Synthesis and structure of 2,2′-Bis(2,2,5-trimethyl-pyrrolidinyl)methane

Article abstract of DOI:10.1515/znb-1999-1106

Reaction of 2,5,5-trimethyl-Δ¹-pyrrolidine-N-oxide with methyl lithium yields 2,2′-bis(1-hydroxy-2,2,5-trimethyl-pyrrolidinyl)methane which is reduced by Raney nickel/hydrogen to the corresponding amine. Both molecules are present in the meso-configuration in the solid state. While the hydroxylamine derivative shows intermolecular O-H...O bridge bonding no intermolecular N...H-N interaction is observed for the amine.

Full text of DOI:10.1515/znb-1999-1106

Synthesis and Structure of 2,2,-Bis(2,2,5-trimethyl-pyrrolidinyl)methane
Herbert Hommer1, Heinrich Nötha, Werner Ponikwar11, and Susana Rojas-Limab
a Institute of Inorganic Chemistry, University of Munich,
Butenandtstr. 5-13, Haus D, D-81377 München, Germany
b Departemento de Quimica, Universita Autonoma de Hidalgo, Pachuca, Hidalgo, Mexico
Reprint requests to Prof. Dr. H. Nöth. Fax: (+49) 89 21807455.
E-mail: H.Noeth@lrz.uni-muenchen.de
Z. Naturforsch. 54 b, 1371-1374 (1999); received July 26, 1999
2,2'-Bis( 1-hydroxy-2,2,5-trimethyl-pyrrolidinyl)methane, 2,2'-Bis(2,2,5-trimethyl-pyrroldi-
nyl)methane, X-Ray Data
Reaction of 2,5,5-trimethyl-Z\'-pyrrolidine-N-oxide with methyl lithium yields 2,2'-bis(l-
hydroxy-2,2,5-trimethyl-pyrrolidinyl)methane which is reduced by Raney nickel/hydrogen to
the corresponding amine. Both molecules are present in the m^o-configuration in the solid
state. While the hydroxylamine derivative shows intermolecular O-H • O bridge bonding no
intermolecular N H-N interaction is observed for the amine.
Sterically demanding amines such as the com- groups should be rather similar, and, consequently
mercially available 2,2,6,6-tetramethylpiperidine
and its conjugate base 1 are versatile ligands
with high steric shielding power. Typical exam-
a study of derivatives of 2,2,5,5-tetramethylpiper-
idine was expected to reveal primarily steric effects.
In attempts to optimize the synthesis of 2,2,5,5-
ples are the 2,2,6,6-tetramethylpiperidino-alkyl- piperidine we observed the formation of the title
compound, and we report here on its synthesis and
idino-imino-boranes [21 both having a dicoordi- structure.
idene boranes [1] and the 2,2,6,6-tetramethylper-
Wechosethereaction sequence (1) forthesynthe-
nated boron atom. Steric shielding should be less
significant for the 2,2,5-5-tetramethylpyrrolidino
group 2, although this ligand aswell asitspiperidino
homologue can be considered as the cyclic ana-
logues of the bis(rm-butyl)amino group. On the
other hand, the electronic effects of all three amino
sis of 2,2,5,5-tetramethylpiperidine, (5) [3]. There
were, however, difficulties in step (lc) of the re-
action because the methylation of the imine oxide
3 in ether led to a rubberlike, highly viscous mass
which was very difficult to stir in order to allow an
effective mixing of the components. For this rea-
son we replaced the Grignard compound by methyl
K
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1372
H. Hommer et cd. ■Synthesis and Structure of 2,2'-Bis(2,2,5-trimethyl-pyrrolidinyl)methane
Fig. 2. Molecular structure of the bis-amine 7 in OR-
TEP description. Thermal ellipsoids are depicted on a
25% probability level. Selected bond lengths (in A):
N1-C2 1.484(2), N1-C5 1.493(2), N1-H1B 0.84, N2-
C9 1.487(2), N2-C7 1.492(2), N2-H2B 0.88, C5-C6
1.541(3), C6-C7 1.542(3), C7-C12, 1.530(3), C5-C13
1.531(3).- Selected bond angles (in degrees): H1B-N1-
C2 108, H1B-N1-C5 104,C2-N1-C5 109.8(1), H2B-N2-
C7 109, H2B-N2-C9 109, C7-N2-C9 110.2(1), N1-C2-
C3 103.6(2), N1-C5-C4 104-8(2), C2-C3-C4 103.8(2),
C3-C2 C14 112.4(2), C6-C5-C13 113.2(2), C5-C6-C7
122.6(2). - Interplanar angles: C2-N1-C5-C4 / C2-C3-
C4 35.7°, C9-N2-C7-C1 /C9-C10-C11 36.2°.
Fig. 1. ORTEP plot of the two independent molecules
of the hydroxylamine derivative 6. Thermal ellipsoids
are presented on a 25% probability level. Selected bond
length (in A): Ol-Nl 1.448(3). 02-N2 1.442(3), 03-
N3 1.436(3), 04-N4 1.450(3), N1-C4 1.470(3), N1C1
1.493(3), N2-C12 1.498(4), N2-C9 1.508(3), N3-C16
1.498(3), N3-C19 1.504(4), N4-C24 1.467(3), N4-C27
1.491(3), C8-C9 1.547(3), C8-C4 1.546(3), C19-C23
1.545(3), C23-C24 1.546(3), Ol-Hl 0.97, 02-H2 0.92,
03-H3 0.89, 04-H4 0.95. - Selected bond angles
(in degrees): HI-Ol-Nl 109. 01-N1-C4 110.9(2), Ol-
Nl-C1 112.1(2), C4-N1-C1 111.2(2), H2-02-N2 101,
02-N2-C12 110.7(2), 02-N2-C9 109.7(2), Cl2-N2-C9
109.5(2), H3-03-N3 104, 03-N3-C16 110.0(2), 03-N3-
C 19 110.2(2), C 16-N3-C19 109.6(2), H4-04-N4 97,04-
N4-C24 111.4(2), 04-N4-C27 111.8(2), C24-N4-C27
111.2(2). N 1-01-H196, N2-02-H2 101, N3-03-H3 104,
N4-04-H4 97.
The bis-hydroxylamine derivative (6)crystallizes
in the triclinic system, space group Pi. There are
two independent molecules in the asymmetric unit
(Fig. 1). These molecules are associated via O-
H -0 bridge bonds as depicted in Fig. 1. Out of
the four OH groups only two are involved in hydro-
gen bonding. The five membered rings are present
in an envelope configuration with atoms C3, CIO,
C16 and C24 occupying the “flap” positions. The
structural parameters show no unusual features with
the exception that the bond angles at the methylene
groups are rather wide (123.9(2) and 123.3(2)°, re-
spectively). These features are also found for the
bis-amine 7 (122.6(2)°). All other structural param-
eters are identical with those of compound 6 within
lithium. However, instead of obtaining the hydrox-
ylamine derivative 4 the “coupling” product 6 was
formed. Compound 6 could bereadily reduced tothe
bis(amine) (7). The formation ofcompound 6 can be
explained by acompetition between the methylation
of the imine-oxide and deprotonation of a methyl
group of compound 3, followed by rapid reaction
of the deprotonated imine-oxide with compound 3
leading to the formation of a methylene bridge as
depicted in the suggested reaction sequence (2) [4],
6 was isolated in 54% yield and was quantitatively
converted into the amine 7 by hydrogen reduction in
the presence of Raney nickel. Analyses of the NMR
data of these compounds indicate that the meso-
forms are present, and this was ascertained by the
determination of the molecular structure by X-ray
diffraction analysis in the solid state.
the limits of the 3
a criterion. Most noticeable, how-
ever, is the absence ofany N-H--Nbonding whether
intra- or intermolecular. Fig. 2 shows the molecular
structure of the bis-amine 7. It is obvious that the
amine 7 in its deprotonated form is a candidate for
the formation of derivatives allowing the formation
of six membered rings, and this aspect is presently
under investigation.
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1373
H. Hommer et al. •Synthesis and Structure of 2,2'-Bis(2,2,5-trimethyl-pyrrolidinyl)methane
Table I. Crystallographic
data and data referring to
data collection and struc-
ture solution of compounds
6 and 7.
Compound
5
6
Chem. formula
Formula weight
Crystal size [mm]
Crystal system
Space group
a[A]
C7.50H.5NO
135.21
0.2 x 0.3 x 0.3
Triclinic
Pi
9.982(4)
12.311(4)
14.616(5)
80.94( 1)
74.76(1)
68.06(1)
1603.8(10)
8
C15H30N2
238.41
0.28 x 0.3 x 0.35
Monoclinic
P2( 1)/n
10.4440(1)
13.6711(2)
11.3116(2)
90.00
109.647(1)
90.00
1521.05(5)
4
1.042
a w'-1=cx2F02+(xP)2 +yP;
P = (F02 +2Fc2)/3.
b
c
[A]
[A]
a[°]
[°]
ß
7 [°J,
V [A3]
Z
1.120
0.074
600
Peak [mg/m3]
p [mm ']
F(000)
0.061
536
Index ranges
-11 < h < 10,-14 < it < 12, -13 < h < 13,-16
16,
_14 < / < 14
-17 < / < 17
49.42
193(3)
5734
3870
20 [°]
Temp. [K]
Refl. collected
Refl. unique
Refl. observed (4a)
(/?(int.)
58.48
193
8805
3138
2387
3210
0.0370
371
0.0300
165
0.0599/0.7885
1.054
No. variables
Weighting schemeax/x 0.0000/1.3035
GOOF
1.217
Final R (4a)
Final wR2
Larg. res. peak [e/A3]
0.0571
0.1343
0.368
0.0600
0.1107
0.164
Experimental
until a syrup remained. This material was transferred into
a separation funnel, and CHCI3(100 ml) was added. Two
phases formed. The heavier chloroform solution was sep-
aratedand dried with sodium sulfate. After the solvent was
removed in vacuum compound 4 was subjected to distil-
lation (b. p. 80 °C/0.7 Torr or 60 °C/0.15 Torr). The liquid
solidified on storing in a refrigerator. 4 turns slowly red
on exposure to air. Yield: 18.0 g (68%). - NMR (CDCI3):
<5'H = 1.38 (s, 6H, 2 Me), 2.00 (s, 3H, Me), 1.95 -2.01
Microanalysis was performed at the institute’s micro-
analytical laboratory. NMR spectra were recorded on a
JEOL 270 MHz spectrometer, IR spectra on a JEOL FT
IR-spectrometer either in solution or as KBr pellets. A
Siemens P4 four circle diffractometer equipped with a
CCD area detector using Mo KQ-radiation, and a graphite
monochromator, was employed for the X-ray structure
determinations.
(m, 2H), 2.53-2.60 (m, 2H). -
6 l3C = 12.6 (C2-Me), 25.0
(Me). 28.6 (C3), 31.7 (C5), 140.6 (C2). - IR (CC14):
KC=N) 1601 cm-1.
2-Methyl-2-nitro-hexane-5-on (3) was prepared ac-
cording to lit. [5], Colorless liquid, 80%, b. p. 105 °C/5
Torror 90 °C / 0.5 Torr. NMR (CDCI3): <§'H = 1.59(s,6H,
2 Me), 2.17 (s, 3H, Me), 2.175 -2.22 (m, H), 2.43 -2.49
(m, 2H); - IR (CC14). ^(CO) = 1721 cm "1.
2,2'-Bis(1-hydroxy-2,5,5-trimethylpyrrolinyl)methane
(6): Compound 4 was dissolved in diethylether (7.63 g,
60.0 mmol in 50 ml). To this solution was added drop-
wise and with stirring a solution of LiMe in diethylether
(45 ml, 1.8 M) within 30 min. After allowing the mixture
to attain ambient temperature 15 ml of water was added
followed by 1 M HC1 until the solution reacted acidic.
Then NaHCO^ was used for neutralization,. The ether
phase was separated and the aqueous solution extracted
four times with ether (20 ml each). The ether solutions
were united, dried with sodium sulfate and the solvent was
2,5,5-Trimethyl-A1-pyrrolidine-N-oxide (4): To a so-
lution of 3 (33.0 g, 207 mmol) in 150 ml of water cooled
by an ice bath ammonium chloride (9.0 g) was added
with vigorous stirring. Then zinc dust (40 g) was added
in portions over a period of 1h [6]. After stirring for ad-
ditional 1 h the solid material was removed by filtration,
and the solid washed several times with hot water (50 ml
each). Water was then removed from the united filtrates
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H. Hommer et al. ■Synthesis and Structure of 2,2'-Bis(2,2,5-trimethyl-pyrrolidinyl)methane
1374
then removed in a rotating evaporator until compound 6
started to crystallize. The colorless crystals had a m. ,p. of
95 -105 °C. On exposure to air the crystals turned slowly
red. Recrystallisation from ether at -20 °C gave 4.7 g of 6
(58%) as the pure compound. NMR (C(lD6): 6'H = 1.20
(s, 2 Me), 1,26 (s. Me), 1.30 (s, 2 Me), 1.34 (m. 2H), 1.53
-1.76 (m, 6 H). 2.05 (m, 2H), 8.0 (broad. 2 OH). -6 ]'C =
30.2, 30.8, 30.9 (3 Me), 39.0, 43.0 (C3, C4), 56.2 (C6),
59.7, 62.8 (C2, C5). - IR (neat): v(OH) = 3295 cm "1.
39.0, 42.0 (C3, C4), 56.2 (C6), 59.7, 62.8 (C2, C5). - IR
(neat): i/(NH) = 3295 cm-1.
Analysis: CisH^oNi (238.41)
Calcd C 75.57 H 12.68 N 11.75%,
Found C 75.01 H 12.76 N 11.65%.
X-ray structure determination: Single crystals were
mounted with perfluoro ether oil on a glass fiber and
cooled with a stream of cold nitrogen gas to 193 K.
After optical alignment the cell parameters were deter-
mined by using the reflections collected on four sets of
15 frames each (program SMART [7]). Data collection
was performed in the hemisphere mode. Data on a total
of 1265 frames were used for data reduction (program
C|5HtoN20 2 (270.42).
Calcd C 66.62 H 11.18 N 10.36%,
Found C 66.60 H 11.16 N 10.33%.
2,2'-Bis(2,2,5-trimethylpyrrolidinyl)methane (1): To 5
ml of a commercial Raney-nickel suspension, which was
treated several times with methanol, was added compound
6 (4.00 g, 14.8 mmol) dissolved in methanol (50 ml).
The flask was degassed in vacuum and subjected to an
atmosphere of hydrogen gas supplied from a hydrogena-
tion apparatus. When no more hydrogen was consumed
the solids were removed by filtration and the filtrate
freed from the solvent in vacuum. Distillation of the
residue gave 3.17 g of 7 (13.3 mmol, 90%) of b. p. 65
-70 °C/0.05 Torr. The colorless liquid turned solid in a
refrigerator: m.p. 32 - 34 °C. - NMR (CDCb): «5'H =
1.08 (2.,2 Me), 1.09 (s, 2 Me), 1.5- 1.7 (m, 10H)-(NH
was not detected). - <$I3C = 30.2, 30.8, 30.9 (Me groups),
SAINT [6]). Data were obtained by rotating
succes-
sively by 0.3° using two different \settings. The structure
solution and refinement was performed with the program
package SHELXTL [8], Non hydrogen atoms were re-
fined anisotropically, all hydrogen atoms were found and
freely refined. Relevant data are summarized in Table I.
Additional data referring to datacollection and refinement
as well as positional parameters etc. are deposited with
the Cambridge Crystallographic Data Center and may be
obtained free ofcharge from the Director, 12 Union Road,
GB-Cambridge CB2 1EZ by quoting the authors, the
Journal citation and the CCDC numbers. 132671 (7) and
132672 (6) (also e-mail: teched@chemcrys.cam.ac.uk).
Grignard compound but only in minor and variable
yield (less than 15%).
[1] B. Glaser, H. Nöth, Angew. Chem. 97, 424 (1988).
[2] H. Nöth, S. Weber, Chem. Z. Naturforsch. 38b. 1460
(1983).
[5] H. Shechter. D. E. Ley. L. Zeldin, J. Amer. Chem.
Soc. 74. 3664(1952).
[3] W. D. Hinsberg. R G. Schultz, R B. Dervan, J. Amer.
Chem. Soc. 104, 766 (1982); A. C. Scott, J. M. Ted-
der, J. C. Watson, S. Mhatre, J. Chem. Soc. Per. II
1980. 260.
[6] R. Bonnett, R. F. C. Brown, V. M. Clark, I. O. Suther-
land, A. Todd, J. Chem. Soc. 1959. 2094.
[7] Siemens Analytical Instruments, version 4.1.
[8] Siemens Analytical Instruments, version 5.0.
[4] The coupling product 6 is also obtained by using the
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