Scholarly article on 1-(cyanomethyl)-4-[2-(methoxycarbonyl)ethyl]benzene 1133313-96-8 from European Journal of Organic Chemistry p. 223

FULL PAPER

DOI: 10.1002/ejoc.200800494

Paracyclophanes: Extending the Bridges. Synthesis^[‡]

Zissis Pechlivanidis,^[a]Henning Hopf,*^[a]and Ludger Ernst^[b]

Keywords: Cyclophanes / Thiacyclophanes / [m.n]Paracyclophanes / Sulfone pyrolysis / Ring contraction

Preparatively satisfactory routes to [3.2]paracyclophane (10),

[4.2]paracyclophane (14), [4.3]paracyclophane (19) as well as

several derivatives of these compounds – among others the

bromides 25, the ester 31, the diesters 40–43 – are described

using well-established methods of cyclophane chemistry

(ring-closure reactions leading to thiacyclophanes, ring con-

traction by sulfone pyrolysis). The parent systems and their

derivatives are now available in gram quantities allowing a

study of their chemical properties.

Germany, 2009)

fulfilled for a small number of the hydrocarbons 1 collected

in Scheme 1, a summary of the [m.n]paracyclophanes with

up to m = n = 4 known today.^[5]

Introduction

Since the serendipitous discovery of [2.2]paracyclophane

(1, m = n = 2) by Brown and Farthing 60 years ago^[2]and

the deliberate development of this area of aromatic chemis-

try by Cram and his students^[3]during the 1950ies and 60ies

this class of layered compounds has fascinated numerous

research groups.^[4]Many important discoveries were made

along a route to increasingly complex structures and more

and more practical applications of a group of compounds,

which originally were available in minute amounts only,

have been reported. Still, looking back from the height

reached by this chemical sexagenarian, knowledge gaps are

also clearly visible. These have not only to do with still un-

known representatives in a series of homologs and analogs

(see below) but – in particular – with little knowledge about

the chemical properties of individual members of the [m.n]-

cyclophanes series. In the often fierce race to prepare a par-

ticular cyclophane, the emphasis often was more on being

first than to study the chemical properties of the presum-

ably “interesting” or even “esthetically pleasing” target

molecules. But besides having novel and surprising struc-

tural properties – which often is the case for [m.n]paracyclo-

phanes – it is the chemical properties of compounds that

make them “interesting”. To learn about chemical behavior

the prerequisite is substrate availability, i.e. preparatively

satisfactory routes to sufficient amounts of starting mate-

rial, meaning at least gram amounts. This condition is only

Scheme 1. The [m.n]paracyclophane family with m and n up to 4

(with a selection of leading references).

Beginning with row 1 of the matrix, the subgroup of the

[0.n]phanes, only one derivative, a dicyano[0.0]paracyclo-

phane has been reported in the literature.^[6,7]In row 2 [1.1]-

paracyclophane (1, m = n = 1) has been prepared, a highly

reactive intermediate that nevertheless could be investigated

by UV/Vis and NMR spectra at –20 °C.^[8]The higher

homologs given in the Table are again unknown.^[9]From m

= 2 on all combinations are known, and many of them have

been thoroughly studied from the structural, spectroscopic

and chemical viewpoint, especially [2.2]-^[4]and [3.3]paracy-

clophane.^[4]For [4.4]paracyclophane^[12]considerably less is

known, and for those representatives with unequal molecu-

lar bridges – [3.2]-,^[10][4.2]-,^[10]and [4.3]paracyclophane,^[11]

respectively – this is even more pronounced. We hence de-

cided to develop efficient routes to these three hydrocarbons

as well as several of their derivatives. The corresponding

[‡] Cyclophanes, LXII. Part LXI: Ref.^[1]

[a] Institut für Organische Chemie, Technische Universität

Braunschweig,

Hagenring 30, 38106 Braunschweig, Germany

Fax: +49-531-391-5388

E-mail: H.Hopf@tu-bs.de

[b] NMR-Laboratorium der Chemischen Institute der Technischen

Universität Braunschweig,

Hagenring 30, 38106 Braunschweig, Germany

Fax: +49-531-391-8192

E-mail: L.Ernst@tu-bs.de

Eur. J. Org. Chem. 2009, 223–237

223

Z. Pechlivanidis, H. Hopf, L. Ernst

FULL PAPER

routes to these targets are described in this paper. In the

following contribution we will discuss the chemical behav-

ior of these compounds, addressing particularly the ques-

tion of chemo- and regioselectivity in electrophilic substitu-

tion of these phanes.

Synthesis of [3.2]- (10), [4.2]- (14) and [4.3]Paracyclophane

(19)

For the preparation of the hydrocarbons collected in

Scheme 1 essentially three approaches have been developed:

cyclizations, ring enlargements and ring contractions. Be-

sides Cram’s classical Wurtz cyclizations of appropriate

α,ω-dibromides^[10,11]more recently Grützmacher has devel-

oped a convenient and efficient route based on the

McMurry cyclization of 1,3-bis(acylphenyl)propanes (pro-

viding for instance the corresponding [3.2]paracycloph-

enes).^[13]To synthesize the appropriate parent systems the

respective dialdehydes have to be ring-closed – and in these

cases the yield is low. Ring enlargements, usually starting

from a [2.2]paracyclophane derivative, have been used

widely.^[14–17]However, besides the time-consuming prepara-

tion of the respective phane precursors, the yields of these

processes are often unsatisfactory. Among the ring contrac-

tion reactions the sulfone pyrolysis appeared most promis-

ing. Not only has this route been applied to the preparation

of [3.3]- and [4.4]paracyclophane already,^[12,18–21]but its

preparative variability (preparation of functionalized deriv-

atives) and often good yield make it particularly attract-

ive.^[22]We hence decided to prepare [3.2]- (10), [4.2]- (14)

and [4.3]paracyclophane (19) by this route.

Scheme 2. A preparatively high-yielding route to [3.2]paracyclo-

pane (10).

mination gave the dibromide 13. Both 12^[25]and 13^[26]have

been described in the chemical literature before, but the

routes presented in Scheme 3 gave far superior yields.

The preparation of 10 is summarized in Scheme 2.

Starting from commercially available methyl 4-methyl-

benzoate (2) this was first converted by NBS bromination,

Kolbe nitrile reaction and saponification to the diester 3,

which after LAH-reduction and treatment of the resulting

diol with HBr in a sealed ampoule yielded the dibromide 4.

From here on the cyclization to the dithiaphane 8 can either

be performed by coupling the dithiol 5, prepared as shown

in Scheme 2, with 1,4-bis(chloromethyl)benzene (6) or by

reacting 4 directly with the symmetrical dithiol 7, the yield

in the last step of the first route being pronouncedly higher

than in the second cyclization. Oxidation of 8 with hydro-

gen peroxide in acetic acid led to the bis-sulfone 9 which on

flash vacuum pyrolysis according to the method of Staab

and Haenel^[23]and Grütze and Vögtle^[24]furnished the hy-

drocarbon 10 in good overall yield (47% from 5). All inter-

mediates and the target cyclophane 10 were characterized

by their analytical and spectroscopic data (see structure dis-

cussion below and Exp. Section), and all compounds are

available in gram amounts.

Scheme 3. A preparatively high-yielding route to [4.2]paracyclo-

pane (14).

Coupling of 13 with 7 under basic conditions in ethanol

To prepare the next higher homolog, [4.2]paracyclophane yielded the disulfide effortlessly which was oxidized to give

(14, Scheme 3), methyl 4-formylbenzoate (11) was first the corresponding bis-sulfone with hydrogen peroxide in

chain-elongated by a Knoevenagel condensation with malo- nearly quantitative yield. Sulfone pyrolysis proceeded in

nic acid to the corresponding cinnamic acid. This was ester- very good yield again (68%) and gave [4.2]paracyclophane

ified via the corresponding acid chloride to 12, which after (14), the structure of which was secured by comparing its

catalytic hydrogenation over Pd/C, LAH reduction and bro- spectroscopic data with those of the authentic material.^[12]

224

www.eurjoc.org

Eur. J. Org. Chem. 2009, 223–237

Paracyclophanes: Extending the Bridges

The last member of this series of unsubstituted hydro- and the terminating flash vacuum pyrolysis provided hydro-

carbons was [4.3]paracyclophane (19), synthesized from its carbon 19 also in a very satisfying 54% yield. Its spectro-

constituting aromatic halves as described in Scheme 4.

scopic data were identical with those of a sample prepared

by another route.^[11,14]

Preparation of Functionalized [3.2]-, [4.2]-, [3.3]-, [4.3]-, and

[4.4]Paracyclophanes

For later regioselectivity studies we also prepared a

number of functionalized [m.n]paracyclophanes. The most

important of these are reported in this section; their prepa-

ration also demonstrates how different functional groups

survive the rather harsh conditions during sulfone pyrolysis.

For the preparation of 5-bromo[3.2]paracyclophane

(25a) and 6-bromo[4.2]paracyclophane (25b) the pathways

sketched in Scheme 5 were followed.

Beginning with 2 this was first brominated to building

block 21 in medium yield. Following the protocols already

discussed in the preceding Schemes 21 was converted into

the dibromide 22a. Likewise, using the saturated diester de-

rived from 12 (which had been prepared during the prepa-

ration of dibromide 13; see Scheme 3 and Exp. Section),

this was converted into the homologous tribromide 22b by

electrophilic bromination, reduction (LAH), and HBr treat-

ment (for details see Exp. Section). When either 22a or b

were coupled with dithiol 7 under basic conditions the two

bromothiaphanes 23a/b resulted in good yield. Hydrogen

peroxide oxidation gave the bis-sulfones 24a/b that split off

Scheme 4. Several routes to [4.3]paracyclophane (19).

The synthesis started with methyl 4-methylcinnamate two equivalents of sulfur dioxide on high-temperature pyr-

(15) and followed more or less the same lines as for the olysis, giving the desired bromo derivatives 25a/b in satisfac-

preparation of 10 and 14 illustrated in Schemes 2 and 3, tory yield again. The given structure of the two compounds

respectively. All intermediate compounds were charac- is derived largely from their NMR spectra which are dis-

terized by the usual spectroscopic methods (see Exp. Sec- cussed below.

tion), and in the end the phane closure was achieved by

Because of the symmetry of one of the coupling partners,

either reacting the dibromide 17 with the dithiol 7 or by the dithiol 7, there only results one cyclophane product in

coupling the dithiol 18 with the dichloride 6. As above the the case of 25a and b. This is not the case for methyl [3.3]-

second alternative gave the dithiaphane – here 20 – in paracyclophane-5-carboxylate (31) whose precursors were

higher yield. Oxidation of 20 with hydrogen peroxide in gla- prepared by coupling of methyl 2,5-bis(bromomethyl)ben-

cial acetic acid gave the bis-sulfone in excellent yield (94%), zoate (26)^[27]with the unsymmetrical dithiol 5. Now two

Scheme 5. Synthesis of 5-bromo[3.2]paracyclophane (25a) and 6-bromo[4.2]paracyclophane (25b).

Eur. J. Org. Chem. 2009, 223–237

www.eurjoc.org

225

Z. Pechlivanidis, H. Hopf, L. Ernst

FULL PAPER

Scheme 6. Several routes to methyl [3.2]paracyclophane-5-carboxylate (31).

coupling products are possible, 27 and 29, and they were

Although these regioisomers could not be separated by

indeed obtained (total yield 54%) in 1:1-ratio (¹H NMR chromatography, fractional crystallization allowed an en-

analysis, Scheme 6).

richment of 29 to 96%. Again the structure assignment of

Scheme 7. The preparation of a selection of [m.n]paracyclopane diesters 40–43.

226

www.eurjoc.org

Eur. J. Org. Chem. 2009, 223–237

Paracyclophanes: Extending the Bridges

1

this compound rests largely on its NMR spectra (see be- Table 1. H and ¹³C NMR chemical shifts of some [m.n]phane hy-

drocarbons.^[a]

low), but in this case an X-ray structural determination of

the [3.2]cyclophane derivative 31^[12]resulting from it by sul-

fone pyrolysis via 32 made the structure proof unambigu-

ous. Furthermore, since 31 could also be connected to 25a

the assignments given for the phane derivatives in Scheme 5

rest on an even more solid basis. The relation between the

bromide 25a and the ester 31 was established as shown in

Scheme 6 by converting the former first into the aldehyde

28, oxidizing it to the acid 30 and esterifying it to 31, iden-

tical in every respect with the sample obtained from 29.

The sulfone pyrolysis also turned out to be the method of

choice for the preparation of several [m.n]paracyclophane

diesters which were needed for the study of transannular

effects (see subsequent publication). As shown in Scheme 7

all these transformations started from dimethyl 2,5-bis(bro-

momethyl)terephthalate (33)^[28,29](Scheme 7).

Paracyclophane

[2.2]

[3.2]

(10)

[4.2]

(14)

[3.3]

[4.3]

(19)

[4.4]

¹H Chemical

shifts

α-H

β-H

o-H

αЈ-H

βЈ-H

oЈ-H

3.07

–

6.48

3.07

–

2.69

2.07

6.56

2.96

–

2.26

1.42

6.51

3.00

–

2.71

2.05

6.67

2.71

2.05

6.67

2.26

1.58

6.52

2.72

2.16

6.67

2.30

1.56

6.67

2.30

1.56

6.67

Coupling with the four different dithiols 5, 34,^[30]18, and

35^[21,26]in the presence of potassium carbonate the four di-

thiaphanes 36–39 were obtained, all in acceptable yield.

Oxidation to the corresponding bis-sulfones posed no prob-

lem and flash vacuum pyrolysis yielded the desired diesters

40–43. The spectroscopic data of the intermediates and the

target molecules are collected either in the experimental

and/or in the following section, in which ¹H and ¹³C NMR

spectroscopic data of key cyclophanes are discussed. The

structure determination of 43 (as well as its parent hydro-

carbon [4.4]paracyclophane) by single-crystal X-ray struc-

tural analysis has already been reported by us earlier.^[12]

6.48

6.37

6.55

¹³C Chemical

shifts

C-α

C-β

C-i

C-o

C-αЈ

C-βЈ

C-iЈ

C-oЈ

35.7

–

35.5

32.9

35.4

29.0

36.0

29.7

35.7

29.5

35.2

28.9

139.6 139.6 139.7 138.4 138.9 139.3

133.0 130.1 128.1 129.7 128.3 128.4

35.7

–

34.3

–

34.3

–

36.0

29.7

36.2

30.3

35.2

28.9

139.6 137.1 137.6 138.4 138.6 139.3

133.0 132.4 131.1 129.7 129.3 128.4

[a] Solvent CDCl₃; references TMS (¹H, δ = 0.00 ppm), CDCl₃

(¹³C, δ = 77.0 ppm).

Structure Determination of Selected [m.n]Paracyclophanes

by NMR Spectroscopy

Similar deviations from the “intuitive” assignments are

found when one tries to assign the NMR spectra of [4.3]-

Having all the important lower [m.n]paracyclophanes at paracyclophane (19) by using the data of [3.3]paracyclo-

1

hand we measured their H and ¹³C NMR spectra under phane and [4.4]paracyclophane, respectively, as starting

comparable conditions and assigned them by two-dimen- points. Here, wrong assignments would be arrived at for the

sional techniques (H,C-HSQC and -HMBC) where neces- pairs of nuclei C-i/iЈ, C-α/αЈ and o/oЈ-H. Along the same

1

sary. The H and ¹³C chemical shifts are given in Table 1. line, we have the finding that the o-Hs possess the same

For the compounds with unequal bridges the upper halves chemical shift in [3.3]paracyclophane and [4.4]paracyclo-

of the ¹H and the ¹³C shift blocks refer to the atoms of and phane (δ = 6.67 ppm) whereas in [4.3]paracyclophane (19)

adjacent to the longer bridge and the lower halves to the o-H is somewhat shielded (δ = 6.52 ppm) relative to oЈ-H (δ

corresponding atoms of the shorter bridge. The data show = 6.67 ppm). From the above it is evident that there exists

that problems arise if the spectra are assigned by simple no simple correlation between bridge length and chemical

comparison without experimental verification. For exam- shifts or even order of the chemical shifts. Probably, the

ple, if one tried to assign the spectra of [3.2]paracyclophane different conformational properties of the bridges of dif-

(10) by comparing them to those of [2.2]- and [3.3]paracy- ferent length are responsible for this behavior.

1

clophane, one would intuitively assume that the chemical

In the H NMR spectrum of 10 in CD₂Cl₂at room tem-

shifts of the three-membered bridge and the adjacent ipso perature the signal of 5-, 9-H appears broader than that of

(i) and ortho (o) atoms are similar to those of [3.3]paracy- 6-, 8-H and the ¹³C NMR signal of C-5, -9 is also broad-

clophane and that the two-membered bridge and its vicinity ened (Scheme 8). Lowering the temperature leads to deco-

are similarly correlated to [2.2]paracyclophane. Inspection alescence of the latter signal at 252Ϯ3 K and to a chemical

of the experimental findings in Table 1 shows that this is shift difference of 2.41 ppm (242.7 Hz) at 183 K with indi-

not true. C-i in [2.2]paracyclophane is deshielded (δ = vidual shifts of 128.65 and 131.06 ppm. These observations

139.6 ppm) relative to C-i in [3.3]paracyclophane (δ = are explained by slow conformational interconversion of the

138.4 ppm), yet C-iЈ (adjacent to the two-membered bridge, three-membered bridge which consists in the forward-back-

δ = 137.1 ppm) in [3.2]paracyclophane is shielded relative to ward flipping of the β-CH₂group between the two ortho

C-i (adjacent to the three-membered bridge, δ = 139.6 ppm) positions. From the above parameters the barrier to

‡

in the same compound.

this flipping process was determined as ∆G_c

=

Eur. J. Org. Chem. 2009, 223–237

www.eurjoc.org

227

Z. Pechlivanidis, H. Hopf, L. Ernst

FULL PAPER

48.2Ϯ0.8 kJ·mol^–1. The spectra at –90 °C were assigned by groups (ketones, esters, acids etc.) survive the harsh condi-

the NOE observed between the syn-ortho proton (δ = tions of the flash vacuum pyrolysis making this method a

6.63 ppm) and the equatorial α-proton (δ = 3.00 ppm) of preparatively useful one for the preparation of [m.n]paracy-

the “half boat” three-membered bridge, from inspection of clophane derivatives as well. The chemical behavior of a

the H,H-coupling patterns and from selective ¹³C{¹H} de- selection of the new derivatives is described in the ac-

coupling. Comparable bridge flipping has been described companying publication.

for [3.3]paracyclophane.^[31,32]There, the barrier was re-

ported to be 49.0Ϯ2.1 kJ·mol^–1at 240 K^[31]and

50.2 kJ·mol^–1at 258 K.^[32]This means that the barrier to Experimental Section

flipping of one bridge in [3.3]paracyclophane is not sub-

stantially affected by shortening the second bridge from

three to two members.

General Remarks: Thin-layer chromatography (TLC): Commercial

TLC sheets of type “Polygram Sil G/UV₂₅₄” by Macherey, Nagel &

Co. (Düren). Column chromatography: Kieselgel 60 (70–230 mesh)

by Merck (Darmstadt). Melting points: Büchi 530 melting point

apparatus, uncorrected values. NMR: With internal tetramethylsil-

ane in the given solvent with the following instruments: Bruker AC-

1

200. H NMR (200.1 MHz), ¹³C NMR (50.3 MHz). Bruker AM-

1

400. H NMR (400.1 MHz), ¹³C NMR (100.6 MHz). Internal ref-

erences: tetramethylsilane (δ_H

= 0.00 ppm), CDCl₃(δ_C=

77.05 ppm). Hydrogen atoms labelled with the letter A point

towards a substituent in an aromatic ring of a cyclophane, whereas

the letter B designates the opposite direction (H_Aand H_B, respec-

tively). IR: Nicolet 320 FT-IR; KBr pellets. UV/Vis: Beckman UV

5230 and HP 8452 A Diode Array. EI-MS: Finnigan MAT 8430

(70 eV). The following intermediates were either commercially

available or prepared by methods described in the literature: 1,4-

bis(chloromethyl)benzene (6, Aldrich), 1,4-bis(mercaptomethyl)-

benzene (7),^[18–20]methyl 2,5-bis(bromomethyl)benzoate (26),^[27]di-

methyl 2,5-bis(bromomethyl)terephthalate (33),^[28,29]1,4-bis(3Ј-

mercaptopropyl)benzene (35).^[21,26]

Scheme 8. The conformational equilibrium of 10. Numbers repre-

1

sent H and ¹³C (C-o only) NMR chemical shifts.

1

Structures of 25a and 25b: In the H NMR spectra of

25a and 25b the protons of the ethano bridges have rather

narrow chemical shift ranges while those of the propano

and butano bridges are spread out considerably with re-

spect to the parent hydrocarbons. This indicates the posi-

tion of the bromo substituent to be ortho to the longer

bridge in both cases. Confirmation of the structure of 25b

Caution: Many of the halide intermediates are strong lachrimators

and should be handled with appropriate care.

1

is provided by exclusion. Complete assignments of the H

Preparation of Building Blocks^[33]

and ¹³C NMR spectra of the only other possible ar-

bromo[4.2]paracyclophane, the 7-bromo isomer, were per-

formed. These spectra are distinctly different from those of

25b (see the next paper in this series). Hence 25b can only

be the 6-bromo isomer.

A) 4-(2Ј-Mercaptoethyl)-1-(mercaptomethyl)benzene (5): To methyl

4-methylbenzoate (2, 80.0 g, 0.53 mol) in carbon tetrachloride

(500 mL) was added NBS (108.0 g, 0.95 mol) and the reaction mix-

ture irradiated with a 500-W lamp until the NBS had vanished.

The reaction mixture was filtered while hot and the solvent was

removed in vacuo. To the residue was added ethanol (200 mL) and

the solution kept in the refrigerator overnight. The precipitated

bromide (91.4 g, 75%; m.p. 55–56 °C, lit.^[34]m.p. 54–55 °C) was

filtered off and used without further purification in the next step. –

A solution of sodium cyanide (39.1 g, 0.8 mol) in water (50 mL)

was added within 15 min to a refluxing solution of methyl 4-(bro-

momethyl)benzoate (91.4 g, 0.4 mol) in methanol (200 mL). The

reaction mixture was heated to reflux for 1 h and poured onto

crushed ice (500 g) after cooling to room temp. The residue formed

(m.p. 61–62 °C; lit. m.p.^[34]60–63 °C; 40.6 g, 60%) was removed by

filtration and used in the next step after drying on air. – Into a

solution of methyl 4-(cyanomethyl)benzoate (40.0 g, 0.23 mol) in

methanol (300 mL) was passed gaseous HCl and the mixture re-

fluxed for 2 h. After cooling the reaction mixture was poured into

ice water (500 mL) and the formed methyl [4-(methoxycarbonyl)-

methyl]benzoate (3) thoroughly extracted with dichloromethane.

The combined organic layers were dried, the solvent was removed

by rotary evaporation and the remaining oil distilled under vac-

uum: 38.7 g (81%) of 3; b.p. 97–9 °C/0.01 Torr, lit.^[35]b.p. 161–

165 °C/8 Torr. ¹H NMR (400 MHz, CDCl₃): δ = 3.67 (s, 2 H, CH₂),

3.68 (s, 3 H, CH₂CO₂CH₃), 3.89 (s, 3 H, ar-CO₂CH₃), 7.36,

8.00 ppm (AAЈXXЈ, 2 H each, ar-H). ¹³C NMR (101 MHz,

CDCl₃): δ = 41.0 (CH₂), 52.1 (2 OCH₃), 129.4, 129.9 (CH, C-2,

Structure of 29: Two of the three isolated methylene

groups show proton shifts (δ = 3.74–3.86, m, 4 H) that are

very similar to those of the unsubstituted compound 8 (δ =

3.78 and 3.79 ppm for 11- and 13-H) while the signal of the

third isolated CH₂group has moved strongly downfield (δ

= 4.51 ppm for the syn-proton 1-H_A) and slightly upfield (δ

= 3.04 ppm for the anti-proton 1-H_B), respectively, in 29

with respect to 8 (δ = 3.32 for 1-H). Such behavior is char-

acteristic of paracyclophane α-protons situated ortho to a

1

carbonyl-containing substituent. Hence the H NMR spec-

trum shows 29 to be the 16-CO₂Me derivative rather than

the 15-isomer, a result that is confirmed by X-ray diffrac-

tion.

Conclusions

The sulfone pyrolysis is the method of choice to synthe-

size [m.n]paracyclophanes with alkano bridges from m = 3

and n = 2 all the way to m = n = 4. The parent hydro-

carbons are obtained in gram amounts, enough for the in-

vestigation of the chemical properties of these bridged hy-

drocarbons on a broad scale. Furthermore, many functional -3, -5, -6), 129.1 (C_q, C-1), 139.2 (C_q, C-4), 166.8 (C_q, ar-C=O),

228

www.eurjoc.org

Eur. J. Org. Chem. 2009, 223–237

Paracyclophanes: Extending the Bridges

171.3 ppm (C_q, CH₂-C=O). – For the reduction of 3 a solution of

38.7 g (0.19 mol) in anhydrous diethyl ether (250 mL) was added

to a suspension of lithium aluminum hydride (11.3 g, 0.3 mol) in

anhydrous diethyl ether (1 L) so slowly to keep the diethyl ether

refluxing. After completion of the reaction the mixture was heated

at reflux for 1 h, and after cooling to room temp. water (11.3 mL),

15% aqueous sodium hydroxide solution (11.3 mL), and water

to reflux until the formation of carbon dioxide stopped. After cool-

ing to room temp. the reaction solution was poured onto ice/concd.

hydrochloric acid. The acid formed began to precipitate, and to

conclude the crystallization process the reaction mixture was kept

in the refrigerator for a few h. The acid was filtered off, washed

with water several times, dried, and recrystallized from ethanol:

34.04 g (90%) methyl (E)-4-(2-carboxyvinyl)benzoate, colorless

again (34 mL) were added for hydrolysis. The precipitate formed needles (ethanol), m.p. 246 °C. IR (KBr): ν = 2953 (w), 2929 (m),

˜

after 1 h of stirring was removed by filtration and washed several

times with diethyl ether. The combined organic fractions were dried

(MgSO₄), the solvent was removed in vacuo and the remaining oil

distilled under vacuum: 25.3 g (89%) 1-(hydroxymethyl)-4-(2-

hydroxyethyl)benzene, b.p. 147 °C/0.01 Torr; m.p. ca. 30 °C. IR

1714 (s), 1683 (m), 1633 (m), 1279 (vs), 992 (w), 992 (w), 943 (w),

855 (w) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 4.00 (s, 3 H, CH₃),

6.56 (d, J = 16.1 Hz, 1 H, α-CH=), 7.87 (d, J = 16.1 Hz, 1 H, β-

CH=), 7.65 and 8.09 ppm (AAЈXXЈ, 2 H each, ar-H). ¹³C NMR

(101 MHz, CDCl₃): δ = 53.4 (OCH₃), 118.9 (CH, =CH-α), 128.7,

130.6 (CH, C-2, -3, -5, -6), 131.4 (C_q, C-1), 138.4 (C_q, C-4), 147.4

(KBr): ν = 3230 (vs), 2940 (s), 2860 (s), 1420 (m), 1050 (vs), 1025

˜

(vs), 1010 (vs), 830 (s), 760 (m), 710 (m) cm^–1. ¹H NMR (400 MHz, (CH, =CH-β), 168.5 (C_q, CO₂CH₃), 172.9 ppm (C_q, CO₂H). UV

CD₃OD): δ = 2.79 (t, 2 H, ar-CH₂-C), 3.71 (t, 2 H, CH₂CH₂OH), (acetonitrile): λ_max(log ε) = 192 (4.32), 284 nm (4.43). MS (EI,

4.54 (s, 2 H, ar-CH₂-O), 7.15 and 7.25 ppm (AAЈBBЈ, 2 H each,

70 eV): m/z (%) = 206 (44) [M⁺], 175 (100), 147 (26). C₁₁H₁₀O₄

ar-H). ¹³C NMR (101 MHz, CD₃OD): δ = 41.1 (CH₂, 4-CH₂), (206.20), calcd. 64.08, H 4.89; found 64.09, H 4.86.

65.4, 66.2 (both CH₂, OCH₂), 129.3, 131.1 (both CH, C-2, -3, -5,

Methyl (E)-4-[2Ј-(Methoxycarbonyl)vinyl]benzoate (12): A mixture

-6), 140.4, 141.6 ppm (both C_q, C-1, -4). UV (acetonitrile): λ_max

of the above acid (34.04 g, 0.17 mmol) and thionyl chloride (40 mL)

(log ε) = 219 (3.06), 198 nm (4.16). MS (EI, 70 eV): m/z (%) = 152

was heated to reflux for 1 h under nitrogen atmosphere. Excess

(100) [M⁺], 134 (20), 121 (80), 105 (16), 104 (33), 91 (33), 77 (21).

thionyl chloride was distilled off under vacuum and to the remain-

C₉H₁₂O₂(152.19): calcd. C 71.03, H 7.95; found C 71.05, H 7.90.

der methanol (100 mL) was added under ice cooling. The mixture

4-(2Ј-Bromoethyl)-1-(bromomethyl)benzene (4): To a solution of the

above diol (7.40 g, 48.6 mmol) in glacial acetic acid (20 mL) was

added HBr in acetic acid (ca. 30%, 30 mL) and the mixture heated

to 100 °C in a sealed thick-walled ampoule. After cooling to room

temp. the ampoule contents were poured onto a mixture of ice and

hydrogen carbonate solution. The precipitate was filtered off, dried

and purified by silica gel column chromatography with carbon tet-

rachloride: 11.0 g (81%) of 4, colorless needles, m.p. 71–72 °C. IR

was heated at reflux; small amounts of methanol were added to

keep 12 in solution. After cooling to room temp. the diester 12

crystallized out and was removed by filtration. The product ob-

tained was pure enough for the next step: 32.4 g (89%), colorless

needles (ethanol), m.p. 125 °C. IR (KBr): ν = 3016 (w), 2957 (w),

˜

1721 (vs), 1437 (m), 1322 (s), 1282 (s), 1201 (m), 1170 (s), 1108 (s),

983 (w) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 3.82, 3.92 (2

OCH₃), 6.52 (d, J = 16.0 Hz, 1 H, α-CH=), 7.56–7.72 (AAЈBBЈ, 4

H, ar-H), 8.05 ppm (d, J = 16.0 Hz, 1 H, β-CH=). ¹³C NMR

(101 MHz, CDCl₃): δ = 51.9, 52.3 (2 OCH₃), 120.2 (CH, =CH-α),

127.9, 130.1 (CH, C-2, -3, -5, -6), 131.4 (C_q, C-1), 138.6 (C_q, C-

4), 143.4 (CH, =CH-β), 166.4, 166.9 ppm (both C_q, CO₂Me). UV

(acetonitrile): λ_max(log ε) = 192 (4.32), 284 nm (4.43). MS (EI,

70 eV): m/z (%) = 220 (59) [M⁺], 205 (16), 189 (100), 161 (21), 145

(26). C₁₂H₁₂O₄(220.22), calcd. C 65.45, H 5.49; found C 65.44, H

5.54.

(KBr): ν = 2920 (w), 1500 (w), 1440 (m), 1430 (m), 1410 (m), 1310

˜

1

(m), 1220 (s), 1190 (s), 1120 (m), 840 (s), 630 (vs) cm^–1. H NMR

(400 MHz, CDCl₃): δ = 3.15 (t, 2 H, CH₂CH₂Br), and 3.55 (t, 2

H, CH₂CH₂Br), 4.48 (s, 2 H, ar-CH₂-Br), 7.37 ppm (AAЈBBЈ, 4 H,

ar-H). ¹³C NMR (101 MHz, CDCl₃): δ = 32.6, 33.3 (2 CH₂Br),

38.9 (CH₂CH₂Br), 129.1, 129.3 (both CH, C-2, -3, -5, -6), 136.4

(C_qC-1), 139.2 ppm (C_q, C-4). UV (acetonitrile): λ_max(log ε) =

235 (4.19), 201 nm (4.45). MS (EI, 70 eV): m/z (%) = 280 (4) [M⁺],

278 (7) [M⁺], 276 (4) [M⁺], 199 (98), 197 (100), 185 (5), 118 (9),

117 (33), 104 (15). C₉H₁₀Br₂(277.99): calcd. C 38.89, H 3.63, Br

57.49; found C 38.87, H 3.60, Br 56.48.

Methyl 4-[2-(Methoxycarbonyl)ethyl]benzoate: To a solution of 12

(35.11 g, 0.16 mol) in ethyl acetate (500 mL) was added 1.5 g of Pd/

C and the suspension hydrogenated at room temp. until the hydro-

gen uptake ceased. The solution was passed through a short col-

umn filled with sodium sulfate, and the solvent was removed by

rotary evaporation. The remaining oil was distilled under vacuum:

35.0 g (99%) of the saturated diester, b.p. 109–110 °C/0.01 Torr. ¹H

NMR (400 MHz, CDCl₃): δ = 2.65, 3.01 (both t, 2 H each,

CH₂CH₂), 3.67 (s, 3 H, CH₂CO₂CH₃), 3.90 (s, 3 H, ar-CO₂CH₃),

4-(2Ј-Mercaptoethyl)-1-(mercaptomethyl)benzene (5): A solution of

dibromide 4 (14.5 g, 0.05 mol) and thiourea (8.40 g, 0.11 mol) in

ethanol (150 mL) was refluxed for 4 h. On cooling to room temp.

the thiuronium salt precipitated which was filtered off and hy-

drolyzed with sodium hydroxide (10.4 g, 0.26 mol) in water

(150 mL) without further purification to the dithiol 5: 8.65 g

(90%), b.p. 97 °C/0.01 Torr. ¹H NMR (400 MHz, CDCl₃): δ = 1.38,

1.75 (both t, 1 H each, SH), 2.72–2.79 (m, 2 H, CH₂CH₂-S), 2.88

(t, 2 H, ar-CH₂C), 3.71 (d, 2 H, ar-CH₂S), 7.11–7.27 ppm (AAЈBBЈ,

4 H, ar-H). ¹³C NMR (101 MHz, CDCl₃): δ = 25.9, 28.5 (2 SCH₂),

39.8 (4-CH₂), 128.1, 128.3 (CH, C-2, -3, -5, -6), 138.6, 139.3 ppm

(C_q, C-1, -4). MS (EI, 70 eV): m/z (%) = 184 (87) [M⁺], 151 (100),

137 (42), 117 (31), 115 (7), 105 (10), 104 (37). C₉H₁₂S₂(184.31),

calcd. C 58.65, H 6.56, S 34.79; C 58.64, H 6.53, S 35.05.

7.26, 7.96 ppm (AAЈXXЈ, 2 H each, 3-, 5-H and 2-, 6-H, resp.). ¹³

C

NMR (101 MHz, CDCl₃): δ = 30.9, 35.2 (CH₂CH₂), 51.7, 52.0 (2

OCH₃), 128.4, 129.9 (CH and C_q, C-1, -2, -3, -5, -6), 145.9 (C_q, C-

4), 167.0 (C_q, ar-CO₂), 173.0 ppm (C_q, CH₂CO₂). The compound

has been described in the lit.^[36]

1-(Bromomethyl)-4-(3Ј-bromopropyl)benzene (13): A solution of the

saturated diester (19.07 g, 85.8 mmol) in anhydrous diethyl ether

(250 mL) was added dropwise to a suspension of lithium aluminum

hydride (7.0 g, 0.18 mol) in diethyl ether (500 mL) at a rate to keep

the solvent gently boiling. After the addition was complete, the

mixture was heated to reflux for 1 h, and then cooled to room temp.

For hydrolysis water (7 mL), sodium hydroxide solution (15% in

water, 7 mL), and water again (21 mL) were added and the mixture

stirred for 1 h at room temp. The precipitate was filtered off,

The preparation of the cyclophanes from the respective building

blocks is described below under General Procedures.

B) 1-(Bromomethyl)-4-(3Ј-bromopropyl)benzene (13): To a solution

of malonic acid (22.82 g, 0.22 mol) in anhydrous pyridine (100 mL)

were added at room temperature methyl 4-formylbenzoate (11,

30.0 g, 0.18 mol) and piperidine (2 mL). The mixture was heated

Eur. J. Org. Chem. 2009, 223–237

www.eurjoc.org

229

Z. Pechlivanidis, H. Hopf, L. Ernst

FULL PAPER

washed several times with diethyl ether, and the combined ether

phases were dried (MgSO₄). After the solvent had been removed

in vacuo the raw diol was dissolved in glacial acetic acid (20 mL)

and HBr/acetic acid (ca. 30%, 40 mL) was added. The reaction

(OCH₃), 118.0(C_q, CϵN), 127.9 (C_q, C-1), 140.5 (C_q, C-4), 128.1

(CH, C-2, -3, -5, -6), 173.1 ppm (C_q, CO₂). UV (acetonitrile): λ_max

(log ε) = 211 (3.95), 196 nm (4.23). MS (EI, 70 eV): m/z (%) = 203

(32) [M⁺], 176 (22), 144 (30), 143 (100), 134 (30), 130 (64), 117 (50),

mixture was heated in a thick-walled ampoule for 8 h at 100 °C. 116 (31), 115 (30), 104 (30), 103 (38). C₁₂H₁₃NO₂(203.24): calcd.

The cooled reaction mixture was poured onto an ice water/soda

mixture and the formed 13 extracted by washing four times with

50 mL portions of dichloromethane. After work-up of the com-

bined organic layers the residue was distilled under vacuum: 14.05 g

(86%) of 13, b.p. 99–101 °C/0.001 Torr. The spectroscopic proper-

ties of the compound agreed with those reported in ref.^[26]

C 70.92, H 6.45, N 6.89; found C 70.87, H 6.46, N 6.79.

4-[(Methoxycarbonyl)methyl]-1-[2Ј-(methoxycarbonyl)ethyl]benzene:

The same procedure as for the hydrolysis described under a) was

employed using 17.43 g (85.8 mmol) of the above nitrile. The raw

product was purified by vacuum distillation: 18.29 g (90%) of 4-

[(methoxycarbonyl)methyl]-1-[2Ј-(methoxycarbonyl)ethyl]benzene,

m.p. 43–44 °C; b.p. 105–107 °C/0.001 Torr. IR (KBr): ν = 3032 (m),

˜

c) 1-(2Ј-Mercaptoethyl)-4-(3Ј-mercaptopropyl)benzene (18): Methyl

4-methylcinnamate (15, 56.19 g, 0.32 mol) was brominated with

NBS as described above. After termination of the process the reac-

tion mixture was filtered while still hot, and the solvent was re-

moved in vacuo. Vacuum distillation afforded 55.60 g (68%) of

methyl (E)-4-(bromomethyl)cinnamate, m.p. 58–59 °C; b.p. 163 °C/

2957 (m), 2930 (m), 1735 (vs), 1690 (m), 1514 (s), 1435 (vs), 1370

(s), 1320 (vs), 1303 (vs), 1259 (vs), 1192 (vs), 1145 (vs), 1105 (m),

1007 (s), 979 (s), 900 (m), 875 (m), 797 (s) cm^–1. ¹H NMR

(400 MHz, CDCl₃): δ = 2.62, 2.93 (both t, 2 H each, CH₂CH₂),

3.59 (s, 2 H, ar-CH₂), 3.66, 3.68 (both s, 3 H each, 2 OCH₃), 7.13–

7.22 ppm (AAЈBBЈ, ar-H). ¹³C NMR (101 MHz, CDCl₃): δ = 30.5

(CH₂CH₂CO₂), 35.6 (CH₂CH₂CO₂), 40.8 (4-CH₂), 51.6 (2 OCH₃),

128.5, 129.4 (both CH, C-2, -3, -5, -6), 131.9 (C_q, C-4), 139.4 (C_q,

C-1), 172.1 (C_q, ar-CH₂CO₂), 173.3 ppm (C_q, CH₂CH₂CO₂). UV

(acetonitrile): λ_max(log ε) = 215 (3.90), 211 (3.93), 196 nm (4.42).

MS (EI, 70 eV): m/z (%) = 236 (48) [M⁺], 205 (12), 177 (49), 176

(100), 163 (24), 117 (72). C₁₃H₁₆O₄(236.27): calcd. C 66.09, H 6.83;

C 66.11, H 6.85.

0.1 Torr. IR (KBr): ν = 3020 (w), 2955 (w), 1725 (vs), 1640 (m),

˜

1600 (m), 1510 (m), 1440 (s), 1320 (vs), 1280 (s), 1230 (s), 1200 (s),

1170 (vs), 985 (s), 930 (m), 835 (s), 785 (m) cm^–1. ¹H NMR

(400 MHz, CDCl₃): δ = 3.81 (s, 3 H, CH₃), 4.49 (s, 2 H, CH₂), 6.44

(d, J = 16.0 Hz, 1 H, α-CH=), 7.39–7.52 (AAЈBBЈ, 4 H, ar-H),

7.67 ppm (d, J = 16.0 Hz, 1 H, β-CH=). ¹³C NMR (101 MHz,

CDCl₃): δ = 32.7 (CH₂), 51.8 (CH₃), 118.5 (CH, =CH-α), 128.5,

129.6 (both CH, C-2, -6, C-3, -5), 134.5 (C_q, C-4), 139.9 (C_q, C-1),

143.9 (CH, =CH-β), 167.2 ppm (C_q, CO₂). UV (acetonitrile): λ_max

(log ε) = 286 (4.47), 223 (sh, 4.08), 218 (4.17), 198 nm (4.17). MS

(EI, 70 eV): m/z (%) = 256 (5) [M⁺], 254 (5) [M⁺], 225 (3), 223(3),

175 (100), 144 (14), 116 (14), 115 (50). C₁₁H₁₁BrO₂(255.11): calcd.

C 51.79, H 4.35, Br 31.32; found C 51.85, H 4.28, Br 31.14.

1-(2Ј-Hydroxyethyl)-4-(3Ј-hydroxypropyl)benzene: As described un-

der a) 4-[(methoxycarbonyl)methyl]-1-[2Ј-(methoxycarbonyl)ethyl]-

benzene (17.03 g) was reduced with lithium aluminum hydride to

the corresponding diol; the raw product obtained was distilled un-

der vacuum: 11.01 g (85%) of 1-(2Ј-hydroxyethyl)-4-(3Ј-hy-

droxypropyl)benzene, b.p. 154 °C/0.001 Torr; m.p. 38 °C. IR (KBr):

Methyl (E)-4-(Cyanomethyl)cinnamate: As described above under

a) (E)-4-(bromomethyl)cinnamate (54.0 g, 0.21 mol) was treated

with sodium cyanide to provide the corresponding nitrile: 25.47 g

(60%), slightly yellow needles (ethanol), m.p. 76–77 °C. IR (KBr):

ν = 3404 (m), 3344 (s), 3248 (m), 2929 (m), 2833 (m), 1515 (m),

˜

1450 (m), 1068 (s), 1053 (vs), 1015 (m), 910 (m), 834 (s), 775 (w)

1

cm^–1. H NMR (400 MHz, CDCl₃): δ = 1.84 (m, 2 H, central pro-

pyl-CH₂), 2.24 (br. s, 2 H, OH), 2.65, 2.81 (both t, 2 H each, ar-

CH₂), 3.62, 3.79 (both t, 2 H each, OCH₂), 7.12 ppm (“s”, 4 H, ar-

H). ¹³C NMR (101 MHz, CDCl₃): δ = 31.6 (CH₂, C-1"), 34.2 (CH₂,

C-2"), 38.7 (CH₂, C-1Ј), 62.1 (CH₂, C-3"), 63.6 (CH₂, C-2Ј), 128.6,

129.0 (d, C-2, -3, -5, -6), 136.0 (C_q, C-1), 139.9 ppm (C_q, C-4). UV

(acetonitrile): λ_max(log ε) = 218 (3.93), 213 (3.92), 197 nm (4.28).

MS (EI, 70 eV): m/z (%) = 180 (47) [M⁺], 150 (32), 149 (45), 132

(33), 131 (100), 118 (18), 117 (32), 105 (33), 104 (43), 91 (35).

C₁₁H₁₆O₂(180.25): calcd. C 73.30, H 8.95; found C 73.24, H 8.99.

ν = 3050 (m), 2950 (m), 2250 (m), 1715 (vs), 1675 (m), 1640 (s),

˜

1430 (s), 1420 (m), 1400 (s), 1330 (s), 1315.8 (s), 1305 (s), 1290 (s),

1200 (vs), 1170 (vs), 1115 (m), 1010 (s), 980 (s), 955 (m), 810 (s)

cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 3.78 (s, 2 H, CH₂), 3.81

(s, 3 H, CH₃), 6.45 (d, J = 16.0 Hz, 1 H, α-CH=), 7.34–7.55

(AAЈBBЈ, 4 H, ar-H), 7.67 ppm (d, J = 16.0 Hz, 1 H, β-CH=). ¹³C

NMR (101 MHz, CDCl₃): δ = 23.5 (CH₂), 51.8 (CH₃), 117.4 (C_q,

CϵN), 118.4 (=CH-α), 128.5, 128.7 (both CH, C-2, -6, C-3, -5),

131.9, 134.3 (both C_q, C-1, -4), 143.7 (=CH-β), 167.2 ppm (C_q,

CO₂). UV (acetonitrile): λ_max(log ε) = 275 (4.38), 223 (sh, 4.08),

218 (4.17), 198 nm (4.17). MS (EI, 70 eV): m/z (%) = 201 (40) [M⁺],

100 (19), 170 (100), 142 (35), 140 (13), 115 (46), 102 (25).

C₁₂H₁₁NO₂(201.22): calcd. C 71.63, H 5.51, N 6.96; found C

71.62, H 5.49, N 6.91.

1-(2Ј-Bromoethyl)-4-(3Ј-bromopropyl)benzene (17): As described

above the diol (15.0 g, 83.2 mmol) was converted into the corre-

sponding dibromide by HBr treatment. The raw product was puri-

fied by vacuum distillation: 20.41 g (82%) of 17, b.p. 127 °C,

0.01 Torr. IR (KBr): ν = 3014 (m), 2958 (s), 2936 (vs), 2858 (m),

˜

1514 (vs), 1432 (vs), 1266 (vs), 1242 (s), 1209 (s), 1126 (m), 1024

(m), 807 (m) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 2.14 (m, 2 H,

2"-H), 2.74 (t, 2 H, 1"-H), 3.12 (t, 2 H, 1Ј-H), 3.37 (t, 2 H, 3"-H),

3.54 (t, 2 H, 2Ј-H), 7.13 ppm (“s”, 4 H, ar-H). ¹³C NMR

(101 MHz, CDCl₃): δ = 33.0, 33.1, 33.6, 34.1 (all CH₂, C-2Ј, -1”,

-2”, -3"), 39.0 (CH₂, C-1Ј), 128.7 (CH, C-2, -3, -5, -6); 136.7 (C_q,

C-1), 139.1 ppm (C_q, C-4). UV (acetonitrile): λ_max(log ε) = 220

(4.05), 213 (4.00), 197 nm (4.45). MS (EI, 70 eV): m/z (%) = 308

(22) [M⁺], 306 (44) [M⁺], 304 (22) [M⁺], 227 (28), 225 (28), 213

(61), 211 (62), 199 (75), 197 (75), 117 (100). C₁₁H₁₄Br₂(306.04):

calcd. C 43.17, H 4.61, Br 52.22; found C 43.84, H 4.68, Br 51.55.

1-(Cyanomethyl)-4-[2Ј-(methoxycarbonyl)ethyl]benzene (16): To

a

solution of methyl (E)-4-cyanomethylcinnamate (20.29 g,

100.8 mmol) in THF (150 mL) was added 1.0 g Pd/C and the reac-

tion mixture hydrogenated at room temp. until the hydrogen uptake

ceased. The solution was filtered through a short column filled with

sodium sulfate, the solvent was removed in vacuo, and the remain-

der was distilled under vacuum: 16.63 g (81%) of 16, m.p. 42–

43 °C; b.p. 134–136 °C/0.001 Torr. IR (KBr): ν = 3035 (w), 2955

˜

(m), 2253 (w), 1733 (vs), 1515 (m), 1434 (s), 1420 (m), 1373 (m),

1297 (m), 1189 (s), 1179 (s), 1161 (s), 1060 (m), 981 (m), 900 (m),

842 (m) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 2.62 (t, 2 H,

CH₂CO), 2.94 (t, 2 H, ar-CH₂), 3.66 (s, 3 H, OCH₃), 3.70 (s, 2 H, 1-(2Ј-Mercaptoethyl)-4-(3Ј-mercaptopropyl)benzene (18): As de-

CH₂CN), 7.18–7.28 ppm (AAЈBBЈ,

H, ar-H). ¹³C NMR scribed above the dibromide 17 (10.0 g, 32.7 mmol) was converted

(101 MHz, CDCl₃): δ = 23.2 (CH₂CN), 30.4, 35.5 (CH₂CH₂), 51.6 into 18; the raw reaction product was purified by vacuum distil-

4

230

www.eurjoc.org

Eur. J. Org. Chem. 2009, 223–237

Paracyclophanes: Extending the Bridges

lation: 4.75 g (68%) of 18, b.p. 98–100 °C/0.001 Torr. ¹H NMR Methyl 3-Bromo-4-[(methoxycarbonyl)methyl]benzoate: As de-

(400 MHz, CDCl₃): δ = 1.37 (m, 2 H, -SH), 1.92–2.88 (m, 10 H, 5 scribed above (see preparation of 5) the above nitrile (13.68 g,

CH₂), 7.11 ppm (“s”, 4 H, ar-H). ¹³C NMR (101 MHz, CDCl₃): δ 53.8 mmol) was saponified to the corresponding diester: 14.05 g

= 24.0 (CH₂, C-3"), 26.1 (CH₂, C-2Ј), 33.9, 35.4 (both CH₂, C-1”, (94%), colorless plates (ethanol), m.p. 97 °C. IR (KBr): ν = 3012

˜

-2"), 39.8 (CH₂, C-1Ј), 128.6, 128.7 (both CH, C-2, -3, -5, -6), 137.4 (w), 2952 (w), 1740 (vs), 1716 (vs), 1438 (s), 1344 (m), 1302 (s),

(C_q, C-1), 139.4 ppm (C_q, C-4).

1290 (vs), 1262 (vs), 1216 (vs), 1197 (m), 1166 (vs), 1117 (m), 968

(m) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 3.72 (s, 3 H,

CH₂CO₂CH₃), 3.84 (s, 2 H, CH₂), 3.91 (s, 3 H, ar-CO₂CH₃), 7.36

(d, J = 7.9 Hz, 1 H, 5-H), 7.93 (dd, J = 7.9, 1.7 Hz, 1 H, 6-H),

8.23 ppm (d, J = 1.7 Hz, 1 H, 2-H). ¹³C NMR (101 MHz, CDCl₃):

δ = 41.5 (CH₂), 52.2, 52.4 (2 OCH₃), 128.6 (CH, C-6), 131.4 (C_q,

C-5), 133.8 (C_q, C-2), 125.0 (C_q, C-3), 130.8 (C_q, C-1), 139.1 (C_q,

C-4), 165.5 ppm (C_q, CO₂). UV (acetonitrile): λ_max(log ε) = 192

(4.56), 208 (4.61), 236 (4.10), 282 nm (3.17). MS (EI, 70 eV): m/z

(%) = 288 (2) [M⁺], 286 (2) [M⁺], 257 (7), 255 (7), 229 (18), 227

(18), 207 (100). C₁₁H₁₁BrO₄(287.11): calcd. C 46.02, H 3.86, Br

27.83; found C 46.02, H 3.86, Br 27.93.

d) 3-Bromo-4-(2Ј-bromoethyl)-1-(bromomethyl)benzene (22a).

–

Methyl 3-Bromo-4-methylbenzoate (21): A suspension of iron pow-

der (2.05 g) and a few mL of bromine in carbon tetrachloride

(8 mL) were stirred for 1 h before methyl 4-methylbenzoate (2,

49.07 g, 0.33 mol) in carbon tetrachloride (75 mL) was added.

While the mixture was kept at reflux bromine (16 mL, 0.33 mol) in

carbon tetrachloride (12 mL) was added dropwise within 2 h. After

refluxing for 14 h the reaction mixture was cooled to room temp.,

and dichloromethane (200 mL) and sodium hydrogen sulfite (15%

in water, 200 mL) were added. The organic layer was separated,

and the aqueous carefully extracted with dichloromethane. The

combined organic phases were washed with water, sat. hydrogen

carbonate solution, and dried (sodium sulfate). After solvent re-

moval in vacuo the remaining oil was distilled under vacuum:

3-Bromo-4-(2Ј-bromoethyl)-1-(bromomethyl)benzene (22a): As de-

scribed above (see preparation of 13) methyl 3-bromo-4-[(meth-

oxycarbonyl)methyl]benzoate (14.10 g, 49.1 mmol) was reduced

with lithium aluminum hydride and the resulting diol treated with

HBr/glacial acetic acid: 12.10 g (68%), colorless rhombs (ethanol),

32.74 g (44%) of 21, b.p. 83–85 °C/0.01 Torr. IR (film): ν = 2952

˜

(w), 1726 (vs), 1604 (w), 1435 (m), 1294 (vs), 1257 (vs), 1115 (m),

758 (m) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 2.43 (s, 3 H, CH₃),

3.90 (s, 3 H, CH₃O), 7.27 (d, J = 7.9 Hz, 1 H, 5-H), 7.85 (dd, J =

7.9, 1.7 Hz, 1 H, 6-H), 8.18 ppm (d, J = 1.7 Hz, 1 H, 2-H). ¹³C

NMR (101 MHz, CDCl₃): δ = 23.2 (CH₃), 52.2 (CH₃O), 124.8 (C_q,

C-3), 128.4 (CH, C-6), 129.5 (C_q, C-1), 130.7 (CH, C-5), 133.4 (CH,

C-2), 143.3 (C_q, C-4), 165.8 ppm (C_q, CO₂). UV (acetonitrile): λ_max

(log ε) = 208 (4.55), 238 nm (4.05). MS (EI, 70 eV): m/z (%) = 230

(55) [M⁺], 228 (55), [M⁺], 199 (100), 197 (100), 171 (18), 169 (18),

149 (6).

m.p. 80–81 °C. IR (KBr): ν = 3033 (w), 2858 (w), 1485 (w), 1444

˜

(m), 1432 (m), 1220 (vs), 1040 (m), 886 (m), 833 (m) cm^–1. ¹H NMR

(400 MHz, CDCl₃): δ = 3.28, 3.58 (both t, J = 7.6 Hz, 2 H each,

CH₂CH₂), 4.41 (s, 2 H, CH₂), 7.24 (d, J = 7.9 Hz, 1 H, 5-H), 7.30

(dd, J = 7.9, 1.7 Hz, 1 H, 6-H), 7.59 ppm (d, J = 1.7 Hz, 1 H, 2-

H). ¹³C NMR (101 MHz, CDCl₃): δ = 30.8, 31.7 (both CH₂Br),

39.2 (CH₂CH₂Br), 124.3 (C_q, C-3), 128.2 (CH, C-6), 131.4 (CH,

C-5), 133.4 (CH, C-2), 138.3, 138.5 ppm (both C_q, C-1, -4). UV

(acetonitrile): λ_max(log ε) = 208 nm (4.57). MS (EI, 70 eV): m/z

(%) = 360 (2) [M⁺], 358 (6) [M⁺], 356 (6) [M⁺], 354 (2) [M⁺], 279

(46), 277 (100), 275 (50), 197 (22), 195 (22). C₉H₉Br₃(356.88):

calcd. C 30.29, H 2.54, Br 67.14; found C 30.27, H 2.54, Br 67.14.

Methyl 3-Bromo-4-(bromomethyl)benzoate: As described above for

the NBS bromination of 2 (see preparation of 5), compound 21

(33.61 g, 0.15 mol) was converted into the corresponding benzyl

e) 3-Bromo-4-(3Ј-bromopropyl)-1-(bromomethyl)benzene (22b).

–

bromide: 22.91 g (51%), m.p. 64–65 °C. IR (KBr): ν = 3000 (w),

˜

Methyl 3-Bromo-4-[2Ј-(methoxycarbonyl)ethyl]benzoate: The satu-

rated diester (20.0 g, 90.0 mmol) prepared from 12 by catalytic hy-

drogenation (see preparation of 13) was brominated as described

above for 2 (see preparation of 22a). Silica gel chromatography

(carbon tetrachloride) provided 22.91 g (51%) of the bromo deriva-

2842 (w), 1715 (vs), 1433 (s), 1393 (vs), 1285 (vs), 1263 (vs), 1227

(s), 1206 (m), 1040 (m), 770 (s), 722 (m) cm^–1. ¹H NMR (400 MHz,

CDCl₃): δ = 3.93 (s, 3 H, CH₃), 4.60 (s, CH₂), 7.53 (d, J = 8.0 Hz,

1 H, 5-H), 7.95 (dd, J = 8.0, 1.6 Hz, 1 H, 6-H), 8.24 ppm (d, J =

1.6 Hz, 1 H, 2-H). ¹³C NMR (101 MHz, CDCl₃): δ = 32.3 (CH₂),

52.5 (OCH₃), 124.3 (C_q, C-3), 129.0 (CH, C-6), 131.1 (CH, C-6),

131.7 (C_q, C-1), 134.4 (CH, C-2), 141.7 (C_q, C-4), 165.2 ppm (C_q,

CO₂). UV (acetonitrile): λ_max(log ε) = 210 (4.52), 248 (4.14),

288 nm (3.31). MS (EI, 70 eV): m/z (%) = 310 (10) [M⁺], 308 (20)

[M⁺], 306 (10) [M⁺], 279 (5), 277 (10), 275 (5), 229 (100), 201 (18),

199 (199). C₉H₈Br₂O₂(307.97): calcd. C 35.10, H 2.62, Br 51.89;

found C 34.89, H 2.59, Br 53.14.

tive, m.p. 66–67 °C. IR (KBr): ν = 2954 (w), 1736 (s), 1718 (vs),

˜

1

1430 (m), 1315 (m), 1298 (s), 1258 (s), 1176 (m), 964 (w) cm^–1. H

NMR (400 MHz, CDCl₃): δ = 2.67 (1Ј-H), 3.12 (t, 2 H, 2Ј-H), 3.68

(s, 3 H, CH₂CO₂CH₃), 3.91 (s, 3 H, ar-CO₂CH₃), 7.33 (d, J =

8.0 Hz, 1 H, 5-H), 7.89 (dd, J = 8.0, 1.6 Hz, 1 H, 6-H), 8.21 ppm

(d, J = 1.6 Hz, 1 H, 2-H). ¹³C NMR (101 MHz, CDCl₃): δ = 31.5

(CH₂, C-1Ј), 33.4 (CH₂, C-2Ј), 51.8, 52.3 (OCH₃), 124.3 (C_q, C-3),

128.6 (CH, C-6), 130.2 (C_q, C-1), 130.3 (CH, C-5), 134.0 (CH, C-

2), 144.9 (C_q, C-4), 165.7 (ar-CO₂), 172.7 ppm (CH₂CO₂). UV (ace-

tonitrile): λ_max(log ε) = 208 (4.58), 238 nm (4.10). MS (EI, 70 eV):

m/z (%) = 302 (1) [M⁺], 300 (1) [M⁺], 271 (6), 269 (6), 221 (100).

Methyl 3-Bromo-4-(cyanomethyl)benzoate: As described above (see

preparation of 5) the nitrile was prepared by Kolbe synthesis from

the above benzyl bromide: 13.96 g (74%), colorless needles (etha-

nol), m.p. 52–54 °C. IR (KBr): ν = 2936 (w), 1724 (vs), 1439 (m), C₁₂H₁₃BrO₄(301.14): calcd. C 47.86, H 4.35, Br 26.53; found C

˜

1410 (m), 1390 (m), 1300 (vs), 1261 (s), 1122 (m), 754 (m) cm^–1. 47.85, H 4.36, Br 26.60. – To prepare 22b from this diester, it

¹H NMR (400 MHz, CDCl₃): δ = 3.90 (s, 2 H, CH₂), 3.94 (s, 3 H,

CH₃), 7.63 (d, J = 8.0 Hz, 1 H, 5-H), 8.02 (dd, J = 8.0, 1.7 Hz, 1

(7.76 g, 25.8 mmol) was reduced to the corresponding diol with

lithium aluminum hydride and this transformed into the tribromide

H, 6-H), 8.27 ppm (d, J = 1.7 Hz, 1 H, 2-H). ¹³C NMR (101 MHz, as described above for 22a; after silica gel chromatography (carbon

CDCl₃): δ = 25.1 (CH₂), 52.6 (OCH₃), 116.3 (C_q, CN), 123.5 (C_q, tetrachloride): 6.33 g (66%), m.p. 72–73 °C. IR (KBr): ν = 3046

˜

C-3), 129.1, 129.6 (both CH, C-5, -6), 131.9 (C_q, C-1), 134.1 (CH, (w), 2955 (w), 1487 (w), 1456 (m), 1288 (m), 1222 (vs), 1040 (m),

C-2), 134.7 (C_q, C-4), 165.1 ppm (C_q, CO₂). UV (acetonitrile): λ_max

(log ε) = 206 (4.59), 232 (4.06), 282 nm (3.08). MS (EI, 70 eV): m/z H, 2Ј-H), 2.89 (t, J = 7.6 Hz, 2 H, 1Ј-H), 3.42 (t, J = 7.6 Hz, 2 H,

(%) = 255 (43) [M⁺], 253 (43) [M⁺], 224 (100), 222 (100), 196 (21),

3Ј-H), 4.41 (s, 2 H, CH₂Br), 7.22 (d, J = 8.0 Hz, 1 H, 5-H), 7.27

194 (21), 115 (36). C₁₀H₈BrNO₂(254.08): calcd. C 47.27, H 3.17, (dd, J = 8.0, 1.6 Hz, 1 H, 6-H), 7.58 ppm (d, J = 1.6 Hz, 1 H, 2-

Br 31.45, N 5.51; found C 47.27, H 3.06, Br 31.45, N 5.50.

H). ¹³C NMR (101 MHz, CDCl₃): δ = 31.8, 32.3, 32.9, 34.2 (CH₂),

888 (m) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 2.12–2.20 (m, 2

Eur. J. Org. Chem. 2009, 223–237

www.eurjoc.org

231

Z. Pechlivanidis, H. Hopf, L. Ernst

124.4 (C_q, C-3), 128.1 (CH, C-6), 130.8 (CH, C-5), 133.3 (CH, C- -12, -13), 37.3 (CH₂, C-15), 128.2, 128.5, 128.7, 128.8 (CH, C-7, -8,

FULL PAPER

2), 137.7 (C_q, C-1), 140.2 ppm (C_q, C-4). UV (acetonitrile): λ_max

-10, -11, -17, -18, -20, -21), 135.6, 137.8, 138.0, 138.2 ppm (C_q, C-

(log ε) = 208 nm (4.55). MS (EI, 70 eV): m/z (%) = 374 (4) [M⁺], 6, -9, -16, -19). UV (acetonitrile): λ_max(log ε) = 256 (3.38), 197 nm

372 (10) [M⁺], 370 (10) [M⁺], 368 (4) [M⁺], 293 (47), 291 (100), 289 (4.54). MS (EI, 70 eV): m/z (%) = 314 (100) [M⁺], 281 (10), 247

(50), 211 (6), 209 (6), 184 (14), 182 (14). C₁₀H₁₁Br₃(370.91): calcd. (812), 210 (40), 209 (36), 164 (24), 163 (47), 149 (24), 131 (22), 117

C 32.38, H 2.99, Br 64.63; found C 32.45, H 2.88, Br 64.31.

(41), 105 (51), 104 (50). C₁₉H₂₂S₂(314.50): calcd. C 72.56, H 7.05,

S 20.39; found C 72.73, H 7.12, S 2015.

Preparation of Dithia[m.n]paracyclophanes

d) 6-Bromo-2,12-dithia[4.3]paracyclophane (23a): 3.98 g (65%) from

7 (2.8 g, 16.7 mmol) and 22a (6.0 g, 16.7 mmol); colorless needles

General Procedure: A solution with equimolar amounts of the ha-

lide and the dithiol to be coupled in toluene (1 L) was added within

24 h to a vigorously boiling solution of potassium hydroxide (8

equiv.) in a mixture of toluene and ethanol (2 L, ratio 70:30) using

a dilution apparatus according to Vögtle.^[37]When the addition was

complete the mixture was heated for a further 2 h period before it

was cooled to room temp. The solvent was removed in vacuo and

the remaining solid residue treated wit water (300 mL) and diethyl

ether (300 mL). The organic phase was separated, the aqueous ex-

tracted with diethyl ether three times. The combined organic layers

were dried (sodium sulfate), the solvent was removed and the re-

mainder was purified by silica gel plate chromatography. The fol-

lowing dithia[m.n]paracyclophanes were prepared by this route.

(ethanol), m.p. 148 °C. IR (KBr): ν = 2913 (m), 1489 (m), 1416

˜

(vs), 1036 (m), 839 (m), 811 (m), 705 (m) cm^–1. ¹H NMR

(400 MHz, CDCl₃): δ = 2.19–2.28 and 2.47–2.57 (both m, 1 H each,

3-H), 3.06–3.12 (m, 1 H, 4-H_B), 3.21 (d, J = 14.3 Hz, 1 H, 1-H_B),

3.35–3.42 (m, 1 H, 4-H_A), 3.46 (d, 1 H, 1-H_A), 3.68–3.84 (m, 4 H,

11-, 13-H), 6.58–7.08 (m, 6 H, 9-, 10-, 15-, 16-, 18-, 19-H), 7.23 ppm

(br. s, 1 H, 7-H). ¹³C NMR (101 MHz, CDCl₃): δ = 33.2, 36.2,

37.4, 38.1, 38.4 (CH₂, C-1, -3, -4, -11, -13), 123.8 (C_q, C-6), 126.1,

127.5, 128.9, 129.1, 129.7, 131.9, 133.1 (CH, C-7, -9, -10, -15, -16,

-18, -19), 136.3, 136.6, 138.4, 138.8 ppm (C_q, C-5, -8, -14, -17). UV

(acetonitrile): λ_max(log ε) = 194 (4.95), 266 nm (3.75). MS (EI,

70 eV): m/z (%) = 366 (4) [M⁺], 364 (4) [M⁺], 285 (79), 216 (6), 214

(6), 147 (100). C₁₇H₁₇BrS₂(365.36): calcd. C 55.89, H 4.69, Br

21.87, S 17.55; found C 55.49, H 4.63, Br 21.38, S 17.52.

a) 2,12-Dithia[4.3]paracyclophane (8): 2.66 g (29%) from 4 (10.80 g,

38.9 mmol) and 7 (6.62 g, 38.9 mmol); 8.14 g (61%) from 5 (8.60 g,

46.7 mmol) and 6 (8.20 g, 46.7 mmol); colorless rhombs (ethanol),

m.p. 153 °C. IR (KBr): ν = 3050 (m), 2950 (m), 2910 (vs), 1510 (s),

˜

e) 7-Bromo-2,13-dithia[5.3]paracyclophane (23b): 2.39 g (56%) from

7 (2.4 g, 14.3 mmol) and 22b (5.3 g, 14.3 mmol), colorless needles

1

1440 (m), 1425 (vs), 1100 (m), 845 (vs), 810 (vs), 770 (s) cm^–1. H

NMR (400 MHz, CDCl₃): δ = 2.52, 2.84 (both m, 2 H each, 3-, 4-

H), 3.32 (s, 2 H, 1-H), 3.78, 3.79 (both s, 2 H each, 11-, 13-H),

6.65–6.87 ppm (m, 8 H, 6-, 7-, 9-, 10-, 15-, 16-, 18-, 19-H). ¹³C

NMR (101 MHz, CDCl₃): δ = 35.6, 35.9 (both CH₂, C-1, -3, -4),

38.3 (CH₂, C-11, -13), 128.0, 128.8, 129.0, 129.1 (CH, C-6, -7, -9,

-10, -15, -16, -18, -19), 135.9, 136.8, 137.8, 138.4 ppm (C_q, C-5,

-8, - 14, -17). UV (acetonitrile): λ_max(log ε) = 197 nm(4.49). MS

(EI, 70 eV): m/z (%) = 286 (100) [M⁺], 150 (7), 149 (36), 136 (67),

118 (16), 117 (28), 104 (54), 91 (94), 89 (21), 77 (51). C₁₇H₁₈S₂

(286.46): calcd. C 71.28, H 6.33, S 22.39; found 71.21, H 6.37, S

22.22.

(ethanol), m.p. 84–85 °C. IR (KBr): ν = 3019 (w), 2949 (s), 2917

˜

(vs), 2855 (m), 1508 (m), 1440 (s), 1420 (vs), 1042 (m), 872 (s), 826

1

(m), 766 (m), 738 (s), 701 (m) cm^–1. H NMR (400 MHz, CDCl₃):

δ = 1.59–1.85, 1.90–2.00 (both m, 2 H each, 3-, 4-H), 2.22–2.31 (m,

1 H, 5-H_B), 2.91–2.99 (m, 1 H, 5-H_A), 3.52, 3.62 (AB, J = 14.2 Hz,

1 H each, 1-H), 3.69–3.84 (m, 4 H, 12-, 14-H), 6.65 (d, J = 7.8 Hz,

1 H, 11-H), 6.85–6.96 (m, 3 H) and 7.04 (“s”, 2 H, 10-, 16-, 17-,

19-, 20-H), 7.26 ppm (d, J = 1.7 Hz, 1 H, 8-H). ¹³C NMR

(101 MHz, CDCl₃): δ = 25.5, 27.6, 33.9, 34.2, 38.2, 38.4 (CH₂, C-

1, -3, -4, -5, -12, -14), 123.6 (C_q, C-7), 127.2, 128.5, 128.6, 128.8,

130.8, 133.3 (CH, C-8, -10, -11, -16, -17, -19, -20), 134.5, 137.1,

137.6, 138.6 ppm (C_q, C-6, -9, -15, -18). UV (acetonitrile): λ_max(log

ε) = 196 nm (4.85). MS (EI, 70 eV): m/z (%) = 299 (100), 161 (99),

105 (77), 91 (50). C₁₈H₁₉BrS₂(379.37): calcd. C 56.99, H 5.05, S

16.90, Br 21.06; found C 56.99, H 4.99, S 1703, Br 21.06.

b) 2,13-Dithia[5.3]paracyclophane: 1.67 g (56%) from 7 (1.70 g,

10.0 mmol) and 13 (2.92 g, 10.0 mmol); colorless rhombs (ethanol),

m.p. 116 0C. IR (KBr): ν = 2927 (vs), 2914 (vs), 2851 (m), 1509

˜

(s), 1425 (vs), 1195 (m), 872 (w), 845 (m), 807 (m), 742 (m) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 1.65–1.75 (m, 2 H, 4-H), 1.96,

2.47 (both t, 2 H each, 3-, 5-H), 3.51 (s, 2 H, 1-H), 3.79 (s, 4 H,

12-, 14-H), 6.69 (d, 2 H), 6.86 (d, 2 H), 6.97 ppm (m, 4 H, 7-, 8-,

10-, 11-, 16-, 17-, 19-, 20-H). ¹³C NMR (101 MHz, CDCl₃): δ =

25.9, 29.3, 33.8, 34.7 (CH₂, C-1, -3, -4, -5), 38.5, 39.0 (CH₂, C-12,

-14), 128.4, 128.5, 128.6, 128.7 (CH, C-7, -8, -10, -11, -16, -17,

-19, -20), 134.9, 136.3, 137.5, 138.7 ppm (C_q, C-6, -9, -15, -18). UV

(acetonitrile): λ_max(log ε) = 192 nm (4.86). MS (EI, 70 eV): m/z

(%) = 300 (100) [M⁺], 196 (14), 195 (14), 164 (24), 163 (57), 162

(30), 149 (20), 117 (30), 105 (39), 104 (35), 91 (38). C₁₈H₂₀S₂

(300.48): calcd. C 71.95, H 6.71, S 21.34; found C 71.98, H 6.80, S

21.39.

f) 16-(Methoxycarbonyl)-2,12-dithia[4.3]paracyclophane (29): 3.7 g

(54%) of a mixture of 27 and 29 (ratio 1:1, ¹H NMR analysis) from

5 (3.68 g, 20.0 mmol) and 26 (6.45 g, 20.0 mmol). The mixture was

dissolved in warm ethanol, and on cooling to room temperature 29

precipitated (ca. 1.7 g). After 2 additional recrystallizations (etha-

nol) 29 was obtained as colorless needles in 96% purity; m.p. 136–

137 °C. IR (KBr): ν = 2950 (m), 2920 (m), 1705 (vs), 1440 (m),

˜

1420 (s), 1277 (vs), 1233 (m), 1195 (s), 1077 (s), 845 (m), 800 (m)

1

cm^–1. H NMR (400 MHz, CDCl₃): δ = 2.34–2.45 (m, 2 H, 3-H),

2.58–2.65 (m, 1 H, 4-H_B), 3.04 (d, J = 14.1 Hz, 1 H, 1-H_B), 3.28–

3.35 (m, 1 H, 4-H_A), 3.74–3.86 (m, 4 H, 11-, 13-H), 3.91 (s, 3 H,

CH₃), 4.51 (d, J = 14.1 Hz, 1 H, 1-H_A), 6.55 (d, J = 7.8 Hz, 18-

c) 2,14-Dithia[5.4]paracyclophane (20): 3.86 g (37.5%) from 7 (5.6 g, H), 6.66 (dd, J = 7.8, 1.8 Hz, 19-H), 6.72–6.77 (m, 2 H), 6.94 (m,

32.7 mmol) and 17 (10.0 g, 32.7 mmol); 4.21 g (60%) from 6 (3.9 g,

22.1 mmol) and 18 (4.7 g, 22.1 mmol); colorless needles (ethanol),

1 H), 6.98 (m, 1 H, 6-, 7-, 9-, 10-, 19-H), 7.61 ppm (d, J = 1.8 Hz,

1 H, 15-H). ¹³C NMR (101 MHz, CDCl₃): δ = 35.9, 36.7, 37.8,

38.2 (CH₂, C-1, -3, -4, -11, -13), 52.0 (OCH3), 128.7, 128.9, 129.3,

130.1, 131.9, 132.4 (CH, C-6, -7, -9, -10, -15, -18, -19); 127.8, 135.8,

137.2, 138.1, 140.8 (C_q, C-5, -8, -14, -16, -17), 167.6 ppm (C_q, CO₂).

m.p. 128–129 °C. IR (KBr): ν = 3048 (w), 3005 (w), 2926 (vs), 2916

˜

(vs), 1510 (s), 1438 (m), 1422 (s), 1098 (m), 823 (m), 771 (w), 703

(s) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.75–1.83, 1.85–1.92,

2.58–2.62, 2.82–2.86 (all m, 2 H each) and 2.55 (t, 2 H, 3-, 4-, 5-, UV (acetonitrile): λ_max(log ε) = 199 nm (4.64). MS (EI, 70 eV):

12-, 13-H), 3.43, 3.56 (both s, 2 H each, 1-, 15-H), 6.78–7.00 ppm

m/z (%) = 344 (100) [M⁺], 312 (27), 194 (68), 162 (31), 149 (38),

(m, 8 H, 7-, 8-, 10-, 11-, 17-, 18-, 20-, 21-H). ¹³C NMR (101 MHz, 135 (22), 117 (51), 104 (32), 91 (42). C₁₉H₂₀S₂O₂(344.49): calcd. C

CDCl₃): δ = 26.8, 29.1, 33.8, 34.2, 34.4, 34.7 (CH₂, C-1, -3, -4, -5, 66.25, H 5.85, S 18.61; found C 66.25, H 5.89, S 18.36.

232

www.eurjoc.org

Eur. J. Org. Chem. 2009, 223–237

Paracyclophanes: Extending the Bridges

Preparation of [m.n]Paracyclophane Bis-Sulfones from Their Dithia-

precursors

1112 (vs), 1083 (m), 980 (m), 876 (m), 824 (w) cm^–1. UV (acetoni-

trile): λ_max(log ε) = 198 nm (4.59). MS (EI, 70 eV): m/z (%) = 408

(1) [M⁺], 377 (2), 280 (50), 265 (7), 248 (7), 118 (51), 117 (100).

General Procedure: The dithiaphane was treated for extended

periods of time (see below) with hydrogen peroxide solution (30%)

in the presence of glacial acetic acid (2–3 mL). After the end of the

oxidation and cooling to room temp. the residual bis-sulfone was

filtered off, washed with diethyl ether and dried under vacuum. The

following [m.n]paracyclophanes bis-sulfones were prepared by this

route.

Flash Vacuum Pyrolysis of [m.n]Paracyclophane Bis-Sulfones

General Procedure: The different bis-sulfones were pyrolyzed in

small portions (800 to 900 mg) in a pyrolysis apparatus according

to Haenel and Staab^[23]and Vögtle, respectively.^[24]The sulfones

were placed in the evaporation zone and the system was evacuated

with a diffusion pump while a stream of nitrogen was passed

through the apparatus with a capillary; the pressure was estimated

to be ca. 0.1 Torr. After the pyrolysis oven had been heated to

600 °C the evaporation oven was heated rapidly to 250 °C and its

a) 2,12-Dithia[4.3]paracyclophane 2,2,12,12-Tetraoxide (9): From 8

(2.7 g, 9.43 mmol) in 75 mL hydrogen peroxide solution for 3 d at

room temp.: 2.98 g (90%), colorless crystals; m.p. Ͼ 250 °C (de-

comp.). IR (KBr): ν = 2975 (w), 2910 (w), 1515 (w), 1310 (s), 1270 temperature subsequently increased to 400 °C within 1 h. Behind

˜

(m), 1140 (w), 1115 (vs), 885 (m) cm^–1. MS (EI, 70 eV): m/z (%) = the pyrolysis zone the pyrolysate was condensed on a cold finger

350 (3) [M⁺], 286 (1), 222 (34), 131 (18), 118 (100), 117 (75), 104

held at –40 °C. The pyrolysates collected from a number of runs

(21). C₁₇H₁₈S₂O₄(350.46): calcd. C 58.26, H 5.18, S 18.30; found were combined and purified either by plate chromatography or

C 58.23, H 5.80, S 18.32.

MPLC on silica gel.

b) 2,13-Dithia[5.3]paracyclophane 2,2,13,13-Tetraoxide: From 2,13-

dithia[5.3]paracyclophane (1.45 g, 4.83 mmol) in 75 mL hydrogen

peroxide solution for 7 d at room temp: 1.67 g (94%), colorless

The following [m.n]paracyclophanes were prepared by this route

(with only those spectroscopic and analytical data given that are

incomplete in the literature).

crystals; m.p. Ͼ 250 °C (decomp.). IR (KBr): ν = 2972 (w), 1513

˜

a) [3.2]Paracyclophane (10): From 2.68 g (7.64 mmol) of 9: 1.54 g

(90%) of 10. ¹H NMR (400 MHz, CDCl₃): δ = 2.07 (br. “qi”, 2 H,

2-H), 2.69 (br. “t”, 4 H, 1-, 3-H), 2.69 (s, 4 H, 10-, 11-H), 6.37

(AAЈXXЈ, 4 H, 6-, 8-, 13-, 17-H), 6.56 ppm (AAЈXXЈ, 4 H, 5-, 9-,

14-, 16-H). ¹³C NMR (101 MHz, CDCl₃): δ = 32.9 (CH₂, C-2),

34.3 (CH₂, C-10, -11), 35.6 (CH₂, C-1, -3), 130.1 (CH, br., C-5,

-9, -14, -16), 132.5 (CH, C-6, -8, -13, -17), 137.2 (C_q, C-7, -12),

139.7 ppm (C_q, C-4, -15), assignments by C,H-HETCOR, C,H-

COLOC and NOEDIF (10-H Ǟ 6-H); for variable-temperature

NMR spectra of 10, see Main Part. MS (EI, 70 eV): m/z (%) = 222

(m), 1318 (vs), 1298 (s), 1272 (vs), 1213 (m), 1116 (vs), 905 (m),

880 (s), 814 (w) cm^–1. UV (acetonitrile): λ_max(log ε) = 192 (4.84),

222 nm (3.96). MS (EI, 70 eV): m/z (%) = 364 (1) [M⁺], 300 (3),

274 (3), 236 (46), 208 (24), 104 (100). C₁₈H₂₀S₂O₄(306.04): calcd.

C 59.32, H 5.53, S 17.59; found C 59.57, H 5.55, S 17.95.

c) 2,14-Dithia[5.4]paracyclophane 2,2,14,14-Tetraoxide: From 2,14-

dithia[5.4]paracyclophane (20; 4.13 g, 13.13 mmol) in 100 mL hy-

drogen peroxide solution for 2 d at reflux: 4.57 g (92%), colorless

crystals; m.p. Ͼ 250 °C (decomp.). IR (KBr): ν = 3447 (w), 2925

˜

(m), 1512 (m), 1300 (vs), 1259 (m), 1153 (m), 1119 (vs), 903 (m), (55) [M⁺], 131 (38), 118 (100), 117 (84), 105 (44), 91 (30).

829 (m) cm^–1. MS (EI, 70 eV): m/z (%) = 378 (9) [M⁺], 314 (76),

b) [4.2]Paracyclophane (14): From 1.32 g (3.63 mmol) of 2,13-di-

313 (65), 295 (10), 251 (229), 250 (100), 248 (17), 222 (39), 207 (12),

145 (18), 131 (37), 118 (90), 117 (83), 104 (66), 91 (17). C₁₉H₂₂S₂O₄

thia[5.3]paracyclophane 2,2,13,13-tetraoxide: 586 mg (68%) of 14;

m.p. 73 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.43 (narrow m, 4

(378.50): calcd. C 60.29, H 5.86, S 16.94; found C 60.30, H 5.92, S

H, 2-, 3-H), 2.26 (narrow m, 4 H, 1-, 4-H), 3.00 (s, 4 H, 11-, 12-

16.79.

H), 6.54 ppm (AAЈBBЈ, 8 H, ar-H). ¹³C NMR (101 MHz, CDCl₃):

d) 6-Bromo-2,12-dithia[4.3]paracyclophane 2,2,12,12-Tetraoxide δ = 29.0 (CH₂, C-2, -3), 34.3, 35.4 (CH₂, C-1, -4, -11, -12), 128.1

(24a): From 23a (3.98 g, 5.78 mmol) in 50 mL hydrogen peroxide

solution for 12 h at reflux: 3.86 g (84%) of 24a, colorless crystals,

(CH, C-6, -10, -15, -17), 131.1 (CH, C-7, -9, -14, -18), 137.6 (C_q,

C-8, -13), 139.7 ppm (C_q, C-5, -16). MS (EI, 70 eV): m/z (%) = 236

(100) [M⁺], 208 (32), 145 (24), 132 (11), 131 (24), 130 (16), 118 (32),

m.p. Ͼ 250 °C (decomp.). IR (KBr): ν = 3058 (w), 2926 (w), 1407

˜

(w), 1321 (m), 1272 (m), 1210 (w), 1113 (vs), 887 (m) cm^–1. UV 104 (97).

(acetonitrile): λ_max(log ε) = 196 (4.89), 228 nm (4.27). MS (EI,

c) [4.3]Paracyclophane (19): From 3.04 g (8.04 mmol) of 20: 1.09 g

70 eV): m/z (%) = 430 (5) [M⁺], 428 (5) [M⁺], 302 (50), 300 (50),

221 (44), 198 (46), 196 (49), 131 (12), 118 (42), 117 (100), 115 (59),

105 (34), 104 (68). HRMS: C₁₇H₁₇BrS₂O₄: calcd. 427.9751; found

427.9751.

(54%) of 19; colorless needles, m.p. 116–118 °C. ¹H NMR

(400 MHz, CDCl₃): δ = 1.57 (m, 4 H, 2-, 3-H), 2.15 (m, 2 H, 12-

H), 2.26 (m, 4 H, 1-, 4-H), 2.71 (m, 4 H, 11-, 13-H), 6.52, 6.68 ppm

(AAЈXXЈ, 4 H each, ar-H). ¹³C NMR (101 MHz, CDCl₃): δ = 29.4

e) 7-Bromo-2,13-dithia[5.3]paracyclophane 2,2,13,13-Tetraoxide (CH₂, C-2, -3), 30.3 (CH₂, C-12), 35.7, 36.2 (CH₂, C-1, -4, -11,

(24b): From 23b (2.12 g, 5.60 mmol) in 100 mL hydrogen peroxide

solution for 24 h at reflux: 2.33 g (94%) of 24b, colorless crystals,

-13), 128.3, 129.2 (CH, C-6, -7, -9, -10, -15, -16, -18, -19), 138.6,

138.8 ppm (C_q, C-5, -8, -14, -17). MS (EI, 70 eV): m/z (%) = 250

(100) [M⁺], 131 (23), 117 (60), 116 (24), 105 (22), 104 (19), 91 (23).

m.p. Ͼ 250 °C (decomp.). IR (KBr): ν = 2891 (w), 2923 (w), 1513

˜

(w), 1313 (s), 1273 (s), 1247 (m), 1147 (m), 1113 (vs), 898 (m), 879

(m) cm^–1. UV (acetonitrile): λ_max(log ε) = 196 nm (4.87). MS (EI,

70 eV): m/z (%) = 444 (1) [M⁺], 442 (1) [M⁺], 316 (20), 314 (20),

288 (5), 286 (5), 235 (14), 184 (25), 182 (25), 104 (100).

C₁₈H₁₉BrS₂O₄(306.04): calcd. C 48.76, H 4.32, S 14.46, Br 18.02;

found C 48.81, H 4.32, S 14.57, Br 17.96.

d) 5-Bromo[3.2]paracyclophane (25a): From 3.73 g (8.68 mmol) of

24a: 1.24 g (47%) of 25a; colorless needles, m.p. 158–160 °C. IR

(KBr): ν = 2948 (m), 2925 (vs), 2853 (m), 1436 (m), 1040 (m), 898

˜

(m), 826 (s), 808 (w) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.85–

1.96 (m, 1 H), 2.30–2.41 (m, 1 H), 2.54–3.08 (m, 8 H, 1-, 2-, 3-,

10-, 11-H), 6.29 (m, 2 H), 6.47 (m, 2 H), 6.62 (dd, 1 H), 6.98 (dd,

1 H, 8-, 9-, 13-, 14-, 16-, 17-H), 6.56 ppm (d, J = 1.7 Hz, 1 H, 6-

f) 16-Methoxycarbonyl-2,12-dithia[4.3]paracyclophane 2,2,12,12-

Tetraoxide (32): From 29 (0.90 g, 2.61 mmol) in 50 mL hydrogen H). ¹³C NMR (101 MHz, CDCl₃): δ = 30.5, 33.7, 34.1, 34.6, 34.9

peroxide solution for 3 d at room temp.: 1.01 g (95%) of 32; color-

(CH₂, C-1, -2, -3, -10, -11), 124.7 (C_q, C-5), 127.2, 130.1, 131.6,

less crystals, m.p. Ͼ 250 °C (decomp.). IR (KBr): ν = 3010 (w), 131.7, 132.2, 132.6, 136.0 (CH, C-6, -8, -9, -13, -14, -16, -17), 136.7,

˜

2915 (w), 1703 (s), 1433 (m), 1311 (s), 1282 (s), 1251 (m), 1213 (m), 138.2, 139.4, 139.7 ppm (C_q, C-4, -7, -12, -15). UV (acetonitrile):

Eur. J. Org. Chem. 2009, 223–237

www.eurjoc.org

233

Z. Pechlivanidis, H. Hopf, L. Ernst

FULL PAPER

λ_max(log ε) = 192 nm (4.80). MS (EI, 70 eV): m/z (%) = 302 (100) -11), 129.9, 130.3, 131.5, 132.5, 133.5, 134.9 (CH, C-6, -9, -13,

[M⁺], 300 (100) [M⁺], 222 (10), 221 (52), 131 (20), 118 (65), 117 -14, -16, -17), 138.0 (CH, C-8), 133.8, 137.0, 138.5, 139.5, 143.4

(99). C₁₇H₁₇Br (301.23): calcd. C 67.79, H 5.69, Br 26.53; found C

67.50, H 5.65, Br 26.72.

(C_q, C-4, -5, -7, -12, -15), 191.7 ppm (CHO). UV (acetonitrile): λ_max

(log ε) = 192 (4.67), 208 (4.56), 286 nm (3.78). MS (EI, 70 eV): m/z

(%) = 250 (69) [M⁺], 146 (26), 145 (17), 118 (27), 117 (100), 115

(25), 105 (42), 91 (26). C₁₈H₁₈O (250.34): calcd. C 86.36, H 7.25;

found 86.63, H 7.25.

e) 6-Bromo[4.2]paracyclophane (25b): From 2.19 g (4.94 mmol) of

24b: 0.820 g (53%) of 25b; colorless rhombs, m.p. 155–156 °C. IR

(KBr): ν = 2940 (vs), 2925 (vs), 2850 (s), 1510 (m), 1440 (s), 1400

˜

(m), 1030 (s), 900 (m), 860 (m), 815 (s), 800 (m) cm^–1. ¹H NMR

(400 MHz, CDCl₃): δ = 1.05 (br., 1 H), 1.30 (br., 1 H), 1.70 (br. m,

1 H), 1.87 (br. m, 1 H, 2-, 3-H), 1.98 (m, 1 H, 4-H_B), 2.10 (m, 1

H, 1-H_B), 2.45 (m, 1 H, 1-H_A), 2.77–2.93 (m, 3 H, 4-H_A, 11-, 12-

H), 3.03–3.17 (m, 2 H, 11-, 12-H), 6.39 (dd, J = 7.6, 1.3 Hz, 1 H,

9-H), 6.44 (d, J = 7.6 Hz, 10-H), 6.48 (dd, 1 H), 6.61–6.72 (m, 3

H, 14-, 15-, 17-, 18-H), 6.90 ppm (d, J = 1.3 Hz, 1 H, 7-H). ¹³C

NMR (101 MHz, CDCl₃): δ = 29.1 (CH₂, C-2, -3), 33.8, 34.1 (CH₂,

C-11, -12), 35.1 (CH₂, C-4), 35.5 (CH₂, C-1), 126.9, 128.6, 130.6,

131.5 (CH, C-14, -15, -17, -18), 129.9 (CH, C-10), 130.3 (CH, C-

9), 135.0 (CH, C-7), 123.5 (C_q, C-6), 137.1, 138.2, 139.9, 140.0 ppm

(C_q, C-5, -8, -13, -16). UV (acetonitrile): λ_max(log ε) = 274 (3.06),

198 nm (3.51). MS (EI, 70 eV): m/z (%) = 316 (49) [M⁺], 314 (49)

[M⁺], 289 (5), 288 (5), 235 (19), 183 (12), 182 (12), 131 (24), 104

(100). C₁₈H₁₉Br (315.25): calcd. C 68.58, H 6.07, Br 25.35; found

C 68.52, H 6.03, Br 25.54.

[3.2]Paracyclophane-5-carboxylic Acid (30): A solution of potas-

sium permanganate (0.5 g, 3.16 mmol) in water (25 mL) was added

dropwise to a boiling solution of 28 (0.344 g, 1.37 mmol) in acetone

(25 mL).^[38]After additional refluxing for 1 h, the solution was

cooled to room temp. and the formed manganese dioxide removed

by filtration. The aqueous phase was acidified (pH 1), the precipi-

tated acid sucked off and washed several times with water. The

raw product was purified by plate chromatography on silica gel

(dichloromethane): 0.330 g (78%), colorless needles, m.p. 204 °C.

IR (KBr): ν = 3064 (w), 3027 (m), 2927 (m), 1684 (vs), 1440 (m),

˜

1

1306 (m), 932 (w), 913 (w) cm^–1. H NMR (400 MHz, CDCl₃): δ

= 2.08–2.27 (m, 2 H, 2-H), 2.50–2.60 (m, 2 H) and 2.88–2.95 (m,

1 H, 1-H_A, 1-H_B, 3-H_B), 3.00–3.05 (narrow m, 4 H, 10-, 11-H),

3.84 (ca. ddd, J ≈ 14, 7, 3 Hz, 1 H, 3-H_A), 6.32–6.69 (m, 6 H, 8-,

9-, 13-, 14-, 16-, 17-H), 7.29 ppm (d, J = 1.9 Hz, 1 H, 6-H). ¹³C

NMR (101 MHz, CDCl₃): δ = 32.2, 33.9, 34.0, 34.6 (br.), 35.1

(CH₂, C-1, -2, -3, -10, -11), 129.7, 130.2, 131.5, 132.8, 133.8 (br.),

134.9, 137.1 (CH, C-6, -8, -9, -13, -14, -16, -17), 127.4 (C_q, C-5),

137.0, 137.8, 139.9, 143.5 (C_q, C-4, -7, -12, -15), 173.0 ppm (C_q,

CO₂H). UV (acetonitrile): λ_max(log ε) = 200 nm (4.66). MS (EI,

70 eV): m/z (%) = 266 (42) [M⁺], 248 (6), 149 (17), 117 (100), 105

(84). C₁₈H₁₈O₂(266.34): calcd. C 81.17, H 6.81; C 80.61, H 6.94. –

Ester 31 from acid 30: The acid (90 mg, 0.34 mmol) was heated

with thionyl chloride (1 mL) for 30 min at reflux. Excess thionyl

chloride was distilled off under vacuum and methanol (10 mL) was

added to the residue under ice cooling. After boiling to reflux for

30 min, the alcohol was removed in vacuo and the remaining solid

purified by MPLC on silica gel with dichloromethane. The spectro-

scopic data of the isolated ester 31 (84 mg, 88%) were identical

with those of the authentic sample described above.

f) Methyl [3.2]Paracyclophane-5-carboxylate (31): From 0.663 g

(1.62 mmol) 32: 0.300 g (66%) 31, colorless needles, m.p. 83–84 °C.

IR (KBr): ν = 2950 (m), 2920 (s), 2850 (m), 1700 (vs), 1600 (m),

˜

1450 (s), 1440 (s), 1290 (vs), 1275 (vs), 1240 (m), 1200 (vs), 1180

1

(s), 1130 (m), 1090 (m), 795 (s), 790 (s), 710 (m) cm^–1. H NMR

(400 MHz, CDCl₃): δ = 2.04–2.13 (m, 2 H, 2-H), 2.46–2.56 (m, 2

H, 1-H), 2.85 (dt, J = 14.0, 5.2 Hz, 1 H, 3-H_B), 2.94–3.02 (m, 4 H,

10-, 11-H), 3.68 (dt, J = 14.0, 5.3 Hz, 1 H, 3-H_A), 3.87 (OCH₃),

6.29 (dd, J = 7.8, 1.8 Hz, 1 H), 6.41 (dd, J = 7.7, 1.9 Hz, 1 H), 6.48

(dd, J = 7.6, 1.9 Hz, 1 H), 6.57–6.63 (m, 2 H, 8-, 13-, 14-, 16-, 17-

H), 6.56 (d, J = 7.7 Hz, 1 H, 9-H), 7.09 ppm (d, J = 1.9 Hz, 1 H,

6-H). ¹³C NMR (101 MHz, CDCl₃): δ = 32.0, 33.9, 34.3, 35.1

(CH₂, C-1, -9, -10, -11), 34.0 (CH₂, br., C-2?), 51.7 (OCH₃), 128.7

(C_q, C-5), 129.5, 130.1, 131.5, 132.7, 133.9 (CH, C-6, -13, -14,

-16, -17), 133.4 (CH, br., C-9?), 136.1 (CH, C-8), 136.9, 137.5 (C_q,

C-7, -12), 139.7 (C_q, C-15), 142.1 (C_q, C-4), 168.1 ppm (C_q, CO₂).

UV (acetonitrile): λ_max(log ε) = 203 nm (4.57). MS (EI, 70 eV):

m/z (%) = 280 (100) [M⁺], 265 (11), 249 (11), 248 (22), 175 (14),

163 (16), 144 (29), 117 (75), 105 (32). C₁₉H₂₀O₂(280.37): calcd. C

81.40, H 7.19; found C 81.14, H 7.21.

Preparation of the Dithia[m.n]paracyclophane Diesters 36–39

General Procedure: An equimolar solution of dimethyl 2,5-bis(bro-

momethyl)terephthalate (33)^[28,29]and the respective dithiol in THF

(500 mL) was added within 12 h to a vigorously boiling solution

of potassium carbonate (4 equiv. with respect to the dithiol) in

methanol (2 L) using the dilutions apparatus described by

Vögtle.^[37]When the addition was complete the reaction mixture

was boiled for another 2 h before it was cooled to room temp. The

solvent was removed completely under vacuum, and to the residue

was given water (300 mL) and diethyl ether (300 mL). The organic

phase was separated and the aqueous washed three times with

100 mL portions of diethyl ether. The combined organic layers were

dried (sodium sulfate), the solvent was removed in vacuo, and the

residue purified by plate chromatography on silica gel with dichlo-

romethane.

Independent Route to 31: To a solution of 25a (895 mg, 2.97 mmol)

in anhydrous diethyl ether (40 mL) was added at room temp. whilst

stirring a solution (5 mL) of nBuLi in hexane (15%, 8.0 mmol).

After 2 h a solution of DMF (650 mg, 8.9 mmol) in diethyl ether

(10 mL) was added, and the mixture was stirred for another 2 h

period. For hydrolysis water was added (20 mL), the organic phase

was separated and carefully washed with water. After solvent re-

moval in vacuo the residue was purified by MPLC using dichloro-

methane as the eluent. Besides 190 mg of 10, 459 mg (62%) of 5-

formyl[3.2]paracyclophane (28) was isolated, colorless plates (etha-

The following dithia[m.n]paracyclophane diesters were prepared by

this route.

1688 (vs), 1237 (w), 867 (w), 793 (w) cm^–1. ¹H NMR (400 MHz, a) Dimethyl 2,12-Dithia[4.3]paracyclophane-15,18-dicarboxylate

CDCl₃): δ = 2.02–2.24 (m, 2 H, 2-H), 2.51–2.60 (m, 2 H, 1-H), (36): From 5 (3.97 g, 20.1 mmol) and 33 (7.60 g, 20.1 mmol) 3.90 g

nol), m.p. 131 °C. IR (KBr): ν = 2952 (m), 2933 (m), 2851 (m),

˜

2.84–2.91 (m, 1 H, 3-H_B), 2.96–3.09 (m, 4 H, 10-, 11-H), 3. 72 (ddd,

J = 14.1, 7.2, 3.1 Hz, 1 H, 3-H_A), 6.24 (dd, J = 7.9, 1.8 Hz, 1 H),

(48%) of 36, colorless needles, m.p. 130–131 °C. IR (KBr): ν =

2947 (w), 2918 (w), 1714 (vs), 1432 (m), 1265.8 (s), 1107 (m), 972

˜

6.46–6.52 (m, 3 H, 13-, 14-, 16-, 17-H), 6.59 (d, J = 7.7 Hz, 1 H, (w), 800 (w) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 2.28–2.42 (m,

9-H), 6.63 (dd, J = 7.8, 1.9 Hz, 1 H, 8-H), 7.03 (d, J = 1.8 Hz, 1 2 H, 3-H), 2.62–2.69 (m, 1 H, 4-H_B), 3.07 and 4.45 (AX, J =

H, 6-H), 10.05 ppm (s, 1 H, CHO). ¹³C NMR (101 MHz, CDCl₃): 14.3 Hz, 1 H each, 1-H_B, 1-H_A), 3.67 and 4.69 (AX, J = 14.7 Hz,

δ = 32.4 (CH₂, br., C-2?), 32.8, 33.8, 34.0, 34.9 (CH₂, C-1, -3, -10, 1 H each, 13-H_B, 13-H_A), 3.33–3.38 (m, 1 H, 4-H_A), 3.71 and 3.86

234

www.eurjoc.org

Eur. J. Org. Chem. 2009, 223–237

Paracyclophanes: Extending the Bridges

(AB, J = 15.1, 1 H each, 11-H), 3.94 and 3.95 (2 s, 3 H each,

CO₂CH₃), 6.68–6.97 (m, 4 H, 6-, 7-, 9-, 10-H), 7.11 (s, 1 H, 16-H),

(OCH₃), 128.5 (CH, C-7, -8, -10, -11), 133.5 (CH, C-19, -22), 132.1,

137.6, 139.0 (C_q, C-6, -9, -17, -18, -20, -21), 167.1 ppm (C_q, 2

7.62 ppm (s, 1 H, 19-H). ¹³C NMR (101 MHz, CDCl₃): δ = 35.7, CO₂Me). UV (acetonitrile): λ_max(log ε) = 194 (4.84), 242 nm

35.9, 36.1 (br.), 36.5, 37.8 (CH₂, C-1, -3, -4, -11, -13), 52.30, 52.32

(2 OCH₃), 128.5, 128.6, 129.0, 129.2, 132.1, 134.5 (CH, C-6, -7,

-9, -10, -16, -19), 131.0, 132.0, 135.9, 137.8, 140.5 (C_q, C-5, -8, -14,

(4.12). MS (EI, 70 eV): m/z (%) = 444 (100) [M⁺], 413 (6), 379 (7),

224 (39), 223 (39), 221 (39), 205 (54), 191 (34), 190 (32).

C₂₄H₂₈O₄S₂(444.61): calcd. C 64.83, H 6.35, S 14.42; found C

-15, -17, -18), 167.0, 167.3 ppm (2 CO₂Me). UV (acetonitrile): λ_max65.04, H 6.62, S 14.70.

(log ε) = 194 nm (4.85). MS (EI, 70 eV): m/z (%) = 402 (100) [M⁺],

371 (17), 370 (52), 284 (12), 253 (15), 251 (15), 221 (39), 220 (41),

205 (22). C₂₁H₂₂O₄S₂(402.53): calcd. C 62.66, H 5.51, S 15.93;

found C 62.67, H 5.55, S 15.90.

Oxidation of the Dithia[m.n]paracyclophane Diesters 36–39

Pyrolysis of the Corresponding Bis-Sulfones: The diesters 36–39

were oxidized according to the general procedure described under

4. above, and the resulting bis-sulfones flash vacuum pyrolyzed as

reported under 5.

b) Dimethyl 2,13-Dithia[5.3]paracyclophane-16,19-dicarboxylate

(37): From 34 (3.79 g, 19.1 mmol; prepared from 13 by the thiourea

route, see above, preparation of 5) and 33 (7.23 g, 19.1 mmol)

a) Dimethyl [3.2]Paracyclophane-5,8-dicarboxylate (40): Diester 36

(3.20 g, 7.95 mmol) was oxidized with hydrogen peroxide solution

(100 mL, reflux for 2 d) to yield 2.97 g (81%) of 15,18-bis(methoxy-

carbonyl)-2,12-dithia[4.3]paracyclopane 2,2,12,12-tetraoxide; m.p.

2.73 g (48%) of 36, colorless needles, m.p. 104 °C. IR (KBr): ν =

˜

2949 (w), 2935 (w), 1714 (vs), 1436 (m), 1302 (m), 1263 (s), 1246

(vs), 1135 (m), 1114 (s), 973 (m), 796 cm–1 (m) cm^–1. ¹H NMR

(400 MHz, CDCl₃): δ = 1.66–1.80 (m, 2 H), 1.85–1.98 (m, 1 H),

2.21–2.30 (m, 1 H), 2.43–2.59 (m, 2 H, 3-, 4-, 5-H), 3.24 and 4.47

(AX, J = 14.0 Hz, 1 H each, 1-H_B, 1-H_A), 3.65 and 4.69 (AX, J =

15.1 Hz, 1 H each, 14-H_B, 14-H_A), 3.71 and 3.85 (AB, J = 15.0 Hz,

1 H each, 12-H), 3.93, 3.95 (2 s, 3 H each, OCH₃), 6.67–6.75 (m,

2 H), 6.91–6.98 (m, 2 H, 7-, 8-, 10-, 11-H), 7.34, 7.68 ppm (2 s, 1

H each, 17-, 20-H). ¹³C NMR (101 MHz, CDCl₃): δ = 26.7, 26.9,

32.3, 33.2, 36.8, 38.6 (CH₂, C-1, -3, -4, -5, -12, -14), 52.31, 52.34

(2 OCH₃), 127.94, 127.89, 128.77, 128.86, 132.8, 133.8 (CH, C-7,

-8, -10, -11, -17, -20), 131.3, 131.8, 136.2, 137.7, 137.8, 139.5 (C_q,

C-6, -9, -15, -16, -18, -19), 167.1, 167.3 ppm (C_q, 2 CO₂Me). UV

(acetonitrile): λ_max(log ε) = 192 nm (4.84). MS (EI, 70 eV): m/z

(%) = 416 (40) [M⁺], 385 (4), 352 (14), 268 (10), 252 (12), 221 (40),

220 (32), 205 (21), 162 (100). C₂₂H₂₄O₄S₂(306.04): calcd. C 63.43,

H 5.81, S 15.39; found C 63.49, H 5.82, S 15.63.

(decomp.) Ͼ 250 °C. IR (KBr): ν = 3014 (w), 2914 (w), 1702 (vs),

˜

1433 (m), 1323 (vs), 1302 (vs), 1283 (vs), 1274 (vs), 1252 (vs), 1194

(m), 1113 (vs), 876 (m) cm^–1. UV (acetonitrile): λ_max(log ε) =

194 nm (4.86). MS (EI, 70 eV): m/z (%) = 466 (1) [M⁺], 435 (5),

402 (6), 388 (100), 323 (17), 306 (22), 219 (14), 118 (17), 117 (28).

C₂₁H₂₂S₂O₈(466.53): calcd. C 54.07, H 4.75, S 13.75; found C

54.07, H 4.72, S 13.80. – Pyrolysis of this bis-sulfone (2.55 g,

5.47 mmol) provided 40 (0.72 g, 39%), colorless needles, m.p.

112 °C. IR (KBr): ν = 2944 (w), 2851 (w), 1712 (vs), 1438 (m),

˜

1

1271 (vs), 1234 (m), 1185 (m), 1107 (vs), 790 (w) cm^–1. H NMR

(400 MHz, CDCl₃): δ = 1.96–2.13 (m, 2 H, 2-H), 2.49–2.58 (m, 2

H), 2.72–2.84 (m, 2 H), 2.97 (ddd, J = 12.8, 10.3, 6.6 Hz, 1 H),

3.11 (t, J = 11.5 Hz, 1 H), 3.63 (m, 1 H, 1-, 3-, 11-H, 10-H_B), 3.89,

3.90 (both s, 3 H each, OCH₃), 4.01 (ddd, J = 12.8, 10.3, 1.2 Hz,

10-H_A), 6.33–6.61 (m, 4 H, 13-, 14-, 16-, 17-H), 7.09, 7.25 ppm

(both s, 1 H each, 6-, 9-H). ¹³C NMR (101 MHz, CDCl₃): δ = 32.1,

33.1, 33.8 (br.), 34.3, 35.1 (CH₂, C-1, -2, -3, -10, -11), 51.96, 52.03

(OCH₃), 129.5, 129.9, 130.5, 132.3 (CH, C-13, -14, -16, -17), 135.5,

136.9 (CH, C-6, -9), 132.4, 133.0 (C_q, C-5, -8), 137.1, 139.7, 140.1,

141.9 (C_q, C-4, -7, -12, -15), 166.5, 167.5 ppm (C_q, CO₂Me). UV

(acetonitrile): λ_max(log ε) = 194 nm (4.97). MS (EI, 70 eV): m/z

(%) = 338 (100) [M⁺], 323 (34), 307 (9), 306 (12), 218 (12), 205 (9),

119 (15), 117 (41), 105 (26). C₂₁H₂₂O₄(338.40): calcd. C 74.54, H

6.55; found C 74.58, H 6.60.

c) Dimethyl 2,14-Dithia[5.4]paracyclophane-17,20-dicarboxylate

(38): From 18 (3.11 g, 14.7 mmol) and 33 (5.59 g, 14.7 mmol) 2.21 g

(39%) of 38, colorless needles, m.p. 127 °C. IR (KBr): ν = 3017

˜

(w), 2927 (m), 1720 (vs), 1435 (s), 1312 (m), 1271 (vs), 1233 (s),

1101 (vs), 963 (m), 824 (m), 795 (m) cm^–1. ¹H NMR (400 MHz,

CDCl₃): δ = 1.75–2.03 (m, 4 H), 2.38–2.61 (m, 4 H), 2.71–2.77 (m,

1 H), 3.21–3.26 (m, 1 H, 3-, 4-, 5-, 12-, 13-H), 3.21 and 4.51 (AX,

J = 14.3 Hz, 1 H each), 3.38 and 4.56 (AX, J = 14.1 Hz, 1 H

each, 1-, 15-H), 3.91, 3.95 (both s, 3 H each, OCH₃), 6.79 and 6.90

(AAЈXXЈ, 2 H each, 7-, 8-, 10-, 11-H), 7.53, 7.62 ppm (both s, 1 H

each, 18-, 21-H). ¹³C NMR (101 MHz, CDCl₃): δ = 27.6, 28.1,

33.0, 33.2, 34.12, 34.17, 35.5 (CH₂, C-1, -3, -4, -5, -12, -13, -15),

52.32, 52.35 (OCH₃), 128.2 (2 C), 128.5 (2 C), 132.6, 133.7 (CH,

C-7, -8, -10, -11, -18, -21), 130.7, 132.1, 137.4, 137.7, 138.1, 140.5

(C_q, C-6, -9, -16, -17, -19, 20), 166.9, 167.0 ppm (C_q, CO₂Me). UV

(acetonitrile): λ_max(log ε) = 194 (4.83), 244 nm (4.12). MS (EI,

70 eV): m/z (%) = 430 (100) [M⁺], 267 (10), 253 (17), 221 (45),

205 (44), 177 (26), 176 (42), 163 (26), 144 (73), 131 (30), 117 (47).

C₂₃H₂₆O₄S₂(430.58): calcd. C 64.16, H 6.09, S 14.89; found C

64.18, H 6.06, S 15.14.

b) Dimethyl [4.2]Paracyclophane-6,9-dicarboxylate (41): Diester 37

(3.23 g, 7.97 mmol) was oxidized with hydrogen peroxide solution

(100 mL, room temp. for 3 d) to yield 3.39 g (91%) of 16,19-bis-

(methoxycarbonyl)-2,13-dithia[5.3]paracyclopane

2,2,13,13-tetra-

oxide; m.p. (decomp.) Ͼ 250 °C. IR (KBr): ν = 3004 (w), 2925 (w),

˜

1707 (vs), 1438 (m), 1318 (s), 1269 (s), 1131.8 (s), 967 (m), 878 (w)

cm^–1. UV (acetonitrile): λ_max(log ε) = 196 (4.84), 212 (4.55), 214

(4.55), 306 nm (3.25). MS (EI, 70 eV): m/z (%) = 480 (1) [M⁺], 449

(6), 416 (10), 352 (65), 337 (10), 324 (20), 320 (15), 293 (15), 220

(15), 204 (39), 131 (41), 104 (100). C₂₂H₂₄S₂O₄(480.55): calcd. C

54.99, H 5.03, S 13.34; found C 54.86, H 5.12, S 13.33. – Pyrolysis

of this bis sulfone (2.40 g, 4.99 mmol) provided 41 (0.814 g, 46%),

d) Dimethyl 2,15-Dithia[5.5]paracyclophane-18,21-dicarboxylate

colorless needles, m.p. 110–111 °C. IR (KBr): ν = 2930 (m), 2860

˜

(39): From 35^[21,26](5.98 g, 26.5 mmol) and 33 (10.03 g, 26.5 mmol) (w), 1715 (vs), 1437 (m), 1259 (vs), 1190 (m), 1098 (vs), 785 (w)

1

4.65 g (46%) of 39, colorless needles, m.p. 107–109 °C. IR (KBr):

ν = 2930 (m), 2854 (w), 1724 (s), 1435 (s), 1268 (vs), 1188 (m), 1102

cm^–1. H NMR (400 MHz, CDCl₃): δ = 1.10–1.70 (br. m, 4 H, 2-,

3-H), 2.10–2.40 (m, 3 H), 2.89 (ddd, J = 12.9, 10.0, 7.5 Hz, 1 H),

˜

(vs), 963 (w), 837 (w) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.74– 3.01–3.18 (m, 2 H, 1-, 2-, 3-, 12-H, 4-H_B, 11-H_B), 3.27 (t, J =

1.97 (m, 8 H, 3-, 4-, 13-, 14-H), 2.53–2.65 (m, 4 H, 5-, 12-H), 3.45

(d, J = 13.8 Hz, 2 H, 1-H_B, 16-H_B), 3.94 (s, 6 H, OCH₃), 4.63 (d,

J = 13.8 Hz, 2 H, 1-H_A, 16-H_A), 6.89 (s, 4 H, 7-, 8-, 10-, 11-H),

11.6 Hz, 1 H, 4-H_A), 3.88, 3.94 (both s, 3 H each, OCH₃), 3.99

(ddd, J = 2.4, 9.6, 13.0 Hz, 1 H, 11-H_A), 6.45–6.52 (m, 2 H), 6.58–

6.66 (m, 2 H, 14-, 15-, 17-, 18-H), 7.20, 7.30 ppm (both s, 1 H each,

7.68 ppm (s, 2 H, 19-, 22-H). ¹³C NMR (101 MHz, CDCl₃): δ = 7-, 10-H). ¹³C NMR (101 MHz, CDCl₃): δ = 28.9, 29.2 (br.), 32.6

28.2, 28.9, 33.3, 33.5 (CH₂, C-1, -3, -4, -5, -12, -13, -14, -16), 52.4 (br.), 33.0, 33.8 (br.), 35.3 (CH₂, C-1, -2, -3, -4, -11, -12), 52.0 (2

Eur. J. Org. Chem. 2009, 223–237

www.eurjoc.org

235

Z. Pechlivanidis, H. Hopf, L. Ernst

FULL PAPER

OCH₃),128.1,128.4,129.8,130.7,133.5,136.0(CH,C-7,-10,-14,-15,

-17, -18), 131.4, 132.7, 137.6, 140.0, 140.1, 141.7 (C_q, C-5, -6, -8,

-9, -13, -16), 167.0, 167.7 ppm (C_q, CO₂Me). UV (acetonitrile): λ_max

C-2, -3, -12, -13), 33.2, 35.1 (CH₂, C-1, -4, -11, -14), 52.0 (OCH₃),

128.1, 128.8, 133.7 (CH, C-7, -10, -16, -17, -19, -20), 131.2 (C_q, C-

6, -9), 139.3, 140.9 (C_q, C-5, -8, -15, -18), 167.5 ppm (C_q, CO₂Me).

(log ε) = 192 (4.82), 264 nm (3.87). MS (EI, 70 eV): m/z (%) = 352 UV (acetonitrile): λ_max(log ε) = 194 (4.84), 202 (4.47), 248 nm

(100) [M⁺], 337 (14), 321 (12), 320 (12), 305 (79), 293 (15), 205 (3.97). MS (EI, 70 eV): m/z (%) = 380 (100) [M⁺], 349 (36), 321

(21),131 (21), 119 (25), 105 (35), 104 (35). C₂₂H₂₄O₄(352.43): calcd. (11), 289 (42), 205 (14), 203 (12), 131 (32), 117 (29), 105 (26), 104

C 74.98, H 6.86; found C 75.11, H 6.92.

(29), 91 (28). C₂₄H₂₈O₄(380.48): calcd. C 75.76, H 7.42; found C

75.54, H 7.44.

c) Dimethyl [4.3]Paracyclophane-6,9-dicarboxylate (42): Diester 38

(2.10 g, 4.88 mmol) was oxidized with hydrogen peroxide solution

(100 mL, room temp. for 3 d) to yield 2.23 g (92%) of 17,20-bis-

Acknowledgments

(methoxycarbonyl)-2,14-dithia[5.4]paracyclopane

2,2,14,14-tetra-

oxide; m.p. (decomp.) Ͼ 250 °C. IR (KBr): ν = 3008 (w), 2954 (w),

˜

We thank Prof. Dr. Matthias Haenel (MPI für Kohlenforschung,

Mülheim/Ruhr) for introducing us to the method of sulfone pyroly-

sis.

1717 (vs), 1435 (m), 1307 (vs), 1285 (vs), 1251 (m), 1149 (m), 1129

(vs), 807 (w) cm^–1. UV (acetonitrile): λ_max(log ε) = 194 (4.86), 214

(4.60), 246 nm (4.01). MS (EI, 70 eV): m/z (%) = 494 (1) [M⁺], 478

(27), 463 (16), 451 (11), 446 (14), 430 (40), 416 (16), 398 (45), 397

(36), 366 (34), 334 (24), 306 (14), 221 (25), 220 (45), 219 (56), 205

(100), 118 (45); 117 (49). HRMS: C₂₃H₂₆S₂O₈: calcd. 494.1069;

found 494.1069. – Pyrolysis of this bis sulfone (1.97 g, 4.36 mmol)

provided 42 (0.828 g, 56%), colorless needles, m.p. 108–109 °C. IR

[1] S. M. Ramm, H. Hopf, P. G. Jones, P. Bubenitschek, B. Ahrens,

L. Ernst, Eur. J. Org. Chem. 2008, 2948–2959.

[2] C. J. Brown, A. C. Farthing, Nature 1949, 164, 915–916.

[3] D. J. Cram, R. B. Hornby, E. A. Truesdale, H. J. Reich, M. H.

Delton, J. M. Cram, Tetrahedron 1974, 30, 1757–1768.

(KBr): ν = 2927 (w), 2862 (m), 1715 (vs), 1440 (m), 1263 (vs), 1239

˜

(s), 1185 (m), 1095 (vs), 811 (w) cm^–1. ¹H NMR (400 MHz, [4] Reviews: a) B. H. Smith, Bridged Aromatic Compounds, Aca-

demic Press, New York, 1964; b) P. M. Keehn, S. M. Rosenfeld

(Eds.) Cyclophanes, vol. I and II, Academic Press, 1983; c) F.

Diederich, Cyclophanes, The Royal Society of Chemistry, Cam-

bridge, 1991; d) H. Takemura (Ed.), Cyclophane Chemistry for

the 21^stCentury, Research Signpost, Trivandrum, 2002; e) R.

Gleiter, H. Hopf (Eds.), Modern Cyclophane Chemistry, Wiley-

VCH, Weinheim, 2004.

CDCl₃): δ = 1.31 (m, 1 H), 1.40 (m, 1 H), 1.79 (m, 2 H), 1.99–2.12

(m, 2 H), 2.12–2.28 (m, 2 H), 2.38 (m, 1 H), 2.54–2.67 (m, 2 H),

2.82 (m, 1 H, 1-, 2-, 3-, 12-, 13-H, 4-H_B, 11-H_B), 3.38 (m, 1 H, 4-

H_A), 3.67 (m, 1 H, 11-H_A), 3.89, 3.91 (both s, 3 H each, OCH₃),

6.51, 6.58, 6.67, 6.71 (all dd, 1 H each, 15-, 16-, 18-, 19-H), 7.14,

7.42 ppm (both s, 1 H each, 7-, 10-H). ¹³C NMR (101 MHz,

CDCl₃): δ = 28.4, 29.3, 29.5, 33.6, 34.0, 35.3, 35.6 (CH₂, C-1, -2,

-3, -4, -11, -12, -13), 51.95, 51.97 (OCH₃), 128.0, 128.3, 128.7,

129.4, 133.3, 134.8 (CH, C-7, -10, -15, -16, -18, -19), 131.4, 132.0

(C_q, C-6, -9), 138.5, 138.8, 140.5, 140.7 (C_q, C-5, -8, -14, -17), 167.6,

167.7 ppm (C_q, CO₂Me). UV (acetonitrile): λ_max(log ε) = 196 nm

(4.79). MS (EI, 70 eV): m/z (%) = 366 (100) [M⁺], 335 (14), 334

(29), 275 (11), 203 (9), 145 (17), 118 (19), 117 (25). C₂₃H₂₆O₄

(366.46): calcd. C 73.38, H 7.15; found 73.17, H 7.09.

[5] In the Table in Scheme 1 the references given only refer to lead-

ing references, i.e. the Table does not try to be a complete re-

flection of the vast chemical literature; see ref.^[4]for the review

literature in this field. The Table begins with the lowest possible

[m.n]paracyclophane and ends with the [4.4]hydrocarbon, since

beyond this limit the phanes are beginning to lose the charac-

teristic deformations and rigidity that are so typical of the

lower members of the series.

[6] T. Tsuji, M. Okuyama, M. Ohkita, T. Imai, T. Suzuki, Chem.

Commun. 1997, 2151–2152.

d) Dimethyl [4.4]Paracyclophane-6,9-dicarboxylate (43): Diester 39

(4.14 g, 9.31 mmol) was oxidized with hydrogen peroxide solution

(100 mL, reflux for 24 h) to yield 3.73 g (79%) of 18,21-bis(meth-

oxycarbonyl)-2,15-dithia[5.5]paracyclopane 2,2,15,15-tetraoxide;

[7] For a recent summary on the preparation of [n]- and [m.n]cy-

clophanes see H. Hopf in Beyond van’t Hoff and LeBel (Ed.:

H. Dodziuk), Wiley-VCH, Weinheim, 2008, in print.

[8] T. Tsuji, M. Ohkita, T. Konno, S. Nishida, J. Am. Chem. Soc.

1997, 119, 8425–8431; cf. T. Tsuji, M. Ohkita, S. Nishida, J.

Am. Chem. Soc. 1993, 115, 5284–5285.

[9] For the preparation of derivatives of [1.4]paracyclophane as

well as higher homologs see: a) H. A. Staab, A. Ruland, C.

Kuo-chen, Chem. Ber. 1982, 115, 1755–1764; b) H. A. Staab,

C. Kuo-chen, A. Ruland, Chem. Ber. 1982, 115, 1765–1774; c)

H. A. Staab, R. Alt, Chem. Ber. 1984, 117, 850–855; d) A. Ru-

land, H. A. Staab, Chem. Ber. 1978, 111, 2297–2300; e) H. A.

Staab, A. Ruland, C. Kuo-Chen, Chem. Ber. 1982, 115, 1755–

1764.

m.p. (decomp.) Ͼ 250 °C. IR (KBr): ν = 3055 (w), 2945 (m), 1711

˜

(vs), 1453 (m), 1410 (m), 1308 (s), 1278 (vs), 1256 (s), 1163 (m),

1

1120 (vs), 963 (w), 801 (m) cm^–1. H NMR (400 MHz, CDCl₃): δ

= 2.05–2.15 (m, 6 H), 2.55–2.85 (m, 6 H, 3-, 4-, 5-, 12-, 13-, 14-H),

3.99 (s, 6 H, OCH₃), 4.03 and 5.57 (AX, J = 14.0 Hz, 2 H each,

1-, 16-H), 6.88 (s, 4 H, 7-, 8-, 10-, 11-H), 8.09 ppm (s, 2 H, 19-, 22-

H). ¹³C NMR (101 MHz, CDCl₃): δ = 20.9 (CH₂, C-4, -13), 32.8

(CH₂, C-5, -12), 47.7, 56.4 (CH₂, C-1, -3, -14, -16), 53.1 (OCH₃),

128.9 (CH, C-7, -8, -10, -11), 135.1 (CH, C-19, -22), 130.9, 133.3,

137.2 (C_q, C-6, -9, -17, -18, -20, -21), 165.9 ppm (C_q, CO₂Me). UV

(acetonitrile): λ_max(log ε) = 194 (4.85), 214 (4.62), 244 nm (3.99).

MS (EI, 70 eV): m/z (%) = 508 (18) [M⁺], 476 (14), 444 (12), 412

(10), 221 (19), 220 (35), 219 (35), 205 (100), 189 (20), 131 (38), 104

[10] D. J. Cram, H. Steinberg, J. Am. Chem. Soc. 1951, 73, 5691–

5704.

[11] N. L. Allinger, D. J. Cram, J. Am. Chem. Soc. 1954, 76, 2362–

2367.

(43). C₂₄H₂₈S₂O₈(508.61): calcd. C 56.68, H 5.55, S 12.61; found [12] P. G. Jones, H. Hopf, Z. Pechlivanidis, R. Boese, Z. Kristallogr.

1994, 209, 673–676.

C 56.61, H 5.66, S 12.56. – Pyrolysis of this bis-sulfone (3.59 g,

7.06 mmol) provided 43 (1.62 g, 60%), colorless needles, m.p.

[13] H.-F. Grützmacher, E. Neumann, F. Ebmeyer, K. Albrecht, P.

Schelenz, Chem. Ber. 1989, 122, 2291–2297.

[14] D. J. Cram, R. C. Helgeson, J. Am. Chem. Soc. 1966, 88, 3515–

3521.

157 °C. IR (KBr): ν = 2933 (w), 2857 (m), 1718 (vs), 1510 (m),

˜

1452 (s), 1428 (m), 1262 (vs), 1139 (m), 1095 (vs), 835 (m), 805 (m)

1

cm^–1. H NMR (400 MHz, CDCl₃): δ = 1.25–1.45 (m, 4 H), 1.80–

[15] E. Hedaya, L. M. Kyle, J. Org. Chem. 1967, 32, 197–199.

[16] E. Hedaya, L. M. Kyle, J. Am. Chem. Soc. 1966, 88, 3667–3669.

[17] H. J. Reich, D. J. Cram, J. Am. Chem. Soc. 1969, 91, 3517–

3526.

1.94 (m, 4 H, 2-, 3-, 12-, 13-H), 2.01–2.14 (m, 4 H, 1-, 14-H), 2.46–

2.53 (m, 2 H, 4-H_B, 11-H_B), 3.39–3.46 (m, 2 H, 4-H_A, 11-H_A), 3.90

(s, 6 H, OCH₃), 6.66 (m, 4 H, 16-, 17-, 19-, 20-H), 7.32 ppm (s, 2

H, 7-, 10-H). ¹³C NMR (101 MHz, CDCl₃): δ = 27.8, 28.9 (CH₂, [18] M. W. Haenel, A. Flatow, Chem. Ber. 1979, 112, 249–259.

236

www.eurjoc.org

Eur. J. Org. Chem. 2009, 223–237

Paracyclophanes: Extending the Bridges

[19] M. W. Haenel, A. Flatow, V. Taglieber, H. A. Staab, Tetrahe-

dron Lett. 1977, 18, 1733–1736.

[20] D. T. Longone, S. H. Küsefoglu, J. A. Gladysz, J. Org. Chem.

1977, 42, 2787–2788.

[21] T. Otsubo, M. Kitasawa, S. Misumi, Bull. Chem. Soc. Jpn.

1979, 52, 1515–1520.

[22] F. Vögtle, L. Rossa, Angew. Chem. 1979, 91, 534–549; Angew.

Chem. Int. Ed. Engl. 1979, 18, 514–529.

[31]

[32]

F. A. L. Anet, M. A. Brown, J. Am. Chem. Soc. 1969, 91, 2389–

2390: [1,1,3,3,10,10,12,12-D₈][3.3]paracyclophane.

K. Sako, T. Meno, H. Takemura, T. Shinmyozu, T. Inazu,

Chem. Ber. 1990, 123, 639–642: [2,2,11,11-D₄][3.3]paracyclo-

phane.

Several of the intermediates described below have been de-

scribed in the chemical literature. However, since the experi-

mental details are often incomplete and spectroscopic data

missing we briefly repeat the syntheses of these compounds

here.

[33]

[23] H. A. Staab, M. W. Haenel, Chem. Ber. 1973, 106, 2190–2202.

[24] J. Grütze, F. Vögtle, Chem. Ber. 1977, 110, 1978–1993 and ref-

erences to earlier literature.

[34]

J. F. Codington, E. Mosettig, J. Org. Chem. 1952, 17, 1035–

1042.

[25] W. S. Emerson, R. A. Heimsch, J. Am. Chem. Soc. 1950, 72,

5152–5154.

[35] G. Komppa, Ber. Dtsch. Chem. Ges. 1935, 68, 1267–1272.

[36] W. S. Emerson, R. A. Heimsch, J. Am. Chem. Soc. 1950, 72,

5152–5154.

[37] F. Vögtle, Chem.-Ztg. 1972, 96, 396–403.

[38] E. Weber, I. Csöregh, B. Stensland, M. Czugler, J. Am. Chem.

Soc. 1984, 106, 3297–3306.

[26] T. Matsuoka, T. Negi, T. Otsubo, Y. Sakata, S. Misumi, Bull.

Chem. Soc. Jpn. 1972, 45, 1825–1833.

[27] M. Hibert, G. Solladie, J. Org. Chem. 1980, 45, 4496–4498.

[28] R. Gray, V. Boekelheide, Angew. Chem. 1975, 87, 138; Angew.

Chem. Int. Ed. Engl. 1975, 14, 107.

[29] R. Gray, V. Boekelheide, J. Am. Chem. Soc. 1979, 101, 2128–

Received: May 20, 2008

Published Online: November 25, 2008

2136.

[30] Prepared from the dibromide 13 as described in the Exp. Sec-

tion.

Eur. J. Org. Chem. 2009, 223–237

www.eurjoc.org

237

Article Doi

Paracyclophanes: Extending the bridges. Synthesis

DOI: 10.1002/ejoc.200800494

Source and publish data:

Authors:

Article abstract of DOI:10.1002/ejoc.200800494

Full text of DOI:10.1002/ejoc.200800494

Products guided by the article

R&D Labs maybe for 1133313-96-8

Relevant to this article

A FORMAL TOTAL SYNTHESIS OF (+/-)-STRIGOL

Synthesis of azole derivatives from 3-phenylaminopropanohydrazide and evaluation of their antimicrobial efficacy

Novel phthalide derivatives: Synthesis and anti-inflammatory activity in vitro and in vivo

Diastereoselective room-temperature Pd-catalyzed α-arylation and vinylation of arylmandelic acid derivatives

Bis(1,3,4-thiadiazolo)-1,3,5-triazinium halides. 2. Intramolecular ring transformation and synthesis of novel highly substituted guanidines

Synthesis of High Carbon Materials from Acetylenic Precursors. Preparation of Aromatic Monomers Bearing Multiple Ethynyl Groups