Synthesis of (hetaryl)alkylamines from the reactions of 2-aminopyrimidine, 2-aminothiazole, and 2-aminothiazoline with benzyl bromide and xylylene dibromides

Article abstract of DOI:10.1080/00397910701771074

Alkylation reactions of 2-aminopyrimidine, 2-aminothiazole, 2-aminothiazoline, and their Cbz-protected derivatives are described. Reactions with benzyl bromide proceed to give monoalkylated products with 2-aminopyrimidine and 2-aminothiazole, but 2-aminot

Full text of DOI:10.1080/00397910701771074

This article was downloaded by: [Ondokuz Mayis Universitesine]
On: 13 November 2014, At: 20:43
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
Synthesis of (Hetaryl)alkylamines from
the Reactions of 2‐Aminopyrimidine,
2‐Aminothiazole, and 2‐Aminothiazoline with
Benzyl Bromide and Xylylene Dibromides
Sudershan R. Gondi a & David Y. Son a
a Department of Chemistry , Southern Methodist University , Dallas, Texas,
USA
Published online: 28 Jan 2008.
To cite this article: Sudershan R. Gondi & David Y. Son (2008) Synthesis of (Hetaryl)alkylamines from the
Reactions of 2‐Aminopyrimidine, 2‐Aminothiazole, and 2‐Aminothiazoline with Benzyl Bromide and Xylylene
Dibromides, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 38:3, 401-410, DOI: 10.1080/00397910701771074
To link to this article: http://dx.doi.org/10.1080/00397910701771074
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”)
contained in the publications on our platform. However, Taylor & Francis, our agents, and our
licensors make no representations or warranties whatsoever as to the accuracy, completeness, or
suitability for any purpose of the Content. Any opinions and views expressed in this publication
are the opinions and views of the authors, and are not the views of or endorsed by Taylor &
Francis. The accuracy of the Content should not be relied upon and should be independently
verified with primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities
whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

Synthetic Communicationsw, 38: 401–410, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701771074
Synthesis of (Hetaryl)alkylamines from the
Reactions of 2-Aminopyrimidine,
2-Aminothiazole, and 2-Aminothiazoline
with Benzyl Bromide and Xylylene
Dibromides
Sudershan R. Gondi and David Y. Son
Department of Chemistry, Southern Methodist University, Dallas,
Texas, USA
Abstract: Alkylation reactions of 2-aminopyrimidine, 2-aminothiazole, 2-aminothia-
zoline, and their Cbz-protected derivatives are described. Reactions with benzyl
bromide proceed to give monoalkylated products with 2-aminopyrimidine and
2-aminothiazole, but 2-aminothiazoline gives a dialkylated product. Reactions with
xylylene dibromides are complicated by the tendency to form intramolecularly
cyclized products with the ortho-dibromide and insoluble products with the meta-
and para-dibromides.
Keywords: amine, heteroaromatic, pyrimidine, thiazole, thiazoline
INTRODUCTION
Pyridylamines have been widely applied for the synthesis of medicinal
agents[1–3] and supramolecular complexes and assemblies.[4–7] By compari-
son, amine derivatives of pyrimidine, thiazole, and thiazoline have received
little attention, perhaps because of the lack of convenient general synthetic
procedures. As part of an ongoing investigation concerning the synthesis of
polydentate ligand scaffolds,[8–10] we describe herein the synthesis and
Received in the USA July 17, 2007
Address correspondence to David Y. Son, Department of Chemistry, Southern
Methodist University, Dallas, Texas 75275-0314, USA. E-mail: dson@smu.edu
401

402
S. R. Gondi and D. Y. Son
characterization of various pyrimidyl-, thiazolyl-, and thiazolinyl-alkylamines
derived from 2-aminopyrimidine, 2-aminothiazole, and 2-aminothiazoline.
RESULTS AND DISCUSSION
In general, the degree of alkylation in amines is difficult to control because of
their tendency to form a variety of polyalkylated products. However, after
experimenting with various organic and inorganic bases, we found that
reaction of benzyl bromide with excess 2-aminopyrimidine and sodium
hydride gave the monoalkylated product 1 in 79% yield [Eq. (1)]:
Applying these conditions to the reaction of benzyl bromide with 2-aminothia-
zole gave the corresponding monoalkylated product 2 in 76% yield.
Applying the same conditions to the reaction of benzyl bromide with
.
2-aminothiazoline HCl salt gave the interesting doubly alkylated product
3 in 65% yield, undoubtedly formed via the reaction sequence shown in
Eq. (2):
With this general procedure in hand, the syntheses of polyfunctional deriva-
tives were attempted. Thus, the reaction of o-xylylene dibromide with 2-ami-
nopyrimidine was attempted with the goal of synthesizing compound 4.
However, the product obtained was 5, resulting from intramolecular
cyclization of the initially formed monosubstituted compound (Scheme 1).
The corresponding cyclized thiazole derivative 6 was formed in 81% yield,
whereas the thiazoline derivative 7 was obtained in only 3.1% yield. The
structures of 5 and 6 were confirmed by single-crystal X-ray crystallographic
analysis.
In another attempt to prepare 4, the amine group of 2-aminopyrimidine
was first protected with the benzyloxycarbonyl (Cbz) group (8), and then
reacted with o-xylylene dibromide in the presence of sodium hydride. After
workup, the bis-substituted compound was not formed, but instead
compound 5 was isolated in 52% yield (Scheme 2). Cbz-protected

Synthesis of (Hetaryl)alkylamines
403
Scheme 1. Synthesis of 5.
Scheme 2. Reactions involving Cbz-protected amines.
2-aminothiazole and 2-aminothiazoline were prepared (9 and 10) and reacted
with o-xylylene dibromide to give the expected products 11 and 12 in 65 and
78% yields, respectively. However, deprotection of 11 and 12 using Pd/H2
was unsuccessful, resulting in recovery of starting material.
Reaction of 2-aminopyrimidine with m-xylylene dibromide and p-
xylylene dibromide gave the expected products 13 and 14 in 57 and 56%
yields, respectively [Eq. (3)]:

404
S. R. Gondi and D. Y. Son
Table 1. General properties of compounds synthesized in this study
Product
Yield (%)
79
Mp (8C)
Solublity
1
75–80
DMSO, conc. HCl, MeOH, MeCN,
THF, DCM, CHCl3, acetone, EtOAc
Same as 1
2
3
76
65
80 (52a)
81
126–128
Oil
157
Same as 1
5
MeOH, MeCN, THF, DMSO
Same as 5
Same as 5
6
141
Oil
7
3.1
50
8
174
124
Same as 5
Same as 5
9
53
55
10
11
12
13
14
156
Same as 5
Same as 5
65
78
176–177
136–138
173–175
219
Same as 5
DMSO, conc. HCl
Same as 13
57
56
aPrepared from 8.
Reactions of 2-aminothiazole and 2-aminothiazoline with m-xylylene
dibromide and p-xylylene dibromide resulted in the isolation of insoluble or
gelatinous solids. The reasons for this difference in reactivity are unclear,
but at least for 2-aminothiazoline may be related to its ability to react
through both nitrogen atoms as in the synthesis of 3.
The general properties of all compounds synthesized in this study are
summarized in Table 1.
EXPERIMENTAL SECTION
All reactions were carried out under a nitrogen atmosphere unless otherwise
noted. All reagents were obtained from either Sigma-Aldrich (Milwaukee,
WI, USA) or Acros (Morris Plains, NJ, USA) and used without further puri-
1
fication. H and 13C NMR spectra were recorded using a 400-MHz Bruker
Avance DRX multinuclear NMR spectrometer. All chemical shifts are
reported in parts per million. Infrared spectra were obtained on a Nicolet
Magna-IR 560 spectrometer E.S.P. Elemental analyses were obtained with a
CE Elantech Thermo-Finnigan Flash 1112 CHN elemental analyzer.
Synthesis of Benzyl-pyrimidin-2-yl-amine (1)
2-Aminopyrimidine (2.2 g, 0.023 mol) was dissolved in THF (50 mL), and
the resulting clear solution was cooled in an ice bath. Sodium hydride

Synthesis of (Hetaryl)alkylamines
405
(0.56 g, 0.023 mol) was added, resulting in effervescence and the formation
of a suspension. The mixture was stirred in the ice bath for 15 min, and
then benzyl bromide (1.0 g, 0.0058 mol) was added dropwise over a
period of 30 min. The mixture was stirred at room temperature for 24 h.
The THF was removed using a rotary evaporator, and water (100 mL)
was added to the residue. The solution was extracted with dichloromethane
(100 mL). The organic layer was washed with water (100 mL), saturated
sodium bicarbonate solution (100 mL), water (100 mL), and brine
(100 mL); then dried over anhydrous magnesium sulfate, and filtered. The
solution was concentrated using a rotary evaporator, and the residue was
chromatographed on silica gel (30:70 EtOAc–hex) to give 1 as a white
solid (0.85 g, 79%). Mp 76–788C (lit. value[11] 75–808C). 1H NMR
(400 MHz, CDCl3): 8.01–8.22 (s, 2H), 7.27–7.14 (m, 5H), 6.42 (br-s,
1H, NH), 6.36–6.34 (t, 1H, J ¼ 4.8 Hz), 4.54–4.52 (d, 2H, J ¼ 5.6 Hz).
13C NMR (100.6 MHz, CDCl3): 162.2, 157.8, 139.0, 128.4, 127.5, 127.0,
110.4, 45.3. IR (KBr): 3232, 2858, 1606, 1525, 1498, 1122, 973 cm21
.
Synthesis of Benzyl-thiazol-2-yl-amine (2)
In the manner described previously, 2-aminothiazole (2.3 g, 0.023 mol) was
treated with benzyl bromide (1.0 g, 0.0058 mol) in the presence of sodium
hydride (0.56 g, 0.023 mol) in THF (50 mL). Column chromatographic puri-
fication (30:70 EtOAc–hex) gave 2 as a reddish solid (0.85 g, 76%). Mp 126–
1
1288C (lit. value[12] 128–1308C). H NMR (400 MHz, CDCl3): 7.29–7.19
(m, 5H), 6.99 (br-s, 1H, NH), 6.79–6.78 (d, 1H, J ¼ 3.3 Hz), 6.32–6.31
(d, 1H, J ¼ 3.3 Hz), 4.33 (s, 2H). 13C NMR (100.6 MHz, CDCl3): 170.6,
138.7, 137.5, 128.5, 127.7, 127.5, 106.0, 50.0. IR (KBr): 3170, 2971, 1568,
1492, 1451, 1163, 913 cm21
.
Synthesis of Benzyl-(3-benzyl-thiazolidin-2-ylidene]-amine (3)
.
In the manner described previously, 2-aminothiazoline HCl salt (3.2 g,
0.023 mol) was treated with benzyl bromide (1.0 g, 0.0058 mol) in the
presence of sodium hydride (1.1 g, 0.046 mol) in THF (100 mL). Column
chromatographic purification (25:75 EtOAc–hex) gave 3 as an oil (1.0 g,
1
65%). H NMR (400 MHz, CDCl3): 7.39–7.29 (m, 10H), 4.13 (s, 2H), 3.69
(s, 2H), 3.04–3.00 (t, 2H, J ¼ 7.0 Hz), 2.64–2.61 (t, 2H, J ¼ 7.4 Hz). 13C
NMR (100.6 MHz, CDCl3): 137.5, 134.3, 128.6, 128.5, 128.4, 128.3, 128.1,
126.9, 117.1, 55.4, 49.5, 36.0, 28.6. IR (neat): 3029, 2920, 2208, 1494,
1453, 1028 cm21. Elemental analysis: calcd. for C17H18N2S: C, 72.30; H,
6.42; N, 9.92. Found: C, 72.80; H, 6.07; N, 9.99.

406
S. R. Gondi and D. Y. Son
Synthesis of 2-Pyrimidin-2-yl-2,3-dihydro-1H-isoindole (5)
From 2-Aminopyrimidine
2-Aminopyrimidine (3.6 g, 0.038 mol) was dissolved in THF (100 mL)
and cooled in an ice bath. Sodium hydride (1.8 g, 0.076 mol) was added,
and the mixture was stirred 30 min. o-Xylylene dibromide (5.0 g,
0.019 mol) was added portionwise over a period of 15 min. The reaction
mixture was stirred at room temperature for 24 h. The THF was removed
using a rotary evaporator, and the residue was quenched by the addition of
water (100 mL). The aqueous solution was extracted with ethyl acetate
(100 mL), and the organic layer was washed with water (100 mL), saturated
sodium bicarbonate solution (100 mL), water (100 mL), and brine (100 mL)
and then dried over anhydrous MgSO4. After filtration and concentration of
the filtrate using rotary evaporation, the residue was purified by column
1
chromatography (20:80 EtOAc–hex) to give 5 (3.0 g, 80%). Mp 1578C. H
NMR (400 MHz, CDCl3): 8.44–8.43 (d, 2H, J ¼ 4.8 Hz), 7.38–7.31
(m, 4H), 6.62–6.59 (t, 1H, J ¼ 4.8 Hz), 4.96 (s, 4H). 13C NMR
(100.6 MHz, CDCl3): 159.8, 157.6, 137.2, 127.1, 122.5, 109.4, 52.7.
IR (KBr): 3043, 3865, 1582, 1458, 1343, 748 cm21. Elemental analysis:
calcd. for C12H11N3: C, 73.07; H, 5.62; N, 21.30. Found: C, 72.66; H, 5.62;
N, 21.14.
From 8
In the manner described previously, compound 8 (1.0 g, 0.0044 mol) was
treated with o-xylylene dibromide (0.59 g, 0.0022 mol) in the presence of
sodium hydride (0.13 g, 0.0054 mol) in THF (40 mL). Column chromato-
graphic purification (20:80 EtOAc–hex) gave 5 (0.23 g, 52%). Further
elution with 70:30 EtOAc–hex gave starting material (0.50 g).
Synthesis of 2-Thiazol-2-yl-2,3-dihydro-1H-isoindole (6)
In the manner described previously, 2-aminothiazole (3.8 g, 0.038 mol) was
treated with o-xylylene dibromide (5.0 g, 0.019 mol) in the presence of
sodium hydride (1.8 g, 0.076 mol) in THF (100 mL). Column chromato-
graphic purification (20:80 EtOAc–hex) gave 6 (3.1 g, 81%). Mp 1418C.
1H NMR (400 MHz, CDCl3): 7.32 (s, 4H), 7.29–7.28 (d, 2H, J ¼ 3.4 Hz),
6.56–6.55 (d, 1H, J ¼ 3.4 Hz), 4.81 (s, 4H). 13C NMR (100.6 MHz,
CDCl3): 167.8, 140.0, 136.7, 127.5, 122.7, 106.6, 55.4. IR (KBr): 3064,
2864, 1544, 1478, 1365 cm21. Elemental analysis: calcd. for C11H10N2S: C,
65.32; H, 4.98; N, 13.85. Found: C, 65.25; H, 5.04; N, 13.75.

Synthesis of (Hetaryl)alkylamines
407
Synthesis of 2-(4,5-Dihydro-thiazol-2-yl)-2,3-dihydro-1H-isoindole (7)
.
In the manner described previously, 2-aminothiazoline HCl salt (5.3 g,
0.038 mol) was treated with o-xylylene dibromide (5.0 g, 0.019 mol) in the
presence of sodium hydride (2.7 g, 0.11 mol) in THF (100 mL). Column chro-
matographic purification (20:80 EtOAc–hex) gave 7 as an oil (0.12 g, 3.1%).
1H NMR (400 MHz, CDCl3): 7.14 (s, 4H), 4.03 (s, 4H), 3.68–3.64 (t, 2H,
J ¼ 6.7 Hz), 3.11–3.08 (t, 2H, J ¼ 6.7 Hz). 13C NMR (100.6 MHz, CDCl3):
139.0, 127.5, 122.7, 59.5, 57.7, 42.3, 30.0. IR (neat): 3054, 2983, 2210,
1453, 736 cm21 Elemental analysis: calcd. for C11H12N2S: C, 64.67; H,
5.92; N, 13.71. Found: C, 64.30; H, 5.81; N, 12.87.
Synthesis of Pyrimidin-2-yl-carbamic Acid Benzyl Ester (8)
This procedure is modified from an earlier reported procedure.[13] 2-Amino-
pyrimidine (5.0 g, 0.053 mol) was dissolved in dichloromethane (75 mL)
and cooled in an ice bath. Pyridine (8.4 g, 0.105 mol) was added, and the
solution was stirred for 15 min. Benzyl chloroformate (10.8 g, 0.063 mol)
was dissolved in dichloromethane (25 mL), and the solution was added
dropwise over a period of 15 min. The reaction mixture was stirred in the
ice bath for 1 h and stirred at room temperature overnight, during which
time a clear yellow solution formed. All volatiles were removed using a
rotary evaporator, and water (100 mL) was added to the residue. The
aqueous solution was extracted with dichloromethane (100 mL ꢀ 2). The
organic layer was washed with water (100 mL), saturated sodium bicarbonate
solution (100 mL), water (100 mL), and brine (100 mL); dried over anhydrous
MgSO4, and filtered. All volatiles were removed using a rotary evaporator,
and the residue was purified using column chromatography (70:30 EtOAc–
1
hex) to give 8 (6.0 g, 50%). Mp 1748C (lit. value[13] 166–1688C). H NMR
(400 MHz, CDCl3): 10.35 (s, 1H, NH), 8.49–8.48 (d, 2H, J ¼ 4.9 Hz),
7.42–7.36 (m, 5H), 6.80–6.78 (t, 1H, J ¼ 4.9 Hz), 5.25 (s, 2H). 13C NMR
(100.6 MHz, CDCl3): 158.2, 157.6, 151.5, 135.5, 128.6, 128.5, 128.4,
115.6, 67.3. IR (KBr): 3400, 3031, 1751, 1654, 1575, 1451, 995 cm21
.
Synthesis of Thiazol-2-yl-carbamic Acid Benzyl Ester (9)
In the manner described previously for 8, 2-aminothiazole (5.0 g, 0.050 mol)
was treated with benzyl chloroformate (10.2 g, 0.060 mol) in the presence of
pyridine (8.0 g, 0.10 mol). Column chromatographic purification (25:75
1
EtOAc–hex) gave 9 (6.2 g, 53%). Mp 1248C. H NMR (400 MHz, CDCl3):
12.68 (br-s, 1H, NH), 7.47–7.38 (m, 5H), 7.24–7.23 (d, 1H, J ¼ 3.6 Hz),
6.86–6.85 (d, 1H, J ¼ 3.6 Hz), 5.33 (s, 2H). 13C NMR (100.6 MHz,
CDCl3): 161.8, 153.8, 136.7, 136.5, 128.6, 128.5, 128.2, 112.3, 67.8. IR

408
S. R. Gondi and D. Y. Son
(KBr): 3185, 3033, 1724, 1584, 1497, 1028 cm21. Elemental analysis: calcd.
for C11H10N2O2S: C, 56.39, H, 4.30, N, 11.96. Found: C, 56.57; H, 4.25;
N, 11.68.
Synthesis of (4,5-Dihydro-thiazol-2-yl)-carbamic Acid Benzyl Ester (10)
In the manner described previously for 8, 2-aminothiazoline hydrochloride
(5.0 g, 0.036 mol) was treated with benzyl chloroformate (7.4 g, 0.044 mol)
in the presence of pyridine (11.6 g, 0.144 mol). Column chromatographic
1
purification (80:20 EtOAc–hex) gave 10 (4.7 g, 55%). Mp 1568C. H NMR
(400 MHz, CDCl3): 10.68 (br-s, 1H, NH), 7.36–7.31 (m, 5H), 5.13 (s, 2H),
3.50–3.46 (t, 2H, J ¼ 7.8 Hz), 3.20–3.16 (t, 2H, J ¼ 8.0 Hz). 13C NMR
(100.6 MHz, CDCl3): 176.9, 161.6, 136.5, 128.3, 128.2, 128.0, 67.1, 45.2,
29.8. IR (KBr): 3173, 2937, 1731, 1679, 1578, 1049 cm21. Elemental
analysis: calcd. for C11H12N2O2S: C, 55.91; H, 5.12; N, 11.86. Found: C,
55.91; H, 5.07; N, 11.64.
Synthesis of 11
In the manner described previously for the synthesis of 5, compound 9 (0.5 g,
0.0021 mol) was treated with o-xylylene dibromide (0.28 g, 0.0010 mol) in
the presence of sodium hydride (62 mg, 0.0025 mol) in THF (100 mL).
Column chromatographic purification (30:70 EtOAc–hex) gave 11 (395 mg,
1
65%). Mp 176–1778C. H NMR (400 MHz, CDCl3): 7.40 (s, 4H), 7.34–
7.26 (m, 8H), 6.98 (s, 2H), 6.91 (s, 2H), 6.40 (s, 2H), 5.39 (s, 4H), 5.21
(s, 4H). 13C NMR (100.6 MHz, CDCl3): 170.2, 162.6, 136.6, 133.2, 128.6,
128.4, 128.3, 128.2, 127.9, 126.2, 108.1, 67.4, 48.2. IR (KBr): 3063, 2935,
1633, 1561, 1451, 980 cm21. Elemental analysis: calcd. for C30H26N4O4S2:
C, 63.14; H, 4.59; N, 9.82. Found: C, 63.17; H, 4.56; N, 9.68.
Synthesis of 12
In the manner described previoysly, compound 10 (1.0 g, 0.0042 mol) was
treated with o-xylylene dibromide (0.56 g, 0.0022 mol) in the presence of
sodium hydride (0.12 g, 0.0051 mol) in THF (40 mL). Column chromato-
graphic purification (50:50 EtOAc–hex) gave 12 (950 mg, 78%). Mp 136–
1
1388C. H NMR (400 MHz, CDCl3): 7.42–7.40 (d, 4H, J ¼ 7.0 Hz), 7.36–
7.28 (m, 8H), 7.21–7.19 (t, 2H, J ¼ 3.3 Hz), 5.19 (s, 4H), 4.85 (s, 4H),
3.56–3.52 (t, 4H, J ¼ 7.7 Hz), 3.11–3.07 (t, 4H, J ¼ 7.7 Hz). 13C NMR
(100.6 MHz, CDCl3): 173.5, 163.0, 136.5, 133.8, 128.8, 128.4, 128.3,
127.9, 67.5, 49.6, 48.0, 26.5. IR (KBr): 3035, 2949, 1659, 1552, 1465,

Synthesis of (Hetaryl)alkylamines
409
1019 cm21. Elemental analysis: calcd. for C30H30N4O4S2: C, 62.70; H, 5.26;
N, 9.75. Found: C, 62.75; H, 5.27; N, 9.66.
Synthesis of N,N0-[1,3-Phenylenebis(methylene)]dipyrimidin-2-
amine (13)
In the manner described previously, 2-aminopyrimidine (2.9 g, 0.030 mol)
was treated with m-xylylene dibromide (1.0 g, 0.0038 mol) in the presence
of sodium hydride (0.73 g, 0.030 mol) in THF (60 mL). Once the crude
product was obtained, water (200 mL) was added, and the slurry was
filtered. The solid was washed with water (200 mL) and ethyl acetate
(100 mL) and dried for 24 h. This solid was further purified by refluxing in
methanol (60 mL) for 15 min, followed by hot filtration. Removal of
volatiles gave 13 (615 mg, 57%). Mp 173–1758C. 1H NMR (400 MHz,
DMSO-d6): 8.23–8.22 (d, 4H, J ¼ 2.9 Hz) 7.64 (s, 2H), 7.25 (s, 1H), 7.21–
7.19 (d, 1H, J ¼ 7.1 Hz), 7.14–7.12 (d, 2H, J ¼ 7.1), 6.55–6.54 (d, 2H,
NH, J ¼ 1.3 Hz), 4.46–4.45 (d, 4H, J ¼ 5.8 Hz). 13C NMR (100.6 MHz,
DMSO-d6): 163.1, 158.7, 141.1, 128.8, 126.5, 126.0, 111.0, 44.7. IR (KBr):
3261, 2933, 1598, 1536, 1455, 987 cm21. Elemental analysis: calcd. for
.
C16H16N6 H2O: C, 61.92; H, 5.85; N, 27.08. Found: C, 62.21; H, 5.39;
N, 26.51.
Synthesis of N,N0-[1,4-Phenylenebis(methylene)]dipyrimidin-2-
amine (14)
In the manner described previously for 13, 2-aminopyrimidine (2.9 g,
0.030 mol) was treated with p-xylylene dibromide (1.0 g, 0.0038 mol) in the
presence of sodium hydride (0.73 g, 0.030 mol) in THF (60 mL).
1
Compound 14 was obtained as a yellow solid (0.60 g, 56%). Mp 2198C. H
NMR (400 MHz, DMSO-d6): 8.24–8.23 (d, 4H, J ¼ 3.6 Hz) 7.63 (t, 2H,
J ¼ 3.6 Hz), 7.21 (s, 4H), 6.56–6.4 (d, 2H, NH, J ¼ 4.5 Hz), 4.45–4.37
(d, 4H, J ¼ 5.9 Hz). 13C NMR (100.6 MHz, DMSO-d6): 163.1, 158.8,
139.4, 127.7, 111.0, 44.5. IR (KBr): 3245, 3017, 1598, 1540, 1452,
1072 cm21. Elemental analysis: calcd. for C16H16N6 H2O: C, 61.92; H,
.
5.85; N, 27.08. Found: C, 62.41; H, 5.40; N, 26.73.
ACKNOWLEDGMENTS
The authors thank the Robert A. Welch Foundation (N-1375) for support of
this research.

410
S. R. Gondi and D. Y. Son
REFERENCES
1. Rauterkus, M. J.; Fakih, S.; Mock, C.; Puscasu, I.; Krebs, B. Cisplatin analogues
with 2,20-dipyridylamine ligands and their reactions with DNA model nucleobases.
Inorg. Chim. Acta 2003, 350, 355–365.
2. Tu, C.; Lin, J.; Shao, Y.; Guo, Z. Toward the design of novel polynuclear platinum
antitumor complexes: a polydentate ligand system based on dipyridylamine and
1,3,5-trimethylenebenzene. Inorg. Chem. 2003, 42, 5795–5797.
3. Tu, C.; Wu, X.; Liu, Q.; Wang, X.; Xu, Q.; Guo, Z. Crystal structure, DNA-binding
ability and cytotoxic activity of platinum(II) 2,20-dipyridylamine complexes.
Inorg. Chim. Acta 2004, 357, 95–102.
4. Plieger, P. G.; Downard, A. J.; Moubaraki, B.; Murray, K. S.; Brooker, S. Dime-
tallic complexes of acyclic pyridine-armed ligands derived from 3,6-diformylpyr-
idazine. J. Chem. Soc., Dalton Trans. 2004, 2157–2165.
5. Chang, J.; Plummer, S.; Berman, E. S. F.; Striplin, D.; Blauch, D. Synthesis and
characterization of bis(di-2-pyridylmethanamine)ruthenium(II). Inorg. Chem.
2004, 43, 1735–1742.
6. Schatz, M.; Leibold, M.; Foxon, S. P.; Weitzer, M.; Heinemann, F. W.;
Hampel, F.; Walter, O.; Schindler, S. Syntheses and characterization of copper
complexes of the ligand (2-aminoethyl)bis(2-pyridylmethyl)amine (uns-penp)
and derivatives. J. Chem. Soc., Dalton Trans. 2003, 1480–1487.
7. Osako, T.; Ueno, Y.; Tachi, Y.; Itoh, S. Structures and redox reactivities of copper
complexes of (2-pyridyl)alkylamine ligands effects of the alkyl linker chain length.
Inorg. Chem. 2003, 42, 8087–8097.
8. Gondi, S. R.; Son, D. Y. Synthesis of N,N-bis(2-thiazolinyl)-, N,N-bis(2-
thiazolyl)-, and N,N-bis(2-pyrimidinyl)-benzene dicarboxamides. Synth.
Commun. 2004, 34, 3061–3072.
9. Gondi, S. R.; Son, D. Y. Mono-, bis-, and tris-1,3-dithiolane aromatic derivatives
by esterification and amidation reactions. J. Sulfur Chem. 2005, 26, 13–19.
10. Gondi, S. R.; Son, D. Y. Cholane derivatives with potential ligating groups at the
3- and 24-positions. Synth. Commun. 2006, 36, 1317–1331.
11. Cherng, Y.-J. Efficient nucleophilic substitution reactions of pyrimidyl and pyrazyl
halides with nucleophiles under focused microwave irradiation. Tetrahedron 2002,
58, 887–890.
12. Abdel-Magid, A. F.; Carson, K. G.; Harris, B. D.; Maryanoff, C. A.; Shah, R. D.
Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride
studies on direct and indirect reductive amination procedures. J. Org. Chem. 1996,
61, 3849–3862.
13. Gotor, V.; Quiros, M.; Liz, R.; Frigola, J.; Fernandez, R. Fungal and bacterial
regioselective hydroxylation of pyrimidine heterocycles. Tetrahedron 1997, 53,
6421–6432.