4,15-Diamino[2.2]paracyclophane, a reusable template for topochemical reaction control in solution

Article abstract of DOI:10.1002/1099-0690(200207)2002:14<2298::AID-EJOC2298>3.0.CO;2-E

An efficient synthesis of [2.2]paracyclophane-4,15-dicarboxylic acid (11) from [2.2]paracyclophane (8) has been developed. The diacid was converted via the diazide 14 into the 4,15-diisocyanato[2.2]paracyclophane (15), a versatile intermediate that could be transformed into many new pseudogeminally substituted derivatives of 8. For example, treatment of 15 with alcohols provided the carbamates 16 and 17. On treatment of 15 with diisopropylamine, the urea 18 was obtained, whereas reduction with lithium aluminium hydride afforded the cyclic urea 20. Hydrolysis of 15 furnished the diamine 19, which was used as a reusable spacer in a [2+2]photoaddition experiment. Thus, treatment of 19 with trans-cinnamoyl chloride (25) provided the bis(amide) 26, which on irradiation in acetone ring-closed to give the cyclobutane 28. Saponification of this yielded 3,4-diphenyl-1,2-cyclobutanedicarboxylic acid (27, β-truxinic acid) and returned the spacer system 19, both in quantitative yield. The X-ray structures of 15 and 20 are reported. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.

Full text of DOI:10.1002/1099-0690(200207)2002:14<2298::AID-EJOC2298>3.0.CO;2-E

FULL PAPER
4,15-Diamino[2.2]paracyclophane, a Reusable Template for Topochemical
Reaction Control in Solution[‡]
Holger Zitt,[a] Ina Dix,[a] Henning Hopf,*[a] and Peter G. Jones[b]
Keywords: Cyclophanes / Isocyanates / Photoadditions / Reusable spacers / Topochemical control
An efficient synthesis of [2.2]paracyclophane-4,15-dicarb-
diamine 19, which was used as a reusable spacer in a
oxylic acid (11) from [2.2]paracyclophane (8) has been de- [2+2]photoaddition experiment. Thus, treatment of 19 with
veloped. The diacid was converted via the diazide 14 into the
4,15-diisocyanato[2.2]paracyclophane (15), a versatile inter-
trans-cinnamoyl chloride (25) provided the bis(amide) 26,
which on irradiation in acetone ring-closed to give the cyclo-
mediate that could be transformed into many new pseudo- butane 28. Saponification of this yielded 3,4-diphenyl-1,2-
geminally substituted derivatives of 8. For example, treat-
ment of 15 with alcohols provided the carbamates 16 and 17.
On treatment of 15 with diisopropylamine, the urea 18 was
obtained, whereas reduction with lithium aluminium hydride
afforded the cyclic urea 20. Hydrolysis of 15 furnished the
cyclobutanedicarboxylic acid (27, β-truxinic acid) and re-
turned the spacer system 19, both in quantitative yield. The
X-ray structures of 15 and 20 are reported.
( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
2002)
˚
Introduction
equate the limiting distance of ca 3.6 A with the ‘‘length’’
of a p-orbital, and it is interesting to note that comparable
dimensions have also been observed in other ‘‘layered struc-
tures’’ (graphite: 3.4 A, distance between the paired bases
In a series of classical papers on the solid-state photo-
chemical behavior of trans-cinnamic acid, Schmidt and co-
workers demonstrated[2Ϫ4] a relationship between the ori-
entation of the acid in the crystal lattice and the success
and the stereochemical outcome of the photoprocess. Thus,
the so-called α modification of trans-cinnamic acid under-
went head-to-tail dimerization, yielding α-truxillic acid. In
contrast, the β modification provided β-truxinic acid as the
result of a head-to-head [2ϩ2]cycloaddition. Finally, γ-
trans-cinnamic acid did not undergo photodimerization at
all. By X-ray crystallographic analysis, Schmidt determined
the distance between the relevant moieties of the two re-
˚
˚
in DNA: 3.4 A). When the crystal structures of the trans-
cinnamic acids are dismantled, by dissolution in an organic
solvent, no [2ϩ2]cycloaddition takes place on irradiation,
and only cis/trans-photoisomerization is observed. Al-
though in principle very attractive for stereoselective syn-
thesis, topochemical reaction control has not become very
important in this field, because its two main limitations
could not be overcome. The crystal structure(s) of the start-
ing material(s) often cannot be ‘‘adjusted’’ to one’s needs
(i.e., the critical distance cannot be chosen or tuned deliber-
ately; it has to be ‘‘accepted’’), and solid-state photochem-
ical reactions, usually being surface processes, are often
cumbersome to carry out and unsatisfactory in terms of
yield.
˚
acting trans-cinnamic acid molecules as 3.6 A in the first
two cases, whereas it was over 4.7 A in the γ case. There
˚
was thus a critical intermolecular threshold beyond which
no product-forming interaction between the two molecules
took place. This so-called ‘‘topochemical principle’’ has
also been observed for the solid-state photochemical be-
havior of Ϫ inter alia[4] Ϫ various styryl derivatives,[5] qui-
nones,[6] chalcones,[7] etc. Figuratively speaking, one can
In order to overcome these limitations, we suggested sev-
eral years ago the use of the [2.2]paracyclophane system as
a proxy for the crystal lattice:[1] it has a layered structure
˚
(intermolecular distance between the rings ca. 3 A, below
˚
the critical distance of 3.6 A), it can readily be
functionalized,[8Ϫ10] and substituted cyclophanes and nu-
merous derivatives are soluble in common organic solvents.
Hence, topochemical reaction control should be possible in
solution, avoiding the above pitfalls of the solid state.
[‡]
Topochemical Reaction Control in Solution, III. Part II: Ref.[1]
[a]
Institut für Organische Chemie, Technische Universität
Braunschweig,
Hagenring 30, 38106 Braunschweig, Germany
Fax: (internat.) ϩ49Ϫ(0)531/391-5388
E-mail: h.hopf@tu-bs.de
[b]
Institut für Anorganische und Analytische Chemie, Technische
Results
Universität Braunschweig,
Postfach 3329, 38023 Braunschweig, Germany
Fax: (internat.) ϩ49Ϫ(0)531/391-5387
E-mail: jones@xray36.anchem.nat.tu-bs.de
To test the viability of these considerations, we prepared
the cyclophane 1a (R ϭ CH3), which very closely resembles
2298
 WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1434Ϫ193X/02/0714Ϫ2298 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2002, 2298Ϫ2307

4,15-Diamino[2.2]paracyclophane, a Reusable Template for Topochemical Reaction Control
FULL PAPER
Schmidt’s β form of trans-cinnamic acid, the main differ-
ence being that the two phenyl rings are now clamped to-
gether tightly by ethano bridges. We were pleased to find
that the intended intramolecular photoaddition not only
yielded the cyclobutane derivative 2a (R ϭ CH3) in 100%
chemical yield in methanol, acetonitrile, cyclohexane, and
other organic solvents, but also occurred stereospecifically
and with the highest quantum yield of any cinnamic acid
or ester dimerization ever studied ( ϭ 0.82 in acetonitrile at
0 °C, ϭ 0.84 in methanol at Ϫ90 °C, Scheme 1). The free
acid 1a (R ϭ H) and the ethyl ester (1a, R ϭ C2H5) behaved
similarly. Furthermore, on irradiation of the vinylogues of
1a, 1b, and 1c (R ϭ C2H5), respectively, the ladderanes 2b
and 2c (R ϭ C2H5) were produced in excellent yields (Ͼ
90% and 83%).[1,11,12] Clearly, the controlling effect of the
cyclophane ‘‘lattice’’ extended beyond its immediate vicin-
ity. On the other hand, irradiation of the tetraene 1d did
not afford a [7]ladderane derivative.[13]
Scheme 2. pseudo-Geminal [2.2]paracyclophanes as reusable
spacers
place, yielding the intramolecular adduct 5. Removal of the
photoproduct 6 regenerates the spacer system 7, ready to
be used in a second cycle.
As far as functional groups are concerned, we are mostly
interested in the pseudo-geminal diethynyl[16] and divinyl de-
rivatives of [2.2]paracyclophane, the dicarboxylic acid, the
bis(phenol),[17] and the diamine. Having prepared all of
these during the last few years, we now describe in this pa-
per the preparation, chemical properties, and the use of
4,15-diamino[2.2]paracyclophane in a cyclic process like the
one described, thus for the first time demonstrating the
feasibility of the above principle.
Scheme 1. Photoaddition reactions in pseudo-geminal cinnamo-
phanes
Although these experiments confirmed that, with a suit-
able scaffold, the result of solid-state photochemical reac-
tions can be mimicked in solution,[14] they shared the com-
mon feature that the lattice (the cyclophane) and the part
of the system in which the actual reaction takes place Ϫ the
double bond(s) Ϫ were connected by carbon-carbon bonds,
making application in synthesis impracticable,[15] since it
would have to involve exclusive or preferential cleavage of
Preparation of 4,15-Diisocyanato[2.2]paracyclophane (15)
The ‘‘natural’’ precursor for 4,15-diamino[2.2]paracyclo-
the bond connecting the controlling/steering and the re- phane is the corresponding dinitro derivative. This was ob-
acting parts of the whole system. tained in the late 1960s by Cram and Reich, by direct nitra-
Any application of topochemical reaction control in solu- tion of [2.2]paracyclophane (8), but the yields were so low
tion with [2.2]cyclophanes as molecular ‘‘work-benches’’[15] (0.7%) that this approach had to be abandoned immedi-
for preparative purposes would have to involve spacer sys- ately.[18] The same authors also prepared the pseudo-gemi-
tems with deliberately introduced breaking or detachment nal nitro-amino[2.2]paracyclophane from the parent hydro-
points. This is illustrated in symbolic form in Scheme 2 for carbon, but the yield of their five-step sequence was even
a substrate molecule 3, still showing some resemblance to worse (0.2%). Meanwhile, several amino[2.2]paracyclo-
trans-cinnamic acid.
phanes have become available in far better yields by a novel
In the first step, the lattice substitute 7, bearing two react- method reported by Langer, Höcker, and co-workers,[19] but
ive centers (open circles) in a pseudo-geminal relationship the 4,15-isomer required for this investigation was not ob-
(i.e., directly opposite each other on the two benzene decks) tained by them.
interacts with the substrate 3 and forms the intermediate 4.
The route described here also started with the parent hy-
In principle, this interaction can be of any type: a covalent drocarbon 8, a commercial product. This was first con-
bond between functional groups, an ionic interaction (salt verted into the 4-methoxycarbonyl derivative 13, by a pro-
formation), a hydrogen bond, etc. With the substrate sec- cedure first described by Psiorz and Schmid,[20] which ac-
tions now in an alignment favorable for reaction, the pro- cording to our experience is the best method for the func-
cess of interest, photoaddition in the case at hand, can take tionalization of 8 known so far. As shown in Scheme 3, it
Eur. J. Org. Chem. 2002, 2298Ϫ2307
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H. Zitt, I. Dix, H. Hopf, P. G. Jones
FULL PAPER
consisted first of the conversion of 8 into the keto acid 14 was heated in toluene it effortlessly underwent the de-
chloride 9 with oxalyl chloride/aluminium trichloride.
sired double Curtius degradation, yielding 4,15-diisocyana-
to[2.2]paracyclophane (15) in practically quantitative yield.
Again, this derivative was a stable solid, and single crystals
of suitable quality for an X-ray structural study were ob-
tained by sublimation (150 °C, 4·10Ϫ3 Torr); the structure
of 15 in the crystal is shown in Figure 1.
Scheme 3. The preparation of [2.2]paracyclophane-4,15-dicarb-
oxylic acid (11) from [2.2]paracyclophane (8); a) (COCl)2/AlCl3,
Ϫ10 °C to Ϫ5 °C, 20 min; b) PhCl, ∆, 40 h; c) CH3OH/CH2Cl2, ∆,
90 h; d) TiCl4/CH3OCHCl2, CHCl2, Ϫ10 ° C Ǟ room temp., 16 h;
e) aq. KOH, refl., 22 h, then 35% H2O2, 10 °C, 20 min Ǟ 6 days,
room temp.
Heating of 9 in refluxing chlorobenzene caused decar-
bonylation, and when the resulting acid chloride 10 was
quenched with methanol, the ester 13 was obtained. The
pseudo-geminal substitution pattern was generated by sub-
jection of 13 to Rieche formylation with α,α-dichloromethyl
methyl ether in the presence of titanium tetrachloride. Al-
though the crude yield (as determined by GC analysis) of
this step was also excellent, the pseudo-geminal formyl ester
12 was only isolated in 77% yield after chromatography/
recrystallization. To oxidize 12 to [2.2]paracyclophane-4,15-
dicarboxylic acid (11), various oxidation reagents were tried
(KMnO4, AgNO3); the best yields were finally obtained
with a large excess of hydrogen peroxide after 12 had been
saponified to the free acid by potassium hydroxide treat-
ment. The diacid is a known compound, having been pre-
pared by Cram[21] and by us,[22] but by steps far less efficient
than those reported here. Note that this derivative already
belongs to the class of compounds discussed in general
form in Scheme 2.
Figure 1. The molecule of compound 15 in the crystal; radii are ar-
bitrary
The molecule displays no imposed symmetry. The cyclo-
phane rings adopt the usual boat conformation. One isocy-
anate group is essentially coplanar with its ring, but the
other is deflected out of plane towards the outside of the
˚
molecule (C17 by 0.55, O1 by 0.95 A). The dimensions of
the isocyanate groups, despite the risk of librational bond
shortening, appear to be normal on comparison with the
To introduce a nitrogen function into the ultimately re-
quired positions, 11 was next converted into the bis(keto
azide) 14 by treatment first with thionyl chloride to yield
the bis(acyl chloride) and then with sodium azide. The pro-
cess could be interrupted at the stage of the acid chloride
(a stable and isolable intermediate[13]), but could also be
carried out as a one-step process as described in Scheme 4.
Scheme 4. The preparation of 4,15-diisocyanato[2.2]paracyclo-
phane (15) from the diacid 11; a) SOCl2, DMF, refl., 2 h, then
NaN3, aq. acetone, 0 °C, 40 min; b) toluene, reflux, 30 min
Again, different substitution conditions were tried, and
the result shown in the scheme is the optimized one. When omitted for clarity; there are two such layers per z axis repeat
Figure 2. Packing of molecules of 15 in the crystal; H atoms are
2300
Eur. J. Org. Chem. 2002, 2298Ϫ2307

4,15-Diamino[2.2]paracyclophane, a Reusable Template for Topochemical Reaction Control
FULL PAPER
few other available data (Cambridge Database refcodes: responding diamino derivative should also be preparable by
BUBVEZ, HAMFIK, VAXRUH) for phenyl rings substi- hydride reduction of 15. Surprisingly, this was not the case.
tuted with isocyanate: NϪC 1.184, 1.196(5), CϪO 1.169, As shown by its spectroscopic data (see Exp. Sect.) and X-
˚
1.145(5) A, NϪCϪO 170.6(5), 171.5(4)°. The crystal pack- ray crystallographic analysis (Figure 3), 15 was reduced to
ing of 15 (Figure 2) involves layers of molecules with a her- the cyclic urea 20 on treatment with lithium aluminium hy-
ringbone pattern.
dride in tetrahydrofuran.
As shown in Figure 3, the additional bridge in 20 does
not affect the overall boat conformation of the rings, but
they are no longer parallel (interplanar angle 9°). The
bridge angles at nitrogen are widened to C4ϪN1ϪC17
126.7° and C15ϪN2ϪC15 127.8(2)°. The molecules are
Several Reactions of 4,15-Diisocyanato[2.2]paracyclophane
(15)
Since isocyanates display very rich preparative chem-
istry,[23] we thought it worthwhile to carry out some explor-
atory reactions with 15 before actually preparing the re-
quired diamine from it. The results of these transformations
are illustrated in Scheme 5.
As expected, 15 reacted rapidly with ethanol to provide
the bis(carbamate) 16 in good yield, and when the diisocy-
anate was treated under high dilution conditions with a diol
Ϫ as a model compound we selected tetraethylene glycol Ϫ
the expected intramolecular double addition took place to
furnish the crown ether 17. Since pseudo-geminally substi-
tuted [2.2]paracyclophanes can generally be rearranged into
their pseudo-meta isomers, which are chiral, by heating, sub-
strates such as 17 should in principle be usable to prepare
novel chiral crown ethers. With excess diisopropylamine, 15
quantitatively provided the bis(urea) derivative 18, again
under very mild conditions (room temperature) and quickly
(15 min). Since 4-isocyanato[2.2]paracyclophane had been
reduced to the corresponding N-methylamino derivative[24]
Figure 3. The molecule of compound 20 in the crystal; radii are ar-
with lithium aluminium hydride, we assumed that the cor- bitrary
Scheme 5. Various reactions of 4,15-diisocyanato[2.2]paracyclophane (15); a) C2H5OH, refl., 30 min; b) HO(ϪCH2CH2OϪ)4H, toluene,
refl., 7 days, high dilution; c) HN(iPr)2, room temp., 15 min; d) LiAlH4, THF, 90 min; e) toluene, HCl, refl., 2d, then KOH; f) C2H5OH,
refl., 2 h, then aq. KOH, refl., 45 h
Eur. J. Org. Chem. 2002, 2298Ϫ2307
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H. Zitt, I. Dix, H. Hopf, P. G. Jones
FULL PAPER
connected by classical hydrogen bonds N1ϪH01···O and functionalized [2.2]paracyclophanes as ‘‘lattice substitutes’’
N2ϪH02···O to form ribbons parallel to the x axis (Fig- is summarized in Scheme 7.
ure 4).
Scheme 7. Topochemical reaction control in solution: application
of 19 as a reusable spacer for the synthesis of 3,4-diphenyl-1,2-
cyclobutanedicarboxylic acid (27, β-truxinic acid): a) 1,4-dioxane,
room temp., 24 h; b) hν, acetone, 7 h; c) concd. HCl, refl., 24 h;
d) solid KOH
Figure 4. Packing of molecules of 20 in the crystal; H atoms (except
those involved in hydrogen bonding) are omitted for clarity; hydro-
gen bonds are indicated by dashed lines
Treatment of 19 with cinnamoyl chloride (25) provided
the unsaturated amide 26 in good yield (80%, not optim-
ized). When this was irradiated in acetone with a 150 W
medium-pressure mercury lamp, the ring-closed product 28
was produced, as confirmed spectroscopically (see Exp.
Sect.), in 76% yield. The reaction was much slower than the
photocyclization of the monoester 1a. That the stereochem-
ical information contained in 26 (both double bonds E-con-
figured) was indeed not lost in the [2ϩ2]cycloaddition step
(i.e., that no E/Z photoisomerization had occurred) was fi-
nally proven by the saponification of 28 with concd. hydro-
chloric acid, which furnished β-truxinic acid (27) exclusively
and in practically quantitative yield (98%). Furthermore, we
were pleased to find that on neutralization of the acidic
filtrate of the saponification experiment, the template mole-
cule, 4,15-diamino[2.2]paracyclophane (19), was recovered
in 97% yield.
To explain the formation of 20, we propose the neighbor-
ing group effect illustrated in Scheme 6. When hydride at-
tacks the carbon center of one of the isocyanate substitu-
ents, bridging to the second NCO group occurs, resulting
in the formation of the triply-bridged intermediate 22.
Clearly, layered molecules of this type can successfully
mimic the stereochemical control exerted by a crystal lat-
tice.
Scheme 6. The hydride reduction of 15 to the cyclic urea 20
Further reduction provides 23, which on hydrolysis
(via the aminal 24) and loss of formaldehyde (most prob-
ably reduced further by excess hydride reagent), yields the
isolated bridged urea 20.
Finally, the diamine 19 was obtained either by heating 15
in toluene under reflux in the presence of dilute hydro-
chloric acid and then liberating the free amine from the
diammonium salt, or by hydrolysis of 16 with aqueous base,
the bis(carbamic acid) presumably being produced as an in-
termediate (Scheme 5).
Experimental Section
General Remarks: Melting points: Mel-Temp II apparatus, uncor-
rected. Analytical TLC: MachereyϪNagel Polygram Sil G/UV254
and Polygram Alox N/UV254. Column chromatography: Merck
Kieselgel 60 (70Ϫ230 mesh). Analytical GC: Dani 86.10, OV-1 ca-
pillary column; 20 m. NMR: Bruker AC 200 F (1H NMR:
200.1 MHz, 13C NMR: 50.3 MHz) and Bruker AM 400 (1H NMR:
400.1 MHz, 13C NMR: 100.6 MHz). In the H NMR spectra, the
1
bridge protons (of the ethano bridge closer to the substituents)
pointing away from the pseudo-geminal substituents are labeled ‘‘a’’
(anti), and ‘‘s’’ (syn) when they are oriented towards these substitu-
ents. In the 13C NMR spectra the signals of the quaternary carbon
atoms that could not be assigned are labeled ‘‘qC’’. MS: Finnigan
MAT 8430 (EI, 70 eV). HRMS: by peak matching, resolution 10
Use of 4,15-Diamino[2.2]paracyclophane (19) as a Reusable
Template
The crucial experiment illustrating the feasibility of our
general approach (Scheme 2) to employ pseudo-geminally 000. GC/MS: Carlo Erba HRGC 5160 coupled to a Finnigan MAT
2302 Eur. J. Org. Chem. 2002, 2298Ϫ2307

4,15-Diamino[2.2]paracyclophane, a Reusable Template for Topochemical Reaction Control
FULL PAPER
3
4515 (EI, 40 eV). IR: Nicolet 320 FT-IR spectrometer. UV/Vis:
H, 1s-H, 2s-H), 6.65 (d, J8-H,7-H
ϭ
3J13-H,12-H ϭ 7.7 Hz, 2 H,
Hewlett Packard 8452 diode array. Elemental analyses: Institutes 8-H, 13-H), 6.70 (dd,3J7-H,8-H
ϭ
3J12-H,13-H ϭ 7.7, J7-H,5-H
ϭ
4
4
of Inorganic and Analytical and of Pharmaceutical Chemistry of
the Technical University of Braunschweig.
4J12-H,16-H ϭ 1.8 Hz, 2 H, 7-H, 12-H), 7.03 (d, J5-H,7-H
ϭ
4J16-H,12-H ϭ 1.8 Hz, 2 H, 5-H, 16-H), 12.19 (br. s, COOH) ppm.
13C NMR (100.6 MHz, [D6]DMSO): δ ϭ 34.0 (C-1, C-2), 34.2 (C-
9, C-10), 131.0 (qC), 133.8, 135.9, 136.3 (C-5, C-16, C-7, C-12, C-
8, C-13), 139.3 (qC), 142.2 (qC), 167.5 (C-17, C-18) ppm. IR (KBr):
ν˜ ϭ 3435 cmϪ1 (m), 3429 (m), 3148 (m), 3135 (m), 3127 (m), 3048
(m), 3018 (m), 3011 (m), 2967 (m), 2879 (m), 2870 (m), 2857 (m),
1688 (vs), 1649 (m), 1639 (m), 1594 (m), 1558 (m), 1489 (m), 1435
(m), 1419 (m), 1401 (m), 1310 (s), 1297 (s), 1277 (s), 1212 (m), 931
(m), 909 (m). UV/Vis (MeCN): λmax (lg ε) ϭ 240 nm (4.05), 306
(3.20). MS (EI, 70 eV): m/z (%) ϭ 296 (5) [Mϩ], 279 (21), 278 (100),
149 (20), 148 (40), 131 (44), 105 (13), 104 (12), 91 (11). C18H16O4
(296.31): calcd. C 72.96, H 5.44; found C 72.82, H 5.46.
Methyl [2.2]Paracyclophane-4-carboxylate (13): was prepared ac-
cording to the procedure of Psiorz and Schmid.[20]
Methyl 15-Formyl[2.2]paracyclophane-4-carboxylate (12): Com-
pound 13 (24.18 g, 0.091 mol) was placed in a three-necked 4 L
flask, equipped with internal thermometer, dropping funnel, and
nitrogen inlet tube, and the apparatus was flushed with nitrogen.
After 1.2 L of dichloromethane had been added, the solution was
cooled to Ϫ10 °C with an ice-salt bath. Over 10 min, titanium(IV)
chloride (37 mL, 64.01 g, 0.337 mol) was added (formation of a
brown color), followed over 5 min by α,α-dichloromethyl methyl
ether (30 mL, 38.70 g, 0.338 mol). During the addition of the re-
agents the internal temperature was kept at Ϫ5 to Ϫ10 °C. The
mixture was stirred for 16 h while the temperature was allowed to
rise to room temp. After decomposition with 400 g of ice in a separ-
ating funnel, the organic phase was removed and the aqueous phase
was washed with dichloromethane (2 ϫ 200 mL). The combined
organic phases were washed with sodium bicarbonate solution,
water, and brine, and dried with magnesium sulfate. The solution
was concentrated to ca. 100 mL and filtered through a silica gel
column. After complete solvent removal, 25.30 g of an amorphous
solid was obtained. According to GC analysis, this consisted of
93% of the desired 12 and three of its isomers produced as trace
components. Recrystallization from cyclohexane (900 mL) yielded
19.11 g of pure crystalline 12 (needles); 1.50 g of additional product
(total yield 20.61 g, 77%) was isolated from the mother liquor. Ana-
lytically pure material was obtained by high-vacuum sublimation
(160 °C, 4·10Ϫ3 mbar). m.p. 169 °C (cyclohexane). 1H NMR
(400.1 MHz, CDCl3): δ ϭ 2.98Ϫ3.17 (m, 6 H, 1a-H, 2a-H, 9-H,
10-H), 3.82 (s, 3 H, 18-H), 4.08Ϫ4.20 (m, 2 H, 1s-H, 2s-H), 6.61
[2.2]Paracyclophane-4,15-dicarbonyl Diazide (14): A solution of so-
dium azide (11.12 g, 0.171 mol) in 85 mL of water was added over
45 min to a suspension of [2.2]paracyclophane-4,15-dicarbonyl
dichloride (5.70 g, 0.017 mol) in acetone (100 mL), prepared from
11 and thionyl chloride according to ref.[13] After the mixture had
been stirred for 1 h, ice water (500 mL) was added, and the precipit-
ate was removed by filtration through a glass frit. The pale yellow
solid was washed with water and dried in a desiccator over phos-
phorus pentoxide: 5.71 g (96%) of 14 as pale yellow microcrystals.
m.p. 102 °C (decomp). 1H NMR (400.1 MHz, [D6]DMSO): δ ϭ
3.08Ϫ3.12 (m, 6 H, 1a-H, 2a-H, 9-H, 10-H), 3.99Ϫ4.11 (m, 2 H,
1s-H, 2s-H), 6.79 (d, 3J8-H,7-H ϭ 3J13-H,12-H ϭ 7.8 Hz, 2 H, 8-H, 13-
H), 6.87 (dd, 3J7-H,8-H ϭ 3J12-H,13-H ϭ 7.8, 4J7-H,5-H ϭ 4J12-H,16-H ϭ
1.8 Hz, 2 H, 7-H, 12-H), 7.10 (d, J5-H,7-H ϭ J16-H,12-H ϭ 1.8 Hz,
2 H, 5-H, 16-H) ppm. 13C NMR (100.6 MHz, [D6]DMSO): δ ϭ
33.4, 33.9 (C-1, C-2, C-9, C-10), 129.9 (qC), 133.7, 136.7, 138.3 (C-
5, C-16, C-7, C-12, C-8, C-13), 140.2 (qC), 142.7 (qC), 172.2 (C-
17, C-18) ppm. IR (KBr): ν˜ ϭ 3457 cmϪ1 (w), 3444 (w), 3424 (w),
3147 (w), 2941 (m), 2858 (w), 2271 (m), 2141 (vs), 1686 (s), 1671
(s), 1260 (s), 1191 (vs), 1158 (s), 1135 (m), 997 (s), 917 (m). UV/
Vis (MeCN): λmax (lg ε) ϭ 308 nm (3.44), 268 (4.16), 216 (4.52),
192 (4.43). MS (EI, 70 eV): m/z (%) ϭ 346 (2) [Mϩ], 290 (9), 263
(11), 144 (15), 145 (100), 131 (25), 116 (12), 90 (13). HR-MS (Mϩ
Ϫ N2): calcd. 311.1117; found 311.1117Ϯ2 ppm.
4
4
3
(d, J8-H,7-H or 13-H,12-H ϭ 7.8 Hz, 1 H, 8-H or 13-H), 6.64 (d,
3J8-H,7-H or 13-H,12-H ϭ 7.8 Hz, 1 H, 8-H or 13-H), 6.69 (dd,
4
3J7-H,8-H or 12-H,13-H ϭ 7.8, J7-H,5-H or 12-H,16-H ϭ 2.0 Hz, 1 H, 7-H
or 12-H), 6.71 (dd, 3J7-H,8-H or 12-H,13-H ϭ 7.8, 4J7-H,5-H or 12-H,16-H ϭ
4
2.0 Hz, 1 H, 7-H or 12-H), 7.07 (d, J5-H,7-H or 16-H,12-H ϭ 2.0 Hz,
4
1 H, 5-H or 16-H), 7.08 (d, J5-H,7-H or 16-H, 12-H ϭ 2.0 Hz, 1 H, 5-
H or 16-H), 9.92 (s, 1 H, 19-H) ppm. 13C NMR (100.6 MHz,
4,15-Diisocyanato[2.2]paracyclophane (15): A solution of 14 (4.23 g,
CDCl3): δ ϭ 31.1, 35.0 (C-1, C-2), 34.6, 34.7 (C-9, C-10), 51.9 (C- 0.012 mol) in 150 mL of anhydrous toluene was heated at reflux
18), 130.8 (qC), 133.7, 134.4 (C-5, C-16), 135.7, 136.1 (C-8, C-13), for 30 min under nitrogen. At ca. 95 °C, gas evolution set in. After
136.0, 138.1 (C-7, C-12), 136.5 (qC), 139.7 (qC), 140.1 (qC), 142.1
the solvent had been removed in vacuo, 3.32 g (94%) of an ochre-
(qC), 143.5 (qC), 167.0 (C-17), 190.6 (C-19) ppm. IR (KBr): ν˜ ϭ colored solid was obtained. An analytically pure sample (colorless
3475 cmϪ1 (w), 3454 (w), 3026 (w), 2943 (m), 2936 (m), 1711 (vs), needles) was obtained by high-vacuum sublimation (150 °C,
1683 (s), 1433 (m), 1290 (m), 1274 (s), 1199 (m), 1074 (s), 983 (w). 4·10Ϫ3 mbar); m.p. 153 °C. 1H NMR (400.1 MHz, CDCl3): δ ϭ
UV/Vis (MeCN): λmax (lg ε) ϭ 252 nm (4.10), 310 (3.40). MS (EI,
2.89Ϫ2.97 (m, 2 H, 1a-H, 2a-H), 2.99Ϫ3.08 (m, 4 H, 9-H, 10-H),
4
4
70 eV): m/z (%) ϭ 294 (100) [Mϩ], 267 (11), 266 (56), 263 (10), 236 3.50Ϫ3.54 (m, 2 H, 1s-H, 2s-H), 6.26 (d, J5-H,7-H ϭ J16-H,12-H
ϭ
3
(12), 163 (10), 162 (72), 147 (25), 133 (42), 132 (33), 119 (22), 105 1.6 Hz, 2 H, 5-H, 16-H), 6.43 (dd, J7-H,8-H
(10), 104 (39), 103 (20), 78 (10), 77 (15). C19H18O3 (294.33):
calcd. C 77.53, H 6.16; found C 77.48, H 6.27.
ϭ
3J12-H,13-H ϭ 7.9,
4J7-H,5-H 4J12-H,16-H ϭ 1.6 Hz, 2 H, 7-H, 12-H), 6.48 (d,
ϭ
3
3J8-H,7-H ϭ J13-H,12-H ϭ 7.9 Hz, 2 H, 8-H, 13-H) ppm. 13C NMR
(100.6 MHz, CDCl3): δ ϭ 31.0 (C-1, C-2), 34.7 (C-9, C-10), 130.1
(C-5, C-16), 130.8 (C-7, C-12), 132.4 (qC), 133.6 (qC), 135.1 (C-8,
C-13), 141.1 (qC) ppm; the carbon atoms of NCO groups were
unresolved. IR (KBr): ν˜ ϭ 3452 cmϪ1 (w), 2856 (w), 2358 (w), 2283
(vs), 1591 (w), 1560 (w), 1070 (w), 882 (w). UV/Vis (MeCN): λmax
(lg ε) ϭ 236 nm (4.19), 204 (4.69). MS (EI, 70 eV): m/z (%) ϭ 290
(32) [Mϩ], 146 (10), 145 (100), 90 (8), 89 (4). C18H14N2O2 (290.31):
calcd. C 74.47, H 4.86, N 9.65; found C 74.31, H 4.91, N 9.32.
[2.2]Paracyclophane-4,15-dicarboxylic Acid (11): A suspension of 12
(15.00 g, 51 mmol) in potassium hydroxide solution (1 , 1.5 L)
was heated under reflux for 22 h. After the mixture had been cooled
to 10 °C, a H2O2 solution (35%, 200 g, 2.05 mol) was added over
20 min, and the mixture was kept at room temp. for 6 days. It was
cooled again (ice-water bath) and acidified with concd. hydro-
chloric acid. The precipitate was removed by filtration, washed with
water, and dried at 100 °C in a drying oven, to give 14.36 g (95%)
of an amorphous, colorless solid. m.p. 336Ϫ342 °C (ref.: 335Ϫ340
Bis(carbamate) 16: A suspension of 15 (0.150 g, 0.52 mmol) in
1
°C[21]). H NMR (400.1 MHz, [D6]DMSO): δ ϭ 2.92Ϫ2.96 (m, 2 25 mL of ethanol was heated under reflux for 30 min. The clear
H, 1a-H, 2a-H), 3.02Ϫ3.05 (m, 4 H, 9-H, 10-H), 4.04Ϫ4.08 (m, 2 solution was cooled to room temp. and the solvent was removed in
Eur. J. Org. Chem. 2002, 2298Ϫ2307
2303

H. Zitt, I. Dix, H. Hopf, P. G. Jones
FULL PAPER
vacuo. The resulting solid was purified by column chromatography
12 H, 19-H, 22-H, 26-H, 29-H or 20-H, 23-H, 27-H, 30-H), 1.33
3
on silica gel (dichloromethane/ethyl acetate ϭ 1:1) to give 0.17 g
(d, J20-H or 19-H,18-H
ϭ
3J23-H or 22-H,21-H
ϭ
3J27-H or 26-H,25-H
ϭ
(86%) of 16 as a colorless, amorphous solid. m.p. 178 °C. 1H NMR 3J30-H or 29-H,28-H ϭ 6.8 Hz, 12 H, 20-H, 23-H, 27-H, 30-H or 19-
3
(400.1 MHz, CDCl3): δ ϭ 1.32 (t, J19-H,18-H
ϭ
3J22-H,21-H
ϭ
H, 22-H, 26-H, 29-H), 2.85Ϫ2.90 (m, 2 H, 1a-H, 2a-H), 2.95Ϫ3.00
7.2 Hz, 6 H, 19-H, 22-H), 2.85Ϫ2.90 (m, 2 H, 1a-H, 2a-H), (m, 4 H, 9-H, 10-H), 3.35Ϫ3.40 (m, 2 H, 1s-H, 2s-H), 3.93
3
2.97Ϫ3.03 (m, 4 H, 9-H, 10-H), 3.29Ϫ3.34 (m, 2 H, 1s-H, 2s-H),
(sept, J18-H,19-H,20-H
ϭ ϭ ϭ
3J21-H,22-H,23-H 3J25-H,26-H,27-H
4.23 (q, J18-H,19-H ϭ J21-H,22-H ϭ 7.2 Hz, 4 H, 18-H, 21-H), 6.42 3J28-H,29-H,30-H ϭ 6.2 Hz, 4 H, 18-H, 21-H, 25-H, 28-H), 6.37 (dd,
3
3
(dd, J7-H,8-H ϭ J12-H,13-H ϭ 7.8, J7-H,5-H ϭ J12-H,16-H ϭ 1.8 Hz, 3J7-H,8-H ϭ J12-H,13-H ϭ 7.7, J7-H,5-H ϭ J12-H,16-H ϭ 1.8 Hz, 2 H,
3
3
4
4
3
4
4
2 H, 7-H, 12-H), 6.51 (d, J8-H,7-H ϭ J13-H,12-H ϭ 7.8 Hz, 2 H, 8- 7-H, 12-H), 6.46 (d, 4J7-H,5-H ϭ 4J12-H,16-H ϭ 1.8 Hz, 2 H, 8-H, 13-
3
3
H, 13-H), 6.59 (ps-s, 2 H, 5-H, 16-H), 6.88 (br. s, 2 H, NH) ppm. H), 6.51 (d, J7-H,8-H ϭ 3J12-H,13-H ϭ 7.7 Hz, 2 H, 5-H, 16-H), 6.74
3
13C NMR (100.6 MHz, CDCl3): δ ϭ 14.6 (C-19, C-22), 31.5 (C-1, (br. s, 2 H, NH) ppm. 13C NMR (100.6 MHz, CDCl3): δ ϭ 21.2,
C-2), 34.7 (C-9, C-10), 61.2 (C-18, C-21), 125.4 (C-5, C-16), 130.0
(C-7, C-12), 131.6 (qC), 134.0 (qC), 135.2 (C-8, C-13), 140.0 (qC),
154.7 (C-17, C-20) ppm. IR (KBr): ν˜ ϭ 3304 cmϪ1 (s), 3057 (w),
22.1 (C-20, C-23, C-27, C-30, C-19, C-22, C-26, C-29), 32.1 (C-1,
C-2), 34.7 (C-9, C-10), 45.5 (C-18, C-21, C-25, C-28), 125.9 (C-5,
C-16), 129.5 (C-7, C-12), 133.1 (qC), 134.9 (C-8, C-13), 137.0 (qC),
3039 (w), 2931 (m), 1727 (vs), 1687 (vs), 1532 (m), 1493 (s), 1423 139.6 (qC), 156.2 (C-17, C-24) ppm. IR (KBr): ν˜ ϭ 3568 cmϪ1 (w),
(m), 1382 (m), 1337 (s), 1226 (s), 1066 (s), 897 (w). UV/Vis (EtOH): 3530 (w), 3502 (m), 3474 (m), 3465 (m), 3448 (m), 3442 (m), 3434
λmax (lg ε) ϭ 236 nm (4.19), 208 (4.67). MS (EI, 70 eV): m/z (%) ϭ (m), 3427 (m), 3413 (m), 1677 (vs), 1665 (s), 1614 (vs), 1576 (m),
382 (44) [Mϩ], 337 (5), 336 (14), 307 (10), 192 (15), 191 (62), 174 1448 (s), 1326 (m), 1031 (vs), 1017 (vs), 998 (s), 974 (m), 884 (m),
(9), 163 (20), 146 (26), 145 (100), 119 (19), 91 (18). C22H26N2O4 767 (s), 754 (s), 719 (m), 691 (s). UV/Vis (MeCN): λmax (lg ε) ϭ
(382.45): calcd. 69.09, H 6.85, N 7.33; found C 69.05, H 6.89, N
7.14.
274 nm (3.55, sh), 246 (4.20), 216 (4.56), 192 (4.51). MS (EI, 70 eV):
m/z (%) ϭ 492 (68) [Mϩ], 450 (9), 449 (26), 393 (11), 391 (41), 348
(61), 291 (12), 265 (10), 246 (30), 204 (14), 146 (24), 145 (30), 128
(27), 120 (14), 119 (41), 100 (38), 91 (15), 86 (88), 58 (19), 44 (30),
43 (100). C30H44N4O2 (492.69): calcd. C 73.13, H 9.00, N 11.37;
found C 73.14, H 8.93, N 11.29.
Crown Ether 17: A solution of 15 (0.200 g, 0.69 mmol) in 100 mL
of anhydrous toluene was placed in a 250-mL flask equipped with
a reflux condenser and a septum. The mixture was heated to reflux,
and tetraethylene glycol (0.140 g, 0.72 mmol) in 42 mL of toluene
was added by motor-driven syringe at 1.5 mL·hϪ1. When addition
was complete, the mixture was heated at reflux for 7 days. After
the mixture had cooled to room temp., the solvent was removed in
vacuo, and the remaining light-brown oil, dissolved in a few mL of
ethyl acetate, was purified by column chromatography on silica gel
with ethyl acetate to give 0.140 g (42%) of 17 as a colorless solid.
[2.2]Paracyclophane-4,15-diamine (19). Variant A: Concd. hydro-
chloric acid (50 mL) was added to a suspension of 15 (1.06 g,
3.7 mmol) in 50 mL of toluene, and the mixture was heated under
reflux with vigorous stirring for 48 h. After the two-phase mixture
had cooled to room temp., the aqueous phase was separated and
the organic phase was extracted three times with 100 mL portions
of concd. hydrochloric acid. The combined aqueous phases were
cooled in a ice-water bath, after which potassium hydroxide solu-
tion was added until the mixture was basic. The precipitated brown
material was removed by filtration, washed with water, and dried
under vacuum in a desiccator over phosphorus pentoxide: 0.54 g
(61%) of the ochre-colored 19. m.p. 205 °C.
1
m.p. 119Ϫ120 °C. H NMR (400.1 MHz, CDCl3): δ ϭ 2.84Ϫ2.89
(m, 2 H, 1a-H, 2a-H), 2.93Ϫ3.03 (m, 4 H, 9-H, 10-H), 3.26Ϫ3.31
(m, 2 H, 1s-H, 2s-H), 3.67Ϫ3.76 (m, 8 H, 20-H, 21-H, 22-H, 23-
H), 3.79Ϫ3.81 (m, 4 H, 19-H, 24-H), 4.28Ϫ4.36 (m, 4 H, 18-H, 25-
H), 6.39 (dd, 3J7-H,8-H ϭ 3J12-H,13-H ϭ 7.8, 4J7-H,5-H ϭ 4J12-H,16-H ϭ
3
3
1.6 Hz, 2 H, 7-H, 12-H), 6.49 (d, J7-H,8-H ϭ J12-H,13-H ϭ 7.8 Hz,
4
4
2 H, 5-H, 16-H), 6.55 (d, J7-H,5-H ϭ J12-H,16-H ϭ 1.6 Hz, 2 H, 7-
H, 12-H), 6.99 (br. s, 2 H, NH) ppm. 13C NMR (100.6 MHz,
CDCl3): δ ϭ 31.4 (C-1, C-2), 34.8 (C-9, C-10), 64.7 (C-18, C-25),
69.6 (C-19, C-24), 70.8 (C-20, C-23), 70.9 (C-21, C-22), 125.5 (C-
5, C-16), 130.1 (C-7, C-12), 131.4 (qC), 135.2 (C-8, C-13), 140.0
(qC), 154.5 (C-17, C-26) ppm; one quaternary carbon atom was
unresolved. IR (KBr): ν˜ ϭ 3434 cmϪ1 (s), 3429 (s), 2928 (s), 2900
(s), 2894 (s), 2858 (s), 1732 (vs), 1702 (s), 1637 (m), 1617 (m), 1600
(s), 1572 (s), 1533 (vs), 1492 (s), 1456 (s), 1439 (m), 1422 (m),1289
(s), 1229 (vs), 1189 (w), 1129 (s), 1102 (s), 1072 (s). UV/Vis
(MeCN): λmax (lg ε) ϭ 236 nm (4.18, sh), 272 (3.35). MS (EI,
70 eV): m/z (%) ϭ 484 (100) [Mϩ], 469 (6), 397 (6), 396 (21), 352
(22), 308 (13), 290 (13), 280 (14), 191 (22), 190 (87), 189 (19), 147
(10), 146 (79), 145 (80), 120 (22), 119 (38), 117 (10), 91 (22), 89
(26), 45 (42). C26H32N2O7 (484.45): calcd. C 64.45, H 6.66, N 5.78;
found C 64.51, H 6.80, N 5.53.
Variant B: A sample of 15 (7.11 g, 0.025 mol) was suspended in
400 mL of ethanol, and the mixture was heated under reflux for
2 h. Aqueous potassium hydroxide solution (20%, 40 mL) was ad-
ded, and the brown suspension was heated under reflux for 45 h.
The cooled reaction mixture was poured into 600 mL of ice-cold
potassium hydroxide solution (20%), and the precipitated light
brown solid was filtered off through a glass frit. The filtrate was
concentrated in a rotary evaporator, yielding additional product.
The combined precipitates were washed with water and dried in
a desiccator over phosphorus pentoxide to provide 4.73 g (81%)
of 19.
An analytically pure sample was obtained by recrystallization from
ethanol, colorless needles, m.p. 203 °C (EtOH). 1H NMR
(400.1 MHz, [D6]DMSO): δ ϭ 2.65Ϫ2.69 (m, 2 H, 1a-H, 2a-H),
2.74Ϫ2.84 (m, 4 H, 9-H, 10-H), 3.33Ϫ3.37 (m, 2 H, 1s-H, 2s-H),
4.53 (br. s, 4 H, NH2; exchangeable with D2O), 5.81 (dd,
3
4
4
Bis(amide) 18: A sample of 15 (0.154 g, 0.53 mmol) was stirred at
3J7-H,8-H ϭ J12-H,13-H ϭ 7.5, J7-H,5-H ϭ J12-H,16-H ϭ 1.7 Hz, 2 H,
room temp. with freshly distilled diisopropylamine. As shown by
7-H, 12-H), 5.84 (d, 4J5-H,7-H ϭ 4J16-H,12-H ϭ 1.7 Hz, 2 H, 5-H, 16-
TLC analysis, the reaction was over after 15 min. Removal of excess H), 6.16 (d, 3J8-H,7-H ϭ 3J13-H,12-H ϭ 7.5 Hz, 2 H, 8-H, 13-H) ppm.
amine in vacuo (first by rotary evaporation, then under high va-
cuum) yielded 0.252 g (97%) of 18 as a colorless, amorphous solid.
Column chromatography on silica gel with dichloromethane/ethyl
13C NMR (100.6 MHz, [D6]DMSO): δ ϭ 29.8 (C-1, C-2), 35.0 (C-
9, C-10), 121.7 (C-7, C-12), 123.1 (C-3, C-14), 123.4 (C-5, C-16),
134.7 (C-8, C-13), 139.5 (C-6, C-11), 147.6 (C-4, C-15) ppm. IR
(KBr): ν˜ ϭ 3456 cmϪ1 (s), 3450 (s), 3442 (s), 3406 (s), 3399 (s),
3375 (s), 3350 (s), 3336 (s), 3218 (m), 2926 (vs), 2852 (m), 1715 (w),
1
acetate (10:1) provided analytically pure material. m.p. 126 °C. H
3
NMR (400.1 MHz, CDCl3): δ ϭ 1.24 (d, J19-H or 20-H,18-H
ϭ
3J22-H or 23-H,21-H ϭ J26-H or 27-H,25-H ϭ J29-H or 30-H,28-H ϭ 6.8 Hz, 1654 (s), 1624 (vs), 1597 (s), 1566 (s), 1542 (m), 1499 (s), 1456 (m),
3
3
2304 Eur. J. Org. Chem. 2002, 2298Ϫ2307

4,15-Diamino[2.2]paracyclophane, a Reusable Template for Topochemical Reaction Control
FULL PAPER
1427 (vs), 1287 (m), 879 (m), 773 (m), 755 (m). UV/Vis (MeCN): 27-H), 7.19Ϫ7.22 (m, 4 H, 22-H, 24-H, 31-H, 33-H), 7.28Ϫ7.33
λmax (lg ε) ϭ 248 nm (3.88), 312 (3.28). MS (EI, 70 eV): m/z (%) ϭ (m, 2 H, 23-H, 32-H), 7.52Ϫ7.54 (m, 4 H, 21-H, 25-H, 30-H, 34-
3
3
238 (45) [Mϩ], 120 (10), 119 (100), 92 (6), 91 (8). C16H18N2 H), 7.81 (d, J19-H,18-H ϭ J28-H,27-H ϭ 15.5 Hz, 2 H, 19-H, 28-H)
(238.32): calcd. C 80.63, H 7.61, N 11.75; found C 80.13, H 7.52,
N 11.63.
ppm. 13C NMR (100.6 MHz, [D6]acetone): δ ϭ 32.1 (C-1, C-2),
34.7 (C-9, C-10), 120.7 (C-18, C-27), 127.0 (C-5, C-16), 128.1 (qC),
128.7 (C-7, C-12), 129.8, 130.8 (C-21, C-22, C-24, C-25, C-30, C-
31, C-33, C-34), 133.2 (C-23, C-32), 134.4 (C-8, C-13), 134.7 (qC),
135.5 (qC), 139.9 (qC), 142.4 (C-19, C-28), 164.9 (C-17, C-26) ppm.
IR (KBr): ν˜ ϭ 3433 cmϪ1 (m), 3423 (m), 3239 (s), 3059 (m), 3028
(m), 2972 (m), 2956 (m), 2929 (s), 2853 (m), 1670 (vs), 1658 (vs),
1628 (vs), 1612 (vs), 1600 (s), 1577 (m), 1564 (s), 1535 (vs), 1490
(s), 1448 (s), 1439 (m), 1417 (s), 1340 (vs), 1205 (s), 1197 (s), 1165
(m), 989 (m), 981 (m), 969 (m), 889 (m), 862 (m), 792 (m), 758 (s).
UV/Vis (MeCN): λmax (lg ε) ϭ 220 nm (4.63, sh), 276 (4.66), 300
(4.51, sh). UV/Vis (MeOH): λmax (lg ε) ϭ 208 nm (4.67), 220 (4.62),
280 (4.68), 290 (4.65, sh). MS (EI, 70 eV): m/z (%) ϭ 498 (63) [Mϩ],
469 (8), 408 (9), 407 (32), 368 (20), 367 (24), 251 (8), 249 (19), 248
(35), 220 (18), 158 (16), 145 (13), 130 (11), 131 (100), 120 (14), 119
(17), 103 (48), 91 (22), 77 (15). C34H30N2O2): (498.60): calcd. C
81.90, H 6.06, N 5.62; found C 81.95, H 6.08, N 5.49.
1,3-Diaza-[3.2.2](1,2,5)(1,2,5)cyclophan-2-one (20): A suspension of
15 (0.500 g, 1.7 mmol) in 100 mL of THF was added over 15 min,
at reflux temperature and under nitrogen, to a suspension of li-
thium aluminium hydride (0.270 g, 7.1 mmol) in 50 mL of anhyd-
rous THF. The reaction mixture was heated for an additional
80 min and then allowed to cool to room temp., and the excess
hydride reagent was destroyed by addition of water (20 mL). The
precipitated inorganic salts were brought into solution by addition
of 10 mL of 2  sulfuric acid, 200 mL of dichloromethane was
added, and after phase separation, the inorganic phase was washed
thoroughly with dichloromethane. The combined organic phases
were washed with bicarbonate solution, water, and brine, and dried
with magnesium sulfate. After solvent removal in a rotary evapor-
ator, the remaining solid was dried under high vacuum to provide
0.32 g (71%) of 20, amorphous, off-white solid that did not melt
1
Cyclobutane Derivative 28: In a photoreactor, acetone (200 mL) was
purged of oxygen by a rapid stream of nitrogen. After 15 min, 26
(0.45 g, 0.9 mmol) was added under nitrogen. The solution was ir-
radiated for 7 h, through a Pyrex filter, and after completion of the
photoaddition the solvent was removed in vacuo. The residue was
purified by column chromatography on silica gel (dichloromethane/
diethyl ether ϭ 10:1) to provide 0.34 g (76%) of a colorless,
amorphous solid. Analytically pure 28 was obtained by recrystal-
lization from methanol/methyl isobutyl ketone ϭ 9:1 (colorless
plates). m.p. 230 °C (decomp.). 1H NMR (400.1 MHz, [D6]ace-
tone): δ ϭ 2.95Ϫ3.07 (m, 6 H, 1a-H, 2a-H, 9-H, 10-H), 3.68Ϫ3.72
below 200 °C. H NMR (200.1 MHz, [D6]DMSO): δ ϭ 2.74Ϫ2.88
(m, 2 H, 1a-H, 2a-H), 2.88Ϫ3.12 (m, 4 H, 9-H, 10-H), 3.33Ϫ3.45
3
(m, 2 H, 1s-H, 2s-H), 6.31 (dd, J7-H,8-H
ϭ
3J12-H,13-H ϭ 7.9,
4J7-H,5-H
3J8-H,7-H
ϭ
4J12-H,16-H ϭ 1.7 Hz, 2 H, 7-H, 12-H), 6.43 (d,
3J13-H,12-H ϭ 7.9 Hz, 2 H, 8-H, 13-H), 6.50 (d,
ϭ
4
4J5-H,7-H ϭ J16-H,12-H ϭ 1.7 Hz, 2 H, 5-H, 16-H), 7.81 (br. s, 2 H,
NH) ppm. 13C NMR (50.3 MHz, [D6]DMSO): δ ϭ 31.4 (C-1, C-
2), 35.0 (C-9, C-10), 131.6, 133.8, 137.9 (C-5, C-16, C-7, C-12, C-
8, C-13), 138.4 (qC), 138.5 (qC), 141.1 (qC), 154.2 (C-17) ppm. IR
(KBr): ν˜ ϭ 3427 cmϪ1 (m), 3422 (m), 3326 (m), 3281 (m), 3271
(m), 3223 (m), 3055 (m), 2935 (m), 2361 (m), 2343 (m), 2333 (m),
1654 (vs, CϭO), 1598 (m), 1560 (m), 1486 (m), 1471 (m), 1452 (m),
1439 (m), 1257 (m), 1231 (m), 1159 (m), 1095 (m), 790 (m), 755
(m). MS (EI, 70 eV): m/z (%) ϭ 264 (100) [Mϩ], 263 (20), 249 (31),
247 (13), 234 (9), 145 (9), 119 (37), 92 (5), 91 (11). C17H16N2O
(264.34): calcd. C 77.25, H 6.10, N 10.60; found C 77.27, H 6.11,
N 10.82.
(m, 2 H, 1s-H, 2s-H), 4.36Ϫ4.38 (m, 2 H, 18-H, 27-H), 4.66Ϫ4.67
3
(m, 2 H, 19-H, 28-H), 6.34 (dd, J7-H,8-H
ϭ
3J12-H,13-H ϭ 7.8,
4J7-H,5-H
3J8-H,7-H
ϭ
3J12-H,16-H ϭ 1.8 Hz, 2 H, 7-H, 12-H), 6.48 (d,
ϭ
3J13-H,12-H ϭ 7.8 Hz, 2 H, 8-H, 13-H), 6.98Ϫ7.12 (m,
10 H, 21-H, 22-H, 23-H, 24-H, 25-H, 30-H, 31-H, 32-H, 33-H, 34-
4
H), 7.86 (d, J5-H,7-H ϭ 3J16-H,12-H ϭ 1.8 Hz, 2 H, 5-H, 16-H), 8.18
(br. s, 2 H, NH). 1H NMR (400.1 MHz, [D4]methanol): δ ϭ
2.95Ϫ3.00 (m, 2 H, 1a-H, 2a-H), 3.01Ϫ3.06 (m, 4 H, 9-H, 10-H),
3.59Ϫ3.63 (m, 2 H, 1s-H, 2s-H), 4.32Ϫ4.33 (m, 2 H, 18-H, 27-H),
Bis(amide) 26: A solution of trans-cinnamoyl chloride (0.427 g,
2.6 mmol) in 5 mL of dioxane was added under nitrogen to a sus-
pension of 19 (0.310 g, 1.3 mmol) in 30 mL of anhydrous dioxane.
4.62Ϫ4.63 (m, 2 H, 19-H, 28-H), 6.37 (dd, 3J7-H,8-H ϭ 3J12-H,13-H ϭ
4
The mixture was stirred for 24 h at room temp, the solvent was 7.8, J7-H,5-H
ϭ
3J12-H,16-H ϭ 1.8 Hz, 2 H, 7-H, 12-H), 6.50 (d,
removed in vacuo, and the residue was dissolved in 50 mL of
dichloromethane. The resulting green suspension was filtered
through a glass frit, and the precipitate was washed with 50 mL
of dichloromethane and then dried under high vacuum to provide
0.104 g of a grayish solid. The solvent was removed from the filtrate
in vacuo, and the residue was taken up in hot ethanol (5 mL). After
the solution had cooled to room temp., pentane was added, and
the precipitate thus formed was removed by filtration and dried,
yielding an additional 0.262 g of 26. Finally, when the solvent from
the mother liquor of this last purification step was removed and
the resulting residue purified by chromatography on silica gel
3J8-H,7-H 3J13-H,12-H ϭ 7.8 Hz, 2 H, 8-H, 13-H), 7.00Ϫ7.13 (m,
ϭ
10 H, 21-H, 22-H, 23-H, 24-H, 25-H, 30-H, 31-H, 32-H, 33-H, 34-
H), 7.72 (d, 4J5-H,7-H ϭ 3J16-H,12-H ϭ 1.8 Hz, 2 H, 5-H, 16-H) ppm.
13C NMR (100.6 MHz, [D6]acetone): δ ϭ 30.4 (C-1, C-2), 36.0 (C-
9, C-10), 42.6 (C-18, C-27), 47.9 (C-19, C-28), 123.3 (C-5, C-16),
126.4 (qC), 126.5 (C-23, C-32), 128.6, 128.9 (C-21, C-22, C-24, C-
25, C-30, C-31, C-33, C-34), 129.0 (C-7, C-12), 135.7 (C-8, C-13),
139.6 (qC), 141.5 (qC), 141.9 (qC), 170.3 (C-17, C-26) ppm. 13C
NMR (100.6 MHz, [D4]methanol): δ ϭ 30.8 (C-1, C-2), 36.3 (C-9,
C-10), 43.2 (C-18, C-27), 49.3 (C-19, C-28), 124.0 (C-5, C-16),
127.0 (C-23, C-32), 127.6 (qC), 128.9, 129.3 (C-21, C-22, C-24, C-
(dichloromethane/diethyl ether ϭ 10:1), an additional 0.150 g of 25, C-30, C-31, C-33, C-34), 129.8 (C-7, C-12), 136.0 (C-8, C-13),
product resulted, providing a total yield of 0.516 g (80%) of 26. An
analytically pure sample was obtained by recrystallization (color-
139.5 (qC), 141.4 (qC), 143.3 (qC), 172.1 (C-17, C-26) ppm. IR
(KBr): ν˜ ϭ 3400 cmϪ1 (s), 3348 (s), 3085 (m), 3058 (m), 3027 (m),
less plates) from acetone. m.p. 142 °C (decomp.). 1H NMR 2853 (m), 1693 (s), 1648 (s), 1602 (m), 1573 (vs), 1530 (vs), 1496
(400.1 MHz, [D6]acetone): δ ϭ 2.77Ϫ2.88 (m, 2 H, 1a-H, 2a-H), (s), 1480 (m), 1473 (m), 1455 (s), 1420 (vs), 1385 (m), 1363 (m),
3.00Ϫ3.11 (m, 4 H, 9-H, 10-H), 3.32Ϫ3.43 (m, 2 H, 1s-H, 2s-H),
1334 (m), 1321 (m), 1303 (m), 1290 (s), 1262 (m), 1238 (m), 1199
(m), 1190 (m), 1155 (m), 1114 (m), 1103 (m), 747 (m). UV/Vis
3
4
6.50 (dd, J7-H,8-H
ϭ ϭ ϭ
3J12-H,13-H ϭ 7.9, J7-H,5-H 3J12-H,16-H
3
3
1.8 Hz, 2 H, 7-H, 12-H), 6.57 (d, J8-H,7-H ϭ J13-H,12-H ϭ 7.9 Hz, (MeCN): λmax (lg ε) ϭ 250 nm (4.33), 258 (4.30, sh). MS (EI,
2 H, 8-H, 13-H), 6.74 (d, J5-H,7-H ϭ J16-H,12-H ϭ 1.8 Hz, 2 H, 5- 70 eV): m/z (%) ϭ 498 (55) [Mϩ], 482 (22), 480 (58), 479 (11), 349
4
3
3
3
H, 16-H), 6.85 (d, J18-H,19-H ϭ J27-H,28-H ϭ 15.5 Hz, 2 H, 18-H, (12), 350 (20), 318 (15), 300 (23), 232 (13), 205 (14), 131 (34), 121
Eur. J. Org. Chem. 2002, 2298Ϫ2307 2305

H. Zitt, I. Dix, H. Hopf, P. G. Jones
(19), 119 (100), 103 (37), 91 (21), 77 (22). C34H30N2O2 (498.64): fractometer (15: Stoe STADI-4; 20: Siemens P4, both with Siemens
FULL PAPER
calcd. C 81.90, H 6.06, N 5.62; found C 81.72, H 6.03, N 5.57.
LT-2 low-temperature attachments). Measurements were per-
formed with monochromated Mo-Kα radiation. Cell constants were
refined from Ϯω-angles (Stoe) or setting angles (Siemens) of ca.
60 reflections to 2θ 25°. Structure solution and refinement: The
structures were solved with direct methods and refined aniso-
tropically against F2 (program SHELXL-97, G.M. Sheldrick, Uni-
versity of Göttingen). The NH hydrogens of 20 were refined freely;
other H atoms were included with a riding model or with rigid
methyl groups. For compound 20, the absolute structure could not
be determined and Friedel opposite reflections were therefore
merged. To improve the stability of refinement, a system of re-
straints to displacement factor components was employed for
both structures.
3,4-Diphenyl-1,2-cyclobutanedicarboxylic Acid (β-Truxinic Acid,
27): The photoproduct 28 (0.12 g, 0.24 mmol) was suspended in
10 mL of concd. hydrochloric acid, and the mixture was heated
under reflux for 24 h. The mixture was poured into 10 mL of water,
and the precipitate was removed by filtration. After drying in a
desiccator over phosphorus pentoxide, 0.070 g (98%) of a colorless
solid was obtained, and identified as 27 by its spectroscopic data
(see below). The filtrate was made basic by addition of potassium
hydroxide, and the solid formed was removed by filtration. After
drying in a desiccator over phosphorus pentoxide, 0.55 g (97%) of
19 was isolated, identified by comparison with an authentic sample
(see above).
CCDC-176589 (15) and 176590 (20) contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or
from the Cambridge Crystallographic Data Centre, 12, Union
Road, Cambridge CB2 1EZ, UK; fax: (internat.) ϩ44Ϫ1223/336-
033; E-mail: deposit@ccdc.cam.ac.uk].
1
β-Truxinic Acid (27): m.p. 209Ϫ212 °C (ref.: 210 °C[25]). H NMR
(400.1 MHz, [D6]DMSO): δ ϭ 3.79Ϫ3.80 (m, 2 H, 2-H, 11-H),
4.19Ϫ4.21 (m, 2 H, 3-H, 12-H), 6.95Ϫ7.10 (m, 10 H, 5-H, 6-H, 7-
H, 8-H, 9-H, 14-H, 15-H, 16-H, 17-H, 18-H), 12.40 (br. s, 2 H,
COOH) ppm. 13C NMR (100.6 MHz, [D6]DMSO): δ ϭ 42.6 (C-2,
C-11), 44.5 (C-3, C-12), 125.9 (C-7, C-16), 127.7 (C-5, C-9, C-14,
C-18); 127.9 (C-6, C-8, C-15, C-17), 139.3 (C-4, C-13), 174.0 (C-1,
C-10) ppm. IR (KBr): ν˜ ϭ 3433 cmϪ1 (m), 3080 (m), 3065 (m),
3047 (m), 3031 (m), 2937 (m), 1704 (vs), 1415 (m), 1281 (m), 1256
(m), 1234 (m), 771 (w). MS (EI, 70 eV): m/z (%) ϭ 278 (9) [Mϩ
H2O], 264 (21), 250 (65), 205 (34), 179 (21), 178 (15), 162 (96), 148
(100), 147 (80), 131 (64), 120 (20), 103 (24), 91 (25), 77 (12).
Ϫ
[1]
H. Hopf, H. Greiving, P. G. Jones, P. Bubenitschek, Angew.
Chem. 1995, 107, 742Ϫ744; Angew. Chem. Int. Ed. Engl. 1995,
34, 685Ϫ687.
[2]
M. D. Cohen, G. M. J. Schmidt, J. Chem. Soc. 1964,
1996Ϫ2000.
G. M. J. Schmidt, J. Chem. Soc. 1964, 2014Ϫ2021; cf.: J. Breg-
X-ray Structure Determinations: Details are presented in Table 1.
Data collection and reduction: Crystals were mounted in inert oil
on glass fibers and transferred to the cold gas stream of the dif-
[3]
man, K. Osaki, G. M. J. Schmidt, F. I. Sonntag, J. Chem. Soc.
1964, 2021Ϫ2030.
For a collection of papers by G. M. J. Schmidt and his collabor-
[4]
ators see: Solid State Photochemistry (Ed.: D. Ginsburg), Ver-
lag Chemie, Weinheim, 1976.
Table 1. Details of X-ray structure analyses of 15 and 20
[5]
B. S. Green, L. Heller, J. Org. Chem. 1974, 39, 196Ϫ201.
[6]
Compound
15
20
R. C. Cookson, D. A. Cox, J. Hudec, J. Chem. Soc. 1961,
4499Ϫ4506; cf.: D. Rabinovich, G. M. J. Schmidt, J. Chem.
Soc. (B) 1967, 144Ϫ149.
Empirical formula
Formula mass
Habit
Crystal size/mm
Crystal system
Space group
C18H14N2O2
290.31
colorless rhomb
0.3ϫ0.23ϫ0.15
monoclinic
P21/n
C17H16N2O
264.32
pale brown prism
0.48ϫ0.3ϫ0.14
orthorhombic
P212121
[7]
D. Rabinovich, G. M. J. Schmidt, J. Chem. Soc. (B) 1970,
6Ϫ10 and refs. cited therein.
P. M. Keehn, S. M. Rosenfeld (Eds.), Cyclophanes I, II, Aca-
demic Press, New York, N. Y., 1983.
F. Vögtle, Cyclophane Chemistry, J. Wiley & Sons, Chichester,
[8]
[9]
Cell constants:
1993.
[10]
˚
a [A]
7.369(2)
11.331(3)
16.570(4)
94.36(3)
1379.5
4
1.398
0.09
608
7.3116(8)
11.6991(16)
14.9534(16)
90
1279.1
4
1.373
0.09
560
H. Hopf, Classics in Hydrocarbon Chemistry, Wiley-VCH,
˚
b [A]
Weinheim, 2000, Chapter 12.3, pp. 337Ϫ368.
H. Greiving, H. Hopf, P. G. Jones, J.-P. Desvergne, H. Bouas-
Laurent, J. Chem. Soc., Chem. Commun. 1994, 1075Ϫ1076.
H. Hopf, H. Greiving, P. G. Jones, P. Bubenitschek, H. Bouas-
Laurent, J.-P. Desvergne, Liebigs Ann. 1995, 1949Ϫ1956; cf.:
H. Hopf, U. Meyer, N. Lahrahar, P. Marsau, H. Greiving, J.-
P. Desvergne, H. Bouas-Laurent, Liebigs Ann. Chem. 1997,
381Ϫ384.
Chr. Beck, Ph. D. Dissertation, Braunschweig, 1999.
B. S. Green, Nature 1994, 371, 320; cf.: S. A. Fleming, C. L.
[11]
˚
c [A]
β [°]
3
[12]
˚
V [A ]
Z
Dx [Mg·mϪ3
]
µ [mmϪ1
F(000)
T [°C]
2θmax
]
[13]
Ϫ130
50
Ϫ100
55
[14]
No. of reflections:
measured
independent
Rint
Bradford, J. J. Gao, in: Molecular and Supramolecular Photo-
chemistry, Vol. 1: Organic Photochemistry (Eds.: V. Ramamur-
thy, K. S. Schanze), Marcel Dekker, Inc., New York, N. Y.,
1997, pp. 210Ϫ212 and refs. quoted.
2675
2420
0.046
199
3265
1705
0.030
189
[15]
Parameters
Restraints
wR (F2, all refl.)
R [F, Ͼ4σ(F)]
S
For the construction and use of chemical work-benches, see: J.
200
194
Mulzer, K. Schein, J.-W. Bats, J. Buschmannn, P. Luger, Angew.
Chem. 1998, 110, 1625Ϫ1628; Angew. Chem. Int. Ed. 1998, 37,
15666Ϫ1569; cf.: J. Mulzer, I. Böhm, J.-W. Bats, Tetrahedron
Lett. 1998, 39, 9643Ϫ9646.
I. Dix, Ph. D. Dissertation, Braunschweig, 2001, cf.: A. J. Boyd-
ston, M. Haley, H. Hopf, I. Dix, L. Bondarenko, T. Weakly,
0.171
0.069
1.02
0.23
0.078
0.037
0.89
0.19
Ϫ3
[16]
˚
Max. ∆ρ [e·A
]
2306
Eur. J. Org. Chem. 2002, 2298Ϫ2307

4,15-Diamino[2.2]paracyclophane, a Reusable Template for Topochemical Reaction Control
FULL PAPER
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J. Hillmer, Ph. D. Dissertation, Braunschweig, 1991.
H. J. Reich, D. J. Cram, J. Am. Chem. Soc. 1968, 91,
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Schmidt, D. J. Cram, J. Am. Chem. Soc. 1974, 97, 3782Ϫ3789.
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A. F. Mourad, H. Hopf, Chem. Ber. 1980, 113, 2358Ϫ2371.
R. Richter, H. Ulrich, in: The Chemistry of Functional Groups
(Ed.: S. Patai), The Chemistry of Cyanates and Their Thio De-
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17, pp. 619Ϫ818.
H. Hopf, W. Grahn, D. G. Barrett, A. Gerdes, J. Hillmer, J.
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[23]
[17]
[18]
[24]
[25]
[19]
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Int. Ed. Engl. 1992, 31, 592Ϫ595.
[20]
[21]
M. Psiorz, R. Schmid, Chem. Ber. 1987, 120, 1825Ϫ1828.
E. A. Truesdale, D. J. Cram, J. Org. Chem. 1979, 45,
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Received February 1, 2002
[O02059]
Eur. J. Org. Chem. 2002, 2298Ϫ2307
2307