Bis-aminals of linear tetraamines: Kinetic and thermodynamic aspects of the condensation reaction

Article abstract of DOI:10.1002/ejoc.200390147

The kinetic and thermodynamic aspects of the condensation reaction of dicarbonyl compounds with linear tetraamines were examined in the light of identification of intermediates and DFT calculations. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, German

Full text of DOI:10.1002/ejoc.200390147

FULL PAPER
Bis-Aminals of Linear Tetraamines: Kinetic and Thermodynamic Aspects of the
Condensation Reaction
[a]
[a]
[a]
[a]
¨
Francoise Chuburu, Raphael Tripier, Michel Le Baccon, and Henri Handel*
¸
Keywords: Bis-aminals / Amines / Imines / Intermediates / Kinetics
The kinetic and thermodynamic aspects of the condensation
reaction of dicarbonyl compounds with linear tetraamines
were examined in the light of identification of intermediates
and DFT calculations.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
For a few years now, bis-aminals obtained by condensa-
tion of glyoxal or butanedione with linear polyamines[1,2]
have been successfully used in the synthesis of polyazacy-
cloalkanes.[3] The bis-aminal bridge acts as an organic tem-
plate which induces pre-organisation of the tetraamine to
favour its subsequent cyclisation. In theory, this condensa-
tion reaction should result in multiple stereoisomers accord-
ing to the vic/gem insertion of the dicarbonyl reagent and
cis/trans configuration of the resulting bis-aminal bridge. In
fact, the reaction is mostly highly selective and leads to only
a few isomers;[3b,4] in some cases, the bis-aminal gives rise
to an isomerisation process[3a,5] which makes understanding
of the reaction sequence more difficult. Finally, the reactiv-
ity of this rigidified tetraamine, particularly its ability to
react with a bis-electrophile to give macrocyclic interme-
diates, strongly depends on its configuration.[3b,6] An under-
standing of this first step, as well as how to control it, are
thus essential for subsequent synthesis of macrocyclic tetra-
amines. These considerations led us to report on a study of
the reactivity of linear tetraamines with a variety of substi-
tuted dicarbonyl derivatives and to propose a mechanism
for the formation of the bis-aminal bridge.
Scheme 1
°C in ethanol (Scheme 1); once the reaction had been com-
pleted, the solvent was carefully removed at Ϫ10 °C under
reduced pressure. Compared with previously published pro-
cedures, this one avoids formation of polymers and gives a
good picture of the early state of the reaction before any
isomerisation.
Identification of the vic/gem configuration was obtained
from 13C NMR spectroscopic data and the recognition of
cis/trans isomers was deduced from the temperature de-
pendence of the spectra. The trans isomer is found to stay
rigid[7] whereas the cis isomer exhibits a fluxional behaviour
consistent with a dynamic process that involves the sequen-
tial inversion of the nitrogen atoms and piperazine rings.
When needed, for the pyruvic aldehyde derivatives, HMQC,
HMBC and COSY sequences were used to elucidate the
localisation of the methyl group on the bis-aminal bridge.[8]
The results are shown in Table 1.
Results and Discussion
The three tetraamines 1,4,7,10-tetraazadecane (222),
1,4,811-tetraazaundecane (232) and 1,5,8,12-tetraazadode-
cane (323) were allowed to react with α-dicarbonyl reagents,
namely glyoxal, pyruvic aldehyde or butanedione, at Ϫ10
[a]
´
UMR CNRS 6521 “Chimie, Electrochimie Moleculaires et
Chimie Analytique”
6, avenue V. Le Gorgeu, 29285 Brest cedex, France
E-mail: henri.handel@univ-brest.fr
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 2003 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/03/0306Ϫ1050 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2003, 1050Ϫ1055

Bis-Aminals of Linear Tetraamines
FULL PAPER
Table 1. Bis-aminals obtained at Ϫ10 °C and 80 °C; Er ϭ relative energies of formation of the isomers (DFT/B3LYP/ 6Ϫ31G**) in
kcal/mol
These data show, firstly, that only a few of the expected depending on the primary or secondary nature of the amine
compounds were actually obtained. Seven-membered cycles concerned. The formation of the aminal function is the con-
are not produced and the formation of rings with a max- sequence of the addition of a second amine on the sp2 car-
imum of six members appears to constitute the driving force bon atom. With dicarbonyl reagents and tetraamine sub-
of the reaction. Moreover, for the bis-aminals resulting strates, one can assume the prior formation of six-mem-
from glyoxal condensation, refluxing for several hours in bered, cyclic diiminium species (Scheme 2). To obtain evid-
ethanol caused some isomerisations to occur, converting the ence of these intermediates, the condensation step was
kinetic adducts observed at Ϫ10 °C into the thermodyn- performed in the presence of sodium borohydride, in order
amic ones (Table 1, entries A and B). With pyruvic aldehyde to trap the diiminium species, which were found to be vari-
and butanedione, one may wonder about the kinetic or ously-substituted piperazines. The data reported in Table 2
thermodynamic nature of the observed bis-aminals, even allow us to draw an important conclusion: the fast forma-
in the lack of a clear isomerisation process over the same tion of a six-membered diiminium ring constitutes the first
temperature range. For this purpose, the calculation of en- step of the reaction. Moreover, the position of the CH ami-
ergies of formation of these bis-aminals offers a clue and nal on the rigidifying bridge (Table 1) indicates that the ke-
the corresponding DFT energies are reported in Table 1 tone function has a higher affinity for a primary amine than
(entries C). These data indicate that, with pyruvic aldehyde, for a secondary one, whereas the aldehyde function reacts
the most stable isomer is always predominantly reached. faster with the latter.[9] This last point was confirmed by a
With butanedione, such general behaviour is not observed,
as condensation with the tetraamine 323 mainly leads to
the less stable bis-aminal, whatever the reaction temper-
ature. The energies of formation of the bis-aminals cannot,
therefore, constitute the only criterion capable of account-
ing for the reaction stereoselectivity. With this aim in view,
we thus studied in detail the mechanism involved in forma-
tion of bis-aminals.
The first step of the nucleophilic addition of amines to
aldehydes or ketones leads to an imine or an iminium ion, Scheme 2
Eur. J. Org. Chem. 2003, 1050Ϫ1055
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F. Chuburu, R. Tripier, M. Le Baccon, H. Handel
FULL PAPER
competitive condensation of glyoxal and butanedione on cis one (Figure 1). The kinetic bis-aminals obtained from
the tetraamine 323, which led exclusively to the glyoxal-de- tetraamine 232, like those resulting from the condensation
rived bis-aminal.
of 222 with butanedione and pyruvic aldehyde, conform to
this mechanism.
Table 2. Piperazine rings trapped by reductive amination of di-
iminium intermediates
Figure 1. Lateral diiminium evolution
Secondly, when the diiminium is central, the two re-
maining nitrogen atoms are borne by the two independent
pendant arms. This situation is found when the tetraamine
222 reacts with glyoxal as well as in the condensation of the
tetraamine 323 with each dicarbonyl derivative. The attack
of the first primary amine leads to an iminium-aminal con-
stituted by two fused six-membered rings, for which two
arrangements around the sp3 aminal carbon have to be con-
sidered. In these two situations, the hydrogen (for glyoxal
and/or pyruvic aldehyde) or methyl (for pyruvic aldehyde
and/or butanedione) bonded to the sp3 aminal carbon can
occupy an axial or equatorial position. These two con-
formations were optimised at the DFT/B3LYP/6Ϫ31G**
level in each case (Figure 2). For the iminium-aminal de-
rived from condensation of tetraamine 222 and glyoxal, the
two conformations where the hydrogen atom lies either in
a pseudo-equatorial (34) or a pseudo-axial position (35) are
isoenergetic, which means that the hydrogen and nitrogen
atoms occupy almost equivalent positions. These two geo-
metries are characterised by a staggered configuration
about the C(sp2)ϪCam bond. In the iminium-aminal ring the
bond between the positively charged sp2 nitrogen and a vi-
cinal sp3 carbon is lengthened, relative to the normal CϪN
bond. These considerations illustrate structural anomeric
effects.[10] For the iminium-aminal derived from tetraamine
323 and glyoxal or butanedione, the most stable conforma-
tion exhibits an axial hydrogen atom or methyl group (37
and 41 respectively) with, in each case, a staggered config-
uration about the C(sp2)ϪCam bond. Finally, the iminium-
As a matter of fact, the reaction of glyoxal with tetra-
amines 222 and 323 involves the two secondary amine func-
tions; the insertion of this dicarbonyl compound is central
(Scheme 2, structure 1). However, with tetraamine 232, the
demand for the formation of a six-membered ring requires
the use of a primary amine, and therefore the insertion of
the glyoxal is lateral (Scheme 2, structure 2).
A primary nitrogen is always implied whenever butane-
dione is allowed to react with tetraamines 222 and 232;
however, the same constraint on the building of the six-
membered cycle imposes the involvement of the two sec-
ondary nitrogens of the tetraamine 323.
Pyruvic aldehyde constitutes an interesting combination
of the previous principles: the reaction of the ketone moiety
with the primary amine and that of the aldehyde with the
secondary amine constitute the favoured way, which leads
to a lateral diiminium ring with tetraamines 222 and 232.
With tetraamine 323, again, the only solution to achieve the
six-membered cycle implies the use of the two secondary
amines.
The formation of the diiminium intermediate is followed
by the subsequent addition of the two remaining nitrogens
on the sp2 carbons; its evolution governs the reaction ste-
reoselectivity. According to the central/lateral location of
the diiminium ring, two different cases have to be consid-
ered.
Firstly, when the diiminium is lateral, the two remaining
nitrogen atoms are borne by a unique pendant arm. Their
approach on the same side of the average plane of the ring
Figure 2. Central diiminium evolution. The energies of formation
of iminium-aminal intermediates are given in Hartrees [1 Ha (a.u.):
is greatly favoured; the main ensuing adduct is the gem- 627.509 kcal/mol]
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Eur. J. Org. Chem. 2003, 1050Ϫ1055

Bis-Aminals of Linear Tetraamines
FULL PAPER
aminal considered in the reaction of tetraamine 323 and side of the iminium carbon (transition state 43) and the
pyruvic aldehyde is the one in which the aldehyde function energetic barrier calculated for this transition state is lower
was the first to react, as shown by the competitive con- than the one calculated for transition state 42 (∆E ϭ 2.03
densation experiment previously described; the correspond- kcal/mol, Table 3). Consequently, the trans transition state
ing hydrogen atom then occupies the equatorial position on is more accessible and the final ring-closure leads to the
the sp3 aminal carbon (38).
kinetic trans bis-aminal, which is consistent with the major
In all these intermediates, the faces of the last sp2 imin- compound obtained at Ϫ10 °C.
ium-aminal carbon atom are now diastereotopic and make
For the tetraamine 323, the transition states which lead
different the approaches of the last nitrogen atom located to the vic-cis bis-aminals 44, 46, 48, are constituted by two
on the remaining pendant arm. To shed light on the stereo- six-membered fused rings and present a staggered arrange-
selectivity of the last nucleophile addition, we carried out ment with respect to the partially pyramidalised carbon
DFT calculations to locate transitions states of the last atom, as expected for reactive conformations in nucleophilic
cyclisation step; the distances calculated for the incipient additions. These situations are greatly favoured, as no bond
C···N(H2) bond are reported in Table 3. The calculated geo- becomes eclipsed during the iminium carbon pyramidalis-
metries are characterised by a partial pyramidalisation of ation.[11,12] As expected, the nucleophilic NH2 attack is
the iminium carbon accompanied by lengthening of the im- nonperpendicular and the N(H2)CC angle was found to be
ine bond in the transition state; the central six-membered around 105°. In these conformations, the trajectory of the
ring presents a half-chair conformation. For the 222 tetra- nucleophilic attack is syn to the CamϪNH bond. In the
amine, in the transition states 42 and 43 leading to the transition states 45, 47 and 49, the nucleophilic attack oc-
vic-cis and vic-trans bis-aminals respectively, the strains im- curs anti to the NH moiety and the calculated geometries
posed by the presence of a five-membered ring result in the show that the free amine function approaches at an angle
eclipse of the iminium double bond by the CϪN bond of of around 102°. The comparison of the energetic barriers
the aminal carbon. The subsequent approach of the nitro- indicates that the favoured attack leads to the formation of
gen lone pair preferentially takes place on the less hindered the cis products with glyoxal and butanedione, whereas the
Table 3. Transition states for the last cyclisation step (DFT/ B3LYP/6Ϫ31G**); activation energies are relative to the reactants
(iminium-aminals)
Eur. J. Org. Chem. 2003, 1050Ϫ1055
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F. Chuburu, R. Tripier, M. Le Baccon, H. Handel
FULL PAPER
45.7, 50.5, 51.3 (NCH2N), 72.2 (NCN) ppm. ESI-MS (MeOH):
m/z ϭ 169.3 [M ϩ H]ϩ.
trans compound is preferentially reached with pyruvic alde-
hyde. This is in good agreement with experimental results
for the bis-aminals derived from tetraamine 323; it therefore
means that the mixtures observed at Ϫ10 °C correspond to
a kinetic situation. The model shows that the nucleophilic
attack occurs anti to the axial substituent of the aminal
carbon, regardless of whether this substituent is a hydrogen
atom or a methyl or amino group. This situation corre-
sponds to an NH2 moiety approach assisted by the σ*
orbital, antiperiplanar to the incipient bond,[13,14] that is,
σ*CN orbital for transition states 43 and 47 and σ*CH or
σ*CC orbitals for transition states 44 and 48. Thus, the
Bis-aminals Obtained by Condensation with N,NЈ-Bis(2-amino-
ethyl)-1,3-propanediamine (232): Colourless oil, 95%. Isomer 5: 13C
NMR (CDCl3): δ ϭ 23.8 (NCH2CH2CH2N), 43.3, 53.4, 54.5
(NCH2N), 70.9, 87.7 (NCN) ppm. Isomer 6: 13C NMR (CDCl3):
δ ϭ 19.2 (NCH2CH2CH2N), 40.2, 46.2, 46.4, 55.3, 56.1, 57.2
(NCH2N), 67.9, 77.5 (NCN) ppm. ESI-MS (MeOH): m/z ϭ 183.3
[M ϩ H]ϩ.
Bis-aminals Obtained by Condensation with N,NЈ-Bis(3-aminopropy-
l)ethylenediamine (323): White powder, 95%. Isomer 7: 13C NMR
(CDCl3): δ ϭ25.4 (NCH2CH2CH2N), 43.8, 51.5, 53.6 (NCH2N),
stereoselectivity of this last cyclisation step is conditioned 78.1 (NCN) ppm. Isomer 8: 13C NMR (CDCl3): δ ϭ 28.8, 32.6
(NCH2CH2CH2N), 39.6, 39.8, 44.3, 47.0, 48.6, 51.8, 53.8
(NCH2N), 76.4, 78.3 (NCN) ppm. ESI-MS (MeOH): m/z ϭ 197.3
[M ϩ H]ϩ.
to the preferential geometry of the iminium-aminals. The
disposition of the aminal carbon substituents and the rigid-
ity of these intermediates impose the direction of the nucle-
ophilic approach towards the best orientated σ*orbital, as
in the Cram cyclic model.[15]
Bis-aminals Derived from Pyruvic Aldehyde
Bis-aminal 9: Brown oil, 68%. 13C NMR (CDCl3): δ ϭ 25.2 (CH3),
39.6, 42.2, 48.2, 48.8, 50.2, 50.8 (NCH2N), 64.7 [NC(CH3)N], 80.2
[NC(H)N] ppm. ESI-MS (MeOH): m/z ϭ 183.3 [M ϩ H]ϩ.
Conclusion
Bis-aminals 13 (90%) and 14 (10%): Yellow oil, quantitative. Isomer
13: 13C NMR (CDCl3): δ ϭ 11.7 (NCH2CH2CH2N), 18.2 (CH3),
37.8, 41.3, 43.5, 52.0, 53.8, 55.2 (NCH2N), 63.8 [NC(CH3)N], 79.9
Analysis of the condensation reaction of various dicar-
bonyl compounds with linear tetraamines revealed that, of
all the possible stereoisomers, only a few were obtained.
Under reductive amination conditions a variety of substi-
tuted piperazines were isolated, which means that fast
formation of a diiminium intermediate is initially involved.
After this first six-membered ring was established, the next
cyclisation steps were modelled and the results were consist-
ent with kinetic control of the subsequent attack. Moreover,
computed transition states provided a model for under-
standing the stereoselectivity of the condensation reaction.
They suggest that the last nucleophilic attack happened
preferentially anti to the axial group of the first formed
aminal carbon. It led to either cis or trans bis-aminals,
depending on the dicarbonyl compound and tetraamine.
Finally, via the isomerisations that occurred with glyoxal
bis-aminals, the kinetic adducts were converted into ther-
modynamic ones.
[NC(H)N] ppm. Isomer 14: 13C NMR (CDCl3):
δ ϭ 11.7
(NCH2CH2CH2N), 18.2 (CH3), 38.5, 43.7, 45.1, 45.6, 48.0, 49.7
(NCH2N), 69.4 [NC(CH3)N], 70.9 [NC(H)N] ppm. ESI-MS
(MeOH): m/z ϭ 197.3 [M ϩ H]ϩ.
Bis-aminals 17 and 18: Yellow oil, 85%. Isomer 17 (75%): 13C NMR
(CDCl3): δ ϭ 7.4 (CH3), 26.6, 27.2, (NCH2CH2CH2N), 39.1, 45.5,
47.5, 49.2, 53.8, 55.5 (NCH2N), 70.1 [NC(H)N], 85.0 [NC(CH3)N]
ppm. Isomer 18 (25%): 13C NMR (CDCl3): δ ϭ 10.3 (CH3), 17.4,
20.2, (NCH2CH2CH2N), 38.6, 42.6, 43.5, 44.5, 46.1, 54.2
(NCH2N), 69.6 [NC(H)N], 84.3 [NC(CH3)N] ppm. ESI-MS
(MeOH): m/z ϭ 211.3 [M ϩ H]ϩ.
Bis-aminals Derived from Butanedione
Bis-aminal 19: Beige powder, 90%. 13C NMR (CDCl3): δ ϭ 12.2,
23.6 (CH3), 40.5, 47.7, 47.7 (NCH2N), 67.7, 76.6 (NCN) ppm. ESI-
MS (MeOH): m/z ϭ 197.3 [M ϩ H]ϩ.
Bis-aminal 21: Beige powder, 95%. 13C NMR (CDCl3): δ ϭ 11.5,
19.0 (CH3), 24.3 (NCH2CH2CH2N), 39.9, 42.7, 46.3, 47.7, 49.7,
51.9 (NCH2N), 68.9, 74.0 (NCN) ppm. ESI-MS (MeOH): m/z ϭ
211.4 [M ϩ H]ϩ.
Experimental Section
General Procedure for the Synthesis of Bis-aminals: A solution of
Bis-aminals 23 and 24: Brown oil, 95%. Isomer 23 (25%): 13C NMR
the dicarbonyl derivative (2 mmol) in ethanol (5 mL) was added (CDCl3): δ ϭ 6.8 (CH3), 27.0, (NCH2CH2CH2N), 39.6, 48.6, 50.0
slowly to a solution of the tetraamine (2 mmol) in ethanol (5 mL)
at Ϫ10 °C. After 2 h of vigorous stirring, the solvent was evapor-
ated at the same temperature and, where necessary, the residue was
purified by extraction with toluene (three times, 5 mL each) and
dried under vacuum.
(NCH2N), 73.8 (NCN) ppm. Isomer 24 (75%): 13C NMR (CDCl3):
δ ϭ 7.8, 17.6 (CH3), 17.8, 29.4, (NCH2CH2CH2N), 39.8, 40.2, 44.8,
46.9, 49.3, 50.2 (NCH2N), 72.2, 73.2 (NCN) ppm. ESI-MS
(MeOH): m/z ϭ 225.4 [M ϩ H]ϩ.
General Procedure for Isomerisations: The bis-aminals obtained by
condensation of each tetraamine with glyoxal, that is, respectively,
a mixture of isomers 3 and 4, the compound 6 and a mixture of
isomers 7 and 8, were heated at 80 °C in ethanol for twelve hours.
The proportions of the resulting mixtures are reported in Table 1.
Bis-aminals Derived from Glyoxal
Bis-aminals Obtained by Condensation with Triethylenetetraamine
(222): Colourless oil, quantitative. Isomer 1: 13C NMR (CDCl3):
δ ϭ 42.9, 47.9, 50.2 (NCH2N), 65.6, 76.0 (NCN) ppm. Isomer 2:
13C NMR (CDCl3): δ ϭ 45.7, 50.5, 51.3 (NCH2N), 71.7, 88.9 General Procedure for Reductive Aminations: A solution of the di-
(NCN) ppm. Isomer 3:13C NMR (CDCl3): δ ϭ 43.6, 48.1, 50.8 carbonyl derivative (2 mmol) in ethanol (5 mL) was slowly added
(NCH2N), 79.5 (NCN) ppm. Isomer 4: 13C NMR (CDCl3): δ ϭ to a mixture of the tetraamine (2 mmol) and sodium borohydride
1054
Eur. J. Org. Chem. 2003, 1050Ϫ1055

Bis-Aminals of Linear Tetraamines
(10 equiv.) in ethanol (5 mL) at Ϫ10 °C. After 2 h of vigorous characterised by frequency analysis. The correlation between the
FULL PAPER
stirring, the reaction was quenched by addition of HCl (4 ) and
the ethanol was evaporated. The acidic aqueous phase was washed
with dichloromethane (3 ϫ 20 mL), neutralised with NaOH (4 ),
then washed with dichloromethane (3 ϫ 20 cm3). The organic
phase was dried with Na2SO4 for one hour, then filtered. The solv-
ent was evaporated and the residue was dried under vacuum. The
products, a mixture of the starting tetraamines and piperazines 25
to 33, were obtained as colourless oils.
calculated transition states, the reactants and the products was
checked with the IRC (Reverse/ Forward) option.
Acknowledgments
We are grateful to IDRIS (CNRS, Orsay) for calculations facilities
´
and to A. Laporte (Universite de Pau et des Pays de l’Adour) for
helpful discussions.
[1]
Compounds Obtained with Glyoxal
H. Stetter, Chem. Ber. 1953, 69Ϫ74.
[2]
B. Fuchs, A. Ellencweig, Journal of the Royal Netherlands
Compound 25: 13C NMR (CDCl3): δ ϭ 38.8, 53.3 (2), 61.2
(NCH2N) ppm. ESI-MS for C8H20N4 (MeOH): m/z ϭ 173.2 [M
ϩ H]ϩ.
Chemical Society, 1979, 3541Ϫ3544.
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´
G. Herve, H. Bernard, N. Le Bris, M. Le Baccon, J. J. Yaou-
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Herve, H. Bernard, N. Le Bris, J. J. Yaouanc, H. Handel, L.
Compound 26: 13C NMR (CDCl3): δ ϭ 26.9 (NCH2CH2CH2N),
41.7, 46.1 (2), 48.4, 52.5, 54.6 (2), 57.3 (NCH2N) ppm. ESI-MS for
C9H22N4 (MeOH): m/z ϭ 187.3 [M ϩ H]ϩ.
[3c]
Toupet, Tetrahedron Lett. 1998, 39, 6861Ϫ6864.
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Compound 27: 13C NMR (CDCl3): δ ϭ 30.3 (NCH2CH2CH2N),
40.6, 53.1 (2), 56.3 (NCH2N) ppm. ESI-MS for C10H24N4 (MeOH):
m/z ϭ 204.4 [M ϩ H]ϩ.
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R. A. Kolinski, F. G. Ridell, Tetrahedron Lett. 1981, 22,
Compound 28: 13C NMR (CDCl3): δ ϭ 21.3 (CH3), 42.3, 46.8, 49.3,
50.2, 52.5, 57.5, 65.5, 67.9 (NCH2N) ppm. ESI-MS for C9H22N4
(MeOH): m/z ϭ 187.3 [M ϩ H]ϩ.
2217Ϫ2220.
F. Boschetti, F. Denat, E. Spinosa, R. Guilard, Chem. Com-
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[9]
Compound 29: 13C NMR (CDCl3): δ ϭ 19.5 (NCH2CH2CH2N),
25.4 (CH3), 40.1, 45.7, 48.2, 50.7, 53.0, 57.0, 60.8 (NCH2N) ppm.
ESI-MS for C10H24N4 (MeOH): m/z ϭ 201.2 [M ϩ H]ϩ.
[10]
[11]
Compound 30: 13C NMR (CDCl3): δ ϭ 21.0 (CH3) 29.1, 29.5
(NCH2CH2CH2N), 40.8 (2), 51.3 (2), 53.5, 55.0, 56.4 (2) (NCH2N)
ppm. ESI-MS for C11H26N4 (MeOH): m/z ϭ 215.3 [M ϩ H]ϩ.
[12]
[13]
[14]
[15]
[16]
Compounds Obtained with Butanedione
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Compound 31: 13C NMR (CDCl3): δ ϭ 23.0 (2) (CH3), 41.7, 47.0,
48.8 (2), 49.2, 49.4, 49.7, 52.4 (NCH2N) ppm. ESI-MS for
C10H24N4 (MeOH): m/z ϭ 201.4 [M ϩ H]ϩ.
M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M.
A. Robb, J. R. Cheesemen, V. G. Zakrzewski, J. A. Montgom-
ery, R. E. Stratmann, J. C. Burant, S. Dapprich, J. M. Millam,
A. D. Daniels, K. N. Kudin, M. C. Strain, O. Farkas, J. Tomasi,
V. Barone, M. Cossi, R. Cammi, M. Mennucci, C. Pomelli, C.
Adamo, S. Clifford, J. Ochterski, G. A. Petersson, P. Y. Ayala,
Q. Cui, K. Morokuma, D. K. Malik, A. D. Rabuk, K. Raghav-
achari, J. B. Foresman, J. Cioslowski, J. V. Ortiz, B. B. Stefanov,
G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts,
R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng,
A. Nanayakkara, G. Gonzalez, M. Challacombe, P. M. W. Gill,
B. G. Johnson, W. Chen, M. W. Wong, J. L. Andres, M. Head-
Gordon, E. S. Replogle, J. A. Pople, Gaussian 98 (Revision
A.1), Gaussian, Inc. Pittsburg PA, 1998.
Compound 32: 13C NMR (CDCl3): δ ϭ 24.5 (2) (CH3), 25.0 (2)
(NCH2CH2CH2N), 37.7, 41.8, 49.7, 52.6 (2), 53.5, 56.9, 58.1
(NCH2N) ppm. ESI-MS for C11H26N4 (MeOH): m/z ϭ 214.4 [M
ϩ H]ϩ.
Compound 33: 13C NMR (CDCl3):
δ ϭ 19.2 (CH3), 24.0
(NCH2CH2CH2N), 37.4, 49.2, 56.4, 57.6 (NCH2N) ppm. ESI-MS
for C12H28N4 (MeOH): m/z ϭ 229.4 [M ϩ H]ϩ.
Computational Methods
All structures were computed by using hybrid density functional
theory (B3LYP) and the 6Ϫ31G** basic set, as implemented in
Gaussian 98.[16] All gas-phase minima and transition states were
Received September 24, 2002
[O02529]
Eur. J. Org. Chem. 2003, 1050Ϫ1055
1055