 g of R-methylstyrene and cumyl
alcohol were recovered. The aqueous phase was acidified with
concd HCl with stirring at <20 °C to precipitate the crude
product 2,4-dinitro-5-methoxyphenol (18.5 g).7 Recrystalliza-
tion from 65% aqueous methanol afforded 15.75 g (80%) of 7:
Attempted cleavage of the methyl ether 7 with HCl-
perchloroethylene at 130 °C (with and without tetraphe-
nylphosphonium chloride) or glacial acetic acid-anhy-
drous HCl (2:1) at 120 °C in a Parr reactor was
unsuccessful. Although not an economical solution,
refluxing 48% HBr (115 °C) overnight gave 100% cleav-
age to the desired 4,6-dinitroresorcinol (3). Hydrochlo-
ride salts of dialkylamides, i.e., dimethylacetamide and
N-methylpyrrolidinone, were also effective reagents for
the ether cleavage.6 At ∼130 °C, the cleavage was
complete in ∼8 h.
,8
mp 110-12 °C (lit. mp 113 °C); 1H NMR MHz (300 MHz,
9
DMSO-d
MHz, DMSO-d
MS m/z 214 (M , calcd for C H N O 214).
7 6 2 6
6
) δ 8.65 (s, 1H), 6.86 (s, 1H), 3.98 (s, 3H); 1 C NMR (75
3
6
+
) δ 158.2, 157.8, 130.2, 158.6, 125.0, 120.8, 57.4;
Attem p ted Hyd r olysis of 2,4-Din itr o-5-ch lor op h en ol (2).
2,4-Dinitro-5-chlorophenol (3.0 g) was heated at 80 °C with 25
mL of 10% NaOH. After 3 h, GC analysis indicated about 10-
1
5% conversion. After 24 h, only traces of 2 and 3 remained.
,4-Dia m in o-5-m eth oxyp h en ol Dih yd r och lor id e (8). A
50 mL, 3-necked, round-bottomed flask was charged with 150
2
2
mL of water, 2,4-dinitro-5-methoxyphenol (21.4 g, 0.1 mol), and
.0 g of 10% Pd/C. The reaction was stirred under a nitrogen
1
atmosphere for 3-4 min. The stirred reaction mixture was
heated to 55 °C and hydrogen gas was sparged below the surface
of the reaction mixture. After 10 min, concd HCl (19.8 g, 0.2
mol) was added through the condenser and hydrogenation
continued for 4 h. The catalyst was removed by filtration and
the filtrate passed into a solution consisting of 0.5 g of stannous
chloride dihydrate and 25 mL of concd HCl. The solution was
saturated with dry HCl gas and cooled to 25 °C. The solvent
was then removed under reduced pressure (15 mm) to yield a
pale, off-white solid. The product was isolated as the dihydro-
chloride salt and dried at 40 °C, to give 2,4-diamino-5-methox-
Although DMAC‚HCl effectively produced ether cleav-
age, recycle of the DMAC HCl was problematic and an
alternative was sought. Fortuitously, ether cleavage of
2
,4-diamino-5-methoxyphenol (8) to 4 was more facile.
Reduction of 7 to 8 was carried out with hydrogen in
yphenol dihydrochloride (21.0 g, 93%).7
O) δ 7.43 (s,1H), 6.85 (s, 1H), 4.78 (bs, 7H), 3.95 (s, 3H);
NMR (75 MHz, D O) δ 156.7, 154.6, 122.2, 113.3, 112.6, 103.6,
,8
1
H NMR (300 MHz,
1
3
D
2
C
2
+
5
9.6; MS m/z 154 (M , calcd for C
,6-Diam in or esor cin ol Dih ydr och lor ide (4). 2,4-Diamino-
-methoxyphenol dihydrochloride (8) (15.0 g, 0.2 mol) and 150
7 10 2 2
H N O 154).
4
5
mL of concd HCl were heated at 150 °C in a Hastelloy B bomb
for 18 h. After cooling, the solids were filtered and washed with
concentrated HCl to give 12.2 g (94%) of DAR‚HCl. Note: Th is
r ea ction r equ ir es a Ha stelloy B r ea ctor . Ha stelloy C is
n ot sta ble u n d er th ese con d ition s.
J O961675G
aqueous propanol and 10% Pd/C as the catalyst. When
(
7) Hashiba, I.; Suzuki, H.; Tokunaga, K.; Sakota, R. Patent Ap-
plication J P 94-209597 940902.
8) Lysenko, Z.; Pews, R. G.; Vosejpka, P. U.S. Patent 5,414,130,
8
was subjected to concentrated HCl in a Hastelloy B
(
(
6) A paper describing this novel cleavage of ethers will be published
May 9, 1995.
elsewhere.
(9) Borsche, W. Ber. Dtsch. Chem. Ges. 1917, 50, 1351.