Preparation of aminals in water

Article abstract of DOI:10.1016/j.tet.2004.02.021

Aminals, which are used as protecting groups in syntheses and are part of many biologically active compounds, are normally prepared from aldehydes and diamines under conditions that remove water in order to shift the equilibrium to the side of the aminal.

Full text of DOI:10.1016/j.tet.2004.02.021

Tetrahedron 60 (2004) 3205–3210
Preparation of aminals in water
*
´ ˇ´ ´
Vaclav Jurcık and Rene Wilhelm
¨ ¨
Institut fur Organische Chemie der Technischen Universitat Clausthal, 38678 Clausthal-Zellerfeld, Germany
Received 5 December 2003; revised 9 February 2004; accepted 11 February 2004
Abstract—Aminals, which are used as protecting groups in syntheses and are part of many biologically active compounds, are normally
prepared from aldehydes and diamines under conditions that remove water in order to shift the equilibrium to the side of the aminal. Here we
report for the first time that aminals can be prepared and isolated in pure water without a catalyst in high yield and purity.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
Since we were interested in preparing imidazolidines in a
fast and easy way, we wanted therefore to investigate, if it
would be also possible to prepare aminals in a similar way.
So far aminals have never been synthesized and isolated in
pure water. There is only one example known in the
literature where the equilibrium constants for the formation
of a few imidazolidines were measured in water via UV
absorbance, however, no products were isolated.18 In
addition an aminal was prepared in a biphasic system of
water and dichloromethane from diamines and glyoxal.19
Aminals,1 which are also known under the term N,N-acetals,
are the aminated equivalents of acetals. The aminals can be
either open chained or cyclic like aminal analogue 1. Cyclic
aminals can be used in synthesis as protecting groups for
aldehydes.2–6 In addition, five-membered ring aminals
(imidazolidines) are important parts of biologically active
compounds, for example, folic acid derivates.7–9 Six-
membered ring aminals (hexahydro-pyrimidines) are also
often incorporated in biologically active molecules.10,11
The preparation of aminals in water is desirable, since
reaction procedures, where water is used as a solvent instead
of an organic solvent have become in recent years more and
more important due to environmental consideration.20,21
Classical methods of preparing aminals involve the use of
various drying agents, for example, potassium carbonate,12
calcium sulfate,13 boric anhydride14 or removal of water by
azeotropic distillation with benzene15 in order to shift the
equilibrium to the product side as shown in Scheme 1. If the
aminals are crystallizing easily, reactions are performed in
methanol or ethanol in the presence of a small amount of
acetic acid.2 If formaldehyde is used in the reaction, often an
ethanol–water mixture is used as the solvent.16
2. Results and discussion
In order to follow the procedure of 0Simion et al. for the
preparation of imines in water,17 N,N -dibenzyl-ethane-1,2-
diamine (2) was strongly stirred in water and benzaldehyde
was added to the emulsion. During 3 h of stirring a white
precipitate formed which was filtered of and washed with
water. After drying under vacuum the desired product 3a
was obtained in 91% yield (Table 1, entry 1) in high purity
according to NMR spectral data and CHN-analysis. In
comparison, when 2 was refluxed with benzaldehyde and a
catalytic amount of p-toluene sulfonic acid in benzene on a
Dean–Stark apparatus, the reaction took 16 h and a flash
column chromatography with deactivated silica gel had to
be performed to get 3a in proper purity. When the reaction
was carried out in abs. ethanol the product had to be purified
again via flash column chromatography or via recrystallisa-
tion, which gave the product in only 62% yield. Finally,
benzaldehyde was added to neat diamine 2 and a strong
exothermic reaction was observed, which was completed
Scheme 1.
We noticed from the literature that imines can be
conveniently prepared in pure water without the presence
of a catalyst from corresponding amines and aldehydes.17
Keywords: Aminals; Water; Solvent; Imidazolidines; Protecting group.
*
Corresponding author. Tel.:þ49-5323-723886; fax:þ49-5323-722834;
e-mail address: rene.wilhelm@tu-clausthal.de
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.02.021

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V. Jurcık, R. Wilhelm / Tetrahedron 60 (2004) 3205–3210
3206
Table 1. Preparation of aminals
Entry
Diamine
Aldehyde
Aminal
Yield (%)
1
2
3
4
2
2
2
2
2
2
2
2
2
2
4
4
4
6
8
8
R1¼Bn, n¼2
Benzaldehyde
3a
R2¼C6H5
91
96
99
99
94
96
92
91
88
85
96
88
93
99
81
80
98
42
67
99
2-Chlorobenzaldehyde
Pyridine-2-carbaldehyde
Thiophene-2-carbaldehyde
2-Methoxybenzaldehyde
2,4-Dichlorobenzaldehyde
Pentafluorobenzaldehyde
4-Chlorobenzaldehyde
2,6-Dichlorobenzaldhyde
Propionaldehyde
3b
3c
3d
3e
3f
3g
3h
3i
R2¼1-(2-Cl–C6H4)
R2¼2-(C5H4N)
R2¼2-(C4SH3S)
R2¼1-(2-MeO–C6H4)
R2¼1-(2,4–Cl2-C6H3)
R2¼1-(C6F5)
5
6a
7
8a
R2¼1-(4-Cl–C6H4)
R2¼1-(2,6-Cl2–C6H3)
R2¼CH2CH3
9a
10b
11
12
13
14
15b
16a,b
17a
18a
19
20c
3j
R1¼Bn, n¼3
R1¼Bn, n¼4
Benzaldehyde
5a
5b
5c
7a
9a
9b
11a
11b
13
15
R2¼C6H5
2-Chlorbenzaldehyde
Pyridine-2-carbaldehyde
2-Chlorobenzaldehyde
2-Chlorobenzaldehyde
4-Chlorobenzaldehyde
2-Chlorobenzaldehyde
Acetaldehyde
R2¼1-(2-Cl–C6H4)
R2¼2-(C5H4N)
R2¼1-(2-Cl–C6H4)
R2¼1-(2-Cl–C6H4)
R2¼1-(4-Cl–C6H4)
R2¼1-(2-Cl–C6H4)
R2¼CH3
R1¼(R)-MeCHPh
R1¼Ph, n¼2
10
10
12
14
R1¼Me, n¼2
Benzaldehyde
2-Chlorobenzaldehyde
R2¼C6H5
Piperidine
21
16
(^)-N,N0-Dibenzyl-1,2-cyclohexanediamine
Pyridine-2-carbaldehyde
17
95
a
Reaction temperature 80 8C.
Reaction time 16 h.
2 equiv. piperidine.
b
c
after 15 min. However, due to the high temperature during
the reaction many impurities next to 3a were detected in the
NMR spectra and again a flash column chromatography had
to be carried out which gave the aminal 3a in 60% yield.
Given those results we concluded that for the preparation of
aminal analogues of 3a a reaction of diamines and
benzaldehydes in water would be the most convenient and
efficient procedure. The results are summarized in Table 1
Scheme 2.
formation of an emulsion containing both reactants (entries
6, 8, 9, 16). When the benzaldehydes were not melted,
yields where significantly lower.
In case of the polyfluorinated aminal 3g (entry 7) the
reaction was carried out in deoxygenated water under a
nitrogen atmosphere. This was necessary to prevent the
rapid oxidation of the aldehyde to the corresponding
carboxylic acid before the formation of the desired aminal
3g was finished. The product 3g was isolated in a good yield
of 92%. Since 3g was a liquid, it was extracted from the
reaction mixture with chloroform. To compare again
methods, an attempt to prepare 3g in benzene with a
Dean–Stark apparatus under reflux was carried out, which
gave no product at all. The same result was observed when
abs. ethanol was chosen as a solvent for the reaction. When
pentafluorobenzaldehyde was added to neat diamine 2 a
strong exothermic reaction was observed, however no
product was isolated, which may be due to the possible
instability of either pentafluorobenzaldehyde or aminal 3g at
higher temperatures.
Scheme 2.
First diamine 2 was reacted with different benzaldehydes to
give the corresponding imidazolidines (entries 1–9). In all
cases the obtained yields were very high (between 91 and
99%) and the products were pure according to NMR spectra
and CHN-analysis. Electron deficient (entries 1–3, 6–9)
and electron rich (entries 4, 5) benzaldehydes gave similar
results. Even the hindered 2,6-dichloro-benzaldehyde gave
the corresponding aminal 3i in a good yield of 88% (entry
9). In cases where the melting points of the benzaldehydes
where higher than room temperature, the mixtures were
heated to 80 8C in order to melt the aldehydes and ensure the
Aliphatic aldehydes can be applied in the described
procedure also. Propionaldehyde gave with diamine 2 the
expected aminal 3j in 85% yield (entry 10). However, due to
the lower reactivity of aliphatic aldehydes the reaction time
had to be prolonged to 16 h. The scope of the reaction was
extended0 with N,N0-dibenzyl-propane-1,3-diamine (4)17,22
and N,N -dibenzyl-butane-1,3-diamine (6)22 which gave

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V. Jurcık, R. Wilhelm / Tetrahedron 60 (2004) 3205–3210
3207
with aldehydes cyclic aminals with a six- or a seven-
membered ring in good yields between 88 and 99% (entries
11–14).
4.2. Preparation of aminals
General procedure. A diamine (1.00 mmol) was added to
water (1.5 mL) and an aldehyde (1.00 mmol) was added.
The mixture was vigorously stirred for 3 h at rt. For
exceptions in temperature and reaction times see Table 1.
The precipitate was isolated by filtration, washed with water
(5 mL) and dried under vacuum to afford the desired
product. In case the product was a liquid, the reaction
mixture was extracted with CHCl3 (3£5 mL) and the
combined organic phases were dried (Na2SO4) and the
solvent evaporated.
Furthermore N,N0-bis-((R)1-phenyl-ethyl)-ethane-1,2-
diamine (8)23 was used in the reaction with 2- and
4-chlorobenzaldehydes in order to have a more hindered
system next to the nitrogen atoms. The reactions were
complete after 16 h and the liquid products were isolated via
extraction with chloroform giving the aminals 9a and 9b in
81 and 80% yield, respectively (entries 14, 15).
In addition N,N0-diphenyl-ethane-1,2-diamine (10) was
forming with 2-chlorobenzaldehyde and acetaldehyde the
aminals 11a and 11b in 98 and 42% yield, respectively
(entries 17, 18). Since the melting point of the diamine 10 is
70 8C the reaction mixture was heated to 80 8C to melt the
diamine. Aminal 13 was obtained in 67% yield from N,N0-
dimethyl-ethane-1,2-diamine (12) and benzaldehyde (entry
19). Open aminals are also accessible as shown in entry 20,
where 2 equiv. of piperidine (14) gave with 2-chloro-
benzaldehyde the expected product in 99% yield (entry 20).
Finally, the (^)-trans-cyclohexanediamine analogue 16
furnished with pyridine-2-carbaldehyde the aminal 17 in
95% yield (entry 21).
4.2.1. 1,3-Dibenzyl-2-phenyl-imidazolidine (3a). As a
white solid (91%). Mp 97–98 8C (Lit.26 99 mp 8C); MS
(EI), m/e 328 (Mþ, 25%), 327 (Mþ2H, 25), 251 (Mþ2Ph,
100), 91 (80); IR (KBr) 2780s, 1490s, 1450s, 1161s,
1
700s cm21; H NMR (200 MHz) d 7.67–7.16 (m, 15H),
3.84 (s, 1H), 3.79 (d, J¼13.0 Hz, 2H), 3.22–3.13 (m, 2H),
3.20 (d, J¼13.2 Hz, 2H), 2.53–2.45 (m, 2H); 13C NMR
(50 MHz) d 140.3, 139.2, 129.5, 128.6, 128.2, 128.1, 126.8,
89.0, 56.9, 50.6. Anal. Calcd for C23H24N2: C, 84.11; H,
7.36; N, 8.53, found: C, 83.80; H, 7.37; N, 8.48. The spectral
data were consistent with literature values.27,28
4.2.2. 1,3-Dibenzyl-2-(2-chloro-phenyl)-imidazolidine
(3b). As a white solid (96%). Mp 96 8C (Lit.29 96–97 8C);
MS (EI), m/e 361 (MþþH, 25%), 251 (100), 91 (75); IR
(KBr) 2793m, 1365m, 1151s, 757vs, 698vs cm21; 1H NMR
(400 MHz) d 8.14 (d, J¼7.8 Hz, 1H), 7.45–7.25 (m, 13H),
4.70 (s, 1H), 3.85 (d, J¼13.2 Hz, 2H), 3.41 (d, J¼13.2 Hz,
2H), 3.26–3.23 (m, 2H), 2.64–2.61 (m, 2H); 13C NMR
(100 MHz) d 139.7, 138.2, 136.0, 131.8, 129.8, 129.3,
128.9, 128.6, 127.7, 127.3, 83.6, 57.3, 51.2. Anal. Calcd for
C23H23ClN2: C, 76.12; H, 6.39; N, 7.72, found: C, 75.82; H,
6.32; N, 7.55.
3. Conclusion
We were able to demonstrate a simple method to prepare
cyclic aminals with various ring sizes in high yield and high
purity in pure water without the presence of a catalyst. In
addition it was possible to get access to aminals which could
not be prepared via several different standard procedures.
4.2.3. 2-(1,3-Dibenzyl-imidazolidin-2-yl)-pyridine (3c).
As a white solid (99%). Mp 80–81 8C; MS (EI), m/e 329
(MþþH, 5%), 251 (100), 197 (10), 238 (10), 91 (80), 65
(10); IR (KBr) 2792m, 1493m, 1434s, 1360m, 1135m,
4. Experimental
4.1. General experimental
1
1148m, 781s, 749s, 696vs cm21; H NMR (400 MHz) d
N,N0-Dibenzyl-ethane-1,2-diamine (2), N,N0-diphenyl-
ethane-1,2-diamine (10), N,N0-dimethyl-ethane-1,2-diamine
(12), piperidine (14) and aldehydes were obtained from
Aldrich and used without further purification. N,N0-
Dibenzyl-propane-1,3-diamine 0 (4),17,22 N,N0-dibenzyl-
butane-1,3-diamine (6),22 N,N -bis-((R)1-phenyl-ethyl)-
ethane-1,2-diamine (8)23 and (^)-N,N0-dibenzyl-1,2-cyclo-
hexanediamine (16)24 were prepared according to literature
procedures. The reactions were carried out in dest. water.
8.56–8.55 (m, 1H), 8.01 (dt, J¼8.0, 1.0 Hz, 1H), 7.79 (td,
J¼7.7, 1.8 Hz, 1H), 7.30–7.20 (m, 11H), 4.14 (s, 1H), 3.86
(d, J¼13.4 Hz, 2H), 3.41 (d, J¼13.4 Hz, 2H), 3.27–3.23
(m, 2H), 2.61–2.57 (m, 2H); 13C NMR (100 MHz) d 161.8,
148.6, 139.4, 137.3, 128.9, 128.5, 127.2, 123.7, 123.5, 89.9,
57.4, 51.3. Anal. Calcd for C22H23N3: C, 80.21; H, 7.04; N,
12.76, found: C, 79.89; H, 7.12; N, 12.88.
4.2.4. 1,3-Dibenzyl-2-thiophen-2-yl-imidazolidine (3d).
As a white solid (99%). Mp 122 8C; MS (EI), m/e 333
(MþþH, 1%), 124 (50), 97 (30), 91 (100); IR (KBr) 1307s,
1161s, 744s, 717s, 698s cm–1; 1H NMR (400 MHz) d 7.42–
6.99 (m, 13H), 4.82 (s, 1H), 3.96 (d, J¼12.9 Hz, 2H), 3.29
(d, J¼12.9 Hz, 2H), 3.20–3.17 (m, 2H), 2.56–2.52 (m, 2H);
13C NMR (100 MHz) d 146.4, 139.4, 129.0, 128.6, 128.0,
127.3, 127.1, 126.2, 84.0, 57.3, 50.7. Anal. Calcd for
C21H22N2S: C, 75.41; H, 6.63; N, 8.38, found: C, 75.41; H,
6.61; N, 8.77.
Flash column chromatography25 was performed on Sorbisil
C-60. All reactions were monitored by TLC with Merck
Silica gel 60 F254 plates. Elemental analyses were carried
out by the Microanalytical Laboratory of the Institut fu¨r
¨
Pharmazeutische Chemie der Universitat Braunschweig.
Infrared spectra were recorded on a Perkin–Elmer 2000
FT-IR System FTIR instrument. NMR spectra were
performed in CDCl3 at ambient temperature on a Bruker
AMX 400 and a Bruker AC 200F. Mass spectra were
recorded on Hewlett–Packard 5898B (at 70 eV). Melting
points were taken with an apparatus after Dr Tottoli and are
uncorrected.
4.2.5. 1,3-Dibenzyl-2-(2-methoxy-phenyl)-imidazolidine
(3e). As a white solid (94%). Mp 70 8C; MS (EI), m/e 357

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V. Jurcık, R. Wilhelm / Tetrahedron 60 (2004) 3205–3210
3208
(MþþH, 20%), 251 (100), 148 (15), 121 (20), 91 (100), 65
(20); IR (KBr) 2795s, 2492s, 1380s, 1239s, 1153s, 752s,
698s cm21; 1H NMR (400 MHz) d 8.00 (dd, J¼7.6, 1.4 Hz,
1H), 7.32–7.03 (m, 12H), 6.87 (d, J¼8.3 Hz, 1H), 3.59 (s,
1H), 3.84 (s, 3H), 3.80 (d, J¼13.2 Hz, 2H), 3.29 (d,
J¼13.2 Hz, 2H), 3.17–3.14 (m, 2H), 2.56–2.52 (m, 2H);
13C NMR (100 MHz) d 159.5, 140.0, 130.3, 129.5, 128.4,
121.5, 110.6, 80.1, 55.9, 51.1. Anal. Calcd for C24H26N2O:
C, 80.41; H, 7.31; N, 7.81, found: C, 80.3; H, 7.43; N, 7.71.
(Mþ, 5%), 251 (Mþ2Et, 100); IR (neat) 2925s, 2785s,
1495s, 1455s, 1345s, 1028s, 700s cm21 1H NMR
;
(200 MHz) d 7.29–7.19 (m, 10H), 3.98 (d, J¼13.1 Hz,
2H), 3.38 (d, J¼13.3 Hz, 2H), 3.14 (t, J¼3.8 Hz, 1H), 2.99–
2.86 (m, 2H), 2.47–2.38 (m, 2H), 1.73–1.60 (m, 2H), 1.11–
0.92 (m, 3H); 13C NMR (50 MHz) d 139.8, 128.6, 128.2,
126.8, 85.6, 58.5, 50.6, 24.4, 8.16. The spectral data were
consistent with literature values.27,28
4.2.11. 1,3-Dibenzyl-2-phenyl-hexahydro-pyrimidine
(5a). As a white solid (96%). Mp 113–114 8C (Lit.30
120 8C); MS (EI), m/e 341 (Mþ2H, 10%), 265 (Mþ2Ph,
100), 91 (95); IR (KBr) 2950s, 2795s, 1490s, 1450s, 1095s,
4.2.6. 1,3-Dibenzyl-2-(2,4-dichloro-phenyl)-imidazoli-
dine (3f). As a yellow solid (96%). Mp 84 8C; MS (EI),
m/e 395 (MþþH, 15%), 251 (100), 91 (80); IR (KBr) 2804s,
1
1
1337s, 1152s, 854s, 697vs cm–1; H NMR (400 MHz) d
700s cm21; H NMR (200 MHz) d 7.69–7.13 (m, 15H),
8.03 (d, J¼8.3 Hz, 1H), 7.39–7.35 (m, 2H), 7.31–7.20 (m,
10H), 4.60 (s, 1H), 3.78 (d, J¼13.1 Hz, 2H), 3.38 (d,
J¼13.1 Hz, 2H), 3.25–3.15 (m, 2H), 2.65–2.55 (m, 2H);
13C NMR (100 MHz) d 139.4, 137.2, 136.4, 134.7, 132.8,
128.9, 128.8, 128.6, 128.1, 127.3, 83.1, 57.2, 51.2. Anal.
Calcd for C23H22Cl2N2: C, 69.52; H, 5.58; N, 7.05, found:
C, 69.33; H, 5.46; N, 6.81.
3.612 (d, J¼13.2 Hz, 2H), 3.608 (s, 1H), 3.02–2.95 (m,
2H), 2.85 (d, J¼13.1 Hz, 2H), 2.11–1.41 (m, 4H); 13C
NMR (50 MHz) d 141.9, 139.7, 129.6, 128.6, 128.3, 128.2,
128.0, 126.6, 89.0, 58.4, 51.8, 24.4. Anal. Calcd for
C24H26N2: C, 84.17; H, 7.65; N, 8.18, found: C, 84.20; H,
7.65; N, 8.13.
4.2.12. 1,3-Dibenzyl-2-(2-chloro-phenyl)-hexahydro-
pyrimidine (5b). As a white solid (88%). Mp 94–96 8C;
MS (EI), m/e 375 (MþþH, 5%), 365 (100), 91 (80); IR
4.2.7. 1,3-Dibenzyl-2-pentafluorophenyl-imidazolidine
(3g). Reaction was carried out in deoxygenated water
under a nitrogen atmosphere. The crude oily product was
purified by flash chromatography (FCC) (eluant: 2.5% ethyl
acetate 20.5% triethylamine–hexane) through a short pad
of silica to afford the title compound 3g as a clear oil (92%).
MS (EI), m/e 418 (Mþ, 10%), 251 (40), 91 (100); IR (KBr)
2795s, 1500s, 954s, 740s, 700s cm21; 1H NMR (400 MHz)
d 7.22–7.18 (m, 10H), 4.61 (s, 1H), 3.75 (d, J¼13.3 Hz,
2H), 3.66 (d, J¼13.2 Hz, 2H), 3.32–3.29 (m, 2H), 2.72–
2.69 (m, 2H); 13C NMR (100 MHz) d 138.8, 128.7, 128.5,
127.5, 79.8, 58.3, 52.0. Anal. Calcd for C23H19N2F5: C,
66.02; H, 4.58; N, 6.70, found: C, 65.67; H, 4.56; N, 6.55.
1
(KBr) 2923s, 1367s, 1098s, 756vs, 739vs, 698vs cm21; H
NMR (400 MHz) d 8.19–8.16 (m, 1H), 7.41–7.19 (m,
13H), 4.34 (s, 1H), 3.58 (d, J¼13.2 Hz, 2H,), 3.03–2.99 (m,
4H), 2.15–2.08 (m, 2H), 1.92–1.83 (m, 1H), 1.51–1.47 (m,
1H); 13C NMR (100 MHz) d 139.9, 136.1, 131.3, 129.5,
128.9, 128.7, 128.5, 128.0, 127.7, 127.1, 83.2, 58.1, 51.3,
25.1. Anal. Calcd for C24H25ClN2: C, 76.48; H, 6.69; N,
7.43, found: C, 76.08; H, 6.69; N, 7.36.
4.2.13. 1,3-Dibenzyl-2-pyridin-2-yl-hexahydro-pyrimi-
dine (5c). As a white solid (93%). Mp 80–81 8C; MS
(EI), m/e 344 (MþþH, 25%), 265 (Mþ2pyridinyl, 100), 91
(80); IR (KBr) 3060s, 2930s, 2790s, 1590s, 1490s, 1450s,
1440s, 1170s, 980s, 820s, 790s cm21; 1H NMR (400 MHz)
d 8.58–8.56 (m, 1H), 8.07–8.04 (m, 1H), 7.77 (td, J¼7.6,
1.7 Hz, 1H), 7.28–7.21 (m, 11H), 3.90 (s, 1H), 3.50 (d,
J¼13.6 Hz, 2H), 3.06 (d, J¼13.6 Hz, 2H), 3.05–3.01 (m,
2H), 2.13 (td, J¼11.8, 2.8 Hz, 2H), 1.94–1.85 (m, 1H),
1.56–1.52 (m, 1H); 13C NMR (100 MHz) d 163.1, 148.4,
139.7, 137.5, 129.0, 128.5, 127.1, 124.0, 123.6, 89.5, 58.7,
51.8, 25.0. Anal. Calcd for C23H25N3: C, 80.43; H, 7.34; N,
12.23, found: C, 80.03; H, 7.28; N, 12.17.
4.2.8. 1,3-Dibenzyl-2-(4-chloro-phenyl)-imidazolidine
(3h). As a white solid (91%). Mp 106 8C (Lit.29 109 8C);
MS (EI), m/e 361 (MþþH, 25%), 251 (75), 152 (20), 125
(20), 91 (100), 65 (20); IR (KBr) 2804m, 1493m, 1148m,
1
1186m, 822s, 698vs cm21; H NMR (400 MHz) d 7.64–
7.61 (m, 2H), 7.44–7.38 (m, 2H), 7.33–7.22 (m, 10H), 4.01
(s, 1H), 3.79 (d, J¼13.2 Hz, 2H), 3.28–3.20 (m, 4H), 2.57–
2.53 (m, 2H); 13C NMR (100 MHz) d 139.6, 139.4, 134.6,
131.2, 128.9, 128.8, 128.6, 127.3, 88.6, 57.3, 51.1. Anal.
Calcd for C23H23ClN2: C, 76.12; H, 6.39; N, 7.72, found: C,
76.00; H, 6.39; N, 7.65.
4.2.14. 1,3-Dibenzyl-2-(2-chloro-phenyl)-[1,3]diazepane
(7a). As a white solid (98%). Mp 67 8C; MS (EI), m/e 390
(MþþH, 1%), 160 (80), 91 (100); IR (KBr) 2791m, 1085s,
4.2.9. 1,3-Dibenzyl-2-(2,6-dichloro-phenyl)-imidazoli-
dine (3i). As a white solid (88%). Mp 145 8C; MS (EI),
m/e 495 (MþþH, 5%), 251 (90), 91 (100); IR (KBr) 2792m,
1492m, 1436s, 1377m, 1337m, 1148m, 782m, 766m, 737vs,
1
1070s, 762vs, 751vs, 697vs cm21; H NMR (400 MHz) d
8.10 (d, J¼4 Hz, 1H), 7.45–7.19 (m, 13H), 5.04 (s, 1H),
3.90–3.84 (m, 2H) 3.70–3.66 (m, 2H) 3.02–2.97 (m, 2H),
2.88–2.82 (m, 2H), 1.71–1.55 (m, 4H); 13C NMR
(100 MHz) d 140.6, 140.4, 135.6, 130.2, 129.2, 128.6,
128.6, 128.5, 127.0, 126.8, 82.6, 55.5, 48.9, 26.2. Anal.
Calcd for C22H23N3: C, 76.80; H, 6.96; N, 7.17, found: C,
76.42; H, 7.05; N, 6.99.
1
698s cm21; H NMR (400 MHz) d 7.37–7.11 (m, 13H),
5.07 (s, 1H), 3.87 (d, J¼13.6 Hz, 2H), 3.58 (d, J¼13.6 Hz,
2H), 3.36–3.33 (m, 2H), 2.62–2.58 (m, 2H); 13C NMR
(100 MHz) d 140.1, 137.7, 135.2, 129.5, 128.6, 128.5,
128.2, 127.1, 85.0, 58.2, 51.8. Anal. Calcd for C23H22Cl2N2:
C, 69.52; H, 5.58; N, 7.06, found: C, 69.47; H, 5.59; N, 6.88.
4.2.10. 1,3-Dibenzyl-2-ethyl-imidazolidine (3j). The crude
oil was purified by flash chromatography (FCC) (eluant:
2.5% ethyl acetate 20.5% triethylamine–hexane) to afford
the title compound 3j as a clear oil. (85%). MS (EI), m/e 280
4.2.15. 2-Chlorophenyl-1,3-bis-((R)-1-phenyl-ethyl)-imi-
dazoline (9a). The crude product was purified by Kugelrohr
distillation (0.5 mbar, 200 8C) to afford the title compound
9a as a clear yellow oil (81%). [a]2D5¼230 (c¼1 in CHCl3),

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V. Jurcık, R. Wilhelm / Tetrahedron 60 (2004) 3205–3210
3209
MS (EI), m/e 391 (MþþH, 15%), 279 (Mþ2PhCl, 100),
105 (65); IR (neat) 2970s, 1490s, 1450s, 1370s, 1030s, 760s,
700s cm21; 1H NMR (400 MHz) d 7.98 (d, J¼8.0 Hz, 1H),
7.38–7.14 (m, 13H), 4.97 (s, 1H), 3.81–3.71 (m, 2H),
3.20–3.14 (m, 1H), 2.90–2.85 (m, 1H), 2.74–2.63 (m, 2H),
1.42 (d, J¼6.5 Hz, 3H), 1.15 (d, J¼6.5 Hz, 3H); 13C NMR
(100 MHz) d 145.0, 144.4, 141.9, 134.6, 132.3, 129.2,
128.9, 128.6, 128.2, 127.9, 127.7, 127.2, 127.1, 126.8, 78.5,
62.2, 55.4, 50.0, 49.1, 44.7, 23.4, 14.4. Anal. Calcd for
C25H27N2Cl: C, 76.81; H, 6.97; N, 7.17, found: C, 76.43; H,
6.95; N, 7.12.
135.8, 129.4, 128.4, 128.2, 128.1, 126.9, 126.7, 124.5,
122.5, 87.8, 69.3, 67.9, 56.9, 52.9, 30.6, 30.3, 25.0, 24.9.
Anal. Calcd for C26H29N3: C, 81.42; H, 7.62; N, 10.96,
found: C, 81.22; H, 7.65; N, 10.90.
Acknowledgements
Financial support by Fonds der Chemischen Industrie,
BMBF, DFG and Nieders. Vorab der Volkswagen Stiftung
is gratefully acknowledged.
4.2.16. 4-Chlorophenyl-1,3-bis-((R)-1-phenyl-ethyl)-imi-
dazoline (9b). The crude product was purified by Kugelrohr
distillation (0.5 T, 200 8C) to afford the title compound 9b
as a clear yellow oil (80%). [a]2D5¼270 (c¼1 in CHCl3),
MS (EI), m/e 391 (MþþH, 25%), 279 (Mþ2PhCl, 100),
1H NMR (400 MHz) d 7.26–7.13 (m, 14H), 4.35 (s, 1H),
3.66 (q, J¼6.5 Hz, 1H), 3.56 (q, J¼6.5 Hz, 1H), 3.14–3.02
(m, 2H), 2.90–2.82 (m, 2H), 1.33 (d, J¼6.5 Hz, 3H), 1.22
(d, J¼6.5 Hz, 3H); 13C NMR (100 MHz) d 144.6, 144.3,
144.4, 133.1, 130.7, 128.5, 128.3, 128.09, 128.06, 127.99,
127.2, 127.1, 82.0, 60.3, 59.2, 48.3, 47.0, 23.7, 17.9. Anal.
Calcd for C25H27N2Cl: C, 76.81; H, 6.97; N, 7.17, found: C,
76.55; H, 7.02; N, 7.16.
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¨
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1H), 2.55–2.49 (m, 1H), 1.83–1.70 (m, 2H), 1.31–1.13 (m,
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