Synthetic Studies of Benzoannulated Metaparacyclophanes

by

Cheung Siu-shing

A thesis submitted in partial fulfilment of the

requirements for the degree of

Master of philosophy in

The Chinese University of Hong Kong

1986

Thesis Committee

Dr. H. N. C. Wong, Chairman

Dr. T. L. Chan

Dr. C. N. Lam

Prof. R. H. Mitchell, External Examiner

Acknowledgements

The author wishes to express his sincere thanks to his

supervisor, Dr. H.N.C. Wong, for his invaluable advice, guidance

and encouragement during the course of research and the

preparation of this thesis.

He is also grateful to Mr. K.W. Kwong and Mr. C.W. Fung for

their assistance in measuring all the 250MHz proton nuclear

magnetic resonance spectra and mass spectra..:

Special thanks are given to the Croucher Foundation for the

award of a'studentship.

June 1986

Cheung Siu-shing

Chemistry Department

The Chinese University

of Hong Kong

CONTENTS

I LIST OF NOMENCLATURE

II ABSTRACT

III INTRODUCTION

IV RESULTS AND DISCUSSION 18

(A) SYNTHESIS OF 1 2-BENZO2, 2]METAPARACYCL0PHANE18

(B) 2-BENZO2,2]METAPARACYCLOPHAN- SYNTHESIS OF

1

9-ENE 33

(C) SYNTHESIS OF 1,2:9,10--DIBENZO2,2]METAPARA-

CYCLOPHANE BY CRAM'S REARRANGEMENT 39

(D) SPECTRAL CHARACTERISTICS OF [2,2]METAPARACYCLO-

PHANES 41

V CONCLUSION- 46

VI EXPERIMENTAL SECTION48

VII REFERENCES 59

VIII SPECTRA 62

4

5

I LIST OF NOMENCLATURE

Trivial: 1,2-benzo-[2,2]metaparacyclophane

IUPAC: 10,ll-dihydro-12,15-etheno-5,9-metheno-benzocyclo-

tridecene

Trivial: 1,2-benzo-[2,2]paracyclophane

IUPAC: 9,10-dihydro-5,8:ll,14-dietheno-benzocyclododecene

(a)

Trivial: 1,2-benzo-10~bromo-[2,2]metaparacyclophane

IUPAC: ll-bromo-10,ll-dihydro-12,15-etheno-5,9-metheno-

benzocyclotridecene

(b)

Trivial: 1,2-benzo-9-bromo-[2,2]metaparacyclophane

IUPAC: 10-bromo-10,ll-dihydro-12,15--etheno-5,9-met:heno-

benzocyclotridecene

Trivial: 1,2-benzo- [2,2. ]metaparacyclophan-9-ene

IUPAC: 12,15-etheno-5,9-metheno-benzocyclotridecene

Trivial: 1,2-benzo-[2,2]paracyclophan-9-ene

IUPAC: 5,8:11,14-dietheno-benzocyclododecene

Trivial: 9,9-dibromo-l,2-benzo-[2,2]paracyclophane

IUPAC: 9,9-dibromo-9,10~dihydro-5,8:ll,14-dietheno-ben:

cyclododecene

Trivial:

IUPAC: 9,12-dihydro-9,12-endoxo-5,8:13,16-dietheno-dibenzo-

cyclododecene

Trivial: 1,2:9,10-dibenzo-[2,2]paracyclophane

IUPAC: 5,8:13,16-dietheno-dibenzocyclododecene

Trivial: 1,2:9,10--dibenzo-[2,2]metaparacyclophane

IUPAC: 14,17-etheno-5,9-metheno-dibenzocyclotridecene

II ABSTRACT

The synthetic methods of [2,2jmetaparacyclophane (2) and its

derivatives were briefly reviewed. 3,4-Bis(bromomethy1)-

1,1':2',1-terpheny1 (2b) was prepared according to VBgtle's

procedures. The dibromide 25 was coupled by treatment with

phenyHithium to give 1,2-benzo~[2,2Jmetaparacyclophane (24) and'VY,

a dimer 52 in 30% and 12, respectively. As an alternative

synthetic approach, treatment of 1,2-benzo-[2,2Jparacyclophane

(32) with HC1-A1C1~-CH0C10 also led to 24 in 22.5 1 yield.

Bromination and subsequent dehydrobromination of 24 gave

1,2-benzo-[2,2]metaparacyclophan-9-ene (30). However, treatment

of 1, 2-benzo-[ 2, 2] paracyclophan--9-ene (4) with HCl-AlCly CH2CI2

did not give the related 1,2-benzo-[2,2]metaparacyclophan-9-ene

(30) but instead, benzo[eJpyrene was produced in 6%.

Moreover, when 1,2:9,10-dibenzo-[2,2Jparacyclophane (35) was

subjected to HCI-AICI2-CH2CI2, a chlorinated [2,2jmetaparacyclo¬

phane 61 was probably produced. The NMR spectra of 24 and 30 have

been analyzed. The UV spectra of [2,2]metaparacyclophanes 24,rVj'

30, and 61 as well as the related [2,2]paracyclophanes 32, 34,

and 35 were recorded.

Ill INTRODUCTION

(A) General Introduction

The synthesis of [m,nJcyclophanes (1) by Professor Cram is

a landmark in the field of cyclophane chemistry. During the past

three decades, although much efforts have been made in this

field, including the preparation of different kinds of

cyclophanes and the study of their properties, many other

interesting features still remain for further investigation.

In this thesis, we will concentrate our attention on [2,2]

metaparacyclophane (2) and its derivatives. The other trivial

name used to describe compound 2 is [2,2](1,3)(1,4)cyclophane.

The numbering system for the nomenclature is illustrated in

Scheme I.

Scheme I

Due to the strain exerted by the short bridges, the two

benzene decks bend from their normal planar configuration. Thus,

the para-substituted ring would lead to a boat form and the meta-

substituted ring would bend to a distorted chair form. Moreover,

the electron clouds of the aromatic rings interact strongly with

each other due to the violation of the normal van der Waals

radius. As a result of ring deformation and closeness of the two

benzene decks, molecule 2 shows a large ring strain (23%

kcalmole). When compared with its symmetric isomers, namely,

[2,2]paracyclophane (3) and [2, 2]metacyclophane (4), it is less

strained than the former (31 kcalmole) but more strained than

the latter (13 kcalmole).

As a consequence of large ring strain and conformational

rigidity of the molecular framework, the geometries of molecule 2

and its derivatives differ from those of the closely related

symmetric [2,2]cyclophanes, 3 and 4. Moreover, in its

5 9-11conformation flipping', the substituent at the 8-position of

the meta-ring in the transition state will fall into the aromatic

Tr-electron cloud of the para-ring (Fig 1). Therefore, this class

of compound is stereochemically intriguing. On the other hand,

they provide a vehicle for the studies of transannular

interactions in cyclophanes.

Figure 1 Conformational flipping of [2,2]metaparacyclophane (2)

In order to investigate and to understand the chemical and

physical properties of these compounds, considerable efforts have

r| obeen put on the synthesis of these cyclophanes'. The following

text would give a brief review on the synthetic approaches which

are most commonly used.

(B) Synthesis of [2,2 ]Metaparacyclophane and its Derivatives

(i) Stevens rearrangement-Hofmann elimination approach

The essential characteristic of this approach involves a two

step sequence: a Stevens rearrangement followed by a Hofmann

11 13 1elimination''. It is an advantageous procedure for the

preparation of [2,2]metaparacyclophane-1,9-diene (10) as well as

other [2,2]metaparacyclophanes with substituents at specific

positions (Scheme II).

11 1 A-It was reported' that 1,3-bis(mercaptomethyl)benzene

(5) condensed with p-xylylene dibromide (6) to give 2,11-dithia-—

[3,3]metaparacyclophane (7). Stevens rearrangement of 7 was

accomplished by treatment with dimethoxycarbonium fluoroborate,

followed by potassium tert-butoxide. The products were isomers 8'X,

and 9 which were subjected to Hofmann elimination. Thus, 8 and 9

Scheme II

QUI SH

(5)rj

Br Br

(6)%

(7)

1) (CH 0) CH+BF,

t2) K0 Bu

S tevens

Re a r ran gemen t

HoCS sch3 h3cs

sc h3

(8) (9:o,

1) (ch3o)2ch+bf4

2) KOBu

Ho f maim

Elimination

ypt

(2) (10)XjXJ

were treated again with dimethoxycarbonium fluoroborate and

potassium tert-butoxide so that [2,2]metaparacyclophane-1,9-diene

(10) was obtained. The hydrogenation of 10 over Adams' catalyst

gave cyclophane 2.•u

The advantages of this approach are the ready availability

of starting materials and the simplicity in carrying out the

reaction steps. Moreover, this approach has also been applied to

prepare the 8-substituted derivatives of 2 and 10, namely, 11 andOAj% rbrV'

12 respectively, by using the corresponding 2-substituted-1,3-

bis(mercaptomethyl)benzene (13).0b

(1 la-d)rVXb%

SH X SH

(13a-d)WXf%

a) X=F

b) X=CN%

c) X=CH0

d) X=D

(ii) Bis(dithiane) Alkylat ion Approach

The application of 1,3-dithiane to the synthesis of

substituted carbonyl compounds was developed by Corey and

Seebach. Boekelheide and his co-workers' made use of this

so-called Umpolung reaction to prepare the parent cyclophane 2 asj

well as its diene 10. The synthetic procedure is shown in Scheme• 'b'b

III.

Scheme III

SH SH

OHC CHO

(14)V

(15)

1) nBuLi

(6)%

HgCl2

Me OH

rAj

NaBH,H

(16) Raney Ni

HO, (OH

TsCl

TsO ,OTs

(2)

(18) (19)KOtBu

(10)rWj

Alkylation of isophthalaldehyde bis(dithioacetal) (15) with

p-xylylene dibromide (6) gave the corresponding substituted

[2,2]metaparacyclophane 16. Compound 2 was obtained by

hydrodesulfurization of 16 with Raney nickel'. On the other

hand, 16 could be hydrolyzed with mercuric chloride in methanol

to give [2,2]metaparacyclophane-l,9-dione (17). Reduction of 17

with sodium borohydride led to a mixture of diastereoisomeric

alcohols 18 which was converted to the corresponding bis-tosylate

19. Compound 19 was treated with potassium tert-butoxide to

furnish the diene 10'.

The dithiane alkylation procedure is suitable for the

preparation of cyclophane derivatives bearing functionality on

the aliphatic bridges.

(iii) Pyrolysis of sulfone compounds

This approach' involves MCPBA oxidation of the 2,11-

dithia-[3,3]metaparacyclophane derivatives 22 which could be

prepared from the condensation of substituted 1,3—

bis(bromomethyl)benzene 20 and 1,4-bis(mercaptomethyl)benzene

(21). The corresponding bis(sulfone) 23, on pyrolysis at

approximately 500 C, would extrude sulfur dioxide to give the

desired products 11 directly (Scheme IV).

In view of the simplicity of the synthetic sequence and the

high yields of all steps, the aforementioned procedure is an

efficient method for the preparation of substituted

[2,2]metaparacyclophanes, such as llk-n.

Scheme IV

Y

Br X Br

(2 0 a- f)W 'X,

Hi

HS

(21)

Y

SX

s

(22a-f)rjfjrj 'Xy

MCPBA

Y

y

(lle-1)'Xy'XyXyVj

Y

SO,

X

SOo

(23a-f)'VXV, a.

u x Y

aOf

b

c

. dOj

e

n

eOy

f'j

ga,

h

i

J

Br

Me

H

H

H

H

H

H

F

no2

Br

OMe

COCHo

X

1) X=F, Y=H

m) X=F, Y=Br

n) X=F, Y=CH„

Y

(Ilk) (11 l-n)ry'Yj 'YJ

17Making use of the pyrolysis of sulfones, Vgtle has

synthesized 1,2-benzo-[2,2jmetaparacyclophane (24) which is the

first example of a benzoannulated [2, 2]metaparacyclophane. 3,4-

Bis(bromomethyl)-1,1':2',1-terphenyl (25) was treated withOAj

,Br

R

CH3CSNH2

s

(25)v.

(26)

H2°2

6nn °r.

(24)

so2

(27)Vb

thioacetamide to provide the cyclic sulfide 26. Oxidation of

with hydrogen peroxide led to sulfone 27, which on pyrolysis at

600°C under reduced pressure, was converted to 24.

(iv) Lewis Acid Catalyzed Rearrangement

The skeletal rearrangement of [2,2]paracyclophane Q) to

[ 2,2 ]me taparacyclophane (2) was first reported by Cram

Thus, treatment of 3 with hydrogen chloride saturated solution of

aluminium chloride in dichloromethane at -10 °C furnished 2 in

18b 20good yield. Moreover, the rearrangement is stereospecific'

A1C1

HCl

ch2CI2

-10 °C

(3)

and the evidence for the stereospecificity is provided by the

studies of the acid catalyzed rearrangement of optically pure

(+)-(S)-4-methy1-[2,2]paracyclophane (28) to optically pure(+)-

(S)-12-methyl[2,2]metaparacyclophane (29).

A1C13

HCl

CH2C12

-10 'c

(28)fj (29)

'w

Furthermore, the mechanism for the rearrangement was

qi 0 rbelieved' to follow the route which is shown in Scheme V.

Scheme V

(28)

++H

+-H

, H

AB

(29)fAj

-H+

H

C

19Release of strain appears to be one of the driving forces

for the rearrangement since product 2 is approximately 8

kcalmole less strained than 3. Another possible driving force is

perhaps due to the fact that meta-dialkylated benzenes are

stronger bases than para-dialkylated benzenes toward proton

'•a 21acids

(C) Aim of Project

In .order to study in details the possible electronic

interactions and charge-transfer character of [2,2]metaparacyclo-

phanes, we would like to synthesize the three benzo-[2,2]meta-

paracyclophanes 24, 30 and 31. Although compound 24 was first

(24)OA, m (31)

a, a,

1 7synthesized by VBgtle, we would like to modify VBgtle

2 2procedures by using Boekelheide's method, since Boekelheide

reported the preparation of 1, 2-benzo-[ 2, 2 ]paracyclophane (32), anrWf

isomer of 24, by coupling dibromide 33 directly with(Aj (jIJ

? ?

pheny Hi thium

Br

Br

(33)rXY

C.H-Li6 5

(32)rAj

Utilization of compound 24 as starting material, 30 and 31ry ryj OOj

would be prepared by bromination, dehydrobromination and trapping

a 22,23procedures'

As an alternative synthetic pathway, we would attempt to

18-20synthesize the target molecules by Cram's rearrangement,

using the corresponding benzo-[ 2, 2 ]paracyclophanes 32',Wi

3422)23 an( 3523 as startj_ng materials.

(34)rV»

(35)w

IV RESULTS AND DISCUSSION

(A) Synthesis of 1,2-benzo-[2,2]metaparacyclophane (24)

(24)

(i) By the VBgtle-Boekelheide method

(a) Synthesis of 3,4-bis(bromomethy1)-1,1':2',1-terpheny1 (25)

(25)

Compound 25 is the precursor for the synthesis of 24. It can

17 25 26be prepared according to the route'' outlined in scheme VI.

The first step of the synthetic sequence is the

2 6transformation of p-toluidine (36) to p-iodo-toluene (37) via

NH1) NaN02

HC1, -20°C

2) KI; i2

r. t.

(36) (37)

Scheme VI

NH_NaN02

H SO,, -20°C2 4

KI, I

r i. t.

(36)

I

(37)ryj

Cu20, 200°C

no2

'C02H

(38)

N°2

(39)

NH2NH2

Raney Ni80°C•

I

(41)

NaN02

HC1, 0°C

KI, I,r. t.

-nh2

(40)

1) n-BuLi, 0°C 3) DDQ

120C

0

(42)Aj

NBS

AIBN

CH2C12

hu

(43) (25)

,Br

.Br

a diazonium salt. Treatment of 36 with sodium nitrite in sulfuricAb

acid gave the diazonium salt which reacted with potassium iodide

to give 37 in 64%. Iodide 37 forms white crystals with m.p. 34-

35 °C. The NMR spectrum of 37 shows a singlet at 62.25 and a

multiplet at 66.80-7.60. The integration ratio of these signals

are three to four. They correlate to the methyl protons and the

phenyl protons of 37, respectively. Moreover, a base peak at meAAt

218 which corresponds to the molecular ion of 37 has been

recorded by mass spectrometry.

The preparation of 4-methy1-2'-nitro biphenyl (39) was notAA»

trivial. The method used by VBgtle involved a simple procedure of

heating mixture of 37, o-nitro-benzoic acid and quinoline to

155 °C, followed by addition of copper (I) oxide. On distillation,

an orange-red viscous liquid product of 39 was obtained in 63%Ab

yield. The distillate product was used for further reaction

without any other purification. However, no spectroscopic data of

2539 have been reported. Hence, the purity of 39 was not clear.

Straightforwardly, we repeated the same procedure used by

25VBgtle. However, the result was not satisfactory. Firstly, the

yield was much lower than expected, for example, 20 g of 37 could

only produce 1 g of the orange-red product, therefore, the yield

I

(IVAi

no2

co2h

(38)

Cu20

quinoline200 °C

N02

(LL

(39)

of 39 was only approximately 5%. Secondly, spectraldata (NMRmvVb

and MS) reveal that the product is not pure and contains a

mixture of 39 and an unknown compound 44. The NMR spectrum

exhibits two singlets at 62.28 and 62.30 and a multiplet at

66.90-8.00 (Figure 2). According to the structure of 39, oneAJ

62.3C 62 .28

3 7~ 6 5 4 3 2-1 0

Figure 2 NMR spectrum of mixture of 4-methyl~2'-nitro biphenyl

(39) and 44

singlet for the methyl protons is expected. Furthermore, in

addition to a peak at me 213 for the molecular ion of 39, thereAJ

is a peak at me 229 (M+ of 39+ 16) in the mass spectrum.— fAj

However, compounds 39 and 44 could not be separated byrj OA,

chromatography.

In order to improve the efficiency of the reaction, various

conditions have been modified. These• included: reaction

temperature, purity of o-nitro-benzoic acid (38) and dryness of

apparatus. Despite various efforts had been tried, the same

result was obtained. Due to the fact, that 39 and 44 wererAj rj

inseparable, the mixture after chromatography was used for

further reaction without further purification. The mechanism for

the production of 44 is still unclear.

25The next stage of synthetic sequence is the reduction of

39 to 40. The mixture containing 39 and 44 was treated with

hydrazine hydrate and Raney nickel in ethanol. After reaction, a

crude colorless product was collected. Again, it was a mixture of

two components 40 and 45 which could not be separated by

. N02

C 441

NH2NH2

Rariey Ni

EtOH

80 °C

• NH2

fAro

fAS

chromatography. This result was confirmed by spectral data. The

NMR spectrum of the mixture of 40 and 45 shows two singlets at

62.28 and 62.30, a singlet at 63.65 and a multiplet at 66.60-7.40

(Figure 3). Moreover, two strong peaks at me. 183 and 199 have

62.30 62.28

87 8 54 3 2 1 o

Figure 3 NMR spectrum of mixture of 2-amino-4'-methy1 biphenyl

(40) and 45

been recorded in the mass spectrum. The former correlates to the

molecular ion of 40 and the latter with me 199 (M+ of 40+ 16)

may correlate to 45. Since 40 and 45 were inseparable, the

mixture containing them was used for the next step.

Mixture of 40 and 45 was treated with sodium nitrite

solution in hydrochloric acid to give a diazonium salt, which was

allowed to react with potassium iodide. Two compounds were

isolated by column chromatography.

,NH2

(40)

(45)

NaN02

HCl, 0 °C

KI I?

V t.

' I

( A1

(h(-

The less polar compound (TLC R:0.39; solvent, hexanes)

shows a base peak at me 294 in its mass spectrum and a singlet

at 62.35 and a multiplet at 66.80-8.10 in its NMR spectrum (NMR-

1). Therefore, this colorless oily liquid sample is expected to

be the required product, namely, 2-iodo-4'-methy 1 biphenyl (41).

The percentage yield of 41 was 39%.

The more polar compound 46. (TLC Rr:0.31; solvent, hexanes)

has a similar NMR spectrum (NMR-2) as 41 but the singlet of 46 is

recorded at 62.30 (0.05 ppm high field shift when compared with

41). The base peak in its mass spectrum appears at me 310 (M+ of

41+ 16).

By examination of its spectral data, compound 46 is

tentatively assigned to be 2-iodo-4'-methyl biphenyl ether (46).

(U6)

Thus, the mass spectrum of it shows peaks of its fragments at me_

183, 168 and 91 and the fragmentation pathway is given in scheme

VII. The tropylium ion, jrn91, is an evidence for the ether

structure since 4-methyl biphenyl compounds would not give this

fragment. Furthermore, compound 46 would have very similar NMR

Scheme VII

I

310

-I

91 -CH

'0

183

0

168

spectrum (NMR-2) as 41 (NMR-1). In addition, compound 4 shows

absorptions at 1021 cm 1239 cm 1469-1605 cm, 2928 cm

and 3072 cm' in its IR spectrum (IR-1). The first two

27absorptions correlate to the symmetric and asymmetric

stretching of C-O-C bond, respectively. The last three correlate

to the stretching of the CC bond in the aromatic rings, the C-H

bonds in the methyl group and the C-H bonds in the aromatic

rings, respectively.

Thus, the unknowns containing in the mixtures with 3$, and 40

could tentatively be assigned structures 44 and 45, accordingly.OA; Ai

This assignment is supported by their NMR and MS data although

more vigorous confirmation is still required.

0

(44)

-nh2

'0

(45)

3,4-Dimethy 1-1,11:2' ,1-terpheny1 (43) could be prepared by

17

a three step-one pot reaction starting from 2-iodo-4'-methyl

biphenyl (41). Lithiation of 41 with n-butyl lithium produced 47

which reacted with 3-methy1-2-cyclohexen-1-one (42) to giveIAJ

alcohol 48 after quenching with sulfuric acid. The dehydration of

48 and aromatization of diene 49 was carried out• simultaneously

by stirring the mixture with sulfuric acid for a few days.

Although the diene 49 could be air oxidized to compound 43 on

stirring. The aromatization process was better carried out by

treatment with DDQ. The overall yield of the reaction was 26%.

Compound 43 is a colorless viscous liquid which shows a base peak

I

(41)

nBuLi, 0 °C

Li

(47)

1)

O

(42)

2) H?SO

HO

(49)(48)

1) air oxidized

2) DDQ

(43)IAj

at me 258 in its mass spectrum. Two singlets of the methyl

protons at 62.25 and 82.30 and a multiplet of the three phenyl

ring protons at 67.00-7.50 can be found in its NMR spectrum.

1Bromination of 43 was accomplished by reaction with two

equivalent of NBS in dichloromethane under irradiation with a

NBS

AIBN

ch2ci2

hv

(43s)

(25)

Br

Br

Br

(50) (51)

Br

200 W sunlamp. Compound 25 and the monobromides 50 and 51 wereOY 'VYf rjj

17isolated in 90% and 7% yields, respectively. Bromination of

the monobromides and 51 with one equivalent of NBS also led

Br

(50) rsn

Br

NBS

AIBN

CH2C12

hv

Br

„ Br

(25)

to 25 in 70% yield. The mass spectrum of 25 shows a pattern of'W 'W,

1:2:1 at _me 414, 416, 418 which gives concrete evidence of a

dibromide. 'The NMR spectrum of 25 exhibits two singlets at 54.-25rVj

and 64.-38 which correlate to the two sets of methylene protons. A

multiplet at 66.90-7.30 correlates to the phenyl-ring protons.

(b) Coupling of 3,4-bis(bromomethy1)-1,1':2',1-terphenyl (25)

with phenyllithium

It has been reported recently that compound 24 has been

synthesized. However, this route consisted of three steps

Br

Br

(25)

CH3CSNH2

s

(26)

H2°2

600 °C

(24)

so„

which started from compound 25 and included a pyrolysis process

at 600 °C under reduced pressure. On the other hand, the

22procedure used by Boekelheide to effect the coupling of

V 4

dibromide 33 to 1,2-benzo-[2,2]paracyclophane (32) with

phenyllithium was essentially- a one step reaction. We,

therefore, have chosen to adopt the second synthetic method.

'Br

Br

C.H Li6 5

Et20

(33) (32)

22When dibromide 25 was subiected to reaction with 1.5

2 8equivalent of pheny Hi thium in ether, the result of the

reaction was not satisfactory. 30% of the starting material 25rj

could be recovered, therefore, the yield of 24 was approximately

10% based on reacted 25. Moreover, a dimer 52 was obtained inrjr

17% yield.

Br

Br

(25)

C,H Li6 5

E tO

(52)

In order to improve the reaction, excess of phenyHithium

was used so that the reaction could be driven to completion.

Furthermore, highly diluted condition was applied in order to

avoid the dimerization of 25. As a result, these modifications

not only increased remarkably the yield of the cyclophane 24 to

30% but also diminished the production of the dimer to 12%.

Moreover, all dibromide 25 could be consumed.rVY

Dimer 52 forms white crystals with m.p. 103-105 °C which

should contain two isomers 53 and 54. Dimer 52 shows a base peakOA fj AA

(53) (54)

at me 512 in its mass spectrum. A multiplet at 6 2.80-3.10

correlates to the ethylene protons and a multiplet at 56.40-7.50

correlates to the six phenyl rings protons are recorded in its

NMR spectrum (NMR-4).

On the other hand, 1,2-benzo-[2,2]metaparacyclophane (24)V

forms colorless needles with m.p. 115-118 °C after

recrystallization from carbon tetrachloride. The base peak in

its mass spectrum appears at me_ 256 which is the molecular ion

17of 24. It has a complicated NMR spectrum (NMR-3) which contains

'VU

a set of multiplets at. 5 2.20-3.30, a singlet at 6 5.43, a set of

multiplets at 56.11-6.22, a set of multiplets at 66.80-7.17 and a

multiplet at o 7.28-7.77. The first set of multiplets correlates»

to the ethylene bridge protons and due to the rigidity of the

molecular framework and different magnetic environment of each

proton, the four protons are nonequivalent and show an ABCD

system (Figure 4). From figure 4, the coupling constants can be

calculated to be Jaq=6«5Hz, JA(.= 11.8Hz, Jg=5.7Hz,

JDn=11.8Hz, and J«n=11.8Hz. From the structure of 24 and the

magnitude of the coupling constants, the position of the protons

JAB 0

Jac=11.8H:

jad=.5HZ

BC=

JBD=11.8Hs

Jcd=11.8H5

ic

v

•~igUre NMR sPectrum of the ethylene birdge protons of 24 and

its analysis

on the ethylene bridge are tentatively assigned as shown in

figure 4. The singlet which appears at 65.43 correlates to the

proton at the 8-position. The high field shift of this aromatic

proton could be explained by the fact that it falls into the

upfxeld region of the para-substituted benzene deck

The second set of multiplets at 66.11-6.22 correlates to two

of the four protons on the para-substituted benzene ring and they

are indicated as protons A and B in figure 5. The high field

shift of these aromatic protons is due to the distortion of the

benzene deck which shows some olefinic character and the effect

of the upfield region of the meta-substituted benzene deck.

Protons A and B can be analyzed and the results afford coupling

constants Jg=8Hz, J=JgY=l• 5Hz, and JaY=BX= at,sorPton

of protons X and Y are obscured by the other aromatic protons

which appear at 6 7.28-7.77. The third set of multiplets at

66.80-7.17 corresponds to the three protons on the meta-

substituted benzene deck (figure 5). It shows an ABC system with

coupling constants ,g=Jg ,,=7.5Hz and t,=0. Therefore,

proton B' is a triplet while the other two are doublets. The

B'

A'. C'

A B

JA 'b' Jb' C'• 5 H z

JA'C'~°

JAB=8Hz

JAX=JBY=1 5Hz

JAY=JBX=0

HR

H .He

Hb

Hx Hy

7.0 6.0

Figure 5 NMR spectrum at 6 6.11-7.17 of 24 and its analysis

complexity of the fourth set of multiplet at 6 7.28-7.77 makes it

difficult to be analyzed and it represents the signals of the

other protons, i.e. X and Y, on the para-substituted benzene ring

and the protons on the ortho-substituted benzene ring.

(iiy By Cram's rearrangement method

When crystals of 1,2-benzo-[2,2]paracyclophane (32)' was

added to a hydrogen chloride gas saturated dichloromethane

solution containing aluminium chloride, a red solution was

generated. After stirring at -10 C for 2 hrs, 32 was recovered in

45% and the desired product 24 was obtained in 22.5% yield. The

aici3

HCl

ch2ci2

-10 °C

(32) (24)

product 24 exhibits NMR spectrum (NMR-5) with the same

characteristic signals which have been described previously.

Moreover, a base peak at me 254 was recorded in its mass

spectrum.

(B) Synthesis of 1,2-benzo-[2,2]metaparacyclophan-9-ene (30)

(i) By bromination, dehydrobromination procedure

The synthetic route towards 30 was shown in scheme VIII.

However, the bromination of compound 24 was not as trivial as the

bromination of 3,4-dimethy1-1,1':2',1-terpheny1 (43) which

Scheme VIII

NBS

AIBN

CH2C12

hv

(24)

Br

(55)

KoSu

THF

r. t.

(30)

has been previously discussed. Treatment of 24 with NBS and AIBN

under irradiation for 12 hrs resulted in the isolation of a

slightly yellowish oil as well as the starting material 24 inOA,

nearly equal amount after chromatography. The NMR spectrum (NMR-

6) of this oil is too complicated to be analyzed and signals

appear throughout the spectrum from 62.30 to 6 8.00. The mass

spectrum of it gives peaks at ne 334, 336, 412, 414, 416,

492, 494, 496 and 498 which represent the molecular ions of 55fAj

and polybrominated products. However, chromatographic studies

revealed that they were inseparable but compound 55 was believedOA

to be one of the major components in the oil. Moreover, the exact

position of the bromine moiety in the monobrominated product 55

cannot be determined due to the complexity of the NMR spectrum.

In order to reduce the amount of the undesired

polybrominated products, the reaction was not allowed to go to

completion. The oily mixture containing compound 55 was subjected

to dehvdrobromination without additional purification.

22Treatment of crude 55 with potassium tert-butoxide

smoothly gave the required product 30 in 13% yield. It forms

white crystals which melt at 89-90 °C (without recrystallization).

The base peak in its mass spectrum appears at _me 254 which

represents the molecular ion of 3£h In its NMR spectrum (NMR-7),

K0 tBu

BrTHF r. t.

(55)rAj

(30)

a singlet at 64.79 for the proton at the 8-position and a

multiplet at 66.72-7.77 for the olefinic and aromatic protons are

observed. The multiplet is tentatively analyzed in figure 6.

The analysis of the spectrum can be divided into four parts.

Firstly, two doublets at 66.72 and 67.22 are assigned to the two

olefinic protons and they show an AX system with coupling

constant J=10.3Hz. Secondly, the sub-multiplet at 6 6.85-7.15

corresponds to the three protons on the meta-substituted benzene

ring. It shows an ABC system with coupling constants

A' B 1 =B' C' an A'C,== Therefore, proton B' is a triplet

while the other two are doublets. Thirdly, the sub-multiplet at

67.38-7.77 correlates to the proton on the ortho-substituted

1

2

3

4;

A, D

B C

I

B

A'. C

sH,

u

u_

u

H

H

Hr

H H

8I

7

Figure—6 NMR spectrum at 56.72-7.77 of 1,2-benzo-[2,2]metapara-

cyclophan-9-ene (30) and its analysis

benzo-group. It is an ABCD system with coupling constants

JAB=JBC= CD,i=' Jg!ijQii=JiiQii= l. 7Hz and Jmqm=0. The low

field shift of protons A and DM is due to the proximity to the

two benzene decks.

Finally, the singlet at 66.95 can be attributed to the four

protons on the para-substituted benzene ring. The appearance of

this singlet, not a multiplet for these protons, might be due to

the reasons that the meta-substituted benzene ring flips rapidly

29or it sits perpendicularly on the para-substituted benzene deck

so that similar environment could be produced by the benzene and

the olefinic moiety. Moreover, the distortion of this benzene

deck to have olefinic character results in the high field shift

of these aromatic protons.

(ii) By Cram's rearrangement method

0 0 o o

When 1,2-benzo-[2,2]paracyclophan-9-ene (34)' was sub-

1 9

jected to HCl-AlCl-CFC at -10°C, an intensely red solution

was obtained. After working up, the desired product 30 would not

be isolated but instead, benzo[e]pyrene (56) was produced in 6%A«A.

A1C13

HCl•

CH2C12

-10'C

(34)

(56)

yield as 2 the only isolable product. Compound 56 forms goldenAj

needles with m.p. 172-175 °C( lita m.p. 178-179 °C). In its mass

spectrum, a base peak at nije 252 is observed and in its NMR

spectrum (NMR-8), sets of multiplets appear at 6 7.77-8. 92 arid it

is analyzed as figure 7. The spectroscopic data are in full

30a- cagreement with the literature value

(m)7.77

(m)o.90

(d)8.92

(s)8.06

(d)8.20;

(t) 8.05

Figure 7 H chemical shift (6) values for benzo[e]pyrene (56)

The production of benzo[e]pyrene (56) might follow the route'Xj'Xj

outlined in scheme IX. The two para-substituted benzene rings in

34 rearrange to meta-substituted benzene rings stepwisely, via

Scheme IX

aici3

HC1

ch2ci2

-10 'C

(34)

A1C13

HC1

CH2C12

-10 'C

trans annular

dehydrogenation

(56) (57)

30, to 1,2-benzo-[2,2]metacyclophan-9-ene (57) in the presence

31

of Lewis acid. Transannular dehydrogenation of 5j7 would lead to

56. The possible driving forces of the rearrangement appear to be

the gain in aromatic stabilization through the production of

compound 56 and the release of strain of the cyclophanes.r s.

(C) Synthesis of 1,2:9,10-dibenzo-[2,2jmetaparacyclophane (31) by

Cram's rearrangement method

The starting material, 1, 2:9,10-dibenzo-[2,2jmetaparacyclo-

phane (35), for the rearrangement can be prepared'

according to scheme X.

Scheme X

1) KoSu

THF'Br

Bi-

CSS)

2)

0

(59)

0

(60)

TiCl.4

LAH

NEt3

THF

(35)

1 9

When compound 35 was treated with HCl-AlCl-CtCl at

-10 °C, it gradually changed to yellow in color on stirring. After

working up, apart from the recovery of 7.5% of the starting

material 35, trace amount of a white solid (0.1 mg) with m.p.rVj

208-210°C was obtained as the only isolable product. From its

spectral data, it may possibly be chlorinated compound 61. Its

A1C1

HC1

ch2CI2

-10 °c

(35)

-CI

mass spectrum shows an 1:3 pattern at me 340 (M++2) and 338 (M+,

base peak) which gives evidence for a monochlorinated compound.

Further evidence is the appearance of peaks at me 303 (M+-C1)

and 302 (M+-HC1). Since the amount of 61 obtained was very small,'W,

it could only produce a weak NMR spectrum (NMR-9), which exhibits

two singlets at 6 5.17 and 6 6.42, and multiplets at 6 6.56-6.84,

and 67.20-7.72. The appearance of a singlet at 65.17 may probably

be an evidence for having a skeleton of a [2,2]metaparacyclophane

since the singlet at this region would correspond to the proton

at the 8-position and it is a characteristic of NMR spectra of

[2,2]metaparacyclophane family. The multiplets at 66.56-6.84

corresponds to the protons on the para-substituted benzene ring

and the meta-substituted benzene ring. The presence of a singlet

at 66.42 might indicate that the chloride atom is on the para

substituted benzene ring. The last multiplet correlates to the

(61)

protons on the two ortho-substituted benzene rings. Due to the

weaknesses of the signals, these peaks cannot be confidently

assigned and thus the exact position of the chlorine atom in

molecule 61 is not completely clear. Furthermore, the molecular

formula of 61 can be further confirmed by high resolution massOA,

spectrum. Due to the fact that compound 35 can be prepared only

in extremely small quantity, our effort in the synthesis and

unequivocal characterization of 61 is seriously hampered.OAj

(D) Spectral characteristics of [2,2]metaparacyclophanes

(i) NMR spectra

Due to the rigidity of the molecular framework and the

specific orientation of the benzene decks, each member in the

class of [2,2]metaparacyclophanes shows its NMR spectrum with

specific feature. The signals exhibit by the protons at 8-

positions (inner proton) are especially interesting because they

fall into the upfield region of the opposite para-substituted

benzene deck. Thus, they show unusual high field shift despite

the fact that they are aromatic protons.

32It has been reported that the signals of the inner protons

of compound 2 and 10 in their NMR spectra appear at 6 5.24 and

64.29, respectively. It seems that shorter bridge distance of the

65.24

f H

(2)

'H

(10)

64.29

two C=C bonds has a overwhelming effect than the widening of the

bridging carbon angle from 109 (sp) to 120 (sp). Hence, the

inner proton in 10 penetrates farther into the u-cavity than doesOA,

the one in 2 and thus the former is more shielded.

When compounds 24, 61 and 30 are compared, the following

observation is obtained. The signals of the inner protons in 24,

61 and 30, respectivelv, exhibit at 65.43, 65.17 and 64.79 in

65.43r H

(24)

' H

(61)

• CI 65.17

64.79f H

(30)

their NMR spectra. The compound with bridges having highest bond

order in this benzoannulated series gives the most shieldedV

i

inner proton, i.e., at 64.79 of compound 30.

(ii) UV spectra

The UV spectra of [2,2]cyclophanes are quite different from

those of simple alkyl benzenes and the main characteristic of the

spectra of the former is that there are usually absorption bands

at longer wavelength (when compared with simple alkyl benzenes).

These longer wavelength absorption bands have been termed the

cyclophane bands''. The position and the intensity of these

bands depend on the mean distance between the two benzene decks

and the deformation of the benzene rings.

The UV spectra of benzoannulated [2,2jmetaparacyclophanes

24, 30 and 61 as well as related [2,2]paracyclophanes 32, 34 and

35 have been recorded and they are represented in a scale of

log£ vs wavelength (nm) in figures 8, 9 and 10.

(24) (32)

(30) (34)

(61)

-CI

(35)

(220,4.65)

-(206.3.794

e

r

]

OJ

too

1—I

.(270.3. 18)

(300,2.24)

(311,2.13;

9nn 250 300 35C 400

(24)-

(32)

Wavelength (nm)

Figure 8 UV spectra of 24 and 32

•m'7.4. 77)

•(260,3.95)

(207,4.34

(266 ,3.42)] (339,2.86)

(310,2.49]

4

3

2

1

u

or-H

300 250 300 350 400

(30)

(34)

Wavelength (nm)

Figure 9 UV spectra of 30 and 34

-(222,4.74)

(266,3.60)

(235,3.25;(295.2.43

L

r

r

1

U)

fcCo

r~I

200 250 300 350 400

-CI

(35)

Wavelength (nm)

Figure 10 UV spectra of 61 and 35

V Conclusion

1,2-benzo-[2,2]metaparacyclophane (24) was synthesized both

179995. 19

by VBgtle-Boekelheide method'' and Cram s rearrangement

and 1,2-benzo~[2,2]metaparacyclophan-9-ene($£) was synthesized

22by the method of bromination and dehydrobromination of 24.

However, the third compound of our target molecules, namely,

1,2:9,10-dibenzo-[2,2]metaparacyclophane (31) still eludesrVj

preparation. Nevertheless, its chlorinated derivative 61 was

19produced by the Cram's rearrangement. Due to the fact that the

starting material 35 for the rearrangement can only beW|

synthesized in small amount, the yield of the rearrangemnt is

very low and the manipulation of the reaction condition is not

easy, therefore, this reaction is not recommended for preparation

of large quantity of 61.

On tne other hand, we might prepare the 1,2:9,10-dibenzo-

[2,2]metaparacyclophane (31) starting from 30 according to scheme

XI. Bromination of 30 might give the dibromide 62.

Dehydrobromination of 62 with potassium ter t--butoxide might giveIAj

an intermediate acetylene 63 which might be trapped with furan to

form epoxide 64. Deoxygenation of 64 might lead to 31.

Scheme XI

Br2

(30)r r(62)

Br

Br

KOtBu

0

0

(64)

TiCl,4

LiAlH,4

NEt3

THF

(63)A A

(31)AiA.

48

VI EXPERIMENTAL SECTION

General

JolvenLs usea were redistilled or purified and dried by

standard methods. All evaporation of solvents of organic solution

were carried out by a rotatory evaporator in conjunction with a

water aspirator.

Proton NMR spectra were recorded on a Jeol C-60HL (60MHz)

spectrometer or on a Bruker Cryopec WM250 (250MHz) spectrometer.

Deuterated chloroform was used as solvent and 6 (ppm) was

measured from TMS which serves as an internal reference. Mass

spectra were recorded on a VG Micromass 7070E spectrometer. UV

spectra were-recorded on a Varian Superscan 3 using ethanol as

solvent. IR spectrum was recorded on a Perkin-Elmer PE-283

spectrometer.

Merck silica gel-60 F254 precoated on aluminium sheets were

used for TLC studies and Merck silica gel (70-230 mesh) was used

for column chromatography. Melting points were measured with hot-

stage microscope and were uncorrected.

P-Iodo-toluene (37 26)

Water (1950 ml) was allowed to mix with 2-toluidine (36)

(150 g 1.4 moles), and then concentrated sulfuric acid (1170 g)

was added. The mixture was cooled to -20'C (.acetone-dry ice

bath). A solution of sodium nitrite (102 g 1.47 moles) in water

(600 ml) was added. Keeping at -20'C, the-resulting mixture was

added in portions to a solution of potassium iodide (392 g 2.36

moles) and iodine (40 g 0.16 moles) in water (400 ml). After the

temperature was allowed gradually to rise to room temperature,

the mixture was warmed to 40 C and kept at this temperature with

stirring for 5 hrs. It was shaken with sodium thiosulfate

solution (0.6 N; 3x300 ml). The aqueous layer was extracted with

chloroform (3x300 ml). The combined chloroform solution was

washed with sodium thiosulfate solution (0.6 N; 3x200 ml). It was

dried over anhydrous sodium sulfate. The solvent was evaporated

and the residue was distilled under reduced pressure (70C 0.3-

0.5 mmHg) to give the crude product. Crystallization from ethanol

led to white crystals 37 (196 g; 64%): m.p. 34-35 C; b.p. 70 C

0.3-0.5 mmHg; 1H NMR, 6 2.25 (s, 3H, -CH3), 6.80-7.60 (m, 4H,

Ar-H); MS, me 218 (M+), 91 (M+-l).

4-methy1-2'-nitro biphenyl (39) and 4-methy1-2'-nitro biphenyl

ether (44)

To a stirring solution of p-iodo-toluene (37) (80 g; 0.37

moles) and o-nitro-benzoic acid (38) (102 g; 0.61 moles) in

quinoline (194 ml) at 155 °C was added rapidly copper (I) oxide

(29.1 g; 0.20 moles). After the violent reaction proceeded for 30

mins at 190-200 C, it was allowed to cooled to room temperature.

Ether (400 ml) was added to dilute the reaction mixture. The

precipitate formed was filtered. The ethereal solution was washed

with hydrochloric acid (2 N; 2x200 ml) and water (2x200 ml). It

was dried over anhydrous sodium sulfate. Quinoline was removed

and the orange-red crude product was distilled (110-140 'C 0.3-

0.5 mmHg) under reduced pressure. The distillate obtained was

chromatographed on silica gel (solvent, hexanesethy1 acetate:

251) and the orange-red fraction containing 4-methy1-2'-nitro

biphenyl (39) and 4-methy 1-2'-nitro biphenyl ether (4,4) (TLC

R:0.30-0.38; solvent,hexanesethyl acetate: 91) was collected

(4.7 g). It was used for further reaction without further

purification: b.p. 110-140 'C0. 3-0. 5 mmHg; NMR, 62.28, 2.30

(2s, 3H, -CH3), 6.90-8.00 (m, 8H, Ar-H); MS, me_ 229 (M+ of 44),

213 (M+ of 39).

252-Amino-4'-methyl biphenyl (40) and 2-amino-4'-methyl biphenyl

ether (45)

A spatula of Raney nickel was added to a solution of the

mixture of 4-methy1-2'-nitro biphenyl (39) and 4-methyl-2'-nitro

biphenyl ether (44) (1 g) in ethanol (8 ml). It was heated to

70C. Hydrazine hydrate (80%; 1 ml) was slowly added. After all

the nitrogen was evolved, an additional spatula of Raney nickel

was added. The mixture was stirred under reflux at 83'C for 3.5

hrs. It was cooled and filtered. The residue was washed with

chloroform. The organic and aqueous layers of the filtrate were

separated and the aqueous layer was extracted with chloroform

(3x30 ml). The combined organic solution was dried over

anhydrous sodium sulfate. The solvent was evaporated and the

residue was chromatographed on silica gel (solvent, hexanesethyl

acetate: 251) to give a mixture of 2-amino-4'-methy1 biphenyl

(4$,) aRd 2-amino-4' -methyl biphenyl ether (45) (TLC R:0.15-0.23;

solvent, hexanes.ethyl acetate: 91) (0.64 g). It was used for

further reaction without additional purification: H NMR, 62.28,

2.30 (2s, 3H, -CH,), 3.65 (s, 2H, -NH2), 6.60-7.40 (m, 8H,

Ar-H); MS, me 183 (M+ of 45), 199 (M+ of 40).

2-Iodo-4'-methyl biphenyl (41) and 2-iodo-4'-methyl biphenyl

ether (46)

A mixture (6.2 g) containing 2-amino-4'-methyl biphenyl (40)

and 2-amino-4'-methyl biphenyl ether (45) was added to a mixture

of water (83 ml) and concentrated hydrochloric acid (9.5 ml). The

resulting mixture was stirred and cooled to 0 C. A cooled

solution (0C) of sodium nitrite (2.5 g; 0.036 moles) in water (6

ml) was added. To the resulting diazonium salt was added a

solution of potassium iodide (11 g; 0.066 moles) and iodine (0.23

g; 0.91 mmoles) in water (21 ml). The reaction mixture was

heated to 35'C. Chloroform (50 ml) was added. The organic layer

was separated and washed with sodium thiosulfate solution (0.6 N;

50 ml) and sodium hydroxide solution (5%; 50 ml) and water (50

ml). It was dried over anhydrous sodium sulfate. The solvent was

evaporated and the residue was chromatographed on silica gel to

give 2-iodo-4'-methyl biphenyl (41) (2.4 g): H NMR (NMR-1),

62.35 (s, 3H, -CH3), 6.80-8.10 (m, 8H, Ar-H); MS, me 294 (M+),

167 (M+-l), 152 (M+-I-CH3) and 2-iodo-4'-methyl biphenyl ether

(46) (6.0 g): 1H NMR (NMR-2), 62.30 (s, 3H, -CH,), 6.70-8.00 (m,

8H, Ar-H); MS, me 310 (M+), 183 (M+-l), 168 (M+-I-CH3), 91

(CyHy); IR, 1021 cm (symmetric stretching of C-O-C), 1239 cm

(asymmetric stretching of C-O-C), 1469-1605 cm (stretching of

C-C), 2928 and 3072 cm (stretching of C-H); exact mass: calc'd

for C13H11I0 309.9856 found 309.9860.

3,4-Dimethy1-1,1':2',1-terphenyl (43)

A solution of 2-iodo-4'-methyl biphenyl (41) (0.9396 g; 3.2rVj

mmoles) in absolute ether (6 ml) was added slowly to a solution

of n-butyllithium (1.7 M in hexane; 2.2 ml, 3.74 mmoles) in ether

(3 ml) under nitrogen at O'C. It was stirred for 0.5 hr. Then, at

the same temperature, a solution of 3-methyl-2-cyclohexen-l-one

() (0.3758 g; 3.42 mmoles) in ether (4 ml) was added. The

mixture was stirred under reflux for 3 hrs and sulfuric acid (2

M; 40 ml) was added. The resulting mixture was stirred for 3 days

and was extracted with ether (3x60 ml). The ethereal solution was

washed with sodium bicarbonate solution (5%; 60 ml), water (60

ml) and was dried over anhydrous sodium sulfate. The solvent was

evaporated to give a residue, to which DDQ (0.6018 g; 2.65

mmoles) and toluene (12 ml) were added. The mixture was stirred

under reflux for 5 hrs. The insoluble components were filtered

and the solvent was evaporated. The residue was chromatographed

on silica gel (solvent, hexanes) to give compound 43 (0.2143 g;

26%): 1H NMR, 62.25, 2.30 (2s, 6H, -CH,), 7.00-7.50 (m, 12H,.

Ar-H); MS, me 258 (M+), 243 (M+-CH3), 228 (M+-2CH3).

3,4-Bis(bromomethy1)-1,1':2',1-terphenyl (25)f,

AIBN (small amount) was added to a stirring mixture of 3,4'1-

dimethyl-1,12',ln-terphenyl (43) (0.2143 g; 0.831 mmoles) andAj

NBS (0.3089 g; 1.74 mmoles) in absolute dichloromethane (10 ml).

The mixture was irradiated with a sunlamp (200 W) for 16 hrs. The

solvent was removed and the residue was chromatographed on

silica gel to give the dibrominated product 25 (0.3075 g; 90%)

as an oil: ~H NMR, 64.25 (s, 2H, CH2-), 4.38 (s, 2H,

6.90-7.36 (m, 12H, Ar-H); MS, me 418 (M++4), 416 (M++2), 414

(M+), 337 (M+-Br+2), 335 (M+-Br) and the monobrominated

compounds 50 and 51 (0.0197 g; 7%): H NMR, 6 2.25-2.30 (2s, 3H,rf rbrb

-CH3), 4.50 (s, 2H, -CH2-), 6.85-7.50 (m, 12H, Ar-H); MS, nj_e

338 (M++2), 336 (M+), 257 (M+-Br).

2 2l,2-Benzo-[2,2]metaparacyclophane (24)

rAJ

3,4M-Bis(bromomethyl)-1,1':2',1M-terpheny1 (25) (0.1260 g;

0.304 mmoles) in dry ether (30 ml) was added slowly to a solution

of phenyHithium (0.6 N; 4.6 ml, 2.76 mmoles) in dry ether (12

ml). It was stirred for 22 hrs. Then,diluted sulfuric acid (1 M;

40 ml) was added. The aqueous layer was extracted with ether

(3x30 ml). The combined ethereal solution was dried over

anhydrous sodium sulfate and the solvent was evaporated. The

residue was chromatographed on silica gel (solvent,

hexanesbenzene: 91) to afford 1,2-benzo-[2,2]metaparacyclophane

(24) (23.1 mg; 30%) which was recrystallized from benzene: m.p.

115-118'C (lit17 m.p. 118-119 'C); 1H NMR (NMR-3), «2.20-3.30 (m,

4H, -(Ct-j ABCD system, AB=' Jq=11.8Hz, Jb=6.5Hz,

Jbc=5.7Hz, Jbd=11.8Hz and JCD= 11.8Hz), 5.43 (s, 1H, Ar-H),

6.11-6.22 (m, 4H, Ar-H, AB system, JAB=8Hz, Jx=JBy=l•5Hz and

Jay=BX=' 6.80-7.17 (m) 3H, Ar-H, ABC system, b=JBq=7•5Hz and

Jac=0) 7.28-7.77 (m, 6H, Ar-H); UV (figure 8), nmlog e,

2063.79, 2902.52, 3002.24; MS me 256 (M+).; exact mass: calc'dV.

for 2qHb 256.1252, found 256.1228. Dimer 52 was also separated

(9.4 g; 12%): m.p. 103-105 °C (without recrystallization); H NMR

(NMR-4), 6 2.80-3.10 (m, 8H, -(CH2)2-), 6.40-7.50 (m, 24H, Ar-H);

MS me 512 (M+); exact mass: calc'd for C4qH32 512.2504, found

512.2497.

1 Q

Lewis acid promoted rearrangement of 1,2-benzo-[2,2]-

paracyclophane (32)'

A suspension of aluminium chloride (125 mg; 0.0938 mmoles)

in dichloromethane (2 ml) was saturated with hydrogen, chloride

gas (from cylinder, Merck) at 0'C. The resulting solution was

cooled to -10'C (acetone-dry ice bath). To this solution, 1,2-

benzo-[2,2]paracyclophane (32) (4 mg; 0.0156 mmoles) was added

and the mixture was stirred at the same temperature for 2 hrs.

The solution was poured into ice and water (5 ml) and was

extracted with chloroform (2x10 ml). The organic layer was washed

successively with hydrochloric acid (2 N; 10 ml) and saturated

sodium bicarbonate solution (10 ml). The organic solution was

dried over anhydrous sodium sulfate and the solvent was removed.

The residue was chromatographed on silica gel (solvent, hexanes)

to furnish the starting material '32 (1.8 mg; 45%) and 1,2-benzo-

[2,2]metaparacyclophane (24) (0.9 mg; 22.5%). The physical and

spectroscopic data of 32 and 24 are identical with authenticrVl OOi

samples.

1,2-benzo-9-bromo-[2,2]metaparacyclophane and

1 71,2benzo-10bromo[2,2]metaparacyclophane mixture (55)

A A.

AIBN (small amount) was added to a mixture of 1,2-benzo-

[2,2]metaparacyclophane (24) (39.8 mg; 0.155 mmoles), NBS (73.4fj

mg; 0.412 mmoles) in dry dichloromethane (5 ml). The mixture was

irradiated with a sunlamp (200 W) for 12 hrs. The solvent was

evaporated and carbon tetrachloride (5 ml) was added. The

succinimide was filtered and the solvent of the filtrate was

removed. The residue was chromatographed on silica gel (solvent,

hexanesbenzene: 91) to afford the starting material 24OA,

(13.6 mg; 34.2%), the isomeric mixture 55 .and some

polybrominated products (TLC RiO.34, solvent, hexanesbenzene:

91) (14.8 mg): 1HNMR (NMR-6), 5 2.30-8.00 (m); MS me 496, 494,

492 (M+ of tribrominated product), _me_ 416, 414, 412 (M+ of

dibrominated product), me 336, 334 (M+ of 55).

? 91,2-Benzo-[2,2]metaparacyclophan-9-ene (30)TY

A solution of potassium tert-butoxide (0.6136 g; 5.473

mmoles) in THF (5 ml) was added dropwisely to a solution of a

crude brominated cyclophanes 55 (18 mg) in THF (3 ml). TherVj

mixture was stirred for 18 hrs.Diluted hydrochloric acid (2 N; 20

ml) was added. The resulting solution was extracted with

dichloromethane (3x30 ml) and the organic extract was dried over

anhydrous sodium sulfate. The solvent was evaporated and the

residue was chromatographed on silica gel (solvent,

hexanesbenzene: 91) to give 1,2-benzo-[2,2]metaparacyclophan-

9-ene (30) (2.3 mg; 13%): m.p. 89-90'C; 1H NMR (NMR-7), 64.79

(s, 1H, Ar-H), 6.72, 7.22 (2d, 2H, olefinic H, AX system,

J=10.3Kz), 6.85-7.15 (m, 3H, Ar-H, ABC system, Jg=Jg,= 7. 5Hz,

JAc=°), 6.95 (s, 4H, Ar-H), 7.38-7.77 (m, 4H, Ar-H, ABCD

s y s t sm j AB~~BC~CD~• 4-H z? BD~AC~ AD~~ (figurG

nmlog e', 2074.34, 2603.95, 339,2.86; MS me_ 254 (M+); exact

mass: calc'd for 2014 254.1095 found 254.1099.

1 Q

Lewis acid promoted rearrangement of 1,2-benzo-[2,2Jparacyclo-

phan-9-ene (34)'

A suspension of aluminium chloride (9.6 mg; 0.29 mmoles) in

dry dichloromethane (2 ml) was saturated with hydrogen chloride

gas (from cylinder; Merck) at 0°C. It was cooled to -10 °C

(acetone-dry ice bath). To this solution was added a solution of

1,2-benzo-[2,2]paracyclophan-9-ene (34) (9.6 mg; 0.0378 mmoles)

in dichloromethane (0.5 ml). The mixture was stirred at the same

temperature for 2 hrs. It was then added to ice and water mixture

(10 ml). The organic phase was washed successively with diluted

hydrochloric acid (2 N; 20 ml), sodium bicarbonate solution (5%;

20 ml) and dried over anhydrous sodium sulfate. The solvent was

evaporated and the residue was chromatographed on silica gel

(solvent, hexanesbenzene: 91) to yield benzo[e]pyrene (56)j

(0.6 mg; 6.3%): m.p. 172.5°G (recrystallized from benzene)

(lit33a m.p. 178-179'C); 1H NMR (NMR-8), 67.77, 8.90 (m, 4H,

Ar-H, 22 system)j 8.05 (t, 2H, Ar-H), 8.06 (s, 2H, Ar-H),

8.20 (d, 2H, Ar-H), 8.92 (d, 2H, Ar-H); MS _me 252 (M+); exact

mass: calc'd for 2012 252.0939 found 252.0942.

9,12-dihydro-9,12-endoxo-5,8:13,16-dietheno-dibenzo-

cyclododecene (59)'

Freshly distilled furan (5 ml; 68.75 mmoles) was added to a

suspension of potassium t_er_t-butoxide (1.0313 g; 9.199 mmoles) in

THF (4 ml) at room temperature. To this stirring mixture, a

solution of 9,9-dibromo-l,2-benzo-[2,2]paracyclophane (58)'

(37 mg; 0.0898 mmoles) in THF (3 ml) was added dropwisely. The

mixture was stirred for 22 hrs. Diluted hydrochloric acid (2 N; 30

ml) was added. The resulting solution was extracted with ether

(3x30 ml) and dried over anhydrous sodium sulfate. The solvent

was evaporated and the residue was chromatographed on silica gel

(solvent, benzene) to give the required product 59 (2.4 mg; 8.4

%): m.p. 205-207 'C (without recrys tallization); H NMR, 65.82 (s,

2H, methine-H), 6.12-6.70 (m, 8H, Ar-H, ABCD system), 7.40-7.59

(m, 4H, Ar-H, AA'BB' system), 7.49 (s, 2H, olefinic H); MS _m_e

320 (M+) and 9,10-dihydro-5,8:11,14-diethenobenzocyclododecene-9-

one (7.6 mg; 31.3%): m.p. 229-232 'C (without

recrystallization); H NMR, 63.88 (s, 2H, -CH2-), 6.63-6.75 (m,

8H, Ar-H), 7.44-7.67 (m, 4H, Ar-H); MS me 270 (M+), 242 (M+-

CO).

1,2:9,10-Dibenzo-[2,2]paracyclophane (35)

THF (5 ml) was added to titanium tetrachloride (0.1 ml;

0.855 mmoles) under nitrogen. Then, lithium aluminium hydride (20

mg; 0.530 mmoles) was added, which was followed by triethylamine

(34.8 mg; 0.348 mmoles) in THF (0.5 ml). The mixture was refluxed

for 0.5 hr. Then, 9 ,12-dihydro-9,12-enaoxo-5,8:13,16-dietheno-

dibenzocyclododecene (59) (2.4 mg; 0.0075 mmoles) in THF (2 ml)

was added and the mixture was stirred at room temperature for 2

hrs and at 60 'C for 15 mins. Saturated potassium carbonate

solution (30 ml) was added and the resulting mixture was stirred

for 3 hrs. It was extracted with dichloromethane C3x30 ml). -The

extracts were dried over anhydrous sodium sulfate and the solvent

was evaporated. The residue was chromatographed on silica gel

(solvent, benzene) to furnish 1,2:9,10-dibenzo-[2,2]

paracyclophane (3,5) (2.2 mg; 93.4%): m.p. 260-265 C (without

recrystallizatiori); ''H NMR, 66.65 (s, 8H, Ar-H), 7.44-7.69 (m,

8H, Ar-H); MS me 304 (M+).

19Lewis acid promoted rearrangement of 1,2:9,10-dibenzo-

[ 2, 2 ]paracyclophane (35)

A suspension of aluminium chloride (1.3 mg; 0.098 mmoles) in

dichloromethane (1 ml) was saturated with hydrogen chloride gas

(from cylinder; Merck) at O'C. It was cooled to -10'C (acetone-

dry ice bath). To this solution, a solution of 35 (4 mg; 0.0132

mmoles) in dichloromethane (0.5 ml) was added and the resulting

mixture was stirred for 3 hrs at the same temperature. The

solution was poured into ice and water mixture (5 ml) and the

organic phase was washed with diluted hydrochloric acid (2 N; 15

ml) and sodium bicarbonate solution (5%; 15 ml). The organic

layer was dried over anhydrous sodium sulfate and the solvent

was evaporated. The residue was chromatographed on silica gel

(solvent, hexanesbenzene: 91) -to give a chlorinated product 61

(0.1 mg): m.p. 208-210 'C (without recrystallizatiori); h NMR

(NMR-9), S 5.17 (s, 1H, Ar-H), 6.42 (s, 1H, Ar-H), 6.61-6.84 (m,

7H, Ar-H), 7.20-7.77 (m, 8H, Ar-H); UV (figure 10), nmlog c,

2353.25, 2952.43; MS me 340 (M++2), 338 (M+), 303 (M+-C1), 302

(M+-HC1); exact mass: calc'd for 3415! 338.0862 found

338.0857.

VII REFERENCES

1. Cram,D.J.; Steinberg,H. J.Am.Chem.Soc. 1951, 73, 5691-5704.

2. Cyclophanes; Keehn,P.M.; Rosenfeld,S.M., Ed.; Academic

Press: New York, 1983; vol 1 and 2.

3. Topics in Current Chemistry; VBgtle,F.,Ed.: Springer-Verlag:

Berlin, 1983; vol 113.

4. Topics in Current Chemistry; VBgtle,F.;Ed.; Springer-Verlag:

Berlin, 1983; vol 115.

5. Cram,D.J.; Cram,J.M. Acc.Chem.Res. 1971, 4, 204-213.

6. Boekelheide,V. In Topics in Current Chemistry; VBgtle,F.,

Ed.; Springer-Verlag: Berlin, 1983; vol 113, pp87-143.

7. Shieh,C.F.; McNally,D.; Boyd,R.H. Tetrahedron 1969, 25, 3653-

3665.

8. Boyd,R.H. Tetrahedron 1966, 22, 119-122.

9. a) Hefelfinger,D.T.; Cram,D.J. J.Am.Chem.Soc. 1971, 93, 4767-

4772.

b) Hefelfinger,D.T.; Cram,D.J. J.Am.Chem.Soc. 1970, 92, 1073-

1074.

c) Akabori,S.; Hayaski,S.; Nawa,M.; Shiomi,K. Tetrahedron

Lett. 1969, 3727-3728.

10. Sherrod, S. A.; da Costa, R.L.; Barnes,R.A.; Beokelheide, V.

J.Am.Chem.Soc. 1974, 96, 1565-1577.

11. Boekelheide,V.; Anderson,P.H.; Hylton,T.A. J.Am.Chem.Soc.

1974, 96, 1558-1564.

12. VBgtle,F.; Neumann,P. Synthesis 1973, 85-103.

13. Boekelheide,V.; Anderson,P.H. Tetrahedron Lett. 1970, 1207-

1208.

14. Boekelheide,V.; Tsai,C.H. J.Org.Chem. 1973, 38, 3931-3934.

15. Seebach.D.; Jones ,N.R.; Corey,E.J. J.Org.Chem. 1968, 33, 300-

305.

16. Hylton.T.; Boekelheide,V. J.Am.Chem.Soc. 1968, 90, 6887-6888.

17. Wittek,H.; V8gtle,F. Chem.Ber. 1982, 115, 1363-1366.

18. a) Cram,D.J.; Helgeson,R.C.; Lock,D.; Singer,L.A. J.Am.Chem.

Soc. 1966, 88, 1324-1325.

b) Delton,M.H.; Gilman,R.E.; Cram,D.J. J. Am. Chem. Soc. 1971,

93, 2329-2330.

19. Hefelfinger,D.T.; Cram,D.J. J.Am.Chem.Soc. 1971, 93, 4754

4766.

20. Gilman,R.E.: Delton,M.M.; Cram,D.J. J.Am.Chem.Soc. 1972, 94,

2478-2482.

21. McCaulay,D.A.; Lien,A.P. J.Am.Chem.Soc. 1952, 74, 6246-6250.

22. Jacobson,N.: Beokelheide,V. Angew.Chem.,Int.Ed.Engl. 1978

17,46-47.

23. Chan,C.W.; Wong,H.N.C. J.Am.Chem.Soc. 1985, 107, 4790-4791.

24. Chan,C.W. Undergraduate Thesis, The Chinese University of

Hong Kong, 1985.

25. Hammerschmidt,E.; VUgtle,F. Chem.Ber. 1979, 112, 1785-1790.

26. Lucas,H.J.; Kennedy,E.R. Org.Syn.Coll.Vol. 1943, 2, 351-352.

27. Avran,M.; Mateescu,G. Infrared Spectroscopy; Wiley

Interscience: New York, 1972; p283.

28. Evans,J.C.W.; Allen,C.F.H. Org.Syn.Coll.Vol. 1943, 2, 517-

518.

29. a) Haenel ,M-.W.; Lintner,B.; Benn,R.; Ruf ihska, A.'; Schroth,G.;

Krllger,C.; Hirsch,S.; Irngartinger ,H.;. Schweitzer ,D.

Chem.Ber. 1985, 118, 4884-4906.

b) Boekelheide,V.; Galuszko,K.; Szeto,K.S. J. Am.Chem.Soc.

1974, 96, 1578-1581.

30. a) Cook,J.W.; Hewett,C.L. J.Chem.Soc. 1933, 398-405.

b) Barfield,H.; Grant,D.M.; Ikenberry,D. J.Am.Chem.Soc. 1975,rjrjrj

97_, 6956-6961.

c) Mitchell,R.H.; Yan,J.S.H.; Dingle,T.W. J.Am.Chem.Soc.

1982, 104, 2551-2559.

31. a) Nishiyama,K.; Hata,K.; Sato,T. Tetrahedron 1975, 31, 239-

244.

b) Sato,T.; Akabori,S.; Muto,S.; Hata,K. Tetrahedron 1968,

24, 5557-5567.

32. Mitchell,R.H. In Cyclophanes; Keehn,P.H.; Rosenfeld,S.M.3

Ed.; Academic Press: New York, 1983; vol 1, pp241-310.

VIII SPECTRA

NMR-1

NMR-2

NMR-3

NMR-4

NMR-5

NMR-6

NMR-7

NMR-8

NMR-9

IR-1

2-iodo-4'-methyl biphenyl (41)

2-iodo-4'-methyl biphenyl ether (46)

1,2-benzo-[2,2]metaparacyclophane (24)

dimer 52

Cram's rearrangement product-

l,2-benzo-[2,2]metaparacyclophane (24)

dibromide mixture 55

l,2-benzo-[_2,2 J me taparacyclophan-9 -ene (30;

Cram's rearrangement product-

benzo[e]pyrene (56)

Cram's rearrangement product-

chlorinated compound 61

2-iodo-4'-methyl biphenyl ether (46)

• NMR-1

.1

8 7 6 5 4 3 2 1

--NMR—2--::

'I

'0

e 8 7 6 5 4 3 2 1 nnm

NMR-3

chci

39

10 9 8 7 6 5 4 3 2

NMR-4

CHC13

3.3 3.0 2.7

8 7 6

CHC13

10 9 8 7 6 54 32 1 0

NMR-5

CHC13

8'- 7 6

£ 2

CHC1

10 9 8 7 6 5 4 3 2 1 0

NMR-6Br

i r iJ t rrrf, 0 o l r y

10 9 8 7 6 5 4 3 2 1 U

CHC13

NMR-7

chci3

8 7

''''' V 6 5 4 3 2 1 0

NMR-8

CHC1

9

r

8

r f

7

CHC10

TrT 1 1' r~~R~r~r~~l' T'' 6-1' 5 r'' r~~4~~r~~1' Q'

NMR-9

CI1C1

•CI

7.0 6.0 5.1

4.0 5.0 MICROMETERSi

6.0 7.0 8.0 P n 10 12 14 ie

IR-1

I

0

3000 2500 2000 1800 1600 1400 WAVENUMBER (CM'1) 1000 800