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Buijnsters, P.J.J.A.

Feiters, M.C.

Gelder, R. de

Nolte, R.J.M.

Reijden, F.P. van der

Sommerdijk, N.A.J.M.

Zwanenburg, B.

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Journal of Chemical Crystallography, Vol. 29, No. 2, 1999
Synthesis and crystal structure of (1)-(2R,3R)-N,
N9-bis-trityl-2,3-bis-aziridine
P. J. J. A. Buijnsters,(1) F. P. van der Reijden,(1) M. C. Feiters,(1) R. de Gelder,(2)
N. A. J. M. Sommerdijk,(1) R. J. M. Nolte,(1)* and B. Zwanenburg(1)*
Received January 4, 1999
A new C2 symmetric bis-aziridine derivative was synthesized starting from L-(1)-tartaric
acid. The molecular structure of (1)-(2R, 3R)-N, N9-bis-trityl-2,3-bis-aziridine 4, was deter-
mined by 1H, 13C NMR and elemental analysis and was confirmed by single-crystal X-ray
diffraction. Crystal data for 4: C42H36N2, orthorhombic, space group: P212121, a 5 12.7633(14),
b 5 14.5661(6), c 5 17.4184(14) A˚, and Z 5 4.
KEY WORDS: Bis-aziridine; C2-symmetric compound; L-(1)-tartaric acid.
Introduction
Aziridine rings are present in many synthetic
and natural compounds of biological importance.1
They have been used in the synthesis of b-lactam
antibiotics,2 amino sugar derivatives,3 and surfac-
tants.4 In this respect chiral aziridines form an inter-
esting class of compounds, since they are available
in enantiopure form starting from simple materials
by various routes.1,5
Enantiopure surfactants can assemble to form
chiral supramolecular structures. The expression of
molecular chirality on a supramolecular level re-
quires a high degree of organization within the aggre-
gates. In particular, the formation of a hydrogen
bonding network of secondary amides has been effec-
tively used6 to achieve this organization. Currently,
the synthesis and aggregation behavior of dimeric or
so-called gemini surfactants is receiving much atten-
tion.7 Therefore, it would be of interest to synthesize
chiral gemini surfactants containing secondary am-
(1) Department of Organic Chemistry, NSR Center for Molecular
Structure, Design and Synthesis, University of Nijmegen, Toer-
nooiveld 1, 6525 ED Nijmegen, The Netherlands.
(2) Department of Inorganic Chemistry, NSR Center for Molecular
Structure, Design and Synthesis, University of Nijmegen, Toer-
nooiveld 1, 6525 ED Nijmegen, The Netherlands.
* To whom correspondence should be addressed.
179
1074-1542/99/0200-0179$16.00/0 Ó 1999 Plenum Publishing Corporation
ides using the synthetic methodology developed in
our laboratory.4 This would require the development
of a bis-aziridine building block starting from tartaric
acid (Scheme 1).
Through known literature procedures, this com-
pound can easily be converted into a bis-aziridine
compound. Acylation of this compound with a suit-
able fatty acid followed by ring opening would result
in amide containing gemini surfactants as depicted
in Scheme 1 in a retrosynthetic manner.
Scheme 1. Retrosynthetic scheme of the synthesis of amide con-
taining gemini surfactants.
180 Buijnsters, van der Reijden, Feiters, de Gelder, Sommerdijk, Nolte, and Zwanenburg
Experimental section
General remarks
Optical rotations were determined with a Per-
kin-Elmer automatic polarimeter, model 241 MC us-
ing 1% solutions at 208C in the solvents indicated.
Melting points were determined using a Reichert
thermopan microscope equipped with crossed polar-
izers, and are uncorrected. 1H NMR experiments
were performed on a Bruker AC 100 (100 MHz, FT
or a Bruker AC 400 (400 MHz, FT) spectrometer
using solutions in CDCl3 (internal standard Me4Si).
Routine FT-IR spectra were recorded on a Biorad
WIN-IR FTS-25 spectrometer. Elemental analyses
were performed on a Carlo Erba CHNS-O EA 1108
element analyzer. Mass spectra were obtained with
Table 1. Crystal Data and Refinement for Compound 4
Empirical formula C42H36N2
CCDC deposit no. CCDC-1003/5488
Color/shape colorless transparent/regular
Formula weight 568.73
Temperature 293(2) K
Crystal system, space group Orthorhombic, P2 12121
Unit cell dimensions a 5 12.7633(14) A˚
(25 reflections b 5 14.5661(6) A˚
20.481 , u , 23.068) c 5 17.4184(14) A˚
Volume 3238.3(5) A˚3
Z, Calculated density 4, 1.167 mg/m3
Absorption coefficient 0.512 mm21
Diffractometer/scan Enraf-Nonius CAD4/u-2u
Radiation/wavelength CuKa (graphite monochrom./
1.54184 A˚)
F(000) 1208
Crystal size 0.29 3 0.17 3 0.09 mm
u range for data collection 3.96 to 69.938
Index ranges 215 # h # 0, 217 # k # 0,
221 # l # 0
Reflections collected 3449
Independent/observed refls. 3449(Rint 5 0.0000)/2473([Io
.2s(Io)])
Absorption correction Semi-empirical from c13
Range of relat. transm. 0.906 and 1.124
factors
Refinement method Full-matrix, least-squares
on F2
Computing SHELXL-939
Data/restraints/parameters 3449/0/542
Goodness-of-fit on F2 1.077
SHELXL-93 weight 0.0679 and 0.4404
parameters
Final R indices [I . 2s (I)] R1 5 0.0535, wR2 5 0.1224
R indices (all data) R1 5 0.0828, wR2 5 0.1394
Extinction coefficient 0.0017(2)
Largest diff. peak and hole 0.197 and 20.164 e. A˚23
a double focusing VG 7070E spectrometer. Diethyl
ether was pre-dried over potassium hydroxide, then
distilled from sodium/benzophenone. Dimethyl for-
mamide was dried by stirring overnight with BaO
followed by distillation under vacuum. Thin-layer
chromatography was carried out on Merck precoated
silica gel 60 F254 plates (0.25 mm) using the eluents
indicated. Spots were visualized with UV or using
molybdate spray. Flash column chromatography was
carried out at a pressure of ca. 1.0 bar, using Merck
Kieselgel 60H.
Synthesis
(2)-(2S, 3S)-1,4-Diazido-2,3-butanediol (2). So-
dium azide (7.0 g, 107 mmol) was added to a solution
of (2S, 3S)-1,4-O-ditosyl threitol7e 1 (11.4 g, 26.5
mmol) in DMF (170 ml) and the mixture was heated
for 2 h at 808C. After cooling, water (150 ml) was
added and the reaction mixture was extracted with
diethyl ether (3 3 50 ml). The combined organic
layers were dried (Na2SO4) and concentrated in
vacuo. The crude product was purified by flash col-
umn chromatography (SiO2, ethyl acetate-hexane,
1 : 1 (v/v)) to give a colorless oil in 59% yield. Rf 5
0.53 (SiO2, ethyl acetate-hexane, 1 : 1 (v/v)); [a]20D
213.0 (c 1.00, CHCl3); IR (KBr, cm21): 3391 (OH),
2931 (CH), 2105 (N3); 1H-NMR (CDCl3, 100 MHz,
ppm): d 2.4 (d, 2H, J 5 4.9 Hz, 2 3 OH), 3.4 (d, 4H,
J 5 6.5 Hz, 2 3 CH2N3), 3.7 (m, 2H, 2 3 CHOH);
MS (EI, m/z, rel. int. (%)): 172 (M1, 4.4), 155
(C4H7N6O1, 4.3), 116 (C3H6N3O21, 24.0), 42 (N31,
54.8), 28 (N21, 100).
(1)-(2R, 3R)-N, N9-bis-trityl-2,3-bis-aziridine
(4). To a solution of 2 (100 mg, 0.58 mmol) in dry
acetonitrile triphenylphosphine (300 mg, 1.14 mmol)
was added and the mixture was stirred at room tem-
perature for 18 h. Subsequently, the reaction mixture
was heated under reflux for 4 h and concentrated in
vacuo. The crude reaction mixture was dissolved in
CH2Cl2 (10 ml) and cooled to 2188C. To the cooled
solution, pyridine (0.4 ml) and trityl chloride (350
mg, 1.28 mmol) were added and the mixture was kept
at 2188C for 1 h. Hereafter the reaction mixture was
allowed to warm to room temperature and stirred
for 1 h. After washing with citric acid (10% (w/w) 2
3 10 ml) and saturated Na2CO3 (10 ml), the reaction
mixture was dried (Na2SO4) and concentrated. The
crude mixture was purified with flash chromatogra-
phy (SiO2, ethyl acetate–hexane, 1 : 12 (v/v)) to afford
(1)-(2R,3R)-N,N9-bis-trityl-2,3-bis-aziridine 181
a colorless solid in 15% overall yield. The compound
could be crystallized by adding 4 dissolved in CHCl3
(1.5 ml) with the help of a Pasteur pipette to the
bottom of a test tube which contained MeOH (0.5
ml). After 1 week colorless crystals were obtained
which were suitable for x-ray analysis. Rf 5 0.56 (SiO2,
Table 2. Atomic Coordinates (3 104) and Equivalent Isotropic
Displacement Parameters (A˚2 3 103) for 4
x/a y/b z/c U(eq)
N(1) 24018(2) 22387(2) 22255(2) 45(1)
C(1) 23121(3) 22628(3) 21744(2) 42(1)
C(2 24535(5 21510(4) 22175(4) 78(2)
C(3) 23928(4) 21724(3) 22867(3) 58(1)
C(10) 22711(3) 23570(3) 22008(2) 43(1)
C(11) 23265(3) 24105(3) 22525(2) 51(1)
C(12) 22927(4) 24986(3) 22706(3) 63(1)
C(13) 22027(4) 25342(3) 22381(3) 64(1)
C(14) 21470(4) 24816(3) 21873(3) 64(1)
C(15) 21795(4) 23946(3) 21689(2) 56(1)
C(20) 23551(3) 22779(3) 2933(2) 49(1)
C(21) 24613(4) 23004(4) 2828(3) 72(1)
C(22) 24983(6) 23197(5) 2106(4) 90(2)
C(23) 24357(6) 23159(4) 518(4) 90(2)
C(24) 23300(6) 22965(4) 432(3) 78(2)
C(25) 22916(4) 22774(3) 2296(2) 58(1)
C(30) 22261(3) 21890(3) 21784(2) 42(1)
C(31) 22288(3) 21115(3) 21321(2) 49(1)
C(32) 1595(4) 2398(3) 21414(3) 62(1)
C(33) 2842(4) 2441(3) 21985(3) 64(1)
C(34) 2802(3) 21197(3) 22454(3) 60(1)
C(35) 21498(3) 21924(3) 22352(2) 49(1)
N(19) 24916(2) 22805(2) 23753(2) 46(1)
C(19) 25955(3) 22885(3) 24151(2) 43(1)
C(29) 23991(4) 22550(5) 24199(3) 75(2)
C(39) 24435(3) 21913(3) 23624(3) 59(1)
C(109) 26771(3) 22989(3) 23504(2) 43(1)
C(119) 26502(4) 23277(4) 22778(2) 61(1)
C(129) 27253(4) 23384(4) 22212(3) 79(2)
C(139) 28293(4) 23212(4) 22366(3) 71(2)
C(149) 28572(4) 22932(4) 23078(3) 62(1)
C(159) 27840(3) 22817(3) 23653(3) 56(1)
C(209) 25928(3) 23807(3) 24586(2) 47(1)
C(219) 25131(5) 24447(4) 24481(3) 71(1)
C(229) 25145(7) 25274(4) 24881(4) 94(2)
C(239) 25915(7) 25477(4) 25384(4) 93(2)
C(249) 26714(6) 24858(4) 25489(3) 83(2)
C(259) 26726(5) 24031(3) 25092(3) 63(1)
C(309) 26188(3) 22072(3) 24673(2) 42(1)
C(319) 25933(3) 22074(3) 25445(2) 47(1)
C(329) 26086(4) 21301(3) 25898(2) 59(1)
C(339) 26477(4) 2512(3) 25578(3) 66(1)
C(349) 26718(4) 2487(3) 24813(3) 63(1)
C(359) 26581(3) 21257(3) 24365(2) 51(1)
a U(eq) is defined as one-third of the trace of the orthogonalized
Uij tensor.
ethyl acetate-hexane, 1 : 12 (v/v)); [a]20D1 156.5 (c
1.00, CHCl3); IR (KBr, cm21) 3100–3000 (CUH,
aryl),* 3000–2900 (CUH, alkyl); 1H-NMR (CDCl3,
400 MHz): d 7.42–7.08 (m, 30H, 2 3 C19H15), 1.62-
1.61 (m, 2H, 2 3 CHH), 1.50–1.45 (m, 2H, 2 3 CH),
1.06–1.05 (m, 2H, 2 3 CHH); 13C-NMR (CDCl3, 35
MHz): d 25.0 (CH2), 33.7 (CH), 74.0 (C(C6H5)3), 126.6
(p-C(C6H5)3), 127.3 (o-C(C6H5)3), 129.5 (m-
C(C6H5)3), 144.5 (C q, arom); MS (FAB1, m/z): 568
(M1), 325 (C23H21N21), 243 (C19H151). Analysis calcd.
for C42H36N2: C, 88.70; H, 6.38; N, 4.93. Found: C,
88.89; H, 6.23; N, 5.23.
X-ray data collection, structure solution
and refinement
Crystals of 4 suitable for X-ray diffraction stud-
ies were obtained by recrystallization from methanol
and chloroform via slow diffusion. A single crystal
was mounted on a glass fiber. Intensity data were
collected at room temperature and were corrected
for Lorentz and polarization effects. The crystal
structure was determined using the program
CRUNCH.8 The structure was refined by full-matrix
least squares on F 2 values using SHELXL9 with aniso-
tropic parameters for the non-hydrogen atoms. All
hydrogen atoms were initially placed at the calculated
positions and were freely refined subsequently. The
plots of the molecule were made with PLATON.10
Table 1 summarizes the crystal data, data collection,
and structure refinement for 4, and the atomic coordi-
nates of the compound are given in Table 2. The
structure and atomic numbering are presented in
Fig. 1.
Fig. 1. ORTEP representation of the crystal structure of 4.
Thermal ellipsoids are at 40% probability.
182 Buijnsters, van der Reijden, Feiters, de Gelder, Sommerdijk, Nolte, and Zwanenburg
Results and discussion
The optically active bistosylate 1 (Scheme 2) was
obtained from L-(1)-tartaric acid using literature
procedures.11 The conversion of 1 into the corre-
sponding diazido butane diol 2 using sodium azide
in DMF at 808C proceeded smoothly in moderate
yield. The diazido diol was transformed into the bis-
aziridine by reaction with triphenylphosphine. In this,
a so-called Staudinger reaction,12 azido alcohol 2 re-
acts with triphenylphosphine under concomitant ex-
trusion of nitrogen to form a phosphazo compound.
Intramolecular addition of the hydroxyl functions
leads to the formation of oxazaphospholidines, which
upon cleavage of the PUN bond, undergo an intra-
molecular substitution reaction with elimination of
triphenylphosphine oxide, to give the bis-aziridine 3
(Scheme 2).
The isolation of this compound was rather cum-
bersome. Distillation and column chromatography
were not successful. Extraction of the crude reaction
mixture with diethyl ether, washing the extract with
water, and subsequent lyophilization afforded a col-
orless oil. Mass spectrometry revealed the molecular
ion peak (84, M1) but other spectral data (1H NMR,
IR) were not conclusive.
Establishment of the bis-aziridine structure was
therefore performed by derivatization. For this pur-
pose, 3 was converted to the N-trityl derivative 4 by
treatment of the crude reaction mixture with trityl
chloride and base in dichloromethane. After column
chromatography and crystallization from chloroform
and methanol, crystals were obtained which were
suitable for X-ray analysis.
Scheme 2. The synthesis of (1)-(2R, 3R)-N, N9-bis-trityl-2,3-bis-
aziridine, 4.
Table 3. Selected Dihedral Angles [8] for 4
Dihedral angle (8)
N(1)UC(1)UC(10)UC(11) 211.13(45)
N(1)UC(1)UC(20)UC(21) 22.51(56)
N(1)UC(1)UC(30)UC(31) 86.44(41)
N(19)UC(19)UC(109)UC(119) 220.54(51)
N(19)UC(19)UC(209)UC(219) 9.38(50)
N(19)UC(19)UC(309)UC(319) 92.52(42)
C(2)UN(1)UC(1)UC(10) 2176.61(40)
C(29)UN(19)UC(19)UC(109) 2170.19(43)
The molecule possesses a slightly distorted C2-
symmetry, as can be deduced from the selected dihe-
dral angles listed in Table 3, which correspond to the
free rotable bonds in the molecule.
The results presented show unambiguously that
a new enantiopure bis-aziridine derivative has been
synthesized starting from tartaric acid. Removal of
the trityl groups allows functionalization of the aziri-
dine rings and the introduction of, for instance, long
alkyl chains in order to synthesize new gemini surfac-
tants. Studies along this line are underway.
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Synthesis and crystal structure of (+)-(2R,3R)-N, N '-bis-trityl-2,3-bis-aziridine

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Synthesis and crystal structure of (+)-(2R,3R)-N, N '-bis-trityl-2,3-bis-aziridine

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