Investigation of the rearrangement in alkyl-bridged bis(carbamoyldiaziridine) derivatives

Article abstract of DOI:10.1002/ejoc.201200518

The thermal treatment of alkyl-bridged bis(carbamoyldiaziridine) derivatives in toluene at 100 °C led to the formation of new saturated five- and six-membered 1,3-diaza-heterocyclic compounds from ethylene- or propylene-bridged bis(carbamoyldiaziridine) derviatives, respectively. Detailed experimental investigations of this reaction revealed an unprecedented intramolecular eliminative rearrangement, involving the two adjacent diaziridine moieties. The loss of a three-carbon fragment by elimination of acetone during the reaction was confirmed by GC-MS measurements. The products of the rearrangement were fully characterized, and their structures were confirmed by X-ray crystal structure analysis. Furthermore, a reaction mechanism of the eliminative rearrangement was proposed, and the reaction pathway was corroborated by DFT calculations of gas-phase model structures at the B3LYP/6-31G** level. Copyright

Full text of DOI:10.1002/ejoc.201200518

Job/Unit: O20518
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Date: 18-07-12 17:08:36
Pages: 8
FULL PAPER
DOI: 10.1002/ejoc.201200518
Investigation of the Rearrangement in Alkyl-Bridged Bis(carbamoyldiaziridine)
Derivatives
Matthias Kamuf,[a] Frank Rominger,[a] and Oliver Trapp*[a]
Keywords: Nitrogen heterocycles / Sigmatropic rearrangement / Reaction mechanisms / Density functional calculations
The thermal treatment of alkyl-bridged bis(carbamoyldiazir-
idine) derivatives in toluene at 100 °C led to the formation of
new saturated five- and six-membered 1,3-diaza-heterocy-
clic compounds from ethylene- or propylene-bridged bis-
(carbamoyldiaziridine) derviatives, respectively. Detailed ex-
perimental investigations of this reaction revealed an un-
precedented intramolecular eliminative rearrangement, in-
volving the two adjacent diaziridine moieties. The loss of a
three-carbon fragment by elimination of acetone during the
reaction was confirmed by GC–MS measurements. The prod-
ucts of the rearrangement were fully characterized, and their
structures were confirmed by X-ray crystal structure analysis.
Furthermore, a reaction mechanism of the eliminative re-
arrangement was proposed, and the reaction pathway was
corroborated by DFT calculations of gas-phase model struc-
tures at the B3LYP/6-31G** level.
such as ketenes, isocyanates, isothiocyanates, and acylating
reagents at elevated temperatures. Under such conditions,
they are prone to ring-expansion reactions, yielding hetero-
cyclic systems.[11]
Introduction
Diaziridines (1,2-diazacyclopropanes)[1] are an intriguing
class of compounds and have been intensively characterized
and investigated, since the pioneering synthetic work of
Schmitz et al. in 1959.[2,3] Similar to aziridines, diaziridines
contain chirotopic nitrogen atoms and typically show rela-
tively high interconversion barriers[4–6] because of the nitro-
gen atoms incorporated into the strained three-membered
ring and the electronic and steric effects, which destabilize
the transition state of the interconversion process. Further-
more, a double interconversion[7] of the chirotopic N-cen-
ters is necessary. These properties allow the separation and
isolation of single stereoisomers, for example, by chromato-
graphic separation techniques, and make the investigation
of the stereochemistry and stereodynamics of these com-
pounds feasible.[8] Depending on the sterics and electronics
of the N-substituents in aziridines and diaziridines, the free
activation energy ΔG‡ for the interconversion of the chiro-
topic nitrogen atoms is in a range between approximately
Results and Discussion
Herein, we report a new intramolecular eliminative re-
arrangement reaction of alkyl-bridged bis(diaziridines) to
form new saturated five- and six-membered 1,3-diaza-het-
erocyclic compounds (see Scheme 1).
Scheme 1. Rearrangement of alkyl-bridged bis(carbamoyldiazirid-
ine) derivatives to give 1,1Ј-(2,2-dimethylimidazolidine-1,3-diyl)-
90 kJ/mol and 130 kJ/mol.[8b,8d,8f,9] Furthermore, diazirid- bis(3-phenylurea) (2a) and 1,1Ј-(2,2-dimethyldiazinane-1,3-diyl)bis-
ines show pronounced neurotropic activity.[10]
(3-phenylurea) (2b).
Despite the relatively weak N–N bond and the highly
strained three-membered ring system, diaziridines are ther-
modynamically stable. Diaziridines are highly reactive and
often undergo electrocyclic ring-opening reactions with
The reactants 2,2Ј-(ethane-1,2-diyl)bis(3,3-dimethyl-N-
phenyldiaziridine-1-carboxamide) (1a) and 2,2Ј-(propane-
1,3-diyl)bis(3,3-dimethyl-N-phenyldiaziridine-1-carbox-
amide) (1b) were synthesized according to a procedure pub-
electron-deficient alkenes, alkynes, or electrophilic reagents
lished by Makhova et al.[12] by starting from acetone
through the preparation of acetone oxime O-sulfonic esters
according to the method of Oxley and Short.[13] The oxime
[a] Organisch-Chemisches Institut, Ruprecht-Karls-Universität
Heidelberg,
esters were then treated with α,ω-diaminoalkanes to give
Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
α,ω-bis(3,3-dimethyldiaziridin-1-yl)alkanes.[12a] The reac-
Fax: +49-6221-54-4904
E-mail: trapp@oci.uni-heidelberg.de
tion of phenyl isocyanate with both diaziridine-NH groups
Homepage: http://trapp.uni-hd.de/
yielded the corresponding carbamoyl-substituted bis(diazir-
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200518.
idine) derivatives (see Scheme 2).[12b]
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M. Kamuf, F. Rominger, O. Trapp
FULL PAPER
Scheme 2. Synthesis of the reactants for the rearrangement reaction. Reagents and conditions: (a) NaOH (5 m solution), HONH3Cl,
RSO2Cl (R = phenyl or p-tolyl), 0 °C, 1 h;[13] (b) dichloromethane, H2NCH2(CH2)xNH2 (x = 1, 2, or 3) (0.5 equiv.), NEt3, 25–30 °C, 5–
11 d;[12a] (c) anhydrous dichloromethane, PhN=C=O (2.4 equiv.).[12b]
We observed that compounds 1a and 1b underwent re- (N,N-dimethylformamide), but almost insoluble in less po-
arrangement in toluene when heated at 100 °C for 18 h. The lar solvents such as acetonitrile, dichloromethane, chloro-
products were formed by a sigmatropic rearrangement reac- form, toluene, or diethyl ether. The rearrangement product
tion occurring with the formal elimination of C3H4 (see 2a was unambiguously identified by X-ray crystal structure
Scheme 1). Previously reported rearrangements of diazirid- analysis (see Figure 1).
ines and, in particular, of N-carbamoyl-substituted diazirid-
ines describe rearrangement pathways involving carbamoyl
groups, which is not the case with our investigated reactions
(see Scheme 3).[14] The unsubstituted bis(diaziridine) 1,2-
bis(3,3-dimethyldiaziridin-1-yl)ethane (tetramezine) did not
react under the reported conditions herein and was com-
pletely reisolated. This indicates that the electron-with-
drawing carbamoyl group was essential for the rearrange-
ment, which is explained by the effective stabilization of the
proposed reaction intermediate (see Mechanistic Insights).
This is also corroborated by the rearrangement of 2,4-dini-
trophenyl-substituted 1,2-bis(3,3-dimethyldiaziridin-1-yl)-
ethane (3a, see Scheme 4 and Figure 4).
Figure 1. X-ray crystal structure of 2a. The compound crystallized
in racemic form. The enantiomers were formed because of the
chirotopic nitrogen atoms in the heterocyclic ring system.
The extended system 2b obtained by the rearrangement
of 1b shows a similar X-ray crystal structure, where the
compound crystallized as a racemic mixture because of the
chirotopic nitrogen atoms in the heterocyclic ring system
(see Figure 2).
Scheme 3. Proposed reaction pathway of the rearrangement reac-
tion. The alternative rearrangement pathway, as described in the
literature,[14] was not observed.
The isolated yields of the rearrangement product de-
ceased with the length of the alkylene bridge and the ring
size. The reaction proceeded in 67% isolated yield for the Figure 2. X-ray crystal structure of 2b.
five-membered ring and 55% for the six-membered ring
product. The reaction leading to the seven-membered ring
The crystal structure of the bis(phenylurea)-substituted
was not observed. The obtained compounds were soluble heterocyclic molecules was stabilized by a network of inter-
in DMSO (dimethyl sulfoxide) and slightly soluble in DMF molecular hydrogen bonds (see Figure 3). This network also
Scheme 4. Rearrangement of 2,4-dinitrophenyl-substituted bis(diaziridine) 3a to N,N-bis(2,4-dinitrophenyl)-2,2-dimethylimidazolidine-
1,3-diamine (3b).
2
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Rearrangement in Alkyl-Bridged Bis(carbamoyldiaziridine) Derivatives
stabilized the enantiomeric forms of the molecules in the Mechanistic Insights
crystal. The corresponding meso form with the cis-oriented
phenylurea groups was not observed in the solid state.
To investigate the mechanism of the rearrangement reac-
tion, we focused first on the formation of the elimination
product. Therefore, we performed the rearrangement reac-
tions in a sealed flask using DMF, a less volatile solvent.
Upon completion of the reactions, all of the samples were
analyzed by GC–MS. We identified acetone as the elimi-
nation product, showing significant EI-MS signals at m/z =
58 [H3C(CO)CH3]+ and 43 [H3CCO]+ at a retention time
of 3.11 min. This suggested that the small traces of water
(18 μL/mmol) in the solvent were sufficient to produce ace-
tone.
To corroborate our proposed reaction mechanism we
performed DFT calculations of gas-phase model structures
at the B3LYP/6-31G** level for possible reaction intermedi-
ates for the rearrangement of 1a to 2a.
Figure 3. Hydrogen-bond network stabilizing the crystal structure
of racemic 2a. Bond lengths of hydrogen bonds and inversion cen-
ters (i) are depicted in the structure.
However, in solution the heterocyclic ring system and the
chirotopic nitrogen centers were prone to rapid conforma-
tional change and inversion, respectively. These processes
resulted in a pronounced peak-broadening at room tem-
perature and –50 °C for all of the NMR signals of the ring
groups. In particular, the 13C NMR signals for all of the
ring carbon atoms were greatly broadened because of the
longer relaxation times.
To probe the hypothesis that an electron-withdrawing
group is essential for this type of rearrangement reaction,
we prepared 2,4-dinitrophenyl-substituted bis(diaziridine)
3a and subjected this compound to our described re-
arrangement conditions. Indeed, the same rearrangement
proceeded with the electron-withdrawing 2,4-dinitrophenyl
groups (see Scheme 4).
We assume that the first step of the reaction mechanism
is a thermal electrocyclic ring opening[15] of one of the diaz-
iridine moieties, which results in an azomethine imine group
isoelectronic to an allyl anion. The formation of an azo-
methine imine intermediate had been previously suggested
for the interconversion of diaziridines and for the
electrocyclic reactions of diaziridines (see Schemes 3 and
5).[8f,11a,11b,14,16] Furthermore, these structures are stabilized
in compounds such as 1-(arylylidene)pyrazolidone 3-beta-
ines.[17] Such compounds are cyclized by UV irradiation to
give the corresponding diaziridines.[18] Upon heating, they
can be retransformed into the azomethine imines. The sta-
bility of these compounds can be attributed to the presence
of the carbonyl group next to the nitrogen atom. We antici-
pate in our investigated reactions that the carbonyl group
stabilizes the ring-opened intermediate in a similar fashion.
Additional stabilization is expected because of hyperconju-
gation.
According to our calculations, the ring opening to inter-
mediate I1 was clearly favored over the bond cleavage to
form I1Ј (see Schemes 5 and 6). In the case of I1 and with
the observed five-membered ring product (Scheme 4), this
reasoning is in line with the more efficient stabilization of
the heteroallyl system by the adjacent carbamoyl group (R).
Similar results were found by DFT calculations for the
opening of the diaziridine ring in 1,2-diazabicyclo[3.1.0]-
hexane-2-ones.[19]
The rearrangement product N,N-bis(2,4-dinitrophenyl)-
2,2-dimethylimidazolidine-1,3-diamine (3b) was isolated
and characterized by X-ray crystal structure analysis (see
Figure 4).
A detailed analysis of the natural bond orbitals (NBOs)
of I1 revealed that the LUMO is located at the N=CMe2
Figure 4. X-ray crystal structure of 3b. The compound crystallized
in racemic form.
Scheme 5. Proposed mechanism of the rearrangement reaction.
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M. Kamuf, F. Rominger, O. Trapp
FULL PAPER
tions as the rearrangement reaction, that is, adding
10 equiv. of acetone to a sealed vial to avoid evaporation of
acetone at elevated reaction temperatures. The formation of
1,1Ј-(2,2-dimethylimidazolidine-1,3-diyl)bis(3-phenylurea)
(2a) was not observed, bis(hydrazine) 4 was completely re-
isolated. From these results, we conclude that the simple
decomposition and recondensation of the bis(hydrazine)
with acetone can be excluded.
Scheme 6. Energy diagram of the calculated energies of the reac-
tant, product, and proposed reaction intermediates.
Conclusions
We presented a new type of an eliminative rearrangement
reaction involving alkyl-bridged bis(carbamoyldiaziridine)
derivatives. This rearrangement represents the first example
of an intramolecular reaction involving two diaziridine
groups. The reaction mechanism was investigated experi-
mentally by GC–MS as well as theoretically by using DFT
calculations of gas-phase model structures. The reaction
may be expanded to other bis(diaziridine) derivatives with
electron-withdrawing substituents and provides a synthetic
pathway towards previously unknown substituted hetero-
cyclic compounds.
group, which can easily be attacked by the lone pair of the
diaziridine nitrogen atom located next to the CH2 group.
Both orbitals are depicted in Figure 5.
Figure 5. LUMO (left) and nitrogen lone pair (right) of intermedi-
ate I1 revealed by NBO analysis at isosurface values of 0.1.
Experimental Section
General Methods: All of the reagents and solvents were obtained
from Acros, ABCR, Alfa Aesar, Sigma–Aldrich, or VWR and were
used without further purification unless otherwise noted. Anhy-
Through an intramolecular attack of the lone pair at the
LUMO, spirocyclic intermediate I2 is formed, followed by
a ring-opening reaction to give intermediate I3. The ad- drous dichloromethane was prepared by using an MBRAUN MB
SCS-800 solvent purification system. The handling of moisture-
sensitive materials was carried out under nitrogen by using Schlenk
techniques. Deuterated solvents were purchased from Sigma–Ald-
rich. The NMR spectroscopic data were recorded with Bruker Av-
ance 500, Bruker Avance 400, or Bruker Avance 300 spectrometers
at room temperature. The chemical shifts (in ppm) were referenced
to the residual solvent protons. The multiplicity of the signals was
assigned as s (singlet), d (doublet), t (triplet), q (quartet), or m
(multiplet). The 13C NMR assignments were achieved by using
HSQC (heteronuclear single quantum correlation) experiments. In-
dition of a water molecule leads to intermediate I4. In the
last step of the reaction, acetone is eliminated to form the
product. The total energy balance is exothermic (about
130 kJ/mol in the gas phase). It is noteworthy that the lat-
tice energy from the crystalline product formation, caused
by the formation of the strong hydrogen bonds (see Fig-
ure 3), has an additional exothermic contribution to the
overall energy balance.
Another possible mechanism includes a simultaneous
electrocyclic ring-opening reaction of both diaziridine rings frared (IR) spectra were recorded with a Bruker TFS66 (Rhein-
stetten, Germany) or a Thermo Fisher Scientific Nicolet 6700 Ad-
vanced FTIR Spectrometer equipped with a Smart iTR ATR Dia-
mond (Madison, WI, USA). HR (ESI) mass spectra were recorded
with a Bruker ApexQe hybrid 9.4 T FT-ICR-MS instrument. HR
(EI) and HR [FAB (fast atom bombardment)] mass spectra were
recorded with a JEOL JMS-700 magnetic sector instrument. GC–
MS measurements were performed with a Thermo Trace GC Polar-
isQ (San Jose, CA, USA) equipped with a split injector (250 °C), a
flame-ionization detector (250 °C), and a quadrupole ion trap mass
spectrometer. An HP5-MS column was used for separating the ana-
followed by cyclization to form I3. However, the probability
for the simultaneous opening of both diaziridine moieties is
highly unlikely.
An alternative mechanism can be proposed by hydrolysis
of the two diaziridine moieties, which would yield a bis(hy-
drazine) derivative and 2 equiv. of acetone. Recondensation
of the bis(hydrazine) derivative with acetone would result
in the observed product (see Scheme 7). To probe this
mechanism, we prepared the bis(hydrazine) 4 by hydrolysis
of 1a. Product 4 was subjected to the same reaction condi- lytes (30 mϫ0.25 mm i.d., 250 nm film thickness). Helium was
Scheme 7. Alternative reaction pathway through the hydrolysis of the two diaziridine moieties to form bis(hydrazine) 4. Attempted
recondensation of 4 with acetone does not yield 1,1Ј-(2,2-dimethylimidazolidine-1,3-diyl)bis(3-phenylurea) (2a).
4
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Rearrangement in Alkyl-Bridged Bis(carbamoyldiaziridine) Derivatives
used as an inert carrier gas at 80 kPa. All of the measurements were
phenyldiaziridine-1-carboxamide) (1b, 423 mg, 1.00 mmol) was sus-
isothermally performed at 80 °C. EI mass spectra were recorded at pended in toluene (20 mL), and the resulting solution was heated
an ion-source temperature of 200 °C and an electron energy of
70 eV. The data acquisitions were performed by using the Xcalibur
software package (Thermo, San Jose, CA, USA). The crystal struc-
tures were recorded with a Bruker APEX or a Bruker Smart CCD.
The intensities of the reflections were corrected for Lorentz and
polarization effects. An empirical absorption correction was ap-
plied by using SADABS (2008/1)[20] based on the Laue symmetry
of the reciprocal space. The structures were solved by direct meth-
ods and refined against F2 with a full-matrix least-squares algo-
rithm by using the SHELXTL software package (2008/4).[21] The
hydrogen atoms were treated by using appropriate riding models.
to 100 °C as it was stirred. The suspended reactant dissolved after
a few minutes. After that time, the stirring was stopped, and the
heating was continued at 100 °C for 18 h. Then, the suspension was
slowly cooled to room temperature. The precipitate was collected
on a suction filter, washed with dichloromethane (10 mL), and
dried under high vacuum.
1,1Ј-(2,2-Dimethylimidazolidine-1,3-diyl)bis(3-phenylurea) (2a): Col-
orless crystals (247 mg, 67%), m.p. 206–207 °C. 1H NMR
(300 MHz, [D6]DMSO, 25 °C): δ = 8.71 (s, 2 H, PhNH), 7.96 (s, 2
3
3
H, NNH), 7.51 (d, JH,H = 7.6 Hz, 4 H, o-CHAr), 7.26 (dd, JH,H
= 7.6 Hz, JH,H = 7.3 Hz, 4 H, m-CHAr), 6.97 (t, JH,H = 7.3 Hz,
2 H, p-CHAr), 3.80–2.60 (br. m, 4 H, CH2), 1.15 (s, 6 H, CH3) ppm.
13C NMR (75 MHz, [D6]DMSO, 25 °C): δ = 156.14 (C=O), 139.47
(ipso-CAr), 128.38 (m-CAr), 121.93 (p-CAr), 119.30 (o-CAr), 81.90
(Cring), 49.95 (CH2), 20.15 (CH3) ppm. HRMS (ESI): calcd. for [M
+ H]+ 369.20335; found 369.20332; calcd. for [M + Na]+ 391.18530;
found 391.18527; calcd. for [M + K]+ 407.15923; found 407.15924;
calcd. for [2 M + H]+ 737.39942; found 737.39959; calcd. for [2 M
+ Na]+ 759.38137; found 759.38136; calcd. for [2 M + K]+
775.35531; found 775.35552. C19H24N6O2 (368.43): calcd. C 61.94,
3
3
General Method for the Synthesis of 2,2Ј-(Alkane-α,ω-diyl)bis(3,3-
dimethyldiaziridine): Acetone oxime O-benzenesulfonate or acetone
oxime O-p-toluenesulfonate are prepared from acetone according
to the synthesis by Oxley and Short.[13] The oxime ester was then
treated with α,ω-diaminoalkane in dichloromethane with triethyl-
amine according to the method of Makhova et al.[12a]
General Method for the Synthesis of 1: Compounds 1a and 1b were
synthesized according to the method of Makhova et al.[12b] 1,2-
Bis(3,3-dimethyldiaziridin-1-yl)ethane (851 mg, 5.00 mmol) or 1,3-
bis(3,3-dimethyldiaziridin-1-yl)propane (921 mg, 5.00 mmol) were
dissolved in anhydrous dichloromethane (20 mL). A solution of
phenyl isocyanate (1.30 mL, 12.0 mmol) in anhydrous dichloro-
methane (35 mL) was added dropwise at 0 °C. The solution was
stirred at 0 °C for 1 h and then at room temperature for 10 min.
The solvent was removed under high vacuum. The white precipitate
formed was washed with diethyl ether (2ϫ5 mL) and dried under
high vacuum.
H 6.57, N 22.81; found C 62.17, H 6.49, N 22.53. IR (KBr): ν =
˜
3094, 3063, 2979, 2938, 1680, 1601, 1530, 1447, 755, 693 cm–1.
1,1Ј-(2,2-Dimethyldiazinane-1,3-diyl)bis(3-phenylurea) (2b): Color-
less crystals (210 mg, 55%), m.p. 201–203 °C. 1H NMR (300 MHz,
[D6]DMSO, 25 °C): δ = 8.67 (s, 2 H, PhNH), 8.09 (br. s, 2 H,
3
3
NNH), 7.55 (d, JH,H = 7.7 Hz, 4 H, o-CHAr), 7.26 (dd, JH,H
=
7.6 Hz, JH,H = 8.1 Hz, 4 H, m-CHAr), 6.97 (t, JH,H = 7.3 Hz, 2
3
3
a
H, p-CHAr), 3.17–2.92 (br. m, 2 H, NCH2 ) 2.94–2.74 (br. m, 2 H,
NCH2b), 2.10–1.72 (br. m, 2 H, CH2), 1.29 (s, 6 H, CH3) ppm. 13C
NMR (75 MHz, [D6]DMSO, 25 °C): δ = 156.00 (C=O), 139.44
(ipso-CAr), 128.26 (m-CAr), 122.03 (p-CAr), 119.90 (o-CAr), 77.91
(Cring), 48.60 (NCH2), 20.85 (CH2), 20.85 (CH3) ppm. HRMS
(ESI): calcd. for [M + H]+ 383.21900; found 383.21923; calcd. for
[M + Na]+ 405.20095; found 405.20119; calcd. for [M + K]+
421.17488; found 421.17515; calcd. for [2 M + Na]+ 787.41267;
found 787.41256; calcd. for [2 M + K]+ 803.38661; found
2,2Ј-(Ethane-1,2-diyl)bis(3,3-dimethyl-N-phenyldiaziridine-1-carbox-
amide) (1a): White solid (1.99 g, 97%), m.p. 144–147 °C. H NMR
1
(500 MHz, CD2Cl2, 25 °C): δ = 8.76 (s, 2 H, NH), 7.51 (d, 3JH,H
=
3
3
7.5 Hz, 4 H, o-CHAr), 7.29 (dd, JH,H = 7.5 Hz, JH,H = 7.5 Hz, 4
H, m-CHAr), 7.06 (t, 3JH,H = 7.4 Hz, 2 H, p-CHAr), 3.32 (dq, 2JH,H
3
a
2
= 2.8 Hz, JH,H = 4.8 Hz, 2 H, CH2 ), 2.75 (dq, JH,H = 2.6 Hz,
3JH,H = 4.7 Hz, 2 H, CH2b), 1.58 (s, 6 H, CH3 ), 1.42 (s, 6 H, CH3
)
a
b
ppm. 13C NMR (125 MHz, CD2Cl2, 25 °C): δ = 160.19 (C=O),
137.87 (ipso-CAr), 128.91 (m-CAr), 123.92 (p-CAr), 119.39 (o-CAr),
803.38664. IR (KBr): ν = 3059, 2940, 1677, 1601, 1529, 1447, 1313,
˜
1232, 753, 692 cm–1.
65.10 (Cring), 53.11 (CH2), 23.07 (CH3b), 18.44 (CH3 ) ppm.
a
HRMS (ESI): calcd. for [M + H]+ 409.23456; found 409.23477;
calcd. for [M + Na]+ 431.21660; found 431.21674; calcd. for [M +
K]+ 447.19053; found 447.19069; calcd. for [2 M + K]+ 839.44397;
found 839.44429.
Hydrolysis of 1a to 4: 2,2Ј-(Ethane-1,2-diyl)bis(3,3-dimethyl-N-
phenyldiaziridine-1-carboxamide) (1a, 204 mg, 500 μmol) was sus-
pended in hydrochloric acid (1 m solution, 5 mL), and the mixture
was heated at reflux for about 20 min. After cooling to room tem-
perature, sodium hydroxide (1 m solution, 10 mL) was added. After
5 min of stirring, the product was collected on a suction funnel,
washed with water (20 mL), and dried under high vacuum in a
desiccator over P4O10.
2,2Ј-(Propane-1,3-diyl)-bis(3,3-dimethyl-N-phenyldiaziridine-1-carb-
oxamide) (1b): White solid (2.01 g, 95%), m.p. 122–124 °C. 1H
NMR (300 MHz, CD2Cl2 25 °C): δ = 8.03 (s, 2 H, NH), 7.46 (d,
3
3
3JH,H = 8.4 Hz, 4 H, o-CHAr), 7.30 (dd, JH,H = 7.6 Hz, JH,H
=
8.2 Hz, 4 H, m-CHAr), 7.09 (t, 3JH,H = 7.4 Hz, 2 H, p-CHAr), 2.99–
2,2Ј-(Ethane-1,2-diyl)bis(N-phenylhydrazinecarboxamide) (4): White
2.86 (m, 2 H, NCH2 ), 2.82–2.69 (m, 2 H, NCH2b), 2.18–2.05 (m,
a
1
solid (155 mg, 94%), m.p. 178–179 °C. H NMR (300 MHz, [D6]-
2 H, CH2), 1.51 (s, 6 H, CH3 ), 1.37 (s, 6 H, CH3b) ppm. 13C NMR
a
DMSO, 25 °C): δ = 8.68 (s, 2 H, PhNH), 7.60 [s, 2 H, R(CO)NH],
7.52 (d, 3JH,H = 7.9 Hz, 4 H, o-CHAr), 7.21 (dd, 3JH,H = 7.6, 8.2 Hz,
4 H, m-CHAr), 6.91 (dd, 3JH,H = 7.3, 7.4 Hz, p-CHAr) 5.06 (s, 2 H,
NHCH2), 2.83 (s, 4 H, CH2) ppm. 13C NMR (100 MHz, [D6]-
DMSO, 25 °C): δ = 156.64 (C=O), 139.83 (ipso-CAr), 128.48 (m-
CAr), 121.49 (p-CAr), 118.43 (o-CAr), 49.10 (CH2) ppm. HRMS
(ESI): calcd. for [M + H]+ 329.17205; found 329.17214; calcd. for
[M + Na]+ 351.15400; found 351.15408; calcd. for [M + K]+
367.12793; found 367.12809; calcd. for [2 M + H]+ 657.33682;
found 657.33746; calcd. for [2 M + Na]+ 679.31877; found
679.31907; calcd. for [2 M + K]+ 695.29271; found 695.29360. IR:
(75 MHz, CD2Cl2, 25 °C): δ = 160.50 (C=O), 137.44 (ipso-CAr),
129.04 (m-CAr), 124.12 (p-CAr), 119.39 (o-CAr), 66.73 (Cring), 51.00
(NCH2), 28.79 (CH2), 22.00 (CH3b), 18.64 (CH3 ) ppm. HRMS
a
(ESI): calcd. for [M + H]+ 423.25030; found 423.25059; calcd. for
[M + Na]+ 445.23225; found 445.23255; calcd. for [M + K]+
461.20618; found 461.20651; calcd. for [2 M + Na]+ 867.47527;
found 867.47392; calcd. for [2 M + K]+ 883.44921; found
883.44886.
General Method for the Rearrangement of 1 to 2: 2,2Ј-(Ethane-1,2-
diyl)bis(3,3-dimethyl-N-phenyldiaziridine-1-carboxamide)
(1a,
409 mg, 1.00 mmol) or 2,2Ј-(propane-1,3-diyl)bis(3,3-dimethyl-N- ν = 3328, 3294, 3232, 3012, 2925, 2863, 1631, 1592, 1569, 1542,
˜
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Job/Unit: O20518
/KAP1
Date: 18-07-12 17:08:36
Pages: 8
M. Kamuf, F. Rominger, O. Trapp
FULL PAPER
[2]
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737, 693 cm–1.
X-ray Crystal Structure Analyses
Crystal Data of 2a: C19H24N6O2, M = 368.44 gmol–1, triclinic,
¯
space group P1,
a = 8.8194(8) Å, b = 9.9670(10) Å, c =
12.6762(12) Å, α = 106.504(2)°, β = 105.951(2)°, γ = 103.066(2)°,
V = 969.72(16) Å3, Z = 2, dcalcd. = 1.262 gcm–1, μ = 0.086 mm–1,
crystal size 0.26ϫ0.17ϫ0.14 mm, number of reflections: 10393,
number of independent reflections: 4788, Rint = 0.0208, R1 = 0.050
[from 4007 unique reflections with I Ͼ 2σ(I)] and wR2 = 0.118
(from all 4788 unique reflections).
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Crystal Data of 2b: C20H26N6O2, M = 382.47 gmol–1, triclinic,
¯
space group P1,
a = 8.8974(3) Å, b = 10.3608(4) Å, c =
12.2434(5) Å, α = 104.666(1)°, β = 104.697(1)°, γ = 100.356(1)°, V
= 1019.61(7) Å3, Z = 2, dcalcd. = 1.246 gcm–1, μ = 0.084 mm–1, crys-
tal size 0.42ϫ0.18ϫ0.07 mm, number of reflections: 10278,
number of independent reflections: 4633, Rint = 0.0549, R1 = 0.049
[from 3376 unique reflections with I Ͼ 2σ(I)] and wR2 = 0.120
(from all 4633 unique reflections).
[6]
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[8]
Crystal Data of 3b: C17H18N8O8, M = 462.39 gmol–1, monoclinic,
space group C2/c, a = 13.492(3) Å, b = 6.9933(14) Å, c =
22.711(4) Å, β = 105.827(4)°, V = 2061.7(7) Å3, Z = 4, dcalcd.
=
1.490 gcm–1, μ = 0.121 mm–1, crystal size 0.26ϫ0.20ϫ0.06 mm,
number of reflections: 11203, number of independent reflections:
1951, Rint = 0.0442, R1 = 0.073 [from 1728 unique reflections with
I Ͼ 2σ(I)] and wR2 = 0.181 (from all 1951 unique reflections).
CCDC-874715 (for 2a), -874716 (for 2b), -876725 (for 3a), -874717
(for 3b), -874710 (for acetone oxime O-benzenesulfonate), -874711
(for acetone oxime O-p-toluenesulfonate), -874712 [for meso-1,2-
bis(3,3-dimethyldiaziridin-1-yl)ethane], -874713 [for racemic 1,2-
bis(3,3-dimethyldiaziridin-1-yl)ethane], and -874714 [for meso-1,4-
bis(3,3-dimethyldiaziridin-1-yl)butane] contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
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Computational Calculations: A conformational search was achieved
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pounds.
[11]
Acknowledgments
Generous financial support by the European Research Council
(ERC) for a Starting Grant (No. 258740, AMPCAT) to O. T. is
gratefully acknowledged.
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6
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Job/Unit: O20518
/KAP1
Date: 18-07-12 17:08:36
Pages: 8
Rearrangement in Alkyl-Bridged Bis(carbamoyldiaziridine) Derivatives
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Received: April 19, 2012
Published Online: ᭿
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O20518
/KAP1
Date: 18-07-12 17:08:36
Pages: 8
M. Kamuf, F. Rominger, O. Trapp
FULL PAPER
Intramolecular Rearrangement
M. Kamuf, F. Rominger,
O. Trapp* ......................................... 1–8
Investigation of the Rearrangement in
Alkyl-Bridged Bis(carbamoyldiaziridine)
Derivatives
Bridged diaziridine moieties are converted
into saturated five- and six-membered 1,3-
diaza-heterocyclic compounds in a new in-
tramolecular sigmatropic eliminative re-
arrangement, occurring at elevated tem-
peratures in toluene. The reaction mechan-
ism was investigated by GC–MS measure-
ments and corroborated by DFT calcu-
lations at the B3LYP/6-31G** level.
Keywords: Nitrogen heterocycles / Sigma-
tropic rearrangement / Reaction mechan-
isms / Density functional calculations
8
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