Controlled synthesis of novel dibenzene-1,2-diol mannich bases

Article abstract of DOI:10.1071/ch00079

The synthesis of a number of novel dibenzene-1,2-diol Mannich bases can be achieved in good yields by the condensation of 2-methoxyphenol, formaldehyde and secondary diamines. The newly developed synthetic method utilizes 2-methoxyphenol instead of benzen

Full text of DOI:10.1071/ch00079

C S I R O P U B L I S H I N G
Australian Journal
of Chemistry
Volume 53, 2000
© CSIRO 2000
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Aust. J. Chem., 2000, 53, 545–549
Controlled Synthesis of Novel Dibenzene-1,2-diol Mannich Bases
Marcus J. Caulfield,A Tiziana RussoA and David H. Solomon A,B
A Polymer Science Group, Department of Chemical Engineering,
The University of Melbourne, Vic. 3010.
B Author to whom correspondence should be addressed.
The synthesis of a number of novel dibenzene-1,2-diol Mannich bases can be achieved in good yields by the con-
densation of 2-methoxyphenol, formaldehyde and secondary diamines. The newly developed synthetic method uti-
lizes 2-methoxyphenol instead of benzene-1,2-diol providing a useful tool for greater control over reaction
products.
Keywords. Aminoalkylation; catechol; Mannich base; synthesis.
Introduction
An alternative method of synthesizing (2) was developed
using a two-step procedure (Scheme 2). 6,6Ј-Dimethoxy-
2,2Ј-[ethylenebis(methyliminomethylene)]diphenol (3) was
formed by the reaction between 2-methoxyphenol, formalde-
hyde and N,NЈ-dimethylethylenediamine (1) in a moderate
yield of 38%. This methoxy intermediate was demethylated
in an acetic acid solution of HBr to give the desired product
with an excellent recovery of 96%. The blocking of the
hydroxy group prevents further aminoalkylation of the aro-
matic ring giving rise to cleaner reaction products.
The patent and scientific literature contains numerous
reports on Mannich base derivatives of phenol regarding
their chemistry and their applications.1–6 Very few refer-
ences, however, are made to Mannich base derivatives of
benzene-1,2-diol, herein referred by its common name cate-
chol, and, in particular, no reports pertaining to our target
class of compounds, the dicatechol products. Our research
program required multigram quantities of a range of dicate-
chol Mannich bases; therefore, an efficient synthetic method
was required. We now report a convenient method for syn-
thesizing these compounds in good yields and free from side
products. This methodology is also generally applicable to
the efficient synthesis mono ortho substituted cate-
cholamines.
Results and Discussion
Our initial attempt to synthesize 3,3Ј-[ethylenebis-
(methyliminomethylene)]di(benzene-1,2-diol) (2) via the
condensation of catechol, N,NЈ-dimethylethylenediamine (1)
and formaldehyde (Scheme 1) resulted in a complex product
mixture. Analysis of the crude reaction mixture by nuclear
magnetic resonance (n.m.r.) indicated that the desired
product was formed but in small amounts.
This methodology was then applied to the synthesis of a
range of previously unknown dicatechol Mannich base prod-
ucts (9)–(11) in good yields (Scheme 3). Although the
methoxy intermediates (6)–(8) of these compounds were iso-
lated and characterized, the crude product mixture from this
initial step can be demethylated directly simplifying the reac-
tion scheme.
Manuscript received 8 June 2000
© CSIRO 2000
10.1071/CH00079
0004-9425/00/070545

546
M. J. Caulfield, T. Russo and D. H. Solomon
bases in good yields. The use of the methyl-blocked catechol,
2-methoxyphenol, provides a means by which greater
control can be exerted over the reaction and the resulting
mixtures. Moreover, the methoxy intermediates are impor-
tant in their own right as they may have potential application
in other biological and pharmacological areas of study.
Greatly increased yields are also observed with this method
in the synthesis of the mono ortho catecholamines.
This methodology allows for easy isolation of the
methoxy intermediates that are important in their own right.
Similar compounds have been reported to exhibit interesting
chemistry that has potential applications in various biologi-
cal and pharmacological areas.7–9 In a subsequent paper we
will report results of biological screening data for a range of
these Mannich bases.
Experimental
Instrumentation
Finally, the applicability of this method to the synthesis a
number of mono ortho substituted catecholamines was
tested. The preparation of 3-(diethylaminomethyl)benzene-
1,2-diol (12) by our method gave the final product in a yield
of 55%. The same product was prepared according to the lit-
erature method described by Jia Quiquan and coworkers,10 in
a comparatively low yield of 33%. The trend of increasing
yields with our method is exemplified when larger amines
are employed. For example, in the synthesis of 3-(dipropyl-
aminomethyl)benzene-1,2-diol (13) a yield of 34% was
achieved compared to a previously obtainable 17%. We
noted, however, that the overall yield is lowered but the
increase is just as significant (Scheme 4). As with the syn-
thesis of the dicatechol Mannich bases, the methoxy inter-
mediates (16)–(19) were isolated and characterized;
however, the crude product mixture from the initial
aminoalkylation step can be demethylated directly.
N.m.r. spectra were obtained in (D)chloroform (99.8%) (Cambridge
Isotope Laboratories) by using a Varian Unity 400 MHz instrument
unless otherwise specified. The abbreviation appr. (apparent) is used to
denote second-order coupling. Infrared (i.r.) spectra were recorded on a
Biorad FTS-60A Fourier-transform spectrometer. Microanalyses were
performed by Chemical and Micro Analytical Services Pty Ltd,
Victoria. Mass spectrometric data were obtained on an Analytical
Concept Kratos ISQ instrument recorded at 70 eV from The University
of Tasmania. Melting points were performed on an Electrothermal
melting point apparatus and are uncorrected.
Liquid chromatography was performed by using Merk Kieselgel 60.
Reagents
Catechol (99%) was purchased from Aldrich and used without
further purification. All amines were also purchased from Aldrich and
distilled over KOH prior to use. 2-Methoxyphenol was obtained from
ICN Biomedicals Inc. and distilled under vacuum prior to use. All sol-
vents were of analytical grade. Dry ethanol was obtained by distillation
over calcium hydride (CaH2) under a nitrogen atmosphere and stored
over 4 Å molecular sieves.
Conclusion
General Procedures
A straightforward synthetic route has been developed to
access previously unknown mono ortho dicatechol Mannich
All reactions were performed under an argon atmosphere.
Demethylation of the methoxy intermediate to give the free hydroxy

Synthesis of Dibenzene-1,2-diol Mannich Bases
547
moiety was achieved by refluxing in a 20% solution of HBr in acetic
acid (v/v) for 48 h.
␦ 52.3; 55.8; 60.9; 111.1; 118.9; 120.7; 121.0; 146.8; 147.9. Mass spec-
trum (e.i.) m/z 358 (30%), 221 (61), 180 (29), 137 (100), 122 (9), 85
(36).
The following standard workup procedure was used for each reac-
tion unless stated otherwise. After the reaction was complete the
solvent was removed under reduced pressure followed by acidification
with concentrated HCl and ice. The aqueous mixture was washed with
diethyl ether (3×20 ml) and neutralized with NaHCO3. The reaction
products were extracted into chloroform (4×20 ml). The organic
extracts were collected, dried over Na2SO4 and concentrated under
vacuum.
Synthesis of 3,3Ј-[Alkanediylbis(alkyliminomethylene)]di(benzene-1,2-
diol) Mannich Bases (2) and (7)–(9)
The desired Mannich bases (2) and (7)–(9) were obtained in excel-
lent yields by the demethylation of the corresponding 6,6Ј-dimethoxy-
2,2Ј-[alkylenebis(alkyliminomethylene)]diphenol intermediate. After
the demethylation was complete a standard workup followed and isola-
tion of the product was achieved by standard purification techniques.
Synthesis of 6,6Ј-Dimethoxy-2,2Ј-[alkanediylbis(alkylimino-
methylene)]diphenols (3) and (4)–(6)
3,3Ј-[Ethylenebis(methyliminomethylene)]di(benzene-1,2-diol) (2)
The desired compounds (3) and (4)–(6) were prepared in good yields
according to the following general method. A solution of finely ground
paraformaldehyde (0.05 mol, 1 equiv.) and the appropriate amine (0.05
mol, 1 equiv.) in dry ethanol (10 ml) was added dropwise to a solution
of 2-methoxyphenol (0.025 mol, 0.5 equiv.) in dry ethanol (10 ml) at
room temperature. After the addition was complete, the reaction was
heated to 40°C and stirred for a further 4 days. A standard workup fol-
lowed and the product was isolated by using standard purification tech-
niques.
Column chromatography (ethyl acetate) afforded (2) as pale yellow
crystals (1.16 g, 96%), m.p. 91–92°C (Found: C, 65.0; H, 7.3; N, 8.5.
C18H24N2O4 requires C, 65.0; H, 7.3; N, 8.4%). I.r. ␯ (KBr) 3450,
max
3394, 1480, 1463, 1265, 1189 cm–1. 1H n.m.r. ␦ 2.27, s, NCH3; 2.65, s,
NCH2CH2N; 3.68, s, NCH2; 6.51, appr. d, J 7.6 Hz, ArH; 6.69, appr. t,
J 7.8 Hz, ArH; 6.85, appr. d, J 8.1 Hz, ArH. 13C n.m.r. ␦ 41.5; 53.7; 61.3;
114.2; 119.5; 119.5; 121.5; 144.4; 144.8. Mass spectrum (e.i.) m/z 332
(4%), 166 (72), 122 (67), 94 (12), 66 (14), 44 (100) (Found: M+ ,
332.17248. C18H24N2O4 requires M+ , 332.17361).
6,6Ј-Dimethoxy-2,2Ј-[ethylenebis(methyliminomethylene)]diphenol (3)
3,3Ј-[Ethylenebis(ethyliminomethylene)]di(benzene-1,2-diol (7)
Recrystallization of the crude material twice from hot ethanol
afforded (3) as white crystals (3.40 g, 38%), m.p. 115–116°C (Found:
The crude product was dissolved in acetone and passed through a
plug of silica to afford (7) as pale yellow crystals (1.61 g, 87%), m.p.
143–144°C (Found: C, 66.7; H, 7.6; N, 8.0. C20H28N2O4 requires C,
C, 66.5; H, 7.9; N, 7.3. C20H28N2O4 requires C, 66.6; H, 7.8; N, 7.7%).
1
I.r. ␯ (KBr) 2846, 2362, 1480, 1465, 1252, 1239 cm–1. H n.m.r. ␦
66.6; H, 7.8; N; 7.8%). I.r. ␯ (KBr) 3451, 2979, 1482, 1468, 1373,
max
max
1289, 1258, 1189 cm–1. 1H n.m.r. ␦ 1.10, s, t, J 7.2 Hz, NCH2CH3; 2.57,
q, J 7.2 Hz NCH2CH3; 2.70, s, NCH2CH2N; 3.73, s, NCH2; 6.50, appr.
d, J 7.5 Hz, ArH; 6.69, appr. t, J 7.7 Hz, ArH; 6.84, appr. d, J 7.9 Hz,
ArH. 13C n.m.r. ␦ 10.9; 47.5; 50.1; 57.3; 113.9; 119.5; 119.5; 121.4;
144.5; 144.7. Mass spectum (e.i.) m/z 360 (11%), 238 (12), 194 (4), 166
(9), 122 (83), 94 (55), 58 (100) (Found: M+ , 360.20518. C20H28N2O4
requires M+ , 360.20491).
2.30, s, NCH3; 2.70, s, NCH2CH2N; 3.70, s, NCH2; 3.86, s, OCH3; 6.57,
appr. d, J 7.3 Hz, ArH; 6.73, appr. t, J 7.7 Hz, ArH; 6.79, appr. d, J 7.2
Hz, ArH. 13C n.m.r. ␦ 41.8; 54.4; 55.8; 61.3; 111.1; 118.8; 120.5; 121.8;
146.9; 147.9. Mass spectrum (e.i.) m/z 360 (3%), 180 (100), 137 (83),
107 (14) 44 (64) (Found: M+ , 360.20356. C20H28N2O4 requires M+ ,
360.20491).
6,6Ј-Dimethoxy-2,2Ј-[ethylenebis(ethyliminomethylene)]diphenol (4)
3,3Ј-[Propane-1,3-diylbis(methyliminomethylene)]di(benzene-1,2-
diol) (8)
Column chromatography (chloroform) afforded (4) as pale yellow
crystals (2.96 g, 41%), m.p. 71–72°C (Found: C, 68.0; H, 8.3; N, 7.2.
The crude product was dissolved in a mixture of acetone and chlo-
roform (1:1) and the solution was filtered to remove any insoluble
residues. The organic filtrate was concentrated under reduced pressure.
Column chromatography (acetone) afforded (8) as pale yellow crystals
(1.73 g, 87%), m.p. 130°C (dec.) (Found: C, 66.0; H, 7.9; N, 7.6.
C22H32N2O4 requires C, 68.0; H, 8.3; N, 7.2%). I.r. ␯ (KBr) 2979,
max
2834, 1468, 1251, 1232, 1064 cm–1. H n.m.r. ␦ 1.07, t, J 7.1 Hz,
1
NCH2CH3; 2.59, q, J 7.2 Hz, NCH2CH3; 2.79, s, NCH2CH2N; 3.74, s,
NCH2; 3.86, s, OCH3; 6.56, appr. d, J 7.5 Hz, ArH; 6.71, appr. t, J 7.5
Hz, ArH; 6.79, dd, J 8.1, 1.4 Hz, ArH. 13C n.m.r. ␦ 11.2; 47.9; 50.6; 55.9;
57.7; 111.0; 118.7; 120.5; 121.9; 147.2; 147.9. Mass spectrum (e.i.) m/z
388 (14%), 251 (2), 194 (96), 137 (100), 122 (4), 107 (12), 58 (84), 39
(11) (Found: M+ , 388.23551. C22H32N2O4 requires M+ , 388.23621).
C19H26N2O4 requires C, 65.9; H, 7.6; N, 8.0%). I.r. ␯ (KBr) 3412,
max
3051, 2962, 2846, 1475, 1354, 1196 cm–1. H n.m.r. ␦ 1.83, quin,
1
NCH2CH2CH2N; 2.31, s, NCH3; 2.52, t, J 7.5 Hz, NCH2CH2CH2N;
3.70, s, NCH2; 6.51, appr. d, J 7.6 Hz, ArH; 6.69, appr. t, J 7.7 Hz, ArH;
6.84, appr. d, J 7.9 Hz, ArH. 13C n.m.r. ␦ 24.6; 41.4; 54.6; 61.1; 113.8;
119.3; 119.4; 121.3; 144.6; 144.6. Mass spectrum (e.i.) m/z 346 (12%),
224 (24), 193 (13), 166 (28), 152 (28), 122 (100), 94 (25), 71 (54), 58
(40) (Found: M+ , 346.18902. C19H26N2O4 requires M+ , 346.18926).
6,6Ј-Dimethoxy-2,2Ј-[propane-1,3-diylbis(methyliminomethylene)]-
diphenol (5)
Column chromatography (ethyl acetate) afforded (5) as orange crys-
tals (2.48 g, 40%), m.p. 78–79°C (Found: C, 67.3; H, 8.1; N, 7.5.
C21H30N2O4 requires C, 67.4; H, 8.1; N, 7.5%). I.r. ␯ (KBr) 2961,
max
3,3Ј-(Piperazine-1,4-diylbismethylene)di(benzene-1,2-diol) (9)
2837, 1478, 1456, 1251, 1238 cm–1. H n.m.r. ␦ 1.87, quin, J 7.1 Hz,
1
Column chromatography (chloroform) afforded (9) as pale yellow
crystals (0.91 g, 90%), m.p. 210°C (dec.) (Found: C, 65.4; H, 6.8; N,
8.4. C18H22N2O4 requires C, 65.4; H, 6.7; N, 8.5%). I.r. ␯max (KBr) 3517,
2935, 2831, 1483, 1347, 1268, 1242, 1170 cm–1. 1H n.m.r. ␦ 2.35, br s,
ring CHaHbCHaCHb; 2.95, br s, ring CHaHbCHaCHb; 3.75, s, NCH2;
6.53, appr. d, J 7.4 Hz, ArH; 6.71, appr. t, J 7.8 Hz, ArH; 6.85, dd, J 8.0,
1.3 Hz, ArH. 13C n.m.r. ␦ 52.4; 60.8; 114.1; 119.7; 119.7; 120.5; 144.1;
144.5. Mass spectrum (e.i.) m/z 330 (20%), 166 (54), 122 (89), 85 (80),
56 (57), 44 (100) (Found: M+ , 330.15705. C18H22N2O4 requires M+ ,
330.15796).
NCH2CH2CH2N; 2.27, s, NCH3; 2.55, t, J 7.4 Hz, NCH2CH2CH2N;
3.70, s, NCH2; 3.87, s, OCH3; 6.58, dd, J 7.4, 1.0 Hz, ArH; 6.73, appr.
t, J 7.8 Hz, ArH; 6.80, dd, J 8.1, 1.4 Hz, ArH. 13C n.m.r. ␦ 24.7; 41.2;
54.9; 55.8; 61.2; 110.9; 118.7; 120.5; 121. 8; 147.1; 147.8. Mass spec-
trum (e.i.) m/z 374 (5%), 207 (11), 180 (36), 166 (30), 150 (5), 137
(100), 101 (26), 58 (30) (Found: M+ , 374.22059. C21H30N2O4 requires
M+ , 374.22056).
6,6Ј-Dimethoxy-2,2Ј-(piperazine-1,4-diylbismethylene)diphenol (6)
Column chromatography (chloroform) followed by recrystallization
from hot ethanol afforded (6) as white needlelike crystals (1.84 g, 31%),
m.p. 197–198°C (Found: C, 67.1; H, 7.3; N, 7.9. Calc. for C20H26N2O4:
C, 67.0; H, 7.3; N, 7.8%). I.r. ␯max (KBr) 2945, 2830, 1460, 1257, 1239
Synthesis of 3-(Dialkylaminomethyl)benzene-1,2-diol Mannich
Bases (Two-Step Method)
1
cm–1. H n.m.r. ␦ 2.37, br s, ring CHaHbCHaCHb; 2.93, br s, ring
The desired Mannich bases (10)–(13) were prepared in good yields
by means of the following general method unless otherwise stated. A
solution of finely ground paraformaldehyde (0.05 mol, 1 equiv.) and the
CHaHbCHaCHb; 3.72, s, NCH2; 3.87, s, OCH3; 6.60, appr. d, J 7.4 Hz,
ArH; 6.75, appr. t, J 7.8 Hz, ArH; 6.81, appr. d, J 7.6 Hz, ArH. 13C n.m.r.

548
M. J. Caulfield, T. Russo and D. H. Solomon
appropriate amine (0.10 mol, 2 equiv.) in dry ethanol (10 ml) was added
dropwise to solution of 2-methoxyphenol (0.05 mol, 1 equiv.) in dry
ethanol (10 ml) at room temperature. After the addition was complete
the reaction mixture was stirred for 72 h. A standard workup followed
and the crude mixture was demethylated. After demethylation a second
workup followed and the product was isolated by standard purification
techniques.
Synthesis of 2-(Diakylaminomethyl)-6-methoxyphenols (14)–(17)
The desired compounds (14)–(17) were obtained in good yields fol-
lowing a general method unless stated otherwise. A solution of finely
ground paraformaldehyde (0.05 mol, 1 equiv.) and the appropriate
amine (0.10 mol, 2 equiv.) in dry ethanol (10 ml) was added dropwise
to a solution of 2-methoxyphenol (0.05 mol, 1 equiv.) at room temper-
ature. After the addition was complete the reaction mixture was stirred
for 72 h. A standard workup followed and the product was isolated by
standard purification techniques.
3-(Diethylaminomethyl)benzene-1,2-diol (10)
Two-step method. Column chromatography (acetone) afforded
(10) as pale yellow grain-like crystals (5.33 g, 55%), m.p. 43–44°C
(lit.10 44–45°C) (Found: C, 67.6; H, 8.6; N, 7.1. Calc. for C11H17NO2:
C, 67.7; H, 8.8; N, 7.2%). I.r. ␯max (KBr) 3436, 2975, 1475, 1261, 1181
cm–1. 1H n.m.r. 1.13, t, J 7.2 Hz, NCH2CH3; 2.65, q, J 7.1 Hz,
NCH2CH3; 3.78, s, CH2N; 6.52, appr. d, J 7.5 Hz, ArH; 6.67, appr. t, J
7.8 Hz, ArH; 6.84, dd, J 7.9, 1.3 Hz, ArH; 8.69 ArOH. 13C n.m.r 11.0;
46.3; 56.2; 113.7; 119.0; 119.5; 121.3; 144.8; 145.1. Mass spectrum
m/z (e.i.) 195 (53%), 166 (2), 137 (4), 123 (45), 72 (19), 58 (100).
Literature method.10 A solution of crushed paraformaldehyde (1
equiv.) and diethylamine (2 equiv.) in dry ethanol (10 ml) was stirred for
1 h. Catechol (1 equiv.) was added and stirred for a further 72 h. Workup
followed by column chromatography (acetone) afforded (10) as pale
yellow grain-like crystals (3.29 g, 33%). The spectroscopic data were
consistent with those obtained from the two-step method.
2-(Dimethylaminomethyl)-6-methoxyphenol (14)
Column chromatography (acetone) followed by recrystallization
from hot petroleum sprits (40–60°C) afforded (14) as white grain-like
crystals (2.97 g, 33%), m.p. 47–49°C (Found: C, 66.1; H, 8.3; N, 7.6.
Calc. for C10H15NO2: C, 66.3; H, 8.3; N, 7.7%). I.r. ␯ (KBr) 2938,
max
1
2834, 1479, 1444, 1266, 1237, 1075 cm–1. H n.m.r. ␦ 2.35, s, NCH3;
3.67, s, CH2N; 3.87, s, OCH3; 6.61, appr. d, J 7.4 Hz, ArH; 6.74, appr.
t, J 7.8 Hz, ArH; 6.81, appr. t, J 8.1 Hz, ArH. 13C n.m.r. ␦ 44.4; 55.8;
62.1; 110.9; 118.5; 120.5; 121.8; 147.3; 147.8. Mass spectrum (e.i.) m/z
181 (100%), 136 (41), 107 (18), 93 (4), 58 (15), 44 (17).
2-(Diethylaminomethyl)-6-methoxyphenol (15)
Column chromatography (chloroform) afforded (15) as an orange
oil (5.79 g, 49%) (Found: C, 68.7; H, 9.2; N, 6.6. C12H19NO2 requires
C, 68.9; H, 9.2; N, 6.7%). I.r. ␯max (KBr) 2971, 2935, 2831, 1471, 1415,
1250, 1239, 1081 cm–1. 1H n.m.r. ␦ 1.09, t, J 7.2 Hz, NCH2CH3; 2.60,
q, J 7.2 Hz, NCH2CH3; 3.75, s, CH2N; 3.84, s, OCH3; 6.56, appr. d, J
7.4 Hz, ArH; 6.69, appr. t, J 7.8 Hz, ArH; 6.77, appr. d, J 8.2 Hz, ArH.
13C n.m.r. ␦ 11.1; 46.2; 55.7; 56.7; 110.5; 118.2; 120.2; 122.1; 147.1;
147.8. Mass spectrum (e.i.) m/z 209 (23%), 195 (36), 137 (87), 107
(16), 72 (21), 58 (100) (Found: M+ , 209.14173. C12H19NO2: requires
M+ , 209.14158).
3-(Dipropylaminomethyl)benzene-1,2-diol (11)
Two-step method. Column chromatography (ethyl acetate)
afforded (11) as pale yellow needlelike crystals (3.84 g, 34%), m.p.
34–35°C (Found: C, 69.7; H, 9.6; N, 6.4. Calc. for C13H21NO2: C, 69.9;
H, 9.5; N, 6.3%). I.r. ␯max (KBr) 3451, 2965, 2940, 1477, 1470, 1361,
1259, 1180 cm–1. 1H n.m.r. (CD3OD) ␦ 0.80, J 7.4 Hz, NCH2CH2CH3;
1.92, m, NCH2CH2CH3; 2.38, m, NCH2CH2CH3; 3.64, s, CH2N; 6.38,
dd, J 7.5, 1.1 Hz, ArH; 6.48, appr. t, J 7.7 Hz, ArH; 6.60, dd, J 7.9, 1.5
Hz, ArH. 13C n.m.r. (CD3OD) ␦ 12.2; 20.7; 56.7; 59.0; 115.7; 120.1;
120.6; 124.2; 146.3; 147.0. Mass spectrum (e.i.) m/z 223 (9%), 194
(12), 122 (24), 72 (100), 43 (20).
3-(Dipropylaminomethyl)-6-methoxyphenol (16)
Column chromatography (ethyl acetate) afforded (16) as a dark
orange oil (5.65 g, 51%) (Found: C, 70.8; H, 9.9; N, 6.0. C14H23NO2
Literature method.10 A solution of crushed paraformaldehyde (0.05
mo1, 1 equiv.) and dipropylamine (0.1 mol, 2 equiv.) was stirred for 1
h. Catechol (0.05 mol, 1 equiv.) was added and stirred for a further 72
h. Workup of the reaction followed by column chromatography (ethyl
acetate) afforded (11) as pale yellow needlelike crystals (1.92 g, 17%).
The spectroscopic data were consistent with those from the two-step
method.
requires C, 70.9; H, 9.8; N, 5.9%). I.r. ␯ (KBr) 2962; 2935, 2874,
max
1
2830 1468, 1415, 1249, 1082 cm–1. H n.m.r. ␦ 0.88, t, J 7.4 Hz,
NCH2CH2CH3; 1.56, m, NCH2CH2CH3; 2.47, m, NCH2CH2CH3; 3.75,
s, CH2N; 3.86, s, OCH3; 6.57, dd, J 7.5, 1.1 Hz, ArH; 6.71, appr. t, J 7.7
Hz,ArH; 6.79, dd, J 8.0, 1.3 Hz,ArH. 13C n.m.r. ␦ 11.8; 19.4; 55.4; 55.8;
55.1; 110.6; 118.3; 120.3; 122.3; 147.5; 147.9. Mass spectrum (e.i.) m/z
237 (11%), 208 (45), 137 (100), 122 (7), 107 (7), 72 (75) (Found: M+ ,
237.17343. C14H23NO2 requires M+ , 237.17288).
3-(Dimethylaminomethyl)benzene-1,2-diol (12)
2-(Dibutylaminomethyl)-6-methoxyphenol (17)
Column chromatography (ethyl acetate) afforded (12) as pale orange
needlelike crystals (2.98 g, 35%), m.p. 67–69°C (Found: C, 64.7; H,
7.9; N, 8.4. C9H13NO2 requires C, 64.7; H, 7.8; N, 8.4%). I.r. ␯max (KBr)
3401, 1473, 1455, 1256, 1201, 1179 cm–1. 1H n.m.r. (CD3OD) ␦ 2.31, s,
NCH3; 3.62, s, CH2N; 6.52, dd, J 7.5, 1.4 Hz, ArH; 6.60, appr. t, J 7.7
Hz, ArH; 6.70; dd, J 7.9, 1.5 Hz, ArH. 13C n.m.r. (CD3OD) ␦ 44.8; 62.8;
115.8; 120.1; 121.0; 123.9; 146.4; 146.9. Mass spectrum (e.i.) m/z 167
(100%), 122 (41), 58 (4), 46 (4).
The reaction mixture was heated at 70°C for 72 h. Workup gave the
crude product as a sticky pale orange residue. The residue was dissolved
in a mixture of chloroform and ethyl acetate (1:1) and the solution was
filtered to remove any insoluble residues. The organic filtrate was con-
centrated under reduced pressure. Column chromatography (chloro-
form) afforded (17) as a dark orange oil (2.10 g, 16%) (Found: C, 72.4;
H, 10.2; N, 5.3. C16H27NO2 requires C, 72.4; H, 10.3; N, 5.3%). I.r. ␯
max
(KBr) 2957, 2932, 1588, 1465, 1249, 1081 cm–1. 1H n.m.r. ␦ 0.88, t, J
7.2 Hz, NCH2CH2CH2CH3; 1.30, m, NCH2CH2CH2CH3; 1.52, m,
NCH2CH2CH2CH3; 2.50, m, NCH2CH2CH2CH3; 3.75, s, CH2N; 3.86,
s, OCH3; 6.57, appr. d, J 7.5 Hz, ArH; 6.71, appr. t, J 7.8 Hz, ArH; 6.79,
appr. d, J 8.1 Hz, ArH. 13C n.m.r. ␦ 13.9; 20.5; 28.3; 53.12; 6.76; 58.0;
110.6; 118.3; 120.3; 122.2; 147.5; 147.8. Mass spectrum (e.i.) m/z 265
(6%), 222 (38), 137 (80), 122 (4), 107 (10), 86 (100), 65 (33) (Found:
M+ , 265.20350. C16H27NO2 requires M+ , 265.20418).
3-(Dibutylaminomethyl)benzene-1,2-diol (13)
The reaction mixture was heated to 70°C and stirred for 72 h.
Column chromatography (acetone) afforded (13) as a yellow oil (3.05
g, 24%) (Found: C, 71.6; H, 10.1; N, 5.5. C15H25NO2 requires C, 71.7;
H, 10.0; N, 5.6%). I.r. ␯max (KBr) 2958, 2933, 2872, 1471, 1364, 1286,
1256, 1189 cm–1. 1H n.m.r. ␦ 0.91, J 7.4 Hz, NCH2CH2CH2CH3; 1.30,
m, NCH2CH2CH2CH3; 1.52, m, NCH2CH2CH2CH3; 2.52, m,
NCH2CH2CH2CH3; 3.76, s, CH2N; 6.51, appr. d, J 7.5 Hz, ArH; 6.67,
appr. t, J 7.7 Hz, ArH; 6.83, appr. d, J 8.1 Hz, ArH. 13C n.m.r. ␦ 13.8;
20.4; 28.2; 53.0; 57.7; 113.4; 118.8; 119.1; 121.7; 144.5; 145.0. Mass
spectrum (e.i) m/z 252 (100%), 208 (46), 123 (26) (Found: M+ ,
251.18919. C15H25NO2 requires M+ , 251.18853).
Acknowledgments
The authors would like to thank Comalco Aluminium
Limited and the Australian Research Council for financial
assistance.

Synthesis of Dibenzene-1,2-diol Mannich Bases
549
6
7
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