Carbene rearrangements, 60. Supramolecular structure-reactivity relationships: Photolysis of a series of aziadamantane@cyclodextrin inclusion complexes in the solid state

Article abstract of DOI:10.1002/adsc.200404142

Photolyses of the α-, β- and γ-cyclodextrin complexes of 2-aziadamantane (1) in the solid state afforded markedly different product distributions, as determined by quantitative GC and HPLC analyses. The results are discussed with respect to the structures of the inclusion complexes.

Full text of DOI:10.1002/adsc.200404142

FULL PAPERS
‡
Carbene Rearrangements, 60. Supramolecular
Structure-Reactivity Relationships: Photolysis of a Series of
Aziadamantane@Cyclodextrin Inclusion Complexes in the Solid
State
a
a
a, b
a,
Daniel Krois, Lothar Brecker, Andreas Werner, Udo H. Brinker *
a
Institut für Organische Chemie der Universität Wien, Währinger Straße 38, 1090 Wien, Austria
Fax: (þ43)-1-4277-52140, e-mail: udo.brinker@univie.ac.at
b
Deceased
Received: May 19, 2004; Accepted: August 20, 2004
th
Dedicated to Professor Johann Mulzer on the occasion of his 60 birthday.
Abstract: Photolyses of the a-, b- and g-cyclodextrin Keywords: carbenes; cyclodextrins; diazirines; photol-
complexes of 2-aziadamantane (1) in the solid state ysis; supramolecular chemistry
afforded markedly different product distributions, as
determined by quantitative GCand HPLCanalyses.
The results are discussed with respect to the structures
of the inclusion complexes.
Introduction
The influence of a supramolecular microenvironment
on the reaction pathways of reactive intermediates has
[
1]
attracted much interest in recent years. We have
been studying in particular reactions of carbenes gener-
ated by photolysis of diazirine precursors within cyclo-
[
2]
dextrin and zeolite hosts in the solid state. 2-Aziada-
3,7
mantane {2-azitricyclo[3.3.1.1 ]decane; (1)} is especial-
[
3]
ly suited for these investigations. A detailed analysis of
the complexes of 1 and a-(6-Cy), b-(7-Cy), and g-cyclo-
dextrin (8-Cy) (Scheme 1) by interpretation of induced
circular dichroism (ICD) titrations has already been re-
[4]
ported. Moreover, the photolysis of the 1:2 complex of
and 6-Cy, i.e., 1@2(6-Cy), in the solid state has opened
up an interesting synthetic route to monofunctionalized
1
[
5]
2’- and 3’-substituted a-cyclodextrins.
Here we wish to compare the results obtained earlier
with new findings for all three cyclodextrins to reveal in- Scheme 1.
teresting structure-reactivity relationships. From these
results we expect to gain new insights into the rather
Results and Discussion
complex reaction pathways for the photochemical de-
composition of diazirines.
Photolysis and Analysis of Reaction Products
The photolyses of the solid cyclodextrin complexes of 1
were carried out in the absence of oxygen at defined
temperatures using a specially doped medium-pressure
mercury lamp to exhibit an emission maximum in the
Adv. Synth. Catal. 2004, 346, 1367–1374
DOI: 10.1002/adsc.200404142
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FULL PAPERS
Daniel Krois et al.
wavelength region of the diazirine chromophore around droxy groups of a-cyclodextrin is markedly reduced. At
[4,5]
l¼380 nm. Thus, rather short exposure times of 1 to 4 all temperatures employed about 1–3% of 6 were
hours could be achieved for complete decomposition of formed which derives from the insertion reaction of ada-
[
7]
[8]
the azi function, which was assessed by UV spectroscopy mantanylidenes Ad: into the OꢀH bond of residual
[
4]
after each photolysis. Then the solid residue was dis- ethanol molecules.
solved in water-dichloromethane and a continuous liq- The b-cyclodextrin complexes contain only traces of
uid-liquid extraction was performed. Quantitative GC solvent molecules such as water and ethanol inside the
[
4]
analysis of the organic extracts provided absolute yields cavity. Therefore, the formation of 2-admantanol (5)
of the adamantane derivatives formed during photolysis is very low, while 2-ethoxyadamantane (6) is not formed
within the cyclodextrin host. In contrast, the absolute at all. The intramolecular 1,3 CꢀH carbene insertion to
[
2a, b]
yields of cyclodextrin and the cyclodextrin derivatives yield 2,4-didehydroadamantane (3)
is highest at
formed were determined after reversed phase (RP) about room temperature and lowest at 203 K, where
HPLCof the aqueous phase with methanol-water as elu- the reduction to adamantane (2) has its maximum. How-
ent. For both chromatographic methods response fac- ever, the proportions of 2 were always well below the
tors were determined using authentic, pure samples. amounts formed from the photolysis of the a-cyclodex-
The so-obtained results are summarized in Tables 1–3.
Some of the particular features of the photolysis of the
Table 2. Absolute yields of adamantanyl residues as recov-
ered (in %) after photolysis of 1@(7-Cy) in the solid state un-
der argon and reduced pressure.
2
:1 complex with a-cyclodextrin have alreadybeen pub-
[5]
[6]
lished. The occurrence of adamantanone-azine 7,
which dominates under almost all photolytic conditions,
does not take place at all, owing to the strict separation
of the adamantanyl moieties by the cyclodextrin hosts.
But also the formation of adamantanone (4) is negligi-
ble, even in the presence of oxygen (compare runs 7
and 9, where the same lot of complex has been photo-
lyzed). This would make the appearance of triplet ada-
mantanylidene (vide infra) unlikely. Striking, on the oth-
er hand, is the high amount of reduction to adamantane
Compound Run
1
2
3
4
5
6
T [K]
303 283 232 203 77 77
3.9 3.5 5.0 6.0 3.1 4.0
10.8 10.1 7.9 5.0 8.6 7.9
2.5 3.0 6.2 5.4 7.1 6.6
0.3 0.4 1.0 0.7 2.2 2.0
0.0 0.0 0.0 0.0 0.0 0.0
2
3
4
5
6
7
AdH2
DDHAd
Ad
¼
O
AdHOH
AdHOEt
Ad¼N-N¼Ad 33.4 29.0 33.8 29.9 33.8 32.6
-Cy-3’-Ad 0.2 0.6 1.2 1.3
7-Cy-6’-Ad
[
a]
7
(
2) which is accompanied by the appearance of oxidized
1
0
17.4 17.6 14.9 13.4 8.3 8.1
7.0 6.5 4.7 7.5 5.4 3.4
5.2 5.9 2.1 4.6 0.5 0.7
3.7 2.8 1.7 2.5 1.3 0.4
1.4 1.3 1.0 1.6 1.0 0.0
85.5 80.3 78.3 77.2 72.5 67.5
82.1 92.6 82.2 91.0 98.7 88.9
a-cyclodextrins as revealed by UV-Vis detection in the
HPLCanalysis (coeluting with unsubstituted 6-Cy).
The temperature influence on the course of the reaction
is not pronounced, only reduction to 2 and insertion into
[a]
7
-Cy-2’-Ad
[a]
7
7
-Cy-Ad2[
a]
-Cy-Ad2
[a]
7-Cy-Ad2
the hydroxy groups of 6-Cy become less frequent at Sum (% adamantanyl)
7
7 K. But, on the other hand, the amount of water pres- Sum (% cyclodextrin)
ent in the crystalsis of critical importance eventuallygiv-
ing rise to high yields of the alcohol 5. Runs 2, 4, 6 and 8
have been performed from the same lot of complex, that
had a particularly low content of water. In the presence
of water the insertion of adamantanylidene into the hy-
[a]
The composition of cyclodextrin insertion products was as-
sessed by LC-MS (see Experimental Section). The substi-
tution pattern of monoadamantanyl derivatives is only ar-
bitrary by comparison with isolated compounds and may
be different.
Table 1. Absolute yields of adamantanyl residues as recovered (in %) after photolysis of 1@2(6-Cy) in the solid state under
argon and reduced pressure.
[a]
Compound
Run
1
2
3
4
5
6
7
8
9
T [K]
303
303
263
263
233
228
77
77
77
2
3
4
5
6
7
8
9
AdH2
DDHAd
22.4
7.5
0.0
29.6
2.7
0.0
21.2
7.8
91.2
97.1
30.6
9.3
0.3
1.0
1.1
29.3
5.3
0.0
8.8
2.6
37.3
8.0
0.9
1.0
1.0
28.1
4.9
0.4
14.2
1.1
0.0
30.5
14.0
93.2
98.1
37.8
6.8
0.7
1.2
0.9
18.3
3.5
0.3
51.1
1.0
0.0
20.4
8.4
103.0
97.4
22.3
5.4
0.0
25.8
1.0
0.0
25.5
13.3
93.3
94.8
18.8
4.2
0.3
48.1
1.3
0.0
13.5
6.0
92.2
95.5
Ad¼O
AdHOH
AdHOEt
Ad¼N-N¼Ad
0.0
0.0
0.0
0.0
6-Cy-3’-Ad
6-Cy-2’-Ad
38.8
19.2
100.3
97.1
32.8
10.7
89.5
94.6
37.4
16.7
102.3
97.2
37.3
16.7
101.4
97.3
Sum (% adamantyl)
Sum (% 6-Cy)
[
a]
Run was started under normal atmospheric pressure in the presence of oxygen.
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Photolysis of Aziadamantane@Cyclodextrin Inclusion Complexes
FULL PAPERS
trin complex. The major cyclodextrin insertion product tanyl moieties were recovered as adamantanone (4) and
0 could be isolated by RP-HPLCand characterized. about 60% as azine 7. The respective cyclodextrin was
1
Its structure could be assigned by NMR experiments retrieved nearly quantitatively and found to be unmodi-
and was identified as the mono-6’-adamantanyl deriva- fied. Identical results were obtained if a concentrated
tive (vide infra). But also the other two possible mono- pentane solution of 1 was evaporated in the presence
derivatives could be detected. However, they were of the appropriate amount of the respective cyclodextrin
formed in significantly smaller amounts and could not and the resulting dry powder was photolyzed.
be isolated. From LC-MS only their mass is known. As
is obvious from Table 2, the formation of cyclodextrin-
OꢀH insertion products in all cases is markedly reduced Identification of Compound 10 by NMR
at lower temperatures. Especially bis-substitution re-
sulting from a two-fold insertion of adamantanylidene The structure of the isolated mono-6’-adamantanyl-sub-
(
Ad:) becomes almost negligible. The recovery of ada- stituted b-cyclodextrin (10) was determined by various
mantanyl derivatives also is decreased at lower temper- 1D and 2D NMR experiments with DMSO-d as sol-
6
atures. Notably, the amount of azine 7 formation (see vent. The linkage position of the adamantane moiety
Scheme 2) is not affected by the temperature.
has been identified by HMQC, HMQC-TOCSY, and
The photolyses of the g-cyclodextrin complex reveal HMBCand was furthermore verified by ROESY spec-
not much selectivity which is in accord with the known tra. In the HMBCspectrum the H-2 of the adamantanyl
3
a
structural flexibility of 8-Cy. Conspicuous is the much substituent shows a J coupling to the C-6’ of the sub-
CH
a
a
higher amount of adamantanol (5) formed, when com- stituted glucose unit (Glc ). Vice versa both H-6’a and
a
3
pared with the results from the photolysis of 1@(7-Cy). H-6’b possess a J coupling to C-2 in the adamantanyl
CH
3
This is due to the presence of more water molecules moiety. These J couplings are indicated in Figure 1. The
[
4]
a
within the supramolecular arrangement of 1@(8-Cy).
downfield shift of the C-6’ (d ¼66.6 ppm) additionally
C
Photolysis of solid physical mixtures of a-, b- or g-cy- indicates an ether linkage at this position. NOEs be-
a
a
a
a
clodextrin with aziadamantane (1) in the appropriate tween H-5’ , H-6’a , and H-6’b from Glc and H-1 and
stoichiometry of the corresponding complexes, always H-3 from the adamantane moiety indicate the spatial
gave the same result, i.e., about 20% of reacted adaman- closeness between these nuclei and hence verify the
linkage position of the adamantane substituent. Fur-
thermore, H-1, H-2, and H-3 show weak NOEs to H-
Table 3. Absolute yields of adamantanyl residues as recov-
ered (in %) after photolysis of 1@(8-Cy) in the solid state un-
der argon and reduced pressure.
b
b
b
5
’ , H-6’a , and H-6’b of one other glucose unit in the
b
b-cyclodextrin. This is likely the Glc which is 1’-4’
bound to Glc and therefore quite close to the adaman-
a
[a]
Compound Run
1
2
3
4
tanyl moiety. All chemical shifts of 10 are listed in Ta-
a
b
bles 6 and 7. There the shifts of Glc and Glc are given
T [K]
AdH2
303
6.5
263
4.9
77
3.1
77
3.3
c
g
in detail. Signals for the five other glucoses (Glc to Glc )
overlap and hence their chemical shifts are only given as
shift regions (Table 6). Stereochemical differentiation
of the two halves of the adamantane moiety is not very
2
3
4
5
6
7
DDHAd
8.6
9.5
13.2
2.4
29.0
3.4
9.5
5.8
11.9
12.2
1.5
30.1
4.9
10.7
5.3
4.2
6.3
9.2
6.6
1.0
26.5
3.8
8.2
10.3
Ad¼O
AdHOH
AdHOEt
1.0 pronounced and hence only two carbons show some
13
Ad¼N-N¼Ad
28.5 shift differences. The other Cand all proton chemical
[
b]
n.i.
shifts, however, are not distinguishable (Table 7).
[
c]
c]
c]
8
8
8
8
-Cy-3’-Ad[
-Cy-6’-Ad[
-Cy-2’-Ad
9.1
6.9
6.9
6.4
4.1
3.0
4.6
3.7
Supramolecular Structure-Reactivity Relationship
[
d]
-Cy-Ad2
5.0
2.2
Sum (% adamantanyl)
Sum (% cyclodextrin)
90.3
99.2
91.3
80.7
70.8
As crystallization of 2-aziadamantane-cyclodextrin
complexes thus far failed to give crystals suited for X-
94.8 102.3 100.6
[
[
[
a]
b]
c]
Run was started under normal atmospheric pressure in the ray diffraction analysis, structure-reactivity considera-
[
4,5]
presence of oxygen.
tions must be deduced indirectly.
1
In the case of
[5]
Approximate sum of not identified (n.i.) GCdetectable
compounds.
@2(6-Cy) this has been already addressed in part.
The comparison of all three types of complexes dis-
cussed here reveals some further interesting features.
Only in the case of 1@2(6-Cy) are the diazirines totally
isolated from each other, since each diazirine is entrap-
ped by two 6-Cyꢁs (see A of Figure 2). Therefore, the
azine formation is prevented. The chemospecific inser-
tion into the secondary hydroxy groups of 6-Cy yielding
The substitution pattern of monoadamantanyl derivatives
is only arbitrary by comparison with the isolated com-
pounds (8, 9, and 10) and may be different.
Several (up to nine) bisadamantanyl derivatives in trace
amounts could be detected by RP-HPLCusing eluent mix-
tures more rich in methanol. Here only the sum is listed;
their composition was assessed by MS.
[
d]
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FULL PAPERS
Daniel Krois et al.
molecule 1 is strikingly similar to the CD of chiral azi-
[
9]
camphane. This close contact with the cyclodextrin ob-
viously also favors the exclusive insertion of Ad: into the
secondary hydroxy groups of 6-Cy and the redox reac-
tion yielding adamantane (2) and oxidized 6-Cy deriva-
tives. Apparently, these reactions do occur less within
the complexes of hosts providing larger cavities. A rea-
sonable mechanism for the redox reaction yielding a hy-
drocarbon like 2 from a singlet carbene has – to the best
of our knowledge – never been proposed. Naturally, not
many suggestions have been put forward because, in
general, only small amounts (<5%) of reduced hydro-
[
10]
carbons are formed. This is true for the b- and g-cyclo-
dextrin complexes of 1 (see Tables 2 and 3). In stark con-
trast, however, for the photolysis of 1@2(6-Cy) with ada-
mantane yields of 30–40%, this becomes one of the ma-
jor reaction paths. Thus, further efforts to explain this
fact are justified. The formation of adamantane (2)
would indicate intersystem crossing (ISC) of adamanta-
nylidene Ad: from the singlet to the triplet state fol-
lowed by H-abstraction. An entrapped carbene might
be able to show a different spin multiplicity, when com-
pared with the corresponding mobile carbene. This
should especially be true, if the singlet-triplet energy
gap is small. Calculations for Ad: arrive at an energy
[
11a]
[11b]
gap of 4.8
and 3.1
kcal/mol, respectively, with
the singlet being the ground state. There are several
mechanisms by which ISCcan take place. Co mpared
to Ad:, Cyꢁs comprise a large molar mass. Hence, Cyꢁs
may provide a collisional mechanism for the ISCof
[
12]
Ad: 2 from the singlet to the triplet state. On the other
hand, the observation that in the presence of air (oxy-
gen) the amount of adamantanone (4) obtained is not
changed at all when compared with the reaction in the
absence of gaseous oxygen, is not indicative of any trip-
Figure 1. Structure and numbering of the adamantane moiety
and the linked glucose unit Glc (A). Sections from HMQC,
HMQC-TOCSY, and HMBC indicating the linkage position
[
13,14]
a
let carbene participation.
Nonetheless, the selective
and very pronounced formation of the 3’- and 2’-cyclo-
of the adamantane moiety to the b-cyclodextrin. Dashed lines dextrin insertion products 8 and 9, respectively, is indeed
1
a
a
[5,15]
show the connection from the J (H-6’a/b /C-6’ ) coupling chemospecific.
Also in accord with the proposed
HC
3
a
in HMQC and HMQC-TOCSY to the J (H-6’a/b /C-2) structure is the fact that no bis-adamantanyl derivatives
HC
2
coupling in HMBC. C-2 is further identified by its J cou-
HC
of 6-Cy are observed at all.
pling to H-1 and H-3 in HMBCand by the coupling in
The dominant formation of azine 7 even at very low
temperatures, which is observed in the case of the b-cy-
clodextrin complex, is in favor of a 2:2 complex where
two aziadamantanes (1) are facing each other with their
respective diazirine moieties. Such a structure has been
verified for the crystals of the complex with the more po-
HMQC-TOCSY. This consecutive connection is also visual-
1
ized by dashed lines. The connection from J (H-2/C-2) in
HC
3
a
HMQC and HMQC-TOCSY to the J (H-2/C-6’ ) is indi-
cated by continuous lines. C-6’ is further identified by its
JHC coupling to H-4’ in HMBCand by the coupling in
HMQC-TOCSY. This successive connection is also visualized
HC
a
2
a
by continuous lines. Dotted lines indicate the positions of the lar guest 5-hydroxy-2-aziadamantane by single-crystal
a
[16]
signals from the C-6’ and C-2 atoms. All further signals be- X-ray diffraction. The clear preference for insertion
long to other atoms of 10 (B).
into the 6’-OH group of 7-Cy is in favor of an arrange-
ment (B) as designated in Figure 2. A similar complexa-
tion with 7-Cy was postulated for the 5-hydroxy-2-azia-
[
16]
8
and 9 makes the proposed structure (A, Figure 2) high- damantane in solution by NMR spectroscopy. Relia-
ly plausible. Furthermore, the adamantane skeleton ble ROESY spectra of the 1@(7-Cy) complex could
must be in close contact with the inner walls of the two not be obtained, because of the very low solubility of
a-cyclodextrin molecules – this is corroborated by the this complex in water. However, the ICD spectra are
[4]
very intense ICD. The induced ellipticity of the achiral very similar to those of the corresponding 5-hydroxy de-
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Photolysis of Aziadamantane@Cyclodextrin Inclusion Complexes
FULL PAPERS
[
20,22]
of 1 could be traced.
While its structure could not be
established, it is formed by direct reaction of Ad: with 1.
An intermediate with the structure X, as shown in
[22]
Scheme 2, has been favored based on calculations. It
seems likely that adamantanone (4) which is only ob-
tained whenever azine 7 is formed (in 50–70% n/n of
) either shares a common intermediate with 7 or is a de-
composition product under the reaction conditions in
the crystal. This is also true for the solid physical mix-
tures of 1 and cyclodextrins.
7
Conclusion
The photolyses of 1 within cyclodextrin hosts give prod-
Figure 2. Proposed Structures for 1@2(6-Cy) (A) and 1@ uct distributions that largely depend on the type of cy-
(
7-Cy) (B).
clodextrin and thus the supramolecular structure. The
amount of reduction to hydrocarbon 2, the proportion
of azine 7 and adamantanone (4), the formation of cyclo-
[17]
rivative. In the solid state the orientation of 5-hy- dextrin ethers (8, 9, 10, etc.), and the insertion into sol-
droxy-2-aziadamantane within the b-cyclodextrin host vent molecules yielding 5 and 6 can be widely controlled
is reversed with respect to the proposed solution struc- by the geometry and composition of the complexes. This
ture. Since this can be explained by the special effect very interesting influence of the host as “catalyst” or
of the hydroxy group in the crystal, it should not apply even as co-reactant can be observed especially well for
[16]
for the unsubstituted adamantane (2).
the photolyses of 1, which primarily yield Ad: that can-
The very low selectivity as shown in the photolysis of not easily stabilize intramolecularly. The formation of
the 1@(8-Cy) complex reflects the relatively large space didehydroadamantane (3) has been known to occur
available for adamantane derivatives within the g-cyclo- only to a small extent, if other inter- and innermolecular
dextrin cavity. This also is corroborated by the rather reaction channels can be followed. And indeed, its yield
[
4]
small complex formation constantK and the faint ICD.
(4–11%) is almost invariable for all three complexes
In the photolysis of diazirines three processes can take studied.
place: firstly, the direct generation of a carbene, second-
ly, the rearrangement to the corresponding linear diazo
compound, and thirdly, a rearrangement in the excited Experimental Section
[18]
state (RIES). The formation of all but two of the prod-
ucts obtained in the solid state photolyses of the three
cyclodextrin complexes studied has been addressed
General Remarks
(
vide supra). However, for the formation of adamanta- The following compounds were prepared according to the liter-
none (4) and azine 7, at present no conclusive decisions ature and identified by their respective spectroscopic and ana-
can be made. As for the azine formation itself, various
mechanisms have been proposed.
an intermediate in the formation of azine 7 by photolysis
[
3a]
[2b]
[23]
[6]
[5]
[5]
lytical data 1, 3, 6, 7, 8, and 9 . Compounds 2, 4, and
were purchased from Fluka. Water was highly purified using a
[
19,20]
5
More recently
ꢂ
Milli-Q system (Millipore ), methanol for HPLCanalyses was
purchased from Merck (LichroSolv ), ethanol for preparative
ꢂ
HPLCwas of technical purity (azeotropic mixture with water)
and distilled; DMSO-d for NMR was 99.9% D (1 mL am-
6
poules) purchased from Sigma. The supramolecular complexes
of 1 with the three cyclodextrins were prepared as already pub-
[4]
lished and are designated as 1@2(6-Cy), 1@(7-Cy), and
@(8-Cy).
1
Photolysis
ꢂ
Photolyses were carried out in flasks of Duran glassware
equipped with a septum. The solid material was accurately
weighed in as a fine powder (50–400 mg) and evenly distribut-
ed on the inner surface of the flask. Then the samples were dea-
erated and Ar saturated several times on a vacuum line and fi-
nally displayed a weak vacuum with some residual Ar. The
Scheme 2.
Adv. Synth. Catal. 2004, 346, 1367–1374
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1371

FULL PAPERS
Daniel Krois et al.
flasks were rotated in a cooling bath (thermostatted water,
ethanol/dry ice or liquid nitrogen) situated below a medium-
pressure mercury lamp (Heraeus TQ718-Z4, 700 W, doped
rapid heating period of 6.7 min to 2508C. This temperature was
held for 5.3 min (total 27 min of analysis) prior to cooling. The
retention times and response factors of compounds 2ꢀ7 were
determined by injecting authentic samples (Table 4).
with FeI ). Photolysis was done for 1–4 h depending on the
2
sample amount. Then some mg of sample were dissolved in
ethanol-water and a UV spectrum (420–320 nm) was taken
to demonstrate complete loss of the diazirine chromophore.
Analytical RP-HPLCanalysis was performed using an
HP1090 instrument equipped with the RI-detector HP1047
and the interface 35900E (Agilent) using a Nucleosil 300–
5
C8 5 mm column (4ꢁ290 mm, FZ Seibersdorf, Austria). The
instrument was equipped with an auto-injector and was run
with the HP ChemStation (Rev. A.08.03; 2000) software. Iso-
cratic elution with a flow rate of 0.5 mL/min was done with var-
ious water-methanol mixtures. Representative data are shown
in Table 5. Response factors were determined for each session
Analysis of Products
Separation of low molecular weight adamantane derivatives
from cyclodextrins was performed by dissolving the solid in wa-
ter (120 mL) and dichloromethane (50 mL) followed by con-
tinuous extraction with the appropriate apparatus (100 mL,
for extraction liquids of higher density). After 24 h the di-
chloromethane was replaced by a new portion, thus giving a
first fraction, and after 48 h a second dichloromethane extract
was collected. In this way one could account for possible evap-
oration of some quite volatile products. These dichlorome-
thane solutions were diluted with 50% v/v hexane, 0.1% of a
standard camphor solution (3.22 mM) was added as internal
standard, and then the samples were directly injected into a
split-splitless GCinjector (5 mL, split ca. 1:15). GCanalysis
was performed on a GC8160 instrument (Fisons) using a PE-
Table 4. Representative data for GCanalysis.
[a]
Compound
Retention time
tR [min]
Response factor
[area (10 ·mV·s)·c
5
ꢀ1
ꢀ1
ꢀ1
ꢀ1
(
mg/mL) ·v (mL) ]
2
3
3.95
4.40
4.75
8.75
9.05
9.40
23.5
16.2
14.8
13.0
14.0
13.2
13.1
13.7
Camphor
4
5
6
7
1
column (Perkin Elmer, 30 m, i.d. 0.32 mm, 0.25 mm dimethyl-
ꢂ
polysiloxane film) using “Chromcard” software (Fisons). De-
tection was accomplished by FID. The flow rate of helium was
held constant at 2.1 mL/min; temperature gradient was: 5 min
at 1008Cfollowed by heating up to 150 8Cwithin 10 min and a
[a]
Representative values were re-determined for every new
session.
Table 5. Representative data for RP-HPLCanalysis.
[a]
Type of compound
Compound
Methanol content [% v/v]
Retention time t [min]
R
underivatized a-cyclodextrin
underivatized b-cyclodextrin
underivatized g-cyclodextrin
6-Cy
7-Cy
8-Cy
8
15
15
15
30
30
30
48
48
30
30
48
48
48
60
60
60
60
30
30
30
48
48
60
60
12.6
17.4
12.6
24.5
29.0
36.5
10.0
11.8
15.0
19.8
10.9
12.0
21.5
8.7
monoadamantanyl a-cyclodextrin
monoadamantanyl a-cyclodextrin
monoadamantanyl a-cyclodextrin
monoadamantanyl a-cyclodextrin
monoadamantanyl a-cyclodextrin
monoadamantanyl b-cyclodextrin
monoadamantanyl b-cyclodextrin
monoadamantanyl b-cyclodextrin
bisadamantanyl b-cyclodextrin
bisadamantanyl b-cyclodextrin
monoadamantanyl b-cyclodextrin
bisadamantanyl b-cyclodextrin
bisadamantanyl b-cyclodextrin
bisadamantanyl b-cyclodextrin
monoadamantanyl g-cyclodextrin
monoadamantanyl g-cyclodextrin
monoadamantanyl g-cyclodextrin
monoadamantanyl g-cyclodextrin
bisadamantanyl g-cyclodextrins
bisadamantanyl g-cyclodextrins
bisadamantanyl g-cyclodextrins
9
8
9
7-Cy-3’-Ad
10
7-Cy-2’-Ad
7-Cy-Ad2
7-Cy-Ad2
7-Cy-2’-Ad
7-Cy-Ad2
7-Cy-Ad2
I
II
I
8.7
II
10.5
21.4
11.4
14.3
22.3
10.2
13–14
10
III
7-Cy-Ad2
8-Cy-3’-Ad
8-Cy-6’-Ad
8-Cy-2’-Ad
8-Cy-2’-Ad
8-Cy-Ad (2)
I
[b]
[b]
2
I
8-Cy-Ad (2)
8-Cy-Ad (7)
2
II
[b]
11–20
2
[
a]
Representative values that can slightly vary according to small variations in solvent mixture, injection volume, and sample
amount.
[
b]
More than one compound, at least as many as given in brackets.
1372
ꢀ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 1367–1374

Photolysis of Aziadamantane@Cyclodextrin Inclusion Complexes
FULL PAPERS
Table 6. Proton (dH [ppm]) and carbon (d [ppm]) chemical shifts of the cyclodextrin moiety.
C
H-1’
H-2’
H-3’
H-4’
H-5’
H-6’a/b
C-1’
C-2’
C-3’
C-4’
C-5’
C-6’
a
b
c
Glc
Glc
Glc -Glc
4.83
4.83
4.83
3.29
3.23
3.28
3.57
3.57
3.61
3.23
3.40
3.36
3.68
3.48
3.52
3.63/3.53
3.77/3.51
3.64/3.57
101.7
101.9
101.9
73.5
72.1
72.2
72.6
72.5
72.8
82.2
81.2
81.4
70.7
71.5
71.8
66.6
59.5
59.7
g
Table 7. Proton (dH [ppm]) and carbon (d [ppm]) chemical shifts of the adamantane moiety.
C
H-1, H-2
H-3
H-4a/b,
H-9a/b
H-5
H-6
H-7
H-8a/b,
H-10a/b
C-1, C-2
C-3
C-4, C-9
C-5
C-6
C-7
C-8, C-10
1.91
3.39 1.73/1.58 1.73 1.63 1.68 1.36/1.94 31.3
81.0 35.9 & 35.7 30.0 37.1 26.8 31.0 & 30.9
with authentic samples of the pure compounds 6-Cy, 7-Cy,
fraction which was identified as 6’-O-adamantanyl-b-cyclodex-
trin (10) (yield: 40 mg, 0.03 mmol, 10%). For HPLCdata see
8
-Cy, 8, 9, and 10.
LC-MS of the 7-Cy derivatives was performed using an
2
0
20
Table 5; mp 305–3088C(dec.); [ a] : þ105.8ꢂ0.38; [a]
:
D
546
HP1100 System (Agilent) on a Zorbax Eclipse XDB-C18 col-
umn (150ꢁ4.6 mm, 5 mm) at 258Cwith 0.5 mL/min flow. The
MS detector was an MDS Sciex API 365 triple-quadrupole
MS (Applied Biosystems) with electrospray ionization (flow-
ing rate 5 mL/min; passive split). As eluents 10 mM ammonium
acetate in water and 10 mM ammonium acetate in methanol
were used. Analyses were performed by gradient elution but
also isocratically (50% methanol) and gave comparable elu-
tion profiles as the normal HPLC(above).
þ124.7ꢂ0.38 (c 1.3, pyridine containing 5% of water);
1
13
H NMR and CNMR data for DMSO- d solution see Ta-
6
bles 6 and 7; MS (ESI): (M calcd. 1268.48) found: m/z 1291.5
þ
ꢀ
(MþNa) and 1267.5(M – H) , respectively; anal. calcd. for
C H O ·1 H O: C48.52, H 6.73; calcd. for 95% content
5
2
84 35
2
[4]
[compare 1@(7-Cy) ]: C46.09, H 6.40; found: C46.15, H 6.47.
Acknowledgements
Mass spectrometry was accomplished with electrospray ion-
ization using the system Agilent 1100 MSD Trap SL both ap-
plying positive and negative ion detection.
We are indebted to the Fonds zur Förderung der wissenschaftli-
chen Forschung in Österreich (Project P12533-CHE) for finan-
cial support. We thank the former American Maize-Products
Company and Wacker Chemie for providing the cyclodextrins
used in our studies. Dr. A. Leitner of the Institut für Analytische
Chemie der Universität Wien (Abteilung Prof. W. Lindner) is
thanked for performing the LC-MS and MS experiments.
All NMR spectra were measured in DMSO-d at 300 K on a
6
Bruker DRX-600 AVANCE spectrometer equipped with a tri-
ple resonance xyz-gradient inverse probe. Irradiation frequen-
1
cies were 600.13 MHz for proton ( H) and 150.86 MHz for car-
13
bon ( C). Both 1D proton and carbon spectra were recorded
with 32,768 data points. After zero filling to 65,536 data points
the free induction decay was directly Fourier-transformed to
1
spectra with a spectral range of 6000 Hz and 22,500 Hz for H
13
and C, respectively. 2D pulse field gradient enhanced
COSY, TOCSY, ROESY, HMQC, HMQC-TOCSY, and
HMBCspectra were recorded using 1024 data points and 256
experiments for each spectrum. After linear prediction to 512
References and Notes
‡ For Part 59, see: T. Nordvik, J.-L. Mieusset, U. H. Brinker,
Org. Lett. 2004, 6, 715–718; Carbenes in Constrained Sys-
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Org. Chem. 2003, 68, 4819–4832.
data points in the t dimension and an appropriate sinusoidal
2
multiplication in both dimensions, the spectra were Fourier-
transformed. Mixing times of TOCSY and ROESY were 100
ms and 225 ms, respectively. Analysis of the spectra was per-
formed using the XWINNMR 3.1 software. Chemical shifts
were referenced to residual DMSO-d (d ¼2.49 ppm) and
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1374
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