Photochemical ring enlargement of macrocyclic N-phenyl imides into cyclophanes

Article abstract of DOI:10.1002/1522-2675(20000809)83:8<1809::AID-HLCA1809>3.0.CO;2-L

Allylic N-phenyl imides containing 12- and 14-membered rings, such as compounds 3 and 12, are easily synthesized by ring enlargement from cycloalkanones and phenyl isocyanates. Irradiation of 3 and 12 in EtOH and MeCN, with high- and low-pressure Hg lamps

Full text of DOI:10.1002/1522-2675(20000809)83:8<1809::AID-HLCA1809>3.0.CO;2-L

Helvetica Chimica Acta ± Vol. 83 (2000)
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Photochemical Ring Enlargement of Macrocyclic N-Phenyl Imides into
Cyclophanes
by Jörg A. Heerklotz, Changchun Fu, Anthony Linden, and Manfred Hesse*
Organisch-chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich
Dedicated to Professor Albert Eschenmoser on the occasion of his 75th birthday
Allylic N-phenyl imides containing 12- and 14-membered rings, such as compounds 3 and 12, are easily
synthesized by ring enlargement from cycloalkanones and phenyl isocyanates. Irradiation of 3 and 12 in EtOH
and MeCN, with high- and low-pressure Hg lamps, led, via the photo-Fries rearrangement, to the same primary
products: the orthocyclophane 8 and the paracyclophane 9 from 3 (Scheme 2), and the corresponding
compounds 13 and 14 from 12 (Scheme 3). Besides the primary photorearrangement products, secondary
products, the aminocyclophanes 10 and 11, or 15 and 16, respectively, were also formed. The total yields of the
four products were very high when the N-phenyl imides were irradiated in MeCN with a low-pressure Hg lamp:
97 and 93%, respectively. If the para-position in 3 or 12 is blocked by a Me group, the para-photo-Fries
rearrangement is prevented. In this case, only one primary photoproduct is formed: the corresponding
orthocyclophane (17 or 23, resp.). The most remarkable result was observed on irradiation of the 12-membered
N-(4-tolyl) imide 5 in MeCN (low-pressure lamp). It reacted nearly quantitatively to give only two products:
15-methyl-1-aza[12]orthocyclophane-2,12-dione (ˆ16-methyl-2-azabicyclo[12.4.0]octadeca-1(14),15,17-triene-
3,13-dione; 17) in 80% yield and 17-amino-14-methyl[11]metacyclophane-1,11-dione (ˆ17-amino-15-methyl-
bicyclo[11.3.1]heptadeca-1(17),13,15-triene-2,12-dione; 19) in 16% yield (Scheme 5).
Introduction. ± Over recent years, it has become easy to prepare macrocyclic N-
phenyl imides of different ring sizes in good yield by ring enlargement from
cycloalkanones with two fewer ring members [1][2]. Treatment of 2-oxocycloalkane-
1-carboxylic acids (e.g., the cyclodecanone derivative 1) with an aryl isocyanate (such as
phenyl isocyanate) leads to the formation of a ring-enlarged imide (like 2), two ring
members larger. The (allyloxy)carbonyl moiety may be removed by using Pd(PPh3)4,
HCO2H, and Et3N [3][4] (Scheme 1).
Results and Discussion. ± We were interested in whether these N-phenyl imides
would be suitable as starting materials for the preparation of cyclophanes; a
transformation for which the photo-Fries rearrangement was expected to be well-
suited (for reviews, see [5]). This photochemical rearrangement had been studied in
detail for acetanilide [6]; in that case, the production of aniline, as well as of the desired
2-amino- and 4-aminoacetophenones had been observed. In terms of the mechanism, it
had been concluded that the cleavage of the NÀC(O) bond proceeds homolytically,
from the singlet state S1 [7][8], and that intramolecular recombination of the two
radicals produced takes place in a solvent ꢀcageꢁ [9]. Cyclic analogs of acetanilide ± N-
phenyl lactams with 7-, 8-, and 13-membered rings ± exclusively form orthocyclophanes
of the general formula 6, with 9-, 10-, or 15-membered rings. Paracyclophanes of type 7

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Scheme 1
a) NaH, diallyl carbonate, THF, 6 h reflux; 91%. b) R ˆ H: NaH, THF, PhNCO; 67%; R ˆ Me: NaH, THF, 4-
tolyl isocyanate; 89%. c) Et3N, HCOOH, THF, Pd(PPh3)4; 85%.
may be obtained from N-phenyl lactams if the ortho-positions of the lactams are
blocked by Me groups, and the ring contains at least seven CH2 groups [10].
Irradiation of N,N-diacetylaniline in MeCN gives rise to the ortho- and para-
rearrangement products 2- and 4-acetamidoacetophenone in 30 and 25% yields,
respectively, as well as the fragmentation product acetanilide (45%) [11]. Secondary
photorearrangement products were not detected. Similar results were obtained on
irradiation of N,N-diacetylnaphthalenamine, in which case a meta-substitution
product was also observed in small amounts (1%) [11]. The N-phenyl imides
mentioned above are cyclic analogs of N,N-diacetylaniline, and consequently should
also be expected to give ortho- and para-rearrangement products on irradiation.
Whether products of double rearrangement ± secondary photorearrangement products,
in other words ± would be detectable remained to be seen. Moreover, it would serve to
clarify whether this method might possibly be suitable for the synthesis of certain
cyclophanes.
If the N-phenyl imide 3 was irradiated in MeCN solution at 08 with a 100-W low-
pressure Hg lamp, the starting material was converted completely after 24 h. Four
isomerization products resulted, in an overall yield of 97%. The results are shown in

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Scheme 2. The two main products are the ortho- and the para-rearrangement products 8
and 9, respectively; the latter, with a yield of 44%, predominating significantly over the
former (33%). The other two isomers, 10 and 11, are the products of secondary
photo-Fries rearrangements of the primary compounds 8 and 9, respectively. The
symmetrical 17-amino[11]metacyclophane-1,11-dione (ˆ17-aminobicyclo[11.3.1]hep-
tadeca-1(17),13,15-triene-2,12-dione; 10) can be formed by irradiation of the
orthocyclophane 8, while 13-amino[11]metacyclophane-1,11-dione (ˆ14-aminobicy-
clo[11.3.1]heptadeca-1(16),13(17),14-triene-2,12-dione; 11) could arise from irradia-
tion of either or both of the primary products 8 and 9. The photochemistry of 3 was also
examined under different experimental conditions; the results are summarized in
Table 1. In EtOH solution, with both high- and low-pressure Hg lamps, the products
are the same as those arising from irradiation in MeCN. The yields are altered,
however.
Scheme 2

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Table 1. Irradiation of N-Phenyl Imide 3. Yields in % (cf. Scheme 2).
Products
High-pressure lamp
EtOH
(c ˆ 10.99  10À3 mol/l), 1.5h
Low-pressure lamp
EtOH
(c ˆ 8.79  10À3 mol/l), 1.5h
Low-pressure lamp
MeCN
(c ˆ 8.79  10À3 mol/l), 24 h
8
9
10
37
23
2
10
4
±
33
44
2
11
4
66
±
14
18
97
Total yield
The homologue of the starting material 3, 1-phenyl-1-azacyclotetradecane-2,14-
dione (12) [4], also undergoes Fries rearrangement on photochemical treatment. The
corresponding homologous products are formed (cf. Scheme 3 and Table 2). Since the
reaction times were different, the yields do not bear direct comparison. The highest
total yield here, 93%, was also found in the case of irradiation in MeCN with a low-pressure
Scheme 3

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Hg lamp. The main product is once more the paracyclophane 14, with a yield of 50%. Its
structure and configuration were verified by X-ray crystal-structure analysis (Fig. 1).
Table 2. Irradiation of N-Phenyl Imide 12. Yields in % (cf. Scheme 3).
Products
High-pressure lamp
EtOH
Low-pressure lamp
EtOH
Low-pressure lamp
MeCN
(c ˆ 13.29  10À3 mmol/l), 45min ( c ˆ 13.29  10À3 mmol/l), 16 h (c ˆ 5.32  10À3 mmol/l), 3 h
13
14
15
16
29a)
25a)
±
34a)
41a)
±
±
75
12
5
12
19
93
0
±
Total yield 54
a) Values relative to consumed 12.
Fig. 1. X-Ray crystal structure of 1-aza[14]paracyclophane-2,14-dione (14) in ORTEPrepresentation (ellipsoids
with 50% probability)
It now also seemed of interest to us to examine how the photo-Fries rearrangement
would be affected by blocking the para-position with a Me group. The synthesis of the
relevant cyclic N-(4-tolyl) imide by ring-enlargement with 4-tolyl isocyanate was
performed with cyclodecanone, analogously to that of 3 (cf. Scheme 1).
1-(4-Tolyl)-1-azacyclododecane-2,12-dione (5) was irradiated in absolute EtOH for
3.5h, with a low-pressure Hg lamp. The orthocyclophane 17 was produced in 31%

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yield, together with 35% of starting material 5. As well as this, the open-chain EtOH
addition product 18 could be isolated in 21% yield (Scheme 4).
Scheme 4
a) In parentheses, the chemical yields with respect to the starting material converted.
Reactions of this kind proceed especially well in polar, protic solvents. However, as
shown in Scheme 4, the risk of side reactions with the solvent is high, and so irradiation
was once more performed in MeCN with a low-pressure Hg lamp. The results of this
experiment are shown in Scheme 5; the reaction was terminated after 15h.
No starting material could be detected by TLC, and fragmentation products and
side products were also evident in only trace amounts. The total product yield of 96%
comprised of only two compounds: the orthocyclophane 17 (80%) and the symmetrical
amino-metacyclophane 19 (16%), as primary and secondary photorearrangement
products, respectively.
It was now only a question of clarifying whether reaction behavior is dependent on
ring size. It was hence considered appropriate to prepare the 14-membered N-(4-tolyl)
imide 22 and to subject it to the same conditions as those under which a 96% conversion
had been achieved for the 12-membered N-(4-tolyl) imide 5.
The preparation of the desired compound 22, starting from the activated cyclo-
dodecanone 20, proceeded analogously to the reactions described above (Scheme 6).
Irradiation was carried out in MeCN, as for the 12-membered 5, for 16.5h, with a low-
pressure Hg lamp.
In contrast with the experiment with the 12-membered imide, starting material was
still present after 16.5-h irradiation of 22. As shown in Scheme 7, orthocyclophane 23
had been produced in 63% chemical yield (74% relative to converted starting
material); no secondary photorearrangement product could be detected. Evidently, the
14-membered N-(4-tolyl) imide 22 is photochemically less reactive than the 12-
membered representative 5.

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Scheme 5
Scheme 6
a) NaH, THF, 4-Tolyl isocyanate; 70%. b) Et3N, HCOOH, THF, Pd(PPh3)4; 80%.
It now also seemed important to us to settle whether further irradiation of the ortho-
cyclophane 23 would produce the symmetrical amino-metacyclophane 24, in analogy
with that of the non-methylated imides 3 and 12. Even after 24-h irradiation of 23, 40%
of the starting material could still be isolated. All the same, the desired and expected
symmetrical amino-metacyclophane 24 had indeed been produced in 16% yield (or
27% relative to converted starting material 23), with the remainder consisting of decompo-
sition products. Continuing the irradiation raised the yield only trivially, but also led to
further decomposition products. The NÀH bond here proves to be highly capable of
dissipating excitation energy without radiation [12]. This confirms observations
according to which amides are generally more likely than not to be photostable [13].
It proved possible to grow crystals of amino-metacyclophane 24 suitable for X-ray
crystal-structure analysis and thus corroborate its structure (see Fig. 2). As had already
been noticed for paracyclophane 14, interpretable NMR spectra could be obtained only
under special measuring conditions, by cooling to 250 K in this instance. This is
presumably due to the multiplicity of conformations existing in solution.

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Scheme 7
In the crystal, each amine H-atom forms an intramolecular H-bond with the
adjacent CˆO O-atom, hence forming a six-membered ring. It should be emphasized
that the plane defined by the benzene system and the NH2 and the two CˆO groups is
almost perpendicular to that of the aliphatic macrocycle. Intermolecular H-bonds are
not formed, as can be seen from the view of the unit cell of 24 in Fig. 3.
Conclusion. ± In this work, it was shown that 12- and 14-membered N-phenyl imides
undergo easy photochemical rearrangement to give ortho-, meta-, and paracyclo-
phanes. The reaction proceeds especially well in MeCN with irradiation from a low-
pressure Hg lamp. The overall yields are higher than 90% in these cases, notably high
for photochemical processes. Since macrocyclic N-phenyl imides are also easily
accessible in good yields by ring-enlargement reactions from cycloalkanones, these
preparations of those cyclophanes described appear to us to be worth recommending as
synthetic methods.
We are grateful to the Swiss National Science Foundation for their support of this work. We also thank Prof.
H.-J. Hansen for discussions and for use of photochemical facilities, and the analytical division of our institute
for NMR and mass spectra.

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Fig. 2. X-Ray crystal structure of 19-amino-16-methyl[13]metacyclophane (24) in ORTEPrepresentation
(ellipsoids with 50% probability)
Fig. 3. View of the unit cell of 19-amino-16-methyl[13]metacyclophane (24)

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Experimental Part
General. All organic solvents were distilled and dried (THF over Na, and MeCN and EtOH over molecular
sieves (3 Š)) and then degassed. All reactions were performed under Ar or N2. Chromatography: Kieselgel
Merck 60 (40 ± 63 mm). FC ˆ flash chromatography. M.p.: Mettler FP-5/FP-52. UV (EtOH): Perkin-Elmer 555;
values in nm (log e). IR (CHCl3): Perkin-Elmer 297; values in [cmÀ1]. 1H-NMR: at 300 or 600 MHz in CDCl3 or
(D6)DMSO; Bruker AC 300, Bruker ARX 300, or Bruker AMX 600; d in ppm relative to TMS (ˆ0 ppm) as
internal standard, J in Hz. 13C-NMR: at 75.6 MHz (Bruker ARX 300) or 131.2 MHz (Bruker AMX 600) in
CDCl3 or (D6)DMSO: d in ppm relative to TMS (ˆ0 ppm) as internal standard; multiplicities from DEPT
experiments. EI (70 eV) and CI-MS: with NH3 as ionizing gas; Finnigan SSQ 700 oder Varian MAT 90; ESI-
MS: Finnigan TSQ 700; values in m/z.
1. Prop-2-enyl 2-Oxocyclodecane-1-carboxylate (1). Cyclooctanone (3.0 g, 19.5mmol) and NaH (0.96 g,
24.0 mmol, 60% NaH in paraffin oil) were added to THF (75ml) and diallyl carbonate (2.85ml, 19.9 mmol) was
slowly added, according to [2][3]. The mixture was heated under reflux for 4 h. It was then cooled to 08,
neutralized with 2.5n aq. HCl, and extracted with CH2Cl2. The extracts were dried (Mg2SO4), solvent was
removed under vacuum, and the residue was purified by FC (hexane/AcOEt 10 :1) to give 1 (3.7 g, 15.6 mmol,
85%). Light yellow oil. IR: 3090w, 2940s, 2860m, 1740s, 1705s, 1605s, 1475m, 1445m, 1380m, 1360w, 1325m, 1225
(br.), 1160m, 1100m, 1030w, 1015w, 990m, 940m. 1H-NMR: 12.89 (s, 0.5H, enol-OH); 6.02 ± 5.81
(m, CHˆCH2); 5.37 ± 5.21 (m, CHˆCH2); 4.69 ± 4.56 (m, CH2O); 3.91 ± 3.86 (m, 0.5H, H ÀC(1)); 2.73 ± 2.45
(m, CH2(3)); 2.43 ± 2.15( m, CH2(10)); 2.00 ± 1.29 (m, 12 H). 13C-NMR (two tautomeric forms or conformers):
208.61 (s, CO); 175.51; 173.15 (2s, COOR); 132.18, 131.53 (d, CHˆCH2); 118.59, 117.60 (t, CHˆCH2); 99.53
(s, C(1), enol); 65.78, 64.72 (t, CH2O); 57.62 (d, keto C(1)); 42.18 (t, C(3)); 30.15, 27.43, 27.23, 25.88, 25.63, 25.26,
.
‡
25.13, 25.09, 25.05, 24.27, 23.46, 23.20, 20.93, 20.42 (14t, 7 CH2). EI-MS: 238 (13, M ), 152 (14), 124 (33), 109
(12), 98 (32), 97 (12), 95 (17), 84 (16), 83 (14), 82 (16), 81 (20), 70 (11), 69 (21), 68 (12), 67 (28), 57 (21), 56
(11), 55 (100), 54 (13), 53 (13).
2. Prop-2-enyl 1-Phenyl-2,12-dioxo-1-azacyclododecane-3-carboxylate (2). To a mixture of 1 (1.0 g,
4.2 mmol) in abs. THF (20 ml) was added NaH (202 mg, 5.1 mmol, 60% NaH in paraffin oil). The mixture was
stirred for 30 min at r.t. Phenyl isocyanate (0.46 ml, 0.50 g, 4.2 mmol) in abs. THF (2 ml) was added dropwise to
the now orange-yellow colored soln., and stirring was continued for 1 h at r.t. After cooling to 08, the soln. was
neutralized with 1n aq. HCl and solvent was evaporated. The residue was extracted with CH2Cl2, dried, and
purified by FC (hexane/AcOEt 5:1) to give 2 (1.01 g, 2.8 mmol, 67%). Colorless oil. IR: 2925s, 2860s, 1740s,
1700s, 1650w, 1595m, 1490m, 1465w, 1445m, 1355m, 1270m, 1175m, 1120m, 1090w, 990m, 935m. 1H-NMR: 7.48 ±
7.37 (m, HÀC(3'), HÀC(4'), HÀC(5')); 7.18 (d, J ˆ 1.7, HÀC(2'), HÀC(5')); 5.93 ± 5.80 (m, CHˆCH2); 5.34 ±
5.18 (m, CHˆCH2); 4.61 ± 4.58 (m, CH2O); 4.30 ± 4.25( dd, J ˆ 4.2, 6.3, HÀC(3)); 2.75± 2.67 ( m, 1 H); 2.28 ±
2.16 (m, 2 H); 2.03 ± 1.85( m, 2 H); 1.56 ± 1.24 (m, 1 H). 13C-NMR: 177.01 (s, C(2)); 172.78 (s, C(12)); 169.34
(s, COOR); 137.80 (d, CHˆCH2); 131.58 (s, C(1')); 129.69 (d, C(2'), C(6')); 128.82 (d, C(4')); 128.23 (d, C(3'),
C(5')); 118.00 (t, CHˆCH2); 65.57 (t, CH2O); 50.61 (d, C(3)); 35.16 (t, C(11)); 29.33 (t, C(4)); 25.19, 24.07,
‡
‡
23.78, 23.66, 23.28 (5t, 6 CH2). CI-MS: 375(20, [ M ‡ NH4] ), 359 (20), 358 (100, [M ‡ H] ), 195(10), 136 (12).
3. 1-Phenyl-1-azacyclododecane-2,12-dione (3). To a soln. of 2 (1.01 g, 2.8 mmol) in abs. THF (20 ml) was
added, with stirring, a mixture of HCO2H (210 ml, 6 mmol) and Et3N (990 ml, 7.5mmol), followed by Ph(PPh 3)4
(163 mg) in abs. THF (2 ml). It was stirred for 1 h at r.t., solvent was removed under vacuum, and the residue
was purified by FC (hexane/AcOEt 20 :1) to give 3 (660 mg, 2.4 mmol, 85%). Colorless crystals. M.p. 73.6 ±
74.98. UV: lmax 210 (4.13), 238 (3.96); lmin 219 (3.79). IR: 2930s, 2860m, 1700s, 1600m, 1490w, 1465w, 1440w,
1350w, 1295w, 1270w, 1160m, 1120m, 1080w. 1H-NMR: 7.48 ± 7.36 (m, HÀC(3'), HÀC(4'), HÀC(5')); 7.15
(d, J ˆ 6.8, HÀC(2'), HÀC(6')); 2.62 ± 2.57 (t, J ˆ 6.4, CH2(3), CH2(11)); 1.81 ± 1.73 (m, 4 H); 1.49 ± 1.41
(m, 10 H). 13C-NMR: 177.66 (s, 2 CO); 138.65( s, C(1')); 129.72 (d, C(2'), C(6')); 128.00 (d, C(4')); 128.19
‡
(d, C(3'), C(5')); 37.71 (t, C(3), C(11)); 25.53, 25.01, 23.94, 23.39 (4t, 7 CH2). CI-MS: 291 (13, [M ‡ NH4] ), 275
.
‡
‡
(19), 274 (100, [M ‡ H] ). EI-MS: 273 (12, M ), 176 (19), 148 (15), 135 (55), 134 (18), 94 (12), 93 (100), 92
(12), 55 (11).
4. 1-Aza[12]orthocyclophane-2,12-dione (ˆ2-Azabicyclo[12.4.0]octadeca-1(14),15,17-triene-3,13-dione;
8), 1-Aza[12]paracyclophane-2,12-dione (ˆ2-Azabicyclo[12.2.2]octadeca-1(16),14(15),17-triene-3,13-dione;
9), 17-Amino[11]metacyclophane-1,11-dione (ˆ17-Aminobicyclo[11.3.1]heptadeca-1(17),13,15-triene-2,12-di-
one; 10), and 13-amino[11]metacyclophane-1,11-dione (ˆ14-Aminobicyclo[11.3.1]heptadeca-1(16),13(17),14-
triene-2,12-dione; 11). 4.1. Irradiation of 3 in EtOH. All irradiation experiments were carried out without filters.
a) Low Pressure. A soln. of 3 (120 mg, 0.4 mmol) in anh. degassed EtOH (c ˆ 8.79  10À3 mol/l) was
irradiated for 5h in a Schlenk vessel at 08 under Ar, with a 100-W low-pressure Hg lamp (Engelhard Hanovia

Helvetica Chimica Acta ± Vol. 83 (2000)
1819
Inc., Newark, N.Y., USA). Solvent was removed and the residue separated by prep. TLC (hexane/AcOEt 9 :1).
Starting material could no longer be detected: 8 (12 mg, 10%, faster-running) and 9 (4.8 mg, 4%).
b) High Pressure. A soln. of 3 (300 mg, 1.1 mmol) in anh., degassed EtOH (c ˆ 10.99  10À3 mol/l) was
irradiated for 1.5h at 18 8 under N2, with a 450-W high-pressure Hg lamp (Engelhard Hanovia Inc.). Solvent was
removed, and the residue was separated by prep. TLC, by which starting material could no longer be detected:
10 (6 mg, 2%, fastest-running), 8 (110 mg, 37%), 11 (11 mg, 4%), and 9 (68 mg, 23%).
4.2. Irradiation of 3 in MeCN. A soln. of 3 (120 mg, 0.4 mmol) in anh. degassed MeCN (c ˆ 8.79  10À3 mol/
l) was irradiated for 24 h in
a Schlenk vessel at 08 under Ar, with a 100-W low-pressure Hg
lamp. Solvent was removed, and the residue was separated by prep. TLC (hexane/AcOEt 9 :1). Starting
material could no longer be detected: 10 (2.4 mg, 2%), 8 (39.6 mg, 33%), 11 (21.6 mg, 18%), and 9 (52.8 mg,
44%).
Data of 8: Colorless crystals. M.p. 110.2 ± 112.38. UV: lmax 234 (4.10), 264 (3.60), 326 (3.31); lsh 272 (3.60);
lmin 214 (3.55), 250 (3.56), 284 (2.85). IR: 3300 (br.), 2920s, 2860m, 1680s, 1660s, 1600w, 1580s, 1510s, 1440s,
1295m, 1160m. 1H-NMR: 10.67 (s, NH); 8.39 (d, J ˆ 8.3, HÀC(14)); 7.71 (d, J ˆ 8.2, HÀC(17)); 7.55 ± 7.52
(m, HÀC(15)); 7.17 ± 7.12 (m, HÀC(16)); 2.96 ± 2.93 (m, 1 CH2); 2.48 ± 2.44 (m, 1 CH2); 1.86 ± 1.71 (m, 2 CH2);
1.39 ± 1.22 (m, 4 CH2); 1.08 ± 1.03 (m, 1 CH2). 13C-NMR: 207.13 (s, CO); 172.58 (s, NHCO); 137.91 (s, C(18));
133.49 (d, C(14)); 129.18 (d, C(17)); 126.59 (s, C(13)); 122.99, 122.87 (2d, C(15), C(16)); 40.51 (t, C(11)); 37.95
.
‡
(t, C(3)); 28.09, 26.82, 25.90, 25.56, 24.95, 22.88 (6t, 7 CH2). EI-MS: 273 (16, M ), 174 (43), 161 (15), 148 (13),
146 (16), 136 (10), 135 (72), 120 (100), 119 (14), 93 (15), 92 (26), 55 (25).
Data of 9: Colorless crystals. Melting range 166 ± 172.08. UV: lmax 204 (4.13), 268 (4.02); lmin 234 (3.60). IR:
3380s, 2995w, 2850m, 1670s, 1600s, 1580w, 1510w, 1440m, 1350 (br.), 1200s, 1085w, 1040w, 1015w, 995w, 925w.
1H-NMR (300 MHz, (D6)DMSO): 9.53 (s, NH); 7.88 (d, J ˆ 8.5, HÀC(15), HÀC(17)); 7.37 (d, J ˆ 8.4,
HÀC(14), HÀC(18)); 2.91 ± 2.86 (t, J ˆ 6.4, CH2(11)); 2.30 ± 2.24 (t, J ˆ 8.4, CH2(3)); 1.64 ± 0.59 (m, 14 H).
13C-NMR (300 MHz, (D6)DMSO): 203.61 (s, CO); 174.47 (s, NHCO); 142.64 (s, C(16)); 135.73 (s, C(13));
129.32 (d, C(15), C(17)); 126.00 (C(14), C(18)); 38.10 (t, C(11)); 32.83 (t, C(3)); 27.56, 27.28, 27.03, 26.43, 26.07,
.
‡
25.70, 23.50 (7t, 7 CH2). EI-MS: 273 (11, M ), 174 (14), 149 (21), 148 (16), 136 (14), 135(100), 120 (78),
119 (26), 93 (32), 92 (17), 91 (22), 85 (10), 84 (27), 77 (11), 72 (23), 69 (19), 66 (30), 59 (44), 57 (23),
55 (43).
Data of 10: Oil with a green cast. IR: 3440s, 3320m, 2920s, 2850m, 2730w, 1665s, 1600m, 1555s, 1440m,
1310w, 1295w, 1220 (br.), 1160w, 1100w, 990w, 95 5w, 920w. 1H-NMR: 8.01 ± 7.88 (br. s, NH2); 7.74 (d, J ˆ 7.7,
HÀC(15), HÀC(13)); 6.68 ± 6.63 (t, J ˆ 7.7, H ÀC(14)); 3.27 ± 3.19 (m, 2 H); 2.42 ± 2.34 (m, 2 H); 1.74 ± 0.70
(m, 14 H). 13C-NMR: 206.70 (s, 2 CO); 148.82 (s, C(17)); 135.77 (d, C(13), C(15)); 120.38 (s, C(12), C(16));
.
‡
‡
112.96 (d, C(14)); 42.50, 28.03, 27.23, 27.18, 26.27 (5t, 9 CH2). EI-MS: 274 (13, [M ‡ H] ), 273 (69, M ), 177
(37), 174 (49), 163 (11), 162 (32), 161 (18), 160 (16), 159 (100), 148 (16), 146 (14), 145(18), 144 (17), 135(48),
133 (15), 120 (25), 119 (28), 93 (40), 91 (21), 85 (21), 83 (24).
Data of 11: Oil with a green cast. IR: 3500m, 3330m, 2930s, 2850m, 1640s, 1610s, 1580m, 1460w, 1440w,
1410w, 1330w, 1305w, 1290w, 1260w, 1220 (br.), 1160m, 1130m, 1095w, 905w, 830w. 1H-NMR (300 MHz,
(D6)DMSO): 8.38 (d, J ˆ 2.0, HÀC(17)); 8.22 ± 7.86 (br., NH2); 7.78 (d, J ˆ 8.9, HÀC(15)); 6.86 (d, J ˆ 8.8,
HÀC(14)); 2.83 ± 2.74 (2m, 4 H); 1.62 ± 1.30 (m, 13 H). 13C-NMR (300 MHz,(D6)DMSO): 203.71 (s, C(1));
198.43 (s, C(11)); 155.49 (s, C(16)); 135.77 (d, C(17)); 133.09 (d, C(15)); 122.48 (s, C(12)); 118.00 (d, C(14));
‡
113.31 (s, C(13)); 38.84, 36.76, 26.62, 24.90, 24.71, 24.56, 24.50, 23.47 (8t, 9 CH2). EI-MS: 274 (18, [M ‡ H] ), 273
.
‡
(100, M ), 177 (11), 174 (46), 162 (15), 161 (13), 148 (12), 135 (13), 133 (14), 120 (14), 119 (32), 91 (19), 55 (27).
5. Prop-2-enyl 1-Phenyl-2,14-dioxo-1-azacyclotetradecane-3-carboxylate. Treatment of 20 [2] (1.01 g,
3.8 mmol), NaH (205mg, 5.1 mmol, 60% NaH in paraffin oil), and PhNCO (0.45ml, 0.49 g, 4.1 mmol) in
abs. THF (20 ml) as in Exper. 2 gave the desired compound (0.85g, 2.2 mmol, 59%) after FC (hexane/AcOEt
5:1) as a colorless oil. IR: 2930 s, 2860s, 1740s, 1705s, 1595w, 1485m, 1440w, 1350m, 1270w, 1120w, 990w, 935w.
1H-NMR: 7.49 ± 7.41 (m, 3 arom. H); 7.14 (d, J ˆ 6.5, HÀC(2'), HÀC(6')); 5.96 ± 5.83 (m, CHˆCH2); 5.34 ± 5.20
(m, CHˆCH2); 4.63 ± 4.60 (m, CH2O); 4.17 ± 4.13 (m, HÀC(3)); 2.78 ± 2.74 (m, 1 H); 2.36 ± 2.28 (m, 1 H);
2.11 ± 2.03 (m, 1 H); 1.94 ± 1.80 (m, 2 H); 1.57 ± 1.28 (m, 16 H). 13C-NMR: 176.38 (s, C(2)); 172.47 (s, C(14));
169.32 (s, COO); 138.54 (s, C(1')); 131.79 (d, CHˆCH2); 129.78 (2d, C(2'), C(6')); 128.90 (d, C(3'), C(5'));
118.32 (t, CHˆCH2); 65.76 (t, CH2O); 52.69 (d, C(3)); 37.04 (t, C(13)); 29.25, 26.26, 26.01, 25.95, 25.88, 25.65,
‡
‡
25.21, 24.85, 24.14 (9t, 9 CH2). CI-MS (NH3): 403 (11, [M ‡ NH4] ), 387 (24), 386 (100, [M ‡ H] ), 284 (13),
267 (17), 195(18), 178 (18).
6. 1-Phenyl-1-azacyclotetradecane-2,14-dione (12). Prop-2-enyl 1-phenyl-2,14-dioxo-1-aza-cyclotetrade-
cane-3-carboxylate (820 mg, 2.1 mmol) in abs. THF (10 ml), HCO2H (160 ml), Et3N (740 ml), and Pd(PPh3)4
(123 mg) in abs. THF (2 ml) were converted into 12 (609 mg, 2.0 mmol, 85%) as per Exper. 3. (FC: hexane/

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Helvetica Chimica Acta ± Vol. 83 (2000)
AcOEt 4 :1). Colorless oil. UV: lmax 212 (4.17); lsh 230 (4.06). UV (MeOH): lmax 225.6. IR: 2930s, 2860s, 1705s,
1595w, 1490w, 1455w, 1435w, 1355w, 1365w, 1120w, 1060m, 900w. 1H-NMR: 7.48 ± 7.37 (m, 3 H); 7.13 ± 7.10
(m, 2 H); 2.63 ± 2.59 (m, 4 H); 1.73 ± 1.64 (m, 4 H); 1.46 ± 1.29 (m, 14 H). 13C-NMR: 176.94 (s, 2 CO); 139.19
(s, C(1')); 129.76 (d, C(2'), C(6')); 128.79 (d, C(3'), C(5')); 128.59 (d, C(4')); 36.84, 26.18, 26.05, 25.91, 24.93,
.
‡
‡
‡
24.77 (6t, 11 CH2). CI-MS: 319 (4, [M ‡ NH4] ), 303 (21), 302 (100, [M ‡ H] ), 236 (7). EI-MS: 301 (18, M ),
204 (16), 148 (10), 135(69), 94 (12), 93 (100), 92 (13), 55(13), 41 (17).
7. 1-Aza[14]orthocyclophane-2,14-dione (ˆ2-Azabicyclo[14.4.0]icosa-1(16),17,19-triene-3,15-dione; 13), 1-
Aza[14]paracyclophane-2,14-dione (ˆ2-Azabicyclo[14.2.2]icosa-1(18),16,19-triene-3,15-dione; 14), 19-Ami-
no[13]metacyclophane-1,13-dione (ˆ19-Aminobicyclo[13.3.1]nonadeca-1(19),15,17-triene-2,14-dione; 15), and
15-Amino[13]metacyclophane-1,13-dione (ˆ16-Aminobicyclo[13.3.1]nonadeca-1(18),15(19),16-triene-2,14-di-
one; 16).
7.1. Irradiation of 12 in EtOH. All irradiation experiments were carried out without filters.
a) Low Pressure: A soln. of 12 (400 mg, 1.3 mmol) in anh. and degassed EtOH (100 ml; c ˆ 13.29 Â
10À3 mol/l) was irradiated for 16 h in a Schlenk vessel at 08 under Ar, with a 100-W low-pressure Hg lamp.
Solvent was removed and the residue separated. The fastest-running fraction, containing starting material 12
and compound 13, was separable only by repeated application of this eluent system; if reclamation of starting
material is not considered important, then it is possible to work with CHCl3/hexane (saturated with NH3) as the
eluent system. (Under these conditions, 12 reacts with NH3 by ring-opening to give N-monophenyl-
tridecanediamide.) The repeated running of prep. TLCs was sometimes abstained from, as reclamation of
starting material was deemed too laborious; running the prep. TLC with hexane/CHCl3 (saturated with NH3)
2 :1 could accelerate and improve the separation of the components: 13 (74 mg, 18 or 34%, resp.) and 14 (91 mg,
23 or 41%, resp.).
b) High Pressure. A soln. of 12 (400 mg, 1.3 mmol) in anh. and degassed EtOH (100 ml; c ˆ 13.29 Â
10À3 mol/l) was irradiated for 45min at 18 8 under N2, with a 450-W high-pressure Hg lamp. After removal of
solvent, the residue was separated by prep. TLC (hexane/AcOEt 4 :1). Only by repeated application of prep.
TLC was it possible to separate starting material from 13 (91 mg, 23 or 29%, resp., fastest-running) and 14
(80 mg, 20 or 25%, resp.).
7.2. Irradiation of 12 in MeCN. All irradiation experiments were carried out without filters. A soln.
of 12 (80 mg, 0.26 mmol) was irradiated in MeCN (50 ml; c ˆ 5.32  10À3 mol/l) for 3 days as described for
Exper. 4.2. Solvent was removed and the residue chromatographed on silica gel (60 mg) with hexane/CHCl3
(saturated with 25% aq. NH4OH): 15 (9.6 mg, 12%), 13 (9.6 mg, 12%), 16 (15.2 mg, 19%), and 14 (40 mg,
50%).
Data of 13: Colorless crystals. Melting range 91.3 ± 95.18. UV (EtOH): lmax 204, 233, 262, 326; lmin 212, 250,
284. IR: 3300 (br.), 2925s, 2860m, 1680s, 1655s, 1605w, 1580s, 1510s, 1450s, 1350w, 1300m, 1265(br.), 1160 w,
1
1120w, 1100w, 970w. H-NMR (300 MHz, (D6)DMSO): 11.72 (s, NH); 8.16 (d, J ˆ 8.3, HÀC(16)); 7.93 (d, J ˆ
7.9, HÀC(19)); 7.55 (t, J ˆ 8.6, HÀC(17)); 7.23 ± 7.17 (m, HÀC(18)); 3.04 ± 3.00 (m, CH2); 2.38 ± 2.34
(m, 1 CH2)); 1.69 ± 1.61 (m, 2 CH2); 1.28 ± 1.11 (m, 7 CH2). 13C-NMR (300 MHz, (D6)DMSO): 205.24
(s, CO); 171.67 (s, NHCO); 138.16 (s, C(20)); 133.56 (d, C(16)); 130.39 (d, C(19)); 126.24 (s, C(15)); 123.36,
121.83 (2d, C(17), C(18)); 39.15( t, C(13)); 37.56 (t, C(3)); 27.24, 26.92, 26.61, 26.38, 26.10, 25.44, 25.13, 22.57
.
‡
‡
(9t, 9 CH2). CI-MS: 303 (16), 302 (100, [M ‡ H] ). EI-MS: 301 (34, M ), 299 (17), 177 (12), 174 (20), 136 (15),
135(100), 120 (49), 93 (23), 57 (16), 45(11), 41 (11).
Data of 14: Colorless crystals. M.p. 157.8 ± 158.48. UV (EtOH): lmax 218, 232, 289; lmin 224, 246. IR: 3420m,
3380s, 2990w, 2920s, 2850m, 1670s, 1600s, 1510m, 1445m, 1400w, 1365(br.), 1340 w, 1320w, 1305w, 1270m, 1110w,
1000m. 1H-NMR (600 MHz, (D6)DMSO, 360 K; assignment based on 2D-NMR experiments): 9.60 (s, NH);
7.77 (d, J ˆ 8.9, HÀC(17), HÀC(19)); 7.64 (d, J ˆ 8.7, HÀC(16), HÀC(20)); 2.84 ± 2.80 (t, J ˆ 6.5, CH2(13));
2.32 (t, J ˆ 6.5, CH2(3)); 1.68 ± 1.53 (m, 4H); 1.29 ± 1.20 (m, 2 H); 1.06 ± 0.81 (m, 8 H); 0.78 ± 0.67 (m, 4 H).
13C-NMR (600 MHz, (D6)DMSO, 360 K; assignment based on 2D-NMR experiments): 201.81 (s, CO); 173.01
(s,NHCO); 142.86 (s, C(18)); 133.11 (s, C(15)); 128.58 (d, C(17), C(19)); 118.95(C(16), C(20)); 38.60
.
‡
(t, C(13)); 35.97 (t, C(3)); 28.75, 27.89, 27.80, 27.57, 27.28, 26.06, 25.39, 24.87 (8t, 9 CH2). EI-MS: 301 (41, M ),
.
‡
‡
148 (14), 135(100), 120 (54). CI-MS: 603 (100, [2 M ‡ H] ), 319 (7, [M ‡ NH4] ), 303 (13), 302 (72, [M ‡
.
‡
‡
H] ), 301 (12, M ), 135(15). Anal. calc. for C 19H27NO2 (301.42): C 75.71, H 9.03, N 4.65; found: C 75.59,
H 8.93, N 4.61.
Single crystals suitable for X-ray crystal-structure determination were obtained from Et2O/hexane (cf.
Fig. 1).
Data of 15: Oil with a light green cast. IR: 3420s, 3305m, 3000w, 2925s, 2850m, 1655s, 1605m, 1555s, 1450m,
1360w, 1310w, 1300w, 1220 (br.), 1160w, 1110w, 1000w, 960w, 910w, 1H-NMR: 8.63 ± 8.57 (br. s, NH2); 7.83

Helvetica Chimica Acta ± Vol. 83 (2000)
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(d, J ˆ 7.8, HÀC(15), HÀC(17), 2 arom. H); 6.61 (t, J ˆ 7.8, HÀC(16)); 3.51 ± 3.32 (br. s, 2 H); 2.52 ± 2.24
(m, 2 H); 1.86 ± 0.63 (m, 18 H). 13C-NMR: 205.89 (s, 2 CO); 151.33 (s, C(19)); 137.04 (d, C(15), C(17)); 119.44
(s, C(14), C(18)); 112.62 (d, C(16)); 41.33, 27.83, 27.70, 27.16, 26.13, 25.99 (6t, 11 CH2). EI-MS: 302 (19,
.
‡
‡
[M ‡ H] ), 301 (100, M ), 177 (37), 174 (14), 162 (23), 149 (45), 136 (12), 135 (68), 134 (11), 133 (13), 120
(31), 55 (13), 41 (20).
Data of 16: Oil with a pale green cast. IR: 3500m, 3330m, 3000w, 2930s, 2860m, 1640s, 1615s, 1580m, 1460w,
1440w, 1415w, 1370w, 1330w, 1300w, 1160m, 1120w, 830w. 1H-NMR: 8.37 (d, J ˆ 2.0, HÀC(19)); 7.96 (d, J ˆ 8.8,
HÀC(17)); 6.94 ± 6.71 (br., NH2); 6.69 (d, J ˆ 8.8, HÀC(16)); 2.95± 2.82 (2 m, 4 H); 1.77 ± 1.67 (m, 4 H); 1.5 1 ±
1.25( m, 14 H). 13C-NMR: 203.66, 199.07 (2s, CO); 154.29 (s, C(18)); 134.29 (d, C(19)); 133.89 (d, C(17));
125.09 (s, C(14)); 117.77 (d, C(16)); 115.49 (s, C(18)); 39.87, 38.29, 27.18, 26.76, 26.66, 26.38, 26.34, 26.07, 26.01,
.
‡
‡
25.48 (10t, 11 CH2). EI-MS: 302 (20, [M ‡ H] ), 301 (100, M ), 299 (12), 202 (15), 190 (21), 189 (12), 188 (11),
177 (47), 174 (50), 163 (14), 162 (71), 161 (19), 160 (10), 148 (28), 146 (14), 135 (24), 133 (17), 120 (25), 119
(40), 91 (19), 69 (14), 55 (43), 43 (40), 42 (17), 41 (60).
8. Prop-2-enyl 1-(4-Tolyl)-2,12-dioxo-1-azacyclododecane-3-carboxylate (4). Treatment of 1 (508 mg,
2.1 mmol), NaH (101 mg, 2.5mmol, 60% NaH in paraffin oil), and 4-tolyl isocyanate (0.30 ml, 0.31 g, 2.4 mmol)
in abs. THF (10 ml) as described in Exper. 2 gave, after FC (hexane/AcOEt 5:1), compound 4 (566 mg,
1.5mmol, 74%). Colorless oil. IR: 2925 s, 2860m, 1740s, 1700s, 1650w, 1585w, 1505m, 1465m, 1440m, 1355m,
1270m, 1175m, 1155m, 1120m, 1085w, 1020w, 990w, 935w. 1H-NMR: 7.24 (2d, J ˆ 8.0, HÀC(2'), HÀC(6')); 7.05
(2d, J ˆ 8.3, HÀC(3'), HÀC(5')); 5.94 ± 5.81 (m, CHˆCH2); 5.34 ± 5.19 (m, CHˆCH2); 4.61 ± 4.59 (m, CH2O);
4.27 ± 4.22 (m, HÀC(3)); 2.79 ± 2.71 (m, 1 H); 2.38 (s, Me); 2.30 ± 2.15( m, 2 H); 2.00 ± 1.89 (m, 2 H); 1.58 ± 1.41
(m, 11 H). 13C-NMR: 176.27 (s, C(2)); 172.93 (s, C(12)); 169.51 (s, COO); 139.00 (s, C(1')); 135.26 (s, C(4'));
131.73 (d, CHˆCH2); 130.46 (2d, C(6')); 128.07 (2d, C(3'), C(5')); 118.09 (t, CHˆCH2); 65.64 (t, CH2O); 50.77
‡
(d, C(3)); 25.31, 24.27, 23.96, 23.80, 23.43 (5t, 6 CH2); 21.11 (q, Me). CI-MS: 389 (18, [M ‡ NH4] ), 373 (22), 372
‡
(100, [M ‡ H] ).
9. 1-(4-Tolyl)-1-azacyclododecane-2,12-dione (5). As described in Exper. 3, compound
4 (518 mg,
1.4 mmol) in abs. THF (5ml), HCO 2H (105 ml), Et3N (490 ml), and Pd(PPh3)4 (80 mg) in abs. THF (1.0 ml)
were treated to give 5 (347 mg, 1.2 mmol, 86%) (FC: hexane/AcOEt 4 :1). Colorless crystals. M.p. 114.0 ±
115.48. UV: lmax 206 (4.10), 227 (3.97); lmin 217 (3.93). IR: 2930s, 2860m, 1700s, 1520m, 1465w, 1445w, 1359m,
1295w, 1275w, 1220m, 1175w, 1160m, 1120m, 1085w. 1H-NMR: 7.24 (d, J ˆ 8.5, HÀC(2'), HÀC(6')); 7.02 (d, J ˆ
8.3, HÀC(3'), HÀC(5')); 2.60 (t, J ˆ 6.3, 4 H); 2.38 (s, Me); 1.80 ± 1.72 (m, 4H); 1.51 ± 1.40 (m, 10 H).
13C-NMR: 177.85( s, 2 CO); 138.68 (s, C(1')); 136.08 (s, C(4')); 130.49 (d, C(2'), C(6')); 127.99 (d, C(3'), C(5'));
.
‡
34.78 (t, C(3), C(11)); 25.65, 26.11, 24.05, 23.50 (4t, 7 CH2); 21.21 (q, Me). EI-MS: 287 (9, M ), 190 (7), 162
(7), 148 (5), 108 (10), 107 (100), 106 (14), 105 (6), 91 (7), 55 (12), 41 (10).
10. 15-Methyl-1-aza[12]orthocyclophane-2,12-dione (ˆ16-Methyl-2-aza[12.4.0]octadeca-1(14),15,17-triene-
3,13-dione; 17). Ethyl 11-[(4-Methylphenyl)amino]-11-oxoundecanoate (18), and 17-Amino-14-methyl[11]meta-
cyclophane-1,11-dione (ˆ17-Amino-15-methylbicyclo[11.3.1]heptadeca-1(17),13,15-triene-2,12-dione; 19). 10.1.
Irradiation of 5 in EtOH. A soln. of 5 (290 mg, 1.0 mmol) was irradiated in EtOH (50 ml; c ˆ 20.21  10À3 mol/l)
for 3.5h, with the low-pressure Hg lamp, as described in Exper. 4.1. The solvent was removed, and the residue
was chromatographed on silica gel, with hexane/AcOEt 4 :1: 5 (100 mg, fastest-running), 17 (90 mg, 47%), and
18 (61 mg, 32%).
10.2. Irradiation of 5 in MeCN. Compound 5 (50 mg, 0.17 mmol) was irradiated in MeCN (50 ml; c ˆ 3.48 Â
10À3 mol/l) for 15h, with the low-pressure Hg lamp, as described in Exper. 4.2. The solvent was removed and the
residue chromatographed on silica gel (30 g), with hexane/AcOEt 5:1: 17 (40 mg, 80%) and 19 (8 mg,
16%).
Data of 17: Colorless crystals. M.p. 106.0 ± 109.08. UV: lmax 236 (4.27), 263 (3.84), 326 (3.35); lmin 216
(3.83), 252 (3.80), 284 (2.95). IR: 3350 (br.), 2925s, 2855m, 1675s, 1660s, 1585m, 1500s, 1450m, 1300m.
1H-NMR: 10.53 (s, NH); 8.25( d, J ˆ 8.4, HÀC(17)); 7.50 (s, HÀC(14)); 7.33 (d, J ˆ 8.4, HÀC(16)); 2.95± 2.92
(m, CH2(11)); 2.46 ± 2.42 (m, CH2(3)); 1.37 ± 1.21 (m, 8 H); 1.09 ± 1.02 (m, 2 H). 13C-NMR: 207.13 (s, CO);
172.27 (s, NHCO); 135.38 (s, C(18)); 134.09 (d, C(14)); 132.46 (s, C(13)); 129.37 (d, C(17)); 126.63 (s, C(15));
122.74 (d, C(16)); 40.43 (t, C(11)); 37.86 (t, C(3)); 28.05, 26.73, 25.81, 25.46, 24.91, 22.81 (6t, 7 CH2); 20.81
.
‡
(q, Me). EI-MS: 288 (17), 287 (100, M ), 244 (12), 188 (36), 176 (10), 175(11), 162 (13), 160 (11), 149 (55),
135(16), 134 (65), 107 (11), 106 (16), 55(12), 41 (18).
Data of 18: Colorless crystals. M.p. 99.88. IR: 3430m, 2920s, 2850m, 1725s, 1680s, 1595w, 1510s, 1400w,
1370w, 1310w, 1175m, 1090m. 1H-NMR: 10.71 (s, NH); 7.46 (d, J ˆ 8.4, HÀC(2'), HÀC(6')); 7.07 (d, J ˆ 8.3,
HÀC(3'), HÀC(5')); 4.03 (q, J ˆ 7.1, COOCH2Me); 2.29 ± 2.25( m, 4 H); 2.23 (s, Me); 1.59 ± 1.48 (m, 4 H); 1.25
(s, 10 H); 1.17 (t, J ˆ 7.1, COOCH2Me). 13C-NMR: 173.01 (s, NHCO); 171.13 (s, COO); 137.03 (s, C(1')); 131.86

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Helvetica Chimica Acta ± Vol. 83 (2000)
(s, C(4')); 129.12 (d, C(2'), C(6')); 119.21 (d, C(3'), C(5')); 59.75 (t, COOCH2Me); 36.53, 33.67, 28.88, 28.81,
‡
28.57, 25.30, 24.61 (7t, 9 CH2); 20.55 (q, Me); 14.27 (q, COOCH2Me). CI-MS: 335(18), 334 (100, [ M ‡ H] ),
290 (33).
Data of 19: Oil with a light green cast. IR: 3440m, 3330m, 2990w, 2920w, 2850s, 1665s, 1550s, 1445m, 1295w,
1230 (br.), 990w, 960w, 915w, 870w. 1H-NMR: 7.55 (s, NH2); 7.27 (s, HÀC(13), HÀC(15)); 3.28 ± 3.20 (m, 2 H);
2.41 ± 2.34 (m, 2 H); 2.33 (s, Me); 1.79 ± 0.67 (m, 14 H). 13C-NMR: 206.73 (s, 2 CO); 146.86 (s, C(17)); 136.16
(d, C(13), C(15)); 121.80 (s, C(12), C(16)); 120.35( s, C(14)); 42.49, 28.04, 27.35, 27.27, 26.31 (5t, 9 CH2); 20.30
.
‡
‡
(q, Me). EI-MS: 288 (32, [M ‡ H] ), 287 (100, M ), 191 (19), 188 (12), 160 (11), 149 (13).
11. Prop-2-enyl 1-(4-Tolyl)-2,14-dioxo-1-azacyclotetradecane-3-carboxylate (21). Treatment of 20 (610 mg,
2.3 mmol), NaH (110 mg, 2.7 mmol, 60% NaH in paraffin oil), and 4-tolyl isocyanate (0.39 ml, 365mg,
2.8 mmol) in abs. THF (15ml), as described in Exper. 2, gave, after chromatography (hexane/AcOEt 10 :1), 21
(639 mg, 1.6 mmol, 70%). Colorless oil. IR: 2925s, 2860m, 1735s, 1700s, 1650w, 1510w, 1450m, 1355m, 1270m,
1170m, 1120w, 1040w, 990w, 940w. 1H-NMR: 7.25( d, J ˆ 7.9, HÀC(2'), HÀC(5')); 7.02 (d, J ˆ 8.3, HÀC(3'),
HÀC(5')); 5.96 ± 5.83 (m, CHˆCH2); 5.34 ± 5.20 (m, CHˆCH2); 4.63 ± 4.60 (m, CH2O); 4.16 ± 4.11
(m, HÀC(3)); 2.85± 2.80 ( m, 1 H); 2.39 (s, Me); 1.94 ± 1.78 (m, 2 H); 1.59 ± 1.37 (m, 17 H). 13C-NMR: 176.55
(s, C(2)); 172.55 (s, C(14)); 169.37 (s, COOR); 138.95( s, C(1')); 135.86 (s, C(4')); 131.81 (d, CHˆCH2); 130.45
(d, C(2'), C(6')); 128.59 (d, C(3'), C(5')); 118.28 (t, CHˆCH2); 65.74 (t, CH2O); 52.66 (d, C(3)); 37.06
(t, C(13)); 29.27 (t, C(4)); 26.25, 26.00, 25.88, 25.62, 25.20, 24.84, 24.17, 21.13 (8t, 9 CH2); 14.16 (q, Me). CI-MS:
‡
‡
417 (20, [M ‡ NH4] ), 401 (23), 400 (100, [M ‡ H] ).
12. 1-(4-Tolyl)-1-azacyclotetradecane-2,14-dione (22). Compound 21 (574 mg, 1.4 mmol) in abs. THF
(10 ml), HCO2H (110 ml), Et3N (500 ml), and Pd(PPh3)4 (100 mg) in abs. THF (0.5ml) were converted into 22
(360 mg, 1.1 mmol, 80%) as described in Exper. 3 (FC: hexane/AcOEt 4 :1). Colorless crystals. M.p. 79.3 ± 80.48.
UV: lmax 208 (4.15); lsh 222 (4.07). IR: 2925s, 2860m, 1700s, 1510m, 1460m, 1440w, 1355m, 1275m, 1240w, 1175w,
1125w, 1085w, 1020w. 1H-NMR: 7.24 (d, J ˆ 7.6, HÀC(2'), HÀC(6')); 6.99 (d, J ˆ 8.2, HÀC(3'), HÀC(5')); 2.61
(t, J ˆ 6.6, 4 H); 2.39 (s, Me); 1.72 ± 1.63 (m, 4 H); 1.45± 1.36 ( m, 14 H). 13C-NMR: 177.06 (s, 2 CO); 138.58
(s, C(1')); 136.49 (s, C(4')); 130.41 (d, C(2'), C(6')); 128.45( d, C(3'), C(5')); 36.79 (t, C(3), C(14)); 26.17, 26.04,
.
‡
‡
25.89, 24.91, 24.76 (5t, 9 CH2); 21.15( q, Me). CI-MS: 317 (20), 316 (100, [M ‡ H] ). EI-MS: 315(31, M ), 178
(12), 149 (469), 108 (12), 107 (100), 106 (20), 105(11), 91 (10), 55(17), 43 (15), 41 (12).
13. 1-Aza-17-methyl[14]orthocyclophane-2,14-dione (ˆ18-Methyl-2-azabicyclo[14.4.0]icosa-1(16),17,19-
triene-3,15-dione; 23). A soln. of 22 (100 mg, 0.3 mmol) was irradiated in MeCN (50 ml; c ˆ 6.35  10À3 mol/
l) for 16.5h, with the low-pressure Hg lamp, as described in Exper. 4.2. Solvent was removed, and the residue
chromatographed on silica gel (40 g), with hexane/AcOEt 4 :1, to give 23 (63 mg, 74%), and 22 (15mg).
Data of 23: M.p. 122.0 ± 124.08. IR: 3300s, 3000w, 2935s, 2860m, 1680s, 1650s, 1590s, 1510s, 1460m, 1415w,
1355w, 1300m, 1250 (br.), 1165w, 1125w, 980w, 910w, 885w, 830m. 1H-NMR: 11.41 (s, NH); 8.51 (d, J ˆ 8.5,
HÀC(19)); 7.64 (s, HÀC(16)); 7.34 (d, J ˆ 8.55, HÀC(18)); 3.00 (t, J ˆ 5.8, CH2(14)); 2.45( t, J ˆ 6.4, HÀC(2));
2.36 (s, Me); 1.84 ± 1.70 (m, 4 H); 1.37 ± 1.23 (m, 14 H). 13C-NMR: 205.70 (s, CO); 172.53 (s, NHCO); 137.60
(s, C(20)); 135.03 (d, C(16)); 131.87 (s, C(15)); 130.48 (d, C(19)); 123.41 (s, C(17)); 121.55 (d, C(18)); 39.23,
‡
39.01, 27.88, 27.67, 27.45, 27.17, 26.74, 26.01, 25.86, 23.22 (10t, 11 CH2); 20.79 (q, Me). EI-MS: 316 (12, [M ‡ H] ),
.
‡
315(62, M ), 287 (11), 188 (38), 175(15), 162 (17), 160 (14), 150 (11), 149 (77), 134 (100), 107 (21), 106 (29),
55 (15), 41 (22).
14. 19-Amino-16-methyl[13]metacyclophane-1,13-dione (ˆ19-Amino-17-methylbicyclo[13.3.1]nonadeca-
1(19),15,17-triene-2,14-dione; 24). A soln. of 23 (50 mg, 0.2 mmol) in MeCN (50 ml; c ˆ 3.17  10À3 mol/l)
was irradiated for 24 h, with the low-pressure Hg lamp, as described in Exper. 4.2. Solvent was removed and the
residue was chromatographed on silica gel (40 g), with hexane/Et2O 4 :1. It was possible to isolate 24 (8.5mg,
27%) as an oil with a light green cast. The oil crystallized later. IR: 3440s, 3320m, 3000w, 2915s, 2869m, 1660s,
1630w, 1550s, 1469w, 1445m, 1350w, 1330w, 1315w, 1290w, 1260w, 1235(br.), 1180 w, 1165w, 1100m, 1000m, 980w,
935w, 880w, 860w, 750 (br.), 660m, 630m. 1H-NMR (600 MHz, 250 K): 8.46 (s, NH2); 7.68 (s, HÀC(15),
HÀC(17)); 3.48 ± 3.44 (m, 2 H); 2.37 ± 2.32 (m ‡ s, CH2, Me); 1.72 ± 1.58 (m, 4 H); 1.27 ± 1.21 (m, 2 H); 1.17 ±
0.93 (m, 8 H); 0.80 ± 0.72 (m, 2 H); 0.69 ± 0.56 (m, 2 H). 13C-NMR (600 MHz, 250 K): 205.83 (s, 2 CO); 149.38
(s, C(19)); 137.39 (d, C(17), C(15)); 121.31, 119.58 (2s, C(14), C(16), C(18)); 41.30 (t, C(2), C(11)); 27.84, 27.76,
.
‡
‡
27.14, 26.18, 26.07 (5t, 9 CH2); 20.40 (q, Me). EI-MS: 316 (20, [M ‡ H] ), 315(100, M ), 202 (10), 191 (19), 188
(20), 176 (31), 162 (14), 160 (13), 149 (41), 148 (13), 147 (10), 146 (14), 134 (25), 133 (21), 120 (12), 107 (57),
106 (16), 105 (25), 91 (21), 84 (12), 79 (11), 77 (11), 69 (17), 57 (17), 55 (37), 43 (30), 42 (10), 41 (40).
Single crystals suitable for X-ray crystal-structure determination were obtained from cyclohexane (Figs. 1
and 2).

Helvetica Chimica Acta ± Vol. 83 (2000)
1823
15. X-Ray Crystal-Structure Determination of 14 and 24 (see Table 3 and Figs. 1 ± 3)1). Intensities were
measured on a Rigaku AFC5R diffractometer with MoKa radiation (graphite monochromator, l ˆ 0.71069 Š)
and a 12-kW rotating-anode generator. Reflection intensities were corrected for Lorentz and polarization
factors, but not absorptions. Structure interpretation using direct methods was with the SHELXS86 program
system [14]. All heavy atoms were refined using anisotropic temp. factors. For 14, all H-atoms were placed in
geometrically calculated positions with an (XÀH) distance of 0.95Š and assigned fixed isotropic factors with a
value of 1.2Ueq of the C- or the N-atom. For 24, it was possible to locate all H-atoms by difference electron-
density calculations; their positions were refined with individual isotropic temp. factors. For refinement, full-
matrix, least-squares procedures were applied against F. In the case of 24, a correction for secondary extinctions
was inserted. The crystals of 14 were very thin needles and only weakly diffracting. They crystallized in a polar
space group; the absolute structure was not determined, however, but selected arbitrarily. Crystallographic data
are given in Table 3, and molecular structures in Figs. 1 ± 3. These figures were produced with the ORTEP-II
Table 3. Crystallographic Data for Compounds 14 and 24
14
24
Crystallized from
Empirical formula
Molecular weight [g molÀ1
Crystal color
Et2O/hexane
C19H27NO2
301.43
colorless
needles
cyclohexane
C20H29NO2
315.45
pale yellow
prisms
]
Crystal form
Crystal size [mm]
Temp. [K]
0.07 Â 0.15 Â 0.55
0.22 Â 0.33 Â 0.48
183(1)
173(1)
Crystal system
Space group
monoclinic
P21
monoclinic
P21/n
Z
2
4
Lattice parameters
Number of centered reflections
17
25
2q Region [8]
a [Š]
b [Š]
c [Š]
b [8]
V [Š3]
11 ± 20
5.110(5)
19.458(3)
8.496(4)
103.49(6)
821(1)
1.219
33 ± 40
10.496(3)
8.523(2)
20.899(2)
103.48(1)
1818.2(6)
1.152
Dx [g cmÀ3
]
m(MoKa) [mmÀ1
Scan type
]
0.0779
w/2q
0.0731
w/2q
2q(max) [8]
5
0
5
Number of measured reflections
Number of symmetry-independent
reflections
Number of reflections used [I > 2sI]
Number of variables
R
wRa)
1666
4689
14854168
862
198
0.0545
0.0416
1.431
2870
325
0.0455
0.0402
Goodness of fit
Secondary extinction coefficient
1.737
±
7.6(8) Â 10À7
Last Dmax/s
D1 (max; min) [e Š
0.0001
0.20; À0.22
0.0002
À3
]
0.23; À0.21
a) Minimized function Sw (j Fo jÀj Fc j )2; w ˆ [s2(Fo) ‡ (0.005Fo)2]À1
1
)
The crystallographic data (excluding structural factors) for 14 and 24 have been deposited at the Cambridge
Crystallographic Data Centre as deposition No. CCDC-138246 and 138247. Copies of the data can be
obtained, free of charge on application to the CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax:
‡44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk).

1824
Helvetica Chimica Acta ± Vol. 83 (2000)
program [15]. Neutral diffraction coefficients for heavy atoms were taken from [16a]; those for H-atoms from
[17]. Anomalous dispersion effects were taken account of in Fc [18]; the values for f ' and f '' come from [16b].
All calculations were performed using the TEXSAN software packet [19].
REFERENCES
[1] T. Koch, V. I. Ognyanov, M. Hesse, Helv. Chim. Acta 1992, 75, 62.
[2] T. Koch, M. Hesse, Helv. Chim. Acta 1994, 77, 819.
[3] J. Tsuji, M. Nisar, I. Shimizu, J. Org. Chem. 1985, 50, 3416.
[4] T. Koch, M. Hesse, Synthesis 1992, 931.
[5] D. Wöhrle, M. W. Tausch, W.-D. Stohrer, ꢀPhotochemieꢁ, Wiley-VCH, Weinheim, 1998.
[6] H. Shizuka, I. Tanaka, Bull. Chem. Soc. Jpn. 1968, 41, 2343.
[7] H. Shizuka, Bull. Chem. Soc. Jpn. 1969, 42, 5 2.
[8] H. Shizuka, Bull. Chem. Soc. Jpn. 1969, 42, 5 7.
[9] J. Franck, E. Rabinowitch, Trans. Faraday Soc. 1934, 30, 120.
[10] M. Fischer, Tetrahedron Lett. 1969, 2281.
[11] Y. Katsuhara, H. Maruyama, Y. Shigemitsu, Y. Odaira, Tetrahedron Lett. 1973, 1323.
[12] J. Stumpe, A. Mehlkorn, K. Schwetlich, J. Photochem. 1978, 8, 1.
[13] J. D. Coyle, Pure Appl. Chem. 1988, 60, 941.
[14] G. M. Sheldrick, ꢀSHELXS86ꢁ, Acta Crystallogr., Sect. A 1990, 46, 467.
[15] C. K. Johnson, ꢀORTEP-II, Report ORNL-5138ꢁ, Oak Ridge National Laboratory, Oak Ridge, Tennessee,
1976.
[16] a) E. N. Maslen, A. G. Fox, M. A. OꢁKeefe, in ꢀInternational Tables for Crystallographyꢁ, Ed. A. J. C.
Wilson, Kluwer Academic Publishers, Dordrecht, 1992, Vol. C, Table 6.1.1.1, S. 477; b) D. C. Creagh, W. J.
McAuley, ibid. Table 4.2.6.8, S. 219.
[17] R. F. Stewart, E. R. Davidson, W. T. Simpson, J. Chem. Phys. 1965, 42, 3175.
[18] J. A. Ibers, W. C. Hamilton, Acta Crystallogr. 1964, 17, 781.
[19] ꢀTEXSAN Single Crystal Structure Analysis Software, Version 5.0ꢁ, Molecular Structure Corporation, The
Woodlands, Texas, 1989.
Received December 23, 1999