Photoinduced hydrogen atom abstraction in N-(adamantyl)phthalimides: structure-reactivity study in the solid state

Article abstract of DOI:10.1016/j.tet.2008.12.010

Adamantyl-functionalized phthalimides were synthesized and the probability of intramolecular photochemical hydrogen atom abstraction in the solid state analyzed by X-ray crystallographic analyses. These analyses and solid-state photolyses showed that the parameters determining photochemical reactivity for typical carbonyl compounds in the solid state can also be extended to phthalimides. Only N-(2-adamantyl)phthalimide underwent a solid-state photochemical reaction, which is the first example in the phthalimide series. This reaction is regio- and stereoselective, resulting in an endo-alcohol. On the other hand, the photoreaction of N-(2-adamantyl)phthalimide in solution gives an exo-alcohol as the main product together with an endo-alcohol and a benzazepindione.

Full text of DOI:10.1016/j.tet.2008.12.010

Tetrahedron 65 (2009) 1438–1443
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Photoinduced hydrogen atom abstraction in N-(adamantyl)phthalimides:
structure–reactivity study in the solid state
a
,
a
a
a
*
´
´
´
Nikola Basaric , Margareta Horvat , Oliver Frankovic , Kata Mlinaric-Majerski ,
Jo¨rg Neudo¨rfl b, Axel G. Griesbeck b
a
ˇ
ˇ
´
Department of Organic Chemistry and Biochemistry, RuCer Boskovic Institute, Bijenicka cesta 54, 10000 Zagreb, Croatia
b Department of Organic Chemistry, University of Cologne, Greinstr. 4, 50939 Ko¨ln, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Adamantyl-functionalized phthalimides were synthesized and the probability of intramolecular photo-
chemical hydrogen atom abstraction in the solid state analyzed by X-ray crystallographic analyses. These
analyses and solid-state photolyses showed that the parameters determining photochemical reactivity
for typical carbonyl compounds in the solid state can also be extended to phthalimides. Only N-(2-
adamantyl)phthalimide underwent a solid-state photochemical reaction, which is the first example in
the phthalimide series. This reaction is regio- and stereoselective, resulting in an endo-alcohol. On the
other hand, the photoreaction of N-(2-adamantyl)phthalimide in solution gives an exo-alcohol as the
main product together with an endo-alcohol and a benzazepindione.
Received 2 September 2008
Received in revised form 12 November 2008
Accepted 4 December 2008
Available online 10 December 2008
Keywords:
Adamantane phthalimides
Photoinduced H-abstraction
Solid-state photochemistry
X-ray analysis
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
The phthalimide group is a very useful chromophore and its
photochemistry has been intensively studied and reviewed by
Griesbeck et al.4 and others.5 It shows typical reactivity of the
excited-state carbonyl chromophore: homolytic C–H activation,
resulting in cycloaddition and photoreduction products. In addi-
tion, the phthalimide chromophore is characterized by a high
oxidation potential of its first excited singlet state and the first and
the second excited triplet states.4d,6 Therefore, in the presence of
electron-rich substrates, homolytic activations are in competition
with electron transfer photochemistry. Due to the versatile photo-
chemical reactivity of phthalimides and its applicability in syn-
thesis,4,5,7 the photochemistry of phthalimides is still a subject of
widespread interest. However, to the best of our knowledge, solid-
state photochemistry of phthalimides has not been reported.
In the context of our work on the synthesis of polycyclic
compounds with different functionality8 we turned our attention
to adamantane derivatives of phthalimides. We discovered that
N-(1-adamantyl)phthalimide (1) does react in a domino photochemical
reaction in solution giving rise to a 2,4-methanoadamantane
derivative of benzazepine A (Eq. 1).9
The Norrish type II reaction is an important deactivation path-
way of the triplet excited state of carbonyl compounds. It has been
thoroughly examined on experimental1 and theoretical grounds,2
as well as in the solid state.3 Scheffer et al. developed a structure–
reactivity relationship for the solid-state intramolecular photo-
chemical g-H abstractions by carbonyl chromophores followed by
Yang cyclization.3 Four parameters direct the reactivity of the
carbonyl group in the excited state. The first of these is the distance
(d) between the carbonyl oxygen and the
value for d is equal to the sum of the van der Waals radii for oxygen
and hydrogen, which is 2.72 Å. The second parameter is defined
as the C]O/H angle, with an optimal value between 90ꢀ and 120ꢀ.
The third parameter is the C–H/O angle ( ), which is expected to
have an optimal value 180ꢀ, whereas the fourth parameter
is the
g-H atom. The optimal
D
q
u
angle by which the g-H atom lies outside the plane defined by C]O
and assumed to adopt an optimal value around 0ꢀ.
θ
H
Δ
d
OH
O
ω
O
h
N
ð1Þ
N
H
O
O
* Corresponding author. Tel.: þ385 1 4561 141; fax: þ385 1 4680 195.
1
A
´
E-mail address: nbasaric@irb.hr (N. Basaric).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.12.010

N. Basari´c et al. / Tetrahedron 65 (2009) 1438–1443
1439
Table 1
In this paper we report the synthesis of five new adamantane
The relevant geometric parameters d,
of phthalimides 1–6
u
,
D
and
q
obtained from the crystal structures
phthalimides (2–6), and the investigation of their structure by
X-ray crystallographic analysis. The investigation of the structure
by X-ray provides information on the probability to form photo-
chemical H-abstraction products on irradiation in the solid state. To
verify the findings obtained by X-ray analysis we performed photo-
lyses of phthalimides 1–6 in the solid state. Phthalimide 4 was also
irradiated in solution and the selectivity of the photoreactions was
compared.
Compound
d (Å)
u
(ꢀ)
D
(ꢀ)
q
(ꢀ)
1a
2.41 (C8O2/H–C14)b
2.41 (C8O2/H–C14A)
2.48 (C1O1/H–C10)
21.98
21.98
57.29
92.59
92.59
94.72
122.87
122.87
96.94
2
2.85 (CO1/H–C11A)
2.87 (CO1/H–C11B)
2.87 (CO4/H–C30B)
2.87 (CO3/H–C37B)
104.90
18.16
10.94
95.44
77.36
101.71
98.22
80.82
103.44
102.50
106.89
109.29
2. Results and discussion
2.1. Synthesis
3
4
5
2.96 (CO2/H21–C10)
3.40 (CO1/H20–C10)
35.56
60.76
83.82
73.05
111.79
103.21
2.29 (CO1/H–C17)
2.36 (CO2/H–C15)
35.37
46.00
108.36
100.93
134.19
132.65
Adamantane phthalimides 1–6 were synthesized by coupling
phthalic anhydride with the corresponding amines 7–12, re-
spectively (Scheme 1). The imide condensations were performed in
moderate yields using a modification of the solvent-free pro-
cedure10 in a melt of phthalic anhydride. Amine 7 was obtained
from commercial sources, amine 8 was prepared from 1-adaman-
tanecarboxylic acid, which was transformed to the cyanide8f and
reduced with LiAlH4.11 Amine 912 was obtained from 1-ada-
mantylacetic acid, which was transformed to its amide13 (treat-
ment with SOCl2 followed by liquid NH3) and reduced with LiAlH4.
For the preparation of amines 10–12, 2-adamantanone was used as
a starting material. Amine 10 was obtained from a reaction with
formamide and subsequent treatment with HCl,14 amine 11 was
prepared by reduction of the corresponding cyanide,15 which was
prepared from adamantanone in a reaction with TosMIC.8e Com-
pound 12 was synthesized from adamantanone, which was trans-
formed to the methylidene nitrile16 by a modification of a literature
procedure17 and reduced with LiAlH4. All new phthalimides 2–6
were characterized by spectroscopic methods (see Section 4).
2.59 (CO2/HA–C11)
2.78 (CO2/H–C18)
3.33 (CO1/H–C10)
80.20
56.04
60.76
84.72
117.70
74.53
121.58
117.19
104.83
6
2.92 (CO2/HA–C10)
3.42 (CO1/HB–C10)
36.90
57.70
83.98
73.67
113.22
102.46
a
Data taken from the Cambridge crystallographic database.
The atom notations correspond to the ORTEP drawings presented in Supple-
b
mentary data.
H-abstraction by the carbonyl moiety of the phthalimide chromo-
phore (dꢁ2.72 Å). The values for the
range 90–120ꢀ or slightly below these values. However, most of the
values for the
angle are not close to 0ꢀ and there are large de-
viations of the angle
from 180ꢀ.
The adamantane H-atoms in 3 and 6 cannot be activated by the
excited state of the phthalimide moiety. The only H-atoms in 3 and
6, which may be available for H-abstraction are in a
the carbonyl at the ethylene spacer (at C10, see Supplementary data
S9 and S18). The distance between the closest -H atom in 3 and 6
D angles are generally in the
u
q
g-position to
g
is, however, slightly larger than the sum of van der Waals radii,
what implies that photochemical H-abstraction in the crystalline
state is not highly feasible.
O
O
O
(CH2)nNH2
N
In phthalimide 1, three H-atoms are at the optimal distance
available for abstraction. However, the abstraction of the H-atom at
C10 (see Supplementary data S3) in the solid state appears to be not
O
(CH2)n
O
7
n = 0
n = 1
n = 2
1 n = 0 (59%)
2 n = 1 (59%)
3 n = 2 (57%)
possible, due to the unfavorable
abstraction of H-atoms at C14 and C14A is also difficult due to the
same reason, low
values (122.87ꢀ).
q
value (96.94ꢀ). Additionally, the
8
9
O
q
O
(CH2)nNH2
(CH2)n
N
Phthalimide 2 crystallized with two independent molecules in
the crystal unit. In each of these two molecules there are two
O
O
H-atoms of the adamantane skeleton at the
bonyl chromophore, at the distance available for the abstraction.
However, the abstraction of only axial -H atoms (H–C11B and
H–C30B, see Supplementary data S6) is expected to be feasible due
to the unfavorable angle for the equatorial H-atoms (H–C11A and
H–C37B). On the other hand, abstraction of the axial H-atoms is also
difficult because of the low value.
d-position to the car-
O
10 n = 0
11 n = 1
12 n = 2
n = 0 (39%)
4
d
5 n = 1 (42%)
6 n = 2 (46%)
u
Scheme 1.
q
2.2. Crystal structures and probability for photochemical
H-abstraction
In phthalimides 4 and 5 there are two H-atoms of the ada-
mantane skeleton, which are at the distance available for the
H-abstraction. In 5, these H-atoms (H–C11 at
at -position, see Supplementary data S15) are, however, at the
angle
(80.20 and 60.76ꢀ, respectively), which is probably too high
for the reaction to take place in the solid state. In 4, available
H-atoms for the abstraction are at the positions C17 and C15 of the
d-position, and H–C18,
In order to investigate the probability of adamantane phthal-
imides 1–6 to undergo photochemical H-abstraction, we examined
their crystal structures (see Supplementary data). The single crys-
tals of adamantane phthalimides 2–6 were obtained by slow
evaporation from their solutions; the crystal structure of ada-
mantane phthalimide 1 has been published earlier.18 The relevant
parameters (vide supra) obtained by X-ray analysis, which indicate
their probability for intramolecular photochemical H-abstraction in
the solid state are compiled in Table 1.
3
u
adamantane (
S12). Although all the parameters (d,
values, and d are slightly lower for the H at C17 suggesting the
d-position to the carbonyl, see Supplementary data
u
,
D
and ) assume similar
q
u
higher reactivity at that position than at the C15.
The crystal structures of phthalimides 1–6 were also examined
for the intermolecular short contacts between the carbonyl oxygen
and hydrogen atoms. Upon excitation of molecules, due to these
As can be seen from the data in Table 1, most of the investigated
compounds have at least one H-atom available for intramolecular

1440
N. Basari´c et al. / Tetrahedron 65 (2009) 1438–1443
O
O
O
2.3 A
h
N
h
N
N
H
OH
OH
H
O
H
3.7 A
BR 1
BR 2
4
O
O
N
O
H
N
O
OH
N
H2O
N
+
OH
HO
O
13
14
INT
15
Scheme 2.
short contacts, intermolecular hydrogen abstractions may take
place. However, in 1–6 most of the short contacts with the carbonyl
oxygen are formed by aromatic H-atoms, which do not undergo
photochemical H-abstractions. The shortest distance between the
aliphatic adamantane H-atoms of one molecule and the carbonyl
oxygen of the other molecule is 2.69 Å (for 1, the distance between
O3 and H42), which is larger than the intramolecular distance to
the potentially reactive hydrogen (Table 1). Consequently, photo-
chemical intermolecular hydrogen abstractions in crystals 1–6 are
not anticipated.
CH3CN and CH3CN/H2O (3:1)). The photochemical reaction gave
three products (13–15, Scheme 2), which were isolated and fully
characterized. The photolysis of 4 was clearly the most efficient in
acetone (F
w0.004),20 suggesting that it occurs via a triplet excited
state. On the other hand, in nonpolar solvents almost no conversion
took place. After 16 h photolysis in cyclohexane, the conversion of 4
was <3%. On addition of water to the CH3CN solution of 4, its
photochemical reactivity was enhanced. Thus, after 16 h photolysis
(100 mg in 200 mL, 16 lamps 8 W, 300 nm), the conversion of 4 in
CH3CN was 35%, whereas in CH3CN/H2O (3:1) (under same condi-
tions), complete conversion was achieved. However, the same ratio
of the photoproducts was obtained on irradiation in CH3CN and
CH3CN/H2O. The structures of the photoproducts were determined
by spectroscopic methods and additionally proven by X-ray analysis
(see Supplementary data).
2.3. Photochemical reactivity
In order to verify the finding obtained by X-ray structural
analysis on the probability of phthalimides to undergo photoin-
duced H-abstraction, we performed irradiation of phthalimides 1–6
in the solid state. For that purpose, crystals of the phthalimides
were grown from CH2Cl2 solution and analyzed by microscopy and
X-ray diffractometer. Irradiation was performed for all samples in
the form of single crystals and in the form of films obtained by the
fast evaporation of CH2Cl2 from the Petri dishes. Although single
crystals and films of the same phthalimide obtained by the evapo-
ration of the solvent differed in particle size, the samples were
isomorphic, as shown by X-ray diffractometry and microscopy.
From the investigated phthalimides, only 4 underwent a solid-
state photochemical reaction, as was predicted from the X-ray
structural analysis. However, the conversion of the reaction was
very much dependant on the size of the particles. Therefore, we
also performed irradiation experiments of phthalimides 1–6 in the
form of microcrystals. To prepare these microcrystals, we applied
the procedure of Garcia-Garibay et al.19 Phthalimides were ground
and suspended in H2O. The (micro)suspension was maintained by
addition of sodium dodecyl sulfate (SDS). Similarly, only 4 un-
derwent photochemical transformation but the photolysis of the
microsuspension was 2–3 times faster than photolysis of the film.
In order to characterize the photoproducts of 4, we have per-
formed preparative solid state and microsuspension irradiations.
After extended irradiation of films (3 days), or microsuspensions
(1 day), the photoproducts were separated by column chromatog-
raphy. Although the photochemical reaction of 4 was slow, it was
selective giving one main product, endo-alcohol 13, which was
isolated in 10% yield. Only traces (less than 1%) of exo-alcohol 14
and benzazepindione 15 were detected by HPLC.
2.4. Mechanism of the photochemical reaction
According to the isolated products 13–15, we propose the
mechanism of the photochemical transformation of 4 in solution
(Scheme 2). After population of the triplet excited state, hydrogen
abstraction of the adamantane-H by the phthalimide moiety takes
place. Due to the molecular motions, several hydrogen atoms of the
adamantane skeleton are available for the abstraction by the
phthalimide carbonyl. Although it is generally known that
abstraction is faster by an order of magnitude than -H abstraction,
in case of 4, two biradicals are formed (BR-1 and BR-2 Scheme 2).
However, the -H atoms are closer to the phthalimide carbonyl than
the corresponding
-H atoms. According to AM1 calculation,21 in
g-H
d
d
g
the most stable ground-state conformer in the gas phase, the dis-
tance between the carbonyl of the phthalimide moiety and the
adamantane-H at position 4 (d-H atoms, at C15 or C17, Supple-
mentary data S12) is 2.3 Å, which coincides with the distance found
in the crystal structure of 4. Moreover, BR-1 is more stable than BR-
2 (w5 kcal/mol). Therefore, formation of BR-1 is favored, as in the
case of solid-state reaction (vide infra). Combination of biradical
BR-2 gives the azetidinol (INT), which is unstable and easily opens
to more stable azepindione 15, which was isolated. On the other
hand, combination of BR-1 gives two products, exo-alcohol 14 and
endo-alcohol 13 in a ratio 3:1.
In the case of solid-state reactions where molecular motions are
restricted, only the closest H-atoms can be abstracted, which are at
the appropriate angle to the phthalimide carbonyl group. The X-ray
The irradiation of phthalimide 4 was also performed in solution
phase, using solvents of different polarity (cyclohexane, acetone,
structural analysis for phthalimide
H-atoms are at the positions C15 and C17 of the adamantane
4 indicated that reactive

N. Basari´c et al. / Tetrahedron 65 (2009) 1438–1443
1441
moiety. Therefore, irradiation of 4 in the solid state gives only BR-1.
Due to restricted molecular motions, cyclization of BR-1 is selective
giving mainly endo-alcohol 13. This result is not surprising since the
geometry of exo-alcohol 14 differs largely from the geometry of
endo-alcohol 13 in comparison with the starting material 4.
Colourless crystals; mp 139–140 ꢀC; 1H NMR (300 MHz, CDCl3)
/ppm: 7.85–7.82 (m, 2H), 7.72–7.69 (m, 2H), 3.37 (s, 2H), 1.95 (br s,
d
3H), 1.67 (d, 3H, J¼12.2 Hz), 1.61 (d, 3H, J¼12.2 Hz), 1.60–1.55 (m,
6H); 13C NMR (75 MHz, CDCl3)
d/ppm: 169.0, 133.7, 132.0, 123.0,
49.6, 40.7, 36.6, 35.4, 28.1; IR (KBr) nmax/cmꢃ1: 2902, 2847, 1767,
1713. Anal. Calcd for C19H21O2N: C 77.26, H 7.17, N 4.74. Found: C
77.19, H 7.24, N 4.83%.
3. Conclusion
N-[2-(1-Adamantyl)ethyl]phthalimide (3) was obtained in 57%
yield (845 mg) from 1-(2-aminoethyl)adamantane (0.86 g,
4.80 mmol).
A series of new adamantane phthalimides 2–6 have been syn-
thesized and characterized by spectroscopic methods and X-ray
crystallographic analysis. The probability of photochemical H-ab-
straction on phthalimides 1–6 in crystalline state was examined by
X-ray analysis. The analysis indicated that parameters determining
the photochemical reactivity of typical carbonyl compounds in the
solid state can be extended to phthalimides. From the investigated
phthalimides, only 4 underwent solid-state photochemical reaction.
Photoreaction of 4 is regio- and stereoselective, giving endo-alcohol
13 as the main product. On the other hand, the photoreaction in the
solution gave a mixture of endo-13 and exo-14, together with the
benzazepindione product 15.
Colourless crystals; mp 158–160 ꢀC; 1H NMR (300 MHz, CDCl3)
d
/ppm: 7.83–7.80 (m, 2H), 7.69–7.67 (m, 2H), 3.71–3.65 (m, 2H),
1.96 (br s, 3H), 1.71 (d, 3H, J¼12.0 Hz), 1.66 (d, 3H, J¼12.0 Hz), 1.61–
1.57 (m, 6H), 1.44–1.39 (m, 2H); 13C NMR (75 MHz, CDCl3)
/ppm:
d
168.2, 133.6, 132.2, 122.9, 42.1, 41.9, 36.9, 33.1, 31.8, 28.4; IR (KBr)
nmax/cmꢃ1: 2910, 2849, 1766, 1717. Anal. Calcd for C20H23O2N: C
77.64, H 7.49, N 4.53. Found: C 77.94, H 7.66, N 4.53%.
N-(2-Adamantyl)phthalimide (4) was obtained in 39% yield
(2.52 g) from 2-aminoadamantane (3.46 g, 22.88 mmol).
Colourless crystals; mp 103–104 ꢀC (lit.23 103 ꢀC); 1H NMR
(300 MHz, CDCl3)
(br s, 1H), 2.57 (br s, 2H), 2.33 (br s,1H), 2.29 (br s,1H),1.96–1.92 (m,
6H), 1.79 (br s, 2H), 1.71–1.66 (m, 2H); 13C NMR (75 MHz, CDCl3)
ppm: 169.4, 133.6, 132.0, 122.6, 61.2, 38.4, 37.6, 32.7, 31.9, 27.5, 26.8.
N-(2-Adamantylmethyl)phthalimide (5) was obtained in 42%
yield (912 mg) from 2-aminomethyladamantane (1.20 g, 2.40 mmol).
Colourless crystals; mp 123–125 ꢀC; 1H NMR (300 MHz, CDCl3)
d/ppm: 7.80–7.77 (m, 2H), 7.69–7.66 (m, 2H), 4.32
4. Experimental part
4.1. General
d
/
1H and 13C NMR spectra were recorded on a Bruker AV-300 or
600 Spectrometer at 300 or 600 MHz, respectively. All NMR spectra
were measured in CDCl3 using tetramethylsilane as a reference.
Melting points were obtained using an Original Ko¨fler Mikro-
heitztisch apparatus (Reichert, Wien). IR spectra were recorded on
a FT-IR ABB Bomem MB 102 spectrophotometer and elemental
analyses were performed at the Central Analytical Laboratory, at
d
/ppm: 7.85–7.82 (m, 2H), 7.72–7.69 (m, 2H), 3.82 (d, 2H, J¼7.8 Hz),
2.17–2.09 (m, 3H), 1.89–1.56 (m, 12H); 13C NMR (75 MHz, CDCl3)
d
/
ppm: 168.6, 133.7, 132.0, 123.0, 42.9, 40.9, 38.6, 38.0, 31.4, 29.9, 27.9,
27.8; IR (KBr) nmax/cmꢃ1: 2915, 2889, 1764, 1708. Anal. Calcd for
C19H21O2N: C 77.26, H 7.17, N 4.74. Found: C 76.85, H 6.77, N 4.96%.
N-[2-(2-Adamantyl)ethyl]phthalimide (6) was obtained in 46%
yield (1.37 g) from 2-(2-aminoethyl)adamantane (1.73 g, 9.64 mmol).
Colourless crystals; mp 128–130 ꢀC; 1H NMR (300 MHz, CDCl3)
ˇ
´
the RuCer Boskovic Institute. The samples were analyzed on a Shi-
madzu HPLC equipped with a diode array detector on a Phenom-
enex Luna 3u C18(2) column using CH3OH/H2O (20%) as a solvent.
Silica gel (Merck 0.05–0.2 mm) was used for chromatographic pu-
rifications. Solvents were purified by distillation. 1-Aminoada-
mantane, 1-adamantanecarboxylic acid, 1-adamantylacetic acid
and 2-adamantanone are commercially available. Irradiations were
performed in a Rayonet reactor equipped with 16 lamps with the
300 nm output or in a Luzchem reactor.
d
/ppm: 7.85–7.81 (m, 2H), 7.47–7.68 (m, 2H), 3.68 (t, 2H, J¼15,1 Hz),
1.91–1.51 (m, 17H); 13C NMR (75 MHz, CDCl3)
d
/ppm: 167.4, 132.8,
131.2, 122.1, 40.9, 38.0, 37.3, 35.6, 30.6, 30.5, 30.4, 27.1, 26.9; IR (KBr)
nmax/cmꢃ1: 2906, 2889, 2872, 2852, 1767, 1703. Anal. Calcd for
C20H23O2N: C 77.64, H 7.49, N 4.53. Found: C 77.71, H 7.10, N 4.68%.
4.3. Photochemistry of adamantane phthalimides in the
solid state
4.2. Preparation of adamantane phthalimides, general
procedure
(A) Adamantane phthalimides 1–6 (10 mg) were dissolved in
CH2Cl2 (10 mL) and solutions were poured into the Petri dishes.
After evaporation of the solvent, the samples were irradiated in
a Luzchem reactor at 300 nm over 3 days. After irradiation,
samples were analyzed by 1H NMR.
(B) Adamantane phthalimides 1–6 (100 mg) were dissolved in
CH2Cl2 (10 mL). The solutions were spread on the walls of
quartz cuvettes (20 mL) to form thin films upon evaporation of
the solvent. The quartz cuvettes with the film of the phthali-
mides were filled with N2 and irradiated in a Rayonet reactor
over 3 days. After irradiation, the samples were analyzed by
HPLC and 1H NMR.
(C) Adamantane phthalimides 1–6 (100 mg, crystals grown from
CH2Cl2) were ground with a mortar and pestle and suspended
in 150 mL H2O to which sodium dodecyl sulfate (100 mg) was
added. The suspension was irradiated over 24 h. The irradiated
mixture was continuously stirred and purged with N2 to
maintain the suspension. After the irradiation, the precipitate
was separated from the solution by centrifugation, dissolved in
CH2Cl2 and dried over anhydrous MgSO4. After filtration, sol-
vent was evaporated on a rotary evaporator to afford crude
mixture, which was analyzed by 1H NMR and HPLC.
In a round bottom flask (50 mL) equipped with a stopper,
phthalic anhydride (1.5 equiv) was melted. To the melt, 1 equiv of
adamantaneamine was added in several portions (sometimes
added as a CH2Cl2 solution). After the addition was complete, the
reaction mixture was stirred over 10 min with the stopper, after
which stopper was removed and stirring continued for another
10 min to remove water. To the cooled reaction mixture, CH2Cl2
(100 mL) was added, and the solution washed with 10% acetic acid
(3ꢂ30 mL) and 10% solution of NaHCO3 (3ꢂ30 mL). Washed organic
layer was dried over anhydrous MgSO4, filtered and the solvent was
removed on a rotary evaporator. The crude reaction mixture was
purified by column chromatography on SiO2 using CH2Cl2 as an
eluent.
N-(1-Adamantyl)phthalimide (1) was obtained in 59% yield
(1.65 g) from 1-aminoadamantane (1.5 g, 9.92 mmol).
Colourles crystals; mp 137–139 ꢀC (lit.22 138–139 ꢀC); 1H NMR
(CDCl3, 600 MHz)
(br s, 3H), 2.16 (br s, 6H), 1.80–1.70 (m, 6H); 13C NMR (150 MHz,
CDCl3) /ppm: 169.6, 133.5, 131.9, 122.4, 60.3, 40.1, 36.1, 29.7.
d/ppm: 7.75–7.74 (m, 2H), 7.66–7.65 (m, 2H), 2.52
d
N-(1-Adamantylmethyl)phthalimide (2) was obtained in 59%
yield (2.11 g) from 1-aminomethyladamantane (2.0 g, 12.10 mmol).

1442
N. Basari´c et al. / Tetrahedron 65 (2009) 1438–1443
2-endo-Hydroxy-10-aza-hexacyclo[9.5.1.112,14.116,18.02,10.03,8]-
4.5. Crystallography
nonadeca-3,5,7-triene-9-one (13). Yield 10 mg (10%). Colourless
crystals; mp 156–168 ꢀC; 1H NMR (CDCl3, 600 MHz)
d
/ppm: 7.74
The single crystals of phthalimides 2–6 and 13–15 were obtained
by slow evaporation of the solvent. Data collections were performed
on a Nonius Kappa-CCD-diffractometer, using a graphite mono-
(dd, 1H, J¼7.6, 0.8 Hz, H-a), 7.62 (ddd, 1H, J¼7.4, 7.6, 1.0 Hz, H-c),
7.55 (d, 1H, J¼7.6 Hz, H-d), 7.47 (ddd, 1H, J¼7.4, 7.6, 0.9 Hz, H-b),
4.20 (t, 1H, J¼4.9 Hz, H-2), 2.80 (m, 1H, H-9), 2.69 (br s, 1H,
OH), 2.60 (t, 1H, J¼3.9 Hz, H-4), 2.32 (br s, 1H, H-5), 2.26 (br s,
1H, H-1), 1.99 (ddd, 1H, J¼12.7, 5.7, 3.3 Hz, H-6), 1.93 (ddd, 1H,
J¼12.9, 6.2, 3.3 Hz, H-8), 1.89 (br s, 1H, H-7), 1.80 (d, J¼12.7 Hz,
H-6), 1.75–1.68 (m, 3H, H-8/10), 1.61–1.59 (m, 2H, H-9/3); 13C
chromated Mo
Ka (0.71073 Å) radiation and the Software
COLLECT.24 Datareduction was preformed with Denzo.25 The struc-
tures were solved with SHELXS97 and refined with SHELXL97.26 The
models were refined using the full matrix least squares refinement.
Hydrogen atoms were located from difference Fourier maps and
refined as free entities for 2, 4, 5, 6, 14, 15 or riding entities for 3 and
13. The atomic scattering factors were those included in SHELXL97.
Molecular geometry calculations were performed with PLATON,27
and molecular graphics were prepared using PLATON, SCHAKAL9928
and CCDC-Mercury.29 Crystallographic and refinement data for
structures are shown in Supplementary data.
NMR (CDCl3, 150 MHz)
d
/ppm: 179.2 (C-20), 151.2 (C-30), 133.7
(C-a), 132.7 (C-40), 129.6 (C-a), 123.9 (C-c), 122.4 (C-b), 98.6 (C-
50), 67.3 (C-2), 46.5 (C-4), 38.9 (C-3), 36.1 (C-6), 35.3 (C-8), 34.6
(C-9), 32.7 (C-10), 32.1 (C-1), 28.5 (C-5), 25.3 (d, C-7); IR (KBr)
nmax/cmꢃ1: 3408, 2911, 1697.
Acknowledgements
4.4. Photochemistry of N-(2-adamantyl)phthalimide (4) in
solution
We thank the Ministry of Science Education and Sports of the
Republic of Croatia (grant No. 098-0982933-2911) and Deutsche
Forschungsgemeinschaft (DFG). The support of DAAD and The
Croatian Ministry of Science, Education and Sports on the bilateral
project is also gratefully acknowledged.
N-(2-Adamantyl)phthalimide (5, 610 mg, 2.17 mmol) in 1 L of
CH3CN (c¼2.17ꢂ10ꢃ3 M) was irradiated over 16 h at 300 nm. Dur-
ing irradiation, solution was continuously purged with N2 and
cooled by H2O. After photolysis, solvent was removed on a rotary
evaporator, and the residue chromatographed on a column filled
with silica gel using CH2Cl2/CH3OH (up to 10%) as eluent. In the first
fraction 496 mg (81%) of the starting phthalimide 5 was isolated,
followed by a mixture (114 mg) of the photochemical products,
which were separated by repeated chromatography on a thin layer
of silica gel using CH2Cl2/CH3OH (2%) and CH2Cl2/Et2O (20%) as
eluent.
Supplementary data
1H NMR and 13C NMR spectra and ORTEP drawings for 2–6 and
13–15, as well as crystallographic and refinement data for struc-
tures. Supplementary crystallographic data for this paper can be
obtained free of charge via www.ccdc.cam.ac.uk/conts/retrie-
ving.html (or from the Cambridge Crystallographic Data Centre, 12,
Union Road, Cambridge CB2 1EZ, UK; fax: þ44 1223 336033; or
deposit@ccdc.cam.ac.uk). CCDC: 699053, 699054, 699055, 699056,
699057, 699058, 699059, and 699060 contain the supplementary
crystallographic data for this paper. Supplementary data associated
with this article can be found in the online version, at doi:10.1016/
j.tet.2008.12.010.
2-endo-Hydroxy-10-aza-hexacyclo[9.5.1.112,14.116,18.02,10.03,8]-
nonadeca-3,5,7-triene-9-one (13). Yield 27 mg (4.4%).
2-exo-Hydroxy-10-aza-hexacyclo[9.5.1.112,14.116,18.02,10.03,8]non-
adeca-3,5,7-triene-9-one (14). Yield 63 mg (10.5%). Colourless
crystals; mp 202–205 ꢀC; 1H NMR (CDCl3, 600 MHz)
d/ppm: 7.69 (d,
1H, J¼7.5 Hz, H-a), 7.56 (ddd, 1H, J¼7.5, 7.3, 0.9 Hz, H-c), 7.49 (d,
1H, J¼7.5 Hz, H-d), 7.45 (ddd, 1H, J¼7.5, 7.3, 0.9 Hz, H-b), 4.04 (t, 1H,
J¼4.8 Hz, H-2), 3.41 (br s, 1H, OH), 3.14 (br s, 1H, H-3), 1.99 (ddd, 1H,
J¼13.2, 5.7, 2.7 Hz, H-10), 1.95 (ddd, 1H, J¼13.2, 5.7, 2.7 Hz, H-10),
1.90 (br s, 1H, H-7), 1.78 (ddd, 1H, J¼9.3, 6.2, 3.1 Hz, H-9), 1.72 (m,
1H, H-6), 1.63–1.67 (m, 2H, H-5, H-9), 1.04 (ddd, J¼14.0, 3.8, 2.0 Hz,
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