Simple one-pot synthesis of new derivatives of the macrocyclic aminal 1,3,7,9,13,15,19,21-octaazapentacyclo-[19.3.1.13,7.1 9,13.115,19]octacosane (OAPO)

Article abstract of DOI:10.1080/00397911.2011.609956

A series of 2,2-(dihydropyrimidine-1,3(2H,4H)-diyldimethanediyl) bis(substituted-phenols) was synthesized using a Mannich-type reaction between the macrocyclic aminal 1,3,7,9,13,15,19,21-octaazapentacyclo[19.3.1.1 ^3,7.1^9,13.1^15,19]octacosane (OAPO) (1) and substituted phenols in basic media. These previously unreported compounds were separated from the reaction mixture by column chromatography in highly pure form with 25-75% yields. The most stable conformer was predicted using AM1-type semiempirical quantum chemical calculations.

Full text of DOI:10.1080/00397911.2011.609956

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Simple One-Pot Synthesis of New
Derivatives of the Macrocyclic Aminal
1,3,7,9,13,15,19,21-Octaazapentacyclo-
[19.3.1.13,7.19,13.115,19]octacosane
(OAPO)
Augusto Rivera a , Jaime Ríos-Motta a , Ginna Paola Trujillo a , Derly
Marcela González a & Daniel Alcázar a
a Departamento de Química, Universidad Nacional de Colombia,
Ciudad Universitaria, Bogotá, Colombia
Accepted author version posted online: 21 Feb 2012.Version of
record first published: 21 Dec 2012.
To cite this article: Augusto Rivera , Jaime Ríos-Motta , Ginna Paola Trujillo , Derly Marcela González
& Daniel Alcázar (2013): Simple One-Pot Synthesis of New Derivatives of the Macrocyclic Aminal
1,3,7,9,13,15,19,21-Octaazapentacyclo-[19.3.1.13,7.19,13.115,19]octacosane (OAPO), Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
43:6, 791-799
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Synthetic Communications1, 43: 791–799, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.609956
SIMPLE ONE-POT SYNTHESIS OF NEW DERIVATIVES
OF THE MACROCYCLIC AMINAL 1,3,7,9,13,15,19,21-
OCTAAZAPENTACYCLO-[19.3.1.13,7.19,13.115,19
OCTACOSANE (OAPO)
]
´
Augusto Rivera, Jaime Rıos-Motta, Ginna Paola Trujillo,
Derly Marcela Gonzalez, and Daniel Alcazar
´
´
´
Departamento de Quımica, Universidad Nacional de Colombia,
Ciudad Universitaria, Bogota, Colombia
´
GRAPHICAL ABSTRACT
Abstract A series of 2,20-(dihydropyrimidine-1,3(2H,4H)-diyldimethanediyl)bis(substituted-
phenols) was synthesized using a Mannich-type reaction between the macrocyclic aminal
1,3,7,9,13,15,19,21-octaazapentacyclo[19.3.1.13,7.19,13.115,19]octacosane (OAPO) (1) and
substitutedphenolsinbasicmedia. Thesepreviouslyunreportedcompoundswereseparatedfrom
the reaction mixture by column chromatography in highly pure form with 25–75% yields.
The most stable conformer was predicted using AM1-type semiempirical quantum chemical
calculations.
Keywords Anomeric effect; hexahydropyrimidine; Mannich bases; ortho-regioselectivity
INTRODUCTION
The chemistry of 1,3-diazacyclohexanes has attracted considerable interest in
recent years because appropriately functionalized compounds of this ring system
either serve as crucial synthetic precursors or are themselves important members
of this class of heterocycles.[1] The condensation of 1,3-diamines with aldehydes is
the most commonly used method for synthesizing this cyclic aminal.[2,3] In the recent
past, Katritzky’s group has reported a convenient method for the preparation of
Received June 29, 2011.
Address correspondence to Augusto Rivera, Departamento de Quımica, Universidad Nacional de
´
´
Colombia, Ciudad Universitaria, Carrera 30 # 45-03, Bogota, D.C., Colombia. E-mail: ariverau@
unal.edu.co
791

792
A. RIVERA ET AL.
N-monosubstituted hexahydropyrimidines using benzotriazole methodology.[4]
More recently, a multicomponent Mannich reaction for the synthesis of N,N0-
disubstituted-1,3-diazacyclohexanes has been described.[5] In addition, it is
known[6,7] that 1,3-propanediamine reacts easily with formaldehyde in aqueous
medium to produce the macrocyclic polyaminal 1,3,7,9,13,15,19,21-octaazapentacy-
clo[19.3.1.13,7.19,13.115,19]octacosane (OAPO, 1), which contains four aminal methyl-
ene groups linking four 1,3-diazacyclohexane units. On the other hand, during the
course of our work on the reactivity of cyclic aminals, we have already reported
the use of these compounds as preformed Mannich electrophiles in basic media.
For example, 1,3,6,8-tetraazatricyclo[4.4.1.13,8]dodecane (TATD, 2) reacts with phe-
nolic compounds in basic media, producing the aromatic Mannich-type bases
2,20-(imidazolidine-1,3-diyldimethanediyl)bis(substituted-phenol) (3).[8–11] In a fur-
ther extension of this methodology, we anticipated that these conditions would be
compatible with a one-pot synthesis of N,N0-disubstituted-hexahydropyrimidine
derivatives using 1,3,7,9,13,15,19,21-octaazapentacyclo[19.3.1.13,7.19,13.115,19]octaco-
sane (OAPO, 1) as the aminomethylating reagent for phenols. Moreover,
N,N0-disubstituted-hexahydropyrimidines are interesting compounds because the
ring system contains one N-C-N moiety, which is a particularly challenging group
known to exhibit peculiar stereoelectronic effects. For example, it has been shown
that the conformations of six-membered 1,3-diazacycles are governed by the general-
ized anomeric effect.[12] The synthesis of the hexahydropyrimidine derivatives 5a–l
provide not only a novel example of aminals usefully employed in Mannich reaction
but also an expansion of the scope of the use of cyclic aminals as preformed electro-
philes in Mannich condensations in basic media. This Mannich condensation offers
simple and efficient access to this family of compounds in a one-pot reaction.
RESULTS AND DISCUSSION
We found that reactions of OAPO (1) with substituted phenols (4a–l) (OAPO–
phenol molar ratio of 1:4) give moderate to good yields of new derivatives of the
saturated heterocyclic hexahydropyrimidine system, namely 2,20-(dihydropyrimi-
dine-1,3(2H,4H)-diyldimethanediyl)bis(substituted-phenol) (5a–l) (Scheme 1). The
experiments were conducted with heating at reflux in 96% ethanol for a time period
between 10 and 72 h as specified for each compound in Table 1. Optimization of
reaction time was made for each phenol. Reaction times and yields obtained are

NEW DERIVATIVES OF OAPO
793
Scheme 1. Reaction between OAPO and phenols 4a–l. (Figure is provided in color online.)
recorded in Table 1. The process was regioselective: The aminomethylation occurred
only at the ortho position to the phenolic hydroxyl group. The reactions are clean
and good yielding, and the products could be easily isolated by simple purification
by column chromatography. This one-step reaction was not affected by electronic
effects of the substituents on the phenyl ring.
The structures of the compounds 5a–l were established through rigorous spec-
troscopic analysis. The infrared (IR) spectra of 5a–l presented the characteristic
bands of the Mannich bases; the presence of intramolecular hydrogen bonds between
the phenolic hydroxyl groups and nitrogen atoms is evident. It is important to note
that broad bands with maximums at approximately 3150 cmꢀ1, which were attribu-
ted to n(O-H), appeared with strong intensity compared with the signals of 3, in
which an IR continuum was shown. These differences suggest a decrease in
Table 1. 2,20-(Dihydropyrimidine-1,3(2H,4H)-diyldimethanediyl)bis(substituted-
phenols) (5a–l) produced via Scheme 1
Phenol
Product
Time (h)
Mp (ꢁC)
Yield (%)
4a
4b
4c
4d
4e
4f
5a
5b
5c
5d
5e
5f
48
36
12
36
72
14
36
20
10
15
60
24
100–102
114–115
188–190
85–86
38.2
59.5
35.7
26.0
31.3
31.1
26.0
24.4
25.6
37.1
27.0
75.5
121–122
160–161
95–96
4g
4h
4i
5g
5h
5i
116–119
177–179
204–206
130–132
142–144
4j
5j
4k
4l
5k
5l

794
A. RIVERA ET AL.
hydrogen-bonding strength in 5a–l, which would be due to the change in the molecu-
lar geometry and different nitrogen lone pair orientation in the hexahydropyrimidine
ring.
1
The H NMR spectra (400 MHz, CDCl3, 30 ꢁC) of the Mannich bases 5a–l
showed the aromatic protons as an ABX spin system and the hexahydropyrimidine
ring protons as a single and two multiplets centered at 3.4, 2.7, and 1.8 ppm, respect-
ively, generated through the interconversion of axial and equatorial hydrogen atoms.
1H NMR spectra at low temperatures for 5d showed line broadening for almost all of
the signals in the aliphatic regions, which indicated that at low temperatures, confor-
mational isomerism is relatively slow on the NMR time scale, leading to broadened
signals. However, variable-temperature studies indicated that the methylene protons
at positions 4, 5, and 6 resonated at very similar chemical shifts and were not
resolved at 400 MHz. In addition, the benzylic protons appeared at approximately
3.8 ppm. Interestingly, the resonance of these protons appeared at a higher field com-
pared with the corresponding benzylic protons in the closely related Mannich bases
(d ¼ 4.0 ppm). These high-field shifts are attributed to the influence of the C-C
anisotropy of the additional methylene (C-5).
For all hexahydropyrimidines 5a–l obtained, the conformational analysis was
performed using the AM1 model, one of the best semiempirical methods suitable for
heteroatom-containing systems, and predicted three types of conformers differing in
the orientation of the N substituents: axial-equatorial, diequatorial, and diaxial
forms (Scheme 2). Because 1,3-diazacyclohexanes, which have no substituents on
C2, possess mainly conformers with diequatorial N substitution, AM1-optimized
geometries in the gas phase indicated that III is the most stable conformer for 5a,
although the energy difference between the syn(III) and anti(II) conformations is
1.92 kCal=mol. This energy difference between the syn conformer and the anti
conformer is consistent with the preferential axial N-alkylation of hexahydropyrimi-
dine.[13] However, it is well known that in these heterocyclic systems, nitrogen inver-
sion is a much faster process than ring inversion;[7] thus, the interconversion between
conformers is very fast. On the other hand, the N–C–N structure is particularly chal-
lenging because the problems presented by the aminalic nitrogen atoms are probably
enhanced by an anomeric effect analogous to that detected in the case of the O–C–O
structure.[14] The AM1 results agree well with the experimental NMR data, especially
with the 13C NMR data.
In conclusion, we have developed a novel method for the synthesis of N,N0-
disubstituted-hexahydropyrimidine derivatives via one-pot Mannich type reaction.
The easy workup procedure, the accessibility of the starting materials, the
Scheme 2. Possible conformers for N,N0-disubstituted hexahydropyrimidines. (Figure is provided in color
online.)

NEW DERIVATIVES OF OAPO
795
operational simplicity of this methodology, and good yields make this method a valid
contribution to the existing methodologies for the synthesis of such heterocycles.
EXPERIMENTAL
OAPO was prepared according Ref. 6. Chemicals were used without further
purification, and IR spectra were recorded on a Perkin-Elmer Fourier transform
1
FT–IR Paragon spectrometer with a KBr disk. H and 13CNMR spectra were mea-
sured on a Bruker Advance 400-MHz spectrometer in CDCl3 operating at 400 and
100 MHz, respectively. Elemental analyses (C, H, N) were determined in a Carlo-
Erba model 1106 analyzer. Melting points (uncorrected) were determined on an
Electrothermal 9100 melting-point apparatus. Thin-layer chromatography (TLC)
was performed with Merck 60 F254 coated silica-gel plates with visualization by
iodine vapor.
General Procedure for the Synthesis of 2,2’(Dihydropyrimidine-
1,3(2H,4H)-diyldimethanediyl)bis(substituted-phenols) (5a–l)
Compounds 5a–l were prepared by the reaction of OAPO with the correspond-
ing phenol as follows:
A solution of OAPO (1) (0.5 mmol) in 96% ethanol (5 mL) was added slowly to
a stirred solution of the appropriate phenol (4a–l) (2.0 mmol) in 96% ethanol (5 mL)
heated under reflux. Upon completion of the addition, the reaction mixture was stir-
red under reflux for the time indicated in Table 1. Then the reflux was stopped, the
solvent was removed on a rotary evaporator under vacuum, and the residue obtained
was chromatographed on silica gel eluting with benzene=AcOEt (gradient elution
with 5% to 20% AcOEt) to afford the respective compound 5a–l.
2,2’-(Dihydropyrimidine-1,3(2H,4H)-diyldimethanediyl)diphenol (5a)
1
White solid, mp 100–102 ꢁC, yield 38.2%; H NMR (CDCl3, 400 MHz): d 3.68
(s, 4H, Ar-CH2-N), 3.42 (s, 2H, N-CH2-N), 2.75 (t, 4H, CH2-40 and CH2-60), 1.82 (m,
2H, CH2-50), 7.16 (t, 2H, ABCD system, J ¼ 7.49 Hz, J ¼ 7.58 Hz, H-5), 6.98 (d, 2H,
ABCD system, J ¼ 7.22 Hz, H-3), 6.83 (d, 2H, ABCD system, J ¼ 8.02 Hz, H-6), 6.77
(t, 2H, ABCD system, J ¼ 7.31 Hz, J ¼ 7.32 Hz, H-4); 13C NMR (CDCl3, 100 MHz):
d 158.1 (C1), 129.5 (C5), 129.3 (C3), 121.0 (C2), 119.7 (C4), 116.7 (C6), 73.5 (N-CH2-
N), 58.0 (CH2-Ar), 51.5 (C40 and C60), 21.9 (C50). Elem. anal. calcd. for C18H22N2O2:
C, 72.46%; H, 7.43%; N, 9.39%. Found: C, 72.37%; H, 7.41%; N, 9.35%.
2,2’-(Dihydropyrimidine-1,3(2H,4H)-diyldimethanediyl)bis(4-
methylphenol) (5b)
1
White solid, mp 114–115 ꢁC, yield 59.5%; H NMR (CDCl3, 400 MHz): d 3.73
(s, 4H, Ar-CH2-N), 3.42 (s, 2H, N-CH2-N), 2.71 (t, 4H, CH2-40 and CH2-60), 2.22 (s,
6H, CH3), 1.77 (m, 2H, CH2-50), 6.85 (dd, 2H, ABX system, J ¼ 2.58 Hz, J ¼ 8.62 Hz,
H-5), 6.78 (d, 2H, ABX system, J ¼ 2.64 Hz, H-3), 6.72 (d, 2H, ABX system,
J ¼ 8.59 Hz, H-6); 13C NMR (CDCl3, 100 MHz): d 155.3 (C1), 129.4 (C3 and C5),

796
A. RIVERA ET AL.
128.3(C4), 120.3 (C2), 115.9 (C6), 73.1 (N-CH2-N), 57.6 (CH2-Ar), 51.1 (C40 and
C60), 21.4 (C50), 20.4 (Ar-CH3). Elem. anal. calcd. for C20H26N2O2: C, 73.59%; H,
8.03%; N, 8.58%. Found: C, 73.58%; H, 7.99%; N, 8.57%.
2,2’-(Dihydropyrimidine-1,3(2H,4H)-diyldimethanediyl)bis(4-tert-
butylphenol) (5c)
White solid, mp 188–190 ꢁC yield 35.7%; 1H NMR (CDCl3, 400 MHz): d ¼ 3.79
(s, 4H, Ar-CH2-N), 3.48 (s, 2H, N-CH2-N), 2.73 (t, 4H, CH2-40 and CH2-60), 1.78 (m,
2H, CH2-50), 1.26 (s, 18H, t-But), 7.18 (dd, 2H, ABX system, J ¼ 2.2 Hz, J ¼ 8.4 Hz,
H-5), 6.97 (d, 2H, ABX system, J ¼ 1.9 Hz, H-3), 6.77 (d, 2H, ABX system, J ¼ 8.4 Hz,
Hz, H-6); 13C NMR (CDCl3, 100 MHz): d 154.9 (C1), 141.7 (C3), 125.3 (C5), 125.2
(C4), 119.5 (C2), 115.3 (C6), 73.1 (N-CH2-N), 57.7 (CH2-Ar), 50.7 (C40 and C60),
33.8 [C(Me)3], 31.2 [C(CH3)3], 21.0 (C50). Elem. anal. calcd. for C26H38N2O2: C,
76.06%; H, 9.33%; N, 6.82%. Found: C, 76.01%; H, 9.29%; N, 6.77%.
2,2’-(Dihydropyrimidine-1,3(2H,4H)-diyldimethanediyl)bis(4-
fluorophenol) (5d)
White solid, mp 85–86 ꢁC yield 26.0%; 1H NMR (CDCl3, 400 MHz): d 3.74 (s,
4H, Ar-CH2-N), 3.39 (s, 2H, N-CH2-N), 2.74 (t, 4H, CH2-40 and CH2-60), 1.81 (m,
2H, CH2-50), 6.85 (td, 2H, ABX system, J ¼ 8.5 Hz, J ¼ 3.0 Hz, H-5), 6.76 (dd, 2H,
ABX system, J ¼ 8.8 Hz, J ¼ 4.8 Hz, H-6), 6.71 (dd, 2H, ABX system, J ¼ 8.6 Hz,
J ¼ 2.9 Hz, H-3); 13C NMR (CDCl3, 100 MHz): d 156.1 (C4), (d, J ¼ 236.8 Hz),
153.5 (C1) (d, J ¼ 2.1 Hz), 121.3 (C6), (d, J ¼ 7.0 Hz), 117.0 (C3), (d, J ¼ 7.9 Hz),
115.4 (C5), (d, J ¼ 1.7 Hz), 115.1 (C2), (d, J ¼ 2.6 Hz), 72.7 (N-CH2-N), 57.3 (CH2-
Ar), 51.2 (C40 and C60), 21.6 (C50). Elem. anal. calcd. for C18H20F2N2O2: C,
64.66%; H, 6.03%; N, 8.38%. Found: C, 64.63%; H, 6.01%; N, 8.32%.
2,2’-(Dihydropyrimidine-1,3(2H,4H)-
diyldimethanediyl)bis(4-chlorophenol) (5e)
1
White solid, mp 121–122 ꢁC, yield 31.3%; H NMR (CDCl3, 400 MHz): d 3.75
(s, 4H, Ar-CH2-N), 3.37 (s, 2H, N-CH2-N), 2.73 (t, 4H, CH2-40 and CH2-60), 1.81 (m,
2H, CH2-50), 7.10 (dd, 2H, ABX system, J ¼ 2.58 Hz, J ¼ 8.62 Hz, H-5), 6.95 (d, 2H,
ABX system, J ¼ 2.64 Hz, H-3), 6.76 (d, 2H, ABX system, J ¼ 8.59 Hz, H-6); 13C
NMR (CDCl3, 100 MHz): d 156.1 (C1), 128.9 (C3), 128.5 (C5), 123.9 (C4), 121.9
(C2), 116.7 (C6), 72.6 (N-CH2-N), 57.2 (CH2-Ar), 52.2 (C-40 and C-60), 21.7 (C50).
Elem. anal. calcd. for C18H20Cl2N2O2: C, 58.86%; H, 5.49%; N, 7.63%. Found: C,
58.83%; H, 5.44%; N, 7.62%.
2,2’-(Dihydropyrimidine-1,3(2H,4H)-diyldimethanediyl)bis(4-
bromophenol) (5f)
Yellow solid, mp 160–161 ꢁC yield 31.1%; 1H NMR (CDCl3, 400 MHz)
d ¼ 3.73 (s, 4H, Ar-CH2-N), 3.37 (s, 2H, N-CH2-N), 2.73 (t, 4H, CH2-40 and
CH2-60), 1.80 (m, 2H, CH2-50), 7.24 (dd, 2H, ABX system, J ¼ 2.40 Hz, J ¼ 8.80 Hz,

NEW DERIVATIVES OF OAPO
797
Hz, H-5), 7.08 (d, 2H, ABX system, J ¼ 2.40 Hz, H-3), 6.72 (d, 2H, ABX system,
J ¼ 8.40 Hz, H-6); 13C NMR (CDCl3, 100 MHz): d 156.9 (C1), 131.0 (C3), 130.5
(C5), 121.5 (C4), 117.3 (C2), 110.2 (C6), 71.8 (N-CH2-N), 56.2 (CH2-Ar), 50.4
(C40 and C60), 20.8 (C50). Elem. anal. calcd. for C18H20Br2N2O2: C, 47.39%; H,
4.42%; N, 6.14%. Found: C, 47.36%; H, 4.39%; N, 6.12%.
2,2’-(Dihydropyrimidine-1,3(2H,4H)-diyldimethanediyl)bis(4-
iodophenol) (5g)
Yellow solid, mp 95–96 ꢁC yield 26.0%; 1H NMR (CDCl3, 400 MHz): d 3.74 (s,
4H, Ar-CH2-N), 3.59 (s, 2H, N-CH2-N), 2.74 (t, 4H, CH2-40 and CH2-60), 1.82 (m,
2H, CH2-50), 7.47 (dd, 2H, ABX system, J ¼ 8.4 Hz, J ¼ 2.4 Hz, H-5), 7.43 (d, 2H,
ABX system, J ¼ 2.4 Hz, H-3), 6.63 (d, 2H, ABX system, J ¼ 8.4 Hz, H-6); 13C
NMR (CDCl3, 100 MHz): d 157.1 (C1), 137.4 (C5), 130.1 (C3), 122.9 (C2), 118.7
(C6), 81.2 (C4), 72.6 (N-CH2-N), 56.9 (CH2-Ar), 51.1 (C40 and C60), 26.7 (C50).
Elem. anal. calcd. for C18H20I2N2O2: C, 39.29%; H, 3.66%; N, 5.09%. Found: C,
39.22%; H, 3.62%; N, 5.08%.
2,2’-(Dihydropyrimidine-1,3(2H,4H)-diyldimethanediyl)bis(2-
methylphenol) (5h)
1
White solid, mp 116–119 ꢁC yield 24.4%; H NMR (CDCl3, 400 MHz): d 3.76
(s, 4H, Ar-CH2-N), 3.42 (s, 2H, N-CH2-N), 2.71 (t, 4H, CH2-40 and CH2-60), 2.23 (s,
6H, Ar-CH3), 1.79 (m, 2H, CH2-50), 7.03 (d, 2H, ABC system, J ¼ 8.0 Hz H-5), 6.84
(d, 2H, ABC system, J ¼ 8.0 Hz, H-3), 6.68 (t, 2H, ABC system, J ¼ 8.0 Hz,
J ¼ 8.0 Hz, H-4);13C NMR (CDCl3, 100 MHz): d 155.8 (C1), 130.2 (C5), 126.4
(C3), 125.1 (C2), 119.9 (C6), 118.8 (C4), 73.1 (N-CH2-N), 57.7 (CH2-Ar), 51.1
(C40 and C60), 21.6 (C50), 15.7 (CH3). Elem. anal. calcd. for C20H26N2O2: C,
73.59%; H, 8.03%; N, 8.58%. Found: C, 73.58%; H, 7.99%; N, 8.57%.
2,2’-(Dihydropyrimidine-1,3(2H,4H)-diyldimethanediyl)bis(4-
chloro-3-methylphenol) (5i)
1
White solid, mp 177–179 ꢁC, yield 25.6%; H NMR (CDCl3, 400 MHz): d 3.70
(s, 4H, Ar-CH2-N), 3.37 (s, 2H, N-CH2-N), 2.72 (s, 4H, CH2-40 and CH2-60), 2.27 (s,
6H Ar-CH3), 1.79 (t, 2H, CH2-50), 6.94 (s, 2H, H-3), 6.71 (s, 2H, H-6); 13C NMR
(CDCl3, 100 MHz): d 156.0 (C1), 136.6 (C3), 128.8 (C5), 124.1 (C4), 119.5 (C2),
118.7 (C6), 72.7 (N-CH2-N), 56.9 (CH2-Ar), 51.2 (C40 and C60), 21.7 (C50), 19.8
(CH3). Elem. anal. calcd. for C20H24Cl2N2O2: C, 60.76%; H, 6.12%; N, 7.09%.
Found: C, 60.71%; H, 6.09%; N, 7.03%.
2,2’-(Dihydropyrimidine-1,3(2H,4H)-diyldimethanediyl)bis(4-chloro-
3,5-dimethylphenol) (5j)
White solid with irregular form, mp 204–206 ꢁC yield 37.1%; 1H NMR (CDCl3,
400 MHz): d 3.81 (s, 4H, Ar-CH2-N), 3.43 (s, 2H, N-CH2-N), 2.69 (t, 4H, CH2-40 and
CH2-60), 2.31 (s, 6H, CH3-C3 or CH3-C5), 2.30 (s, 6H, CH3-C3 or CH3-C5), 1.78 (m,

798
A. RIVERA ET AL.
2H, CH2-50), 6.62 (s, 2H, H-6); 13CNMR (CDCl3, 100 MHz): d 156.2 (C1), 136.6
(C3), 134.0 (C5), 125.3 (C4), 116.5 (C2), 73.2 (N-CH2-N), 54.0 (C40 and C60), 50.9
(CH2-Ar), 21.0 (C50), 16.6 (CH3). Elem. anal. calcd. for C22H28Cl2N2O2: C,
62.41%; H, 6.67%; N, 6.62%. Found: C, 62.36%; H, 6.65%; N, 6.59%.
2,2’-(Dihydropyrimidine-1,3(2H,4H)-diyldimethanediyl)bis(2-tert-
butyl-4-methoxy-phenol) (5k)
1
White solid, mp 130–132 ꢁC, yield 27.0%; H NMR (CDCl3, 400 MHz): d 3.77
(s, 10H, Ar-CH2-N and OCH3), 3.49 (s, 2H, N-CH2-N), 2.74 (s, 4H, CH2-40 and
CH2-60), 1.80 (s, 2H, CH2-50), 1.43 [s, 18H, C(CH3)3], 6.83 (d, 2H, AB system,
J ¼ 3.5 Hz, H-3), 6.47 (d, 2H, AB system, J ¼ 3.4 Hz, H-5); 13CNMR (CDCl3,
100 MHz): d 151.7 (C4), 150.5 (C1), 138.0 (C6), 121.3 (C2), 112.9 (C5), 111.3 (C3),
73.4 (N-CH2-N), 58.0 (OCH3), 55.7 (CH2-Ar), 50.6 (C40 and C60), 34.8 [Ar-C-
(CH3)3], 29.4 [(CH3)3], 21.1 (C50). Elem. anal. calcd. for C28H42N2O4: C, 71.46%;
H, 8.99%; N, 5.95%. Found: C, 71.41%; H, 8.93%; N, 5.91%.
2,2’-(Dihydropyrimidine-1,3(2H,4H)-diyldimethanediyl)bis(2-
naphthol) (5l)
1
White solid, mp 142–144 ꢁC, yield 75.5%; H NMR (CDCl3, 400 MHz): d 4.25
(s, 2H, ArCH2-N), 3.62 (s, 2H, N-CH2-N), 2.78 (t, 4H, CH2-40 and CH2-60), 1.84 (m,
2H, CH2-50), 7.92 (d, 2H, ABCD system, J ¼ 8.58 Hz, H-3), 7.76 (d, 2H, ABCD sys-
tem, J ¼ 8.08 Hz, H-6), 7.69 (d, 2H, AB system, J ¼ 8.85 Hz, H-7), 7.43 (t, 2H,
ABCD system, J ¼ 7.77 Hz, J ¼ 7.83 Hz, H-4), 7.26 (t, 2H, ABCD system,
J ¼ 7.04 Hz, J ¼ 7.85 Hz, H-5), 7.04 (d, 2H, AB system J ¼ 8.86 Hz, H-8); 13CNMR
(CDCl3, 100 MHz): d 157.2 (C1), 134.0 (C9 and C10), 130.0 (C7), 129.5 (C6), 127.0
(C4), 123.2 (C5), 122.2 (C3), 119.9 (C8), 112.0 (C2), 75.0 (N-CH2-N), 53.0 (CH2-Ar),
52.0 (C40 and C60), 23.5 (C50). Elem. anal. calcd. for C28H42N2O4: C, 78.36%; H,
6.58%; N, 7.03%. Found: C, 78.34%; H, 6.53%; N, 7.01%.
ACKNOWLEDGMENTS
´
We acknowledge the Direccion de Investigaciones Sede Bogota (DIB) of
Universidad Nacional de Colombia for financial support, and D. M. G. acknowl-
´
´
edges the Vicerrectorıa Academica de la Universidad Nacional de Colombia for a
´
fellowship.
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