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. '. | I-‘ " I "— 'v- - u . . ' fi .'
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ABSTRACT

IDENTIFICATION OF A THERMAL ADDITION PRODUCT OF
7-METHOXYCYCLOHEPTATRIENE AND
DIMETHYL ACETYLENEDICARBOXYLATE

BY

John Cord Van Heertum

Cycloheptatrienes are reported to yield substituted
6,7—dicarbomethoxy—tricyclo[3.2.2.02'4]nona—6,8-dienes as
the major reaction products from their condensation with
dimethyl acetylenedicarboxylate. In one case3, 3,4—dicarbo-
methoxy4bicyclo[3.2.2]nona-2,6,8-triene (g) has been identi-
fied as a byproduct from the cycloaddition of cyclohepta-
triene (l) to dimethyl acetylenedicarboxylate. No other
addition products have been reported in the literature.

We have found that 7-methoxycycloheptatriene (E) forms
a complicated mixture when reacted with dimethyl acetylene-
dicarboxylate. The expected product, 6,7—dicarbomethoxy-3-
methoxy-tricyclo[3.2.2.02:4]nona-6,8-diene (Q) was not de-
tected in the reaction mixture. One product has been iso-
lated and identified as 3,4,5,6,10,11-hexacarbomethoxy-7-
methoxy—tricyclo[6.3.2.02I7]trideca-3,5,9,12-tetraene (1)
based on its ir, uv, nmr, mass spectrum, and elemental

analyses.

John Cord Van Heertum

 

E = COZCH3

This 3:1 adduct Z, of dimethyl acetylenedicarboxylate and
Q, has been found to be very unreactive toward bromination
and low pressure hydrogenation. Oxidation yielded intract-
able mixtures. High pressure hydrogenation as well as
treatment with acid and heating above its melting point re—
sulted in the loss of methanol from ‘Z to give 3,4-dicarbo-
methoxy-6,7—(2',3',4',5'—tetracarbomethoxy-benzo)-bicyclo-

[3.2.2]nona-2,6,8—triene (g).

E = COZCH3

IDENTIFICATION OF A THERMAL ADDITION PRODUCT OF
7~METHOXYCYCLOHEPTATRIENE AND
DIMETHYL ACETYLENEDICARBOXYLATE

BY

John Cord Van Heertum

A THESIS

Submitted to
Michigan State University
in partial fulfillment of the requirements
for the degree of

MASTER OF SCIENCE

Department of Chemistry

1974

To My Wife

Linda

ii

ACKNOWLEDGMENTS

The author wishes to express his sincere appreciation
to Dr. Eugene LeGoff for suggesting this project and for his
guidance during the investigation.

The author is also grateful to the following people for
their assistance: Dr. Lowell Markley for his many sugges-
tions and advice during the investigation; Dr. Michael Gross
for determining the nmr coupling constants of the 3:1
adduct (2).; Dr. Robert Iwamasa for confirming the nmr
coupling constants of Z and for performing a shift reagent
experiment which confirmed the proposed structure of Z;
and to Dr. Jack Arrington for his suggestions concerning
the preparation of this thesis.

The author is particularly appreciative to The Dow
Chemical Company for providing the analytical services,
laboratory facilities and financial support necessary to

complete this investigation.

iii

 

 

 

 

TABLE OF CONTENTS

Page
INTRODUCTION . . . . . . . . . . . . . . . . . . . . . 1
RESULTS 0 O 0 O 0 0 O O O O O 0 0 0 0 O O O O O O O O 4

EXPERIMENTAL . . . . . . . . . . . . . . . . . . . . . 19

General Procedures . . . . . . . . . . . . . . . 19
7-Methoxycycloheptatriene (é) . . . . . . . . 20

3,4,5,6,10,11—Hexacarbomethoxy-7-methoxy-
tricyclo[6.3.2.02:7]trideca—3,5,9,12-
tetraene (Z) . . . . . . . . . . . . . . . . . 20

3—Methoxycycloheptatriene (2). . . . . . . . . 21

Reaction of 3-methoxycycloheptatriene (2) with
dimethyl acetylenedicarboxylate . . . . . . . 21

1—Methoxycycloheptatriene (12) . . . . . . . . 22

Reaction of 1-methoxycycloheptatriene (12) with
dimethyl acetylenedicarboxylate . . . . . . . 22

3,4-Dicarbomethoxy-6,7(2',3',4',5'-tetracarbo—
methoxy-benzo)—bicyclo[3.2.2]nona—2,6,8-triene
(g) 0 O O O O O O O O O O O O O O O O O O O O 22
Attempted bromination of Z’. . . . . . . . . . 24
Attempted hydrogenation of Z’. . . . . . . . . 24
Ruthenium dioxide oxidation of Z’. . . . . . . 25

Potassium permanganate oxidation of Z . . . . 25
BIBLIOGRAPIN O O O O O O O O O O O O O O C O O O O O O 27

APPENDIX . O O O O C . O C O O O O O O O O O O O O O C 28

iv

Figure

1.

10.
11.

12.

LIST OF FIGURES

Possible configurations for the 3:1 adduct 1

Nmr comparisons of compounds Z’and 8’. . . .

Proposed mechanism for preparation of 1

Infrared Spectrum of 7—methoxycycloheptatriene

(g)

Infrared spectrum of 3-methoxycycloheptatriene

(9’) O O O O O O O O C O O O O 0
Infrared Spectrum of 3:1 adduct
Infrared spectrum of 3:1 adduct

Infrared spectrum of derivative

Nmr Spectrum of 7—methoxycycloheptatriene (g)
Nmr Spectrum of 3—methoxycycloheptatriene (g)

Nmr spectrum of 3:1 adduct 1 . . . .

Nmr spectrum of derivative 8 . .

~

Z,
3,

£3,

Page

7

18

28

28
29
29
30
30
31
31

32

stud.

MC.

1am

ne

‘elc

Until

y

 

 

CRY]

U»

Ln

INTRODUCTION

Cycloheptatrienes are perhaps the most thoroughly
studied of the odd—numbered cyclic-polyenes CH2(CH=CH)n,
(n = 1,2,...).1 They are often characterized by derivatiza—
tion with a strong dienophile such as dimethyl acetylene-
dicarboxylate. The thermal cycloaddition of dimethyl acety-
lenedicarboxylate to cycloheptatriene (1) has been shown to
yield 6,7—dicarbomethoxy43jcyclo[3.2.2.02o4]nona-6,8-diene
(2) and involves norcaradiene (g) as an intermediate.2
Until recently analogs of 2 were the only identified pro-
ducts of the thermal addition of dimethyl acetylenedicar-

boxylate to cycloheptatrienes.

 

E-CEC-E ,/' // E

 

 

(DJ

E = COZCHa

In 1965, Goldstein3 reported the isolation of 3,4-di-
carbomethoxy—bicyclo[3.2.2]nona—2,6,8—triene (i) as a minor
reaction product from the thermal addition of dimethyl
acetylenedicarboxylate to 13 The following mechanism was

proposed for this reaction:

 

 

01

(I)
Ff

 

Other than 3 and analogs of 2/ no other reaction products of
the thermal addition of dimethyl acetylenedicarboxylate to
cycloheptatrienes have been reported in the chemical
literature.

In 1967, while investigating the photochemistry of
7-methoxycycloheptatriene (5), J. P. Szendry4 attempted to
derivatize 5 with dimethyl acetylenedicarboxylate. The
expected products, 6,7—dicarbomethoxy-3—methoxy—tricyclo-
[3.2.2.02a4]nona—6,8—diene (Q), was not detected in the
reaction mixture, however. The only product isolated was
shown by nmr, mass Spectroscopy, and elemental analysis to
be a 3:1 adduct of dimethyl acetylenedicarboxylate and 5;

No structure was determined for this 3:1 adduct.

/__\ +E—CEC-E ___. ll/ /EE

2

20')

E = COZCH3

The purpose of this work was to determine the structure
of this 3:1 adduct by re—examination of the analytical data
and by chemical derivatization and to prOpose a possible

mechanism for the reaction.

RESULTS

Based on results to be given below, the structure of
the 3:1 adduct4 formed from the thermal addition of dimethyl
acetylenedicarboxylate to 7-methoxycycloheptatriene (5) has
been shown to be 3,4,5,6,10,11-hexacarbomethoxy—7-methoxy—

tricyclo[6.3.2.02'7]trideca—3,5,9,12-tetrene (Z).

 

COZCH3

Redetermination of the mass spectrum and the 100 MHz
nmr again confirmed that the compound is a 3:1 adduct of
dimethyl acetylenedicarboxylate and 7-methoxycyclohepta—
triene (5). The mass Spectrum did not give a molecular ion.
The highest ion observed wasiflzm/e 516 which corresponds to
7-CH3OH from the loss of the methoxy group and the adjacent
proton from Z; The nmr afforded perhaps the most useful
information. The chemical Shifts and coupling constants,
determined by decoupling, for the individual protons are

6 7.23(d of d,1,g1,4 = 8.5 Hz and g1,5 = 1.3 Hz, H1),
4

5
6.28(t,1,g_2,3 = 8 Hz, 92,4 = 7 Hz and g2,7 = 1 H2, Hz), 5.90
(t,1,g3l2 = 8 Hz, g3’7 I 6.5 Hz and £3’4 = 1 H2, H3), 4.28

(t,1,g4’1 = 8.5 Hz, g4’2 = 7 Hz and 14'3 = 1 Hz, H4), 3.88

(d of d,1,g5’7 = 3 Hz and 25,1 = 1.3 Hz, H5), 3.86(s,1,H6)
and 3.79 ppm (m,1,__q'7’2 = 1 Hz, J7’3 = 6.5 Hz and £7,5 =

3 Hz, H7). The ester groups and the methoxy group were
found at o 3.78 (8,9), 3.72 (5,3), 3.71 (s,3), 3.62 (5,3)
and 3.30 ppm (s,3). The singlet at 3.78 ppm split into
three singlets when the nmr sample was warmed.

Attempted high pressure hydrogenation (PtO catalyst in
methanol, 1000, 500 psi of hydrogen, 24 hours) afforded
3,4—dicarbomethoxy—6,7-(2',3',4',5'—tetracarbomethoxy-
benzo)—bicyclo[3.2.2]nona—2,6,8-trene (8), formed by the

loss of methanol from 7, as the only isolable product.

 

E = COZCH3

Hydrogenation reactions under milder conditions (5% Pd/C,
PtO or 5% Rh/C catalyst, atmospheric pressure or 50 psi of
hydrogen in methanol) gave no reaction.

Heating 7 above its melting point or treating it with

acid also gave 8. The 60 MHZ nmr provided the most useful

6
information available for determining the structure of 8;
The chemical shifts and coupling constants for the individ—
ual protons are 6 7.43 (d of d,1,g1'4 = 9 Hz and 21,6 =
1.5 Hz, H1), 6.70 (t,1,g2’é = 7.5 Hz and g2’4 = 7.5 Hz, H2),
6.23 (t,1,g_3’2 = 7.5 Hz and £3,6 = 7.5 Hz, H5) and 4.47 ppm
(m,2,H4 and H5). Proton H6 is found among the carbo-
methoxy groups. The ester protons are found at 6 4.02
(5,3), 3.94 (5,3), 3.90 (5,6), 3.77 (5,3), and 3.67 ppm
(5,3). A

Oxidation of Z with ruthenium tetroxide or potassium
permanganate gave intractable mixtures as might be expected
considering the proposed structure of Z.

The attempted bromination of Z using carbon tetra—
chloride, N,N-dimethylformamide or ethyl acetate as solvents
gave no reaction even after standing for several months at
room temperature. Refluxing in carbon tetrachloride still
gave no reaction.

The eight possible structures for 1 (not counting
enantiomers) are listed in Figure 1. Figure 2 can be used
to compare the nmr positions of the individual protons in
(Z and 8;

In order to represent all of the structures in Figure 1
it should be noted that the positions of the methoxy group
and proton H6 can be interchanged in Z'as shown in Figure 2.
The nmr data for Z and 8 together with the reactivity data
can be used to verify the proposed structure of Z, When

mathanol is lost from Z to give 8 the chemical shifts of

KM posgom Hum 93 now mcoflumusmamcoo manammom .H onsmam
mmoaoo n m

_m m .m m

m?
[:1

 

O?
O

on?
n12

 

Hm pom .M mocsomaoo mo mCOmHHmmEoo HEZ .N wusmam

mmoaoo n m

00?
4:1

 

Aso.m-mo.vv

9

H1, H2, H3, H4, and H7 move downfield 0.20, 0.42, 0.33,
0.19, and 0.68 ppm respectively. The movement of H5 is
uncertain, since H5 is found among the ester groups in the
nmr of 8:

The fact that H2 and H3 had a greater chemical shift
change than H1 can be accounted for if the cyclohexadiene
ring in Z faces H2 and H3 as in structures Q, Ex g” and E,
of Figure 1. The carbon-carbon double bonds would lie
above H2 and H3 and thus cause some shielding in the nmr.
Withemomatization the shielding effect would be removed and
H2 and H3 would indicate some deshielding since they would
be found slightly out of the plane of the aromatic ring.
Proton H1 should also indicate the same Shielding due to
the aromatic ring. The net effect would be a much greater
downfield shift of H2 and H3 than H1 in going from the nmr
of Z,t° 8.

The lack of reactivity of Z toward hydrogenation and
bromination would also support the fact that the carbon-
carbon double bond between H2 and H3 is covered on at least
one side by a very bulky group such as the cyclohexadiene
ring and its four ester groups.

Proton H7 shows a much greater downfield chemical
shift change than H4 between Z and 8’ If the methoxy group
is adjacent to H4 as in structures Q” Q” Ex and g'in Figure
1, then the chemical shift difference between having an ad-
jacent methoxy group and an adjacent aromatic ring would be

much smaller than the difference between an adjacent

10
tertiary hydrogen and an aromatic ring. Proton H7 would
thus show a much greater shift change than H4.

Both H6 and H7 are allylic and adjacent to an ester
group. Proton H6, however, is also adjacent to a methoxy
group and should be expected to be found further downfield
in the nmr of Z than H7 which it is. Also when a model of
Z is built, the dihedral angle between H6 and H7 is nearly
900 when the cyclohexadiene ring faces H2 and H3. This
Should result in a coupling constant close to zero between
H6 and H7 as has been observed in the spectrum.

Finally the shift change of H5 was uncertain. If H5
lies above the aromatic ring in 8 then it should be shielded
and the resultant chemical shift change from the spectrum
of 1 should move the position of H5 further upfield among
the ester groups. If the ester group lies above the aromatic
ring, however, then H5 would lie to the side of the aromatic
ring and Should have a downfield chemical shift change at
least as large as that found for H1, since it would be found
at almost the same distance from the ring and from the plane
of the ring as H1. This would make H5 visible in the nmr
of 8. This is not the case so H5 must lie above the ring.
Since the ester group would then lie above the carbon-carbon
double bond between H2 and H3, it would be expected to make
the double bond even less reactive. Being hindered on both
Sides the double bond might be expected to be extremely
unreactive toward bromination and hydrogenation as was ob-

served.

11

Structure A'in Figure 1 is the only structure that
agrees with all of the observed data and should, therefore,
be the correct configuration of Z.

No other possible structures have been found that fit
the analytical data as well as the proposed structure for Z.

The remainder of this paper will be used to discuss a
possible mechanism to obtain the 3:1 adduct 1 from 5, The
3:1 adduct Z was first formed by heating 5 and dimethyl
acetylenedicarboxylate in xylene at 1400-1450 for 24 hours,4
and is obtained in a 6 percent yield as a white crystalline
solid. It is also obtained when the reaction is run in the
dark, suggesting no photochemical process is involved.
At 1500 5 is converted by a rapid (k1 = 4.4 x 10-4
secul), nonreversible, transannular 1,5-hydrogen migration

to 3—methoxycycloheptatriene (g).5r5

H OCH3
OCH3

 

 

 

OCH3

 

201

10 11

A slower (k2 = 3 x 10"5 sec-1), reversible (K2 = 10)

isomerization then converts 9 to 1-methoxycycloheptatriene
(lQ)-5'6

Another even slower, reversible (K3 3 0.01) isomeriza-
tion converts 12.to 2-methoxycycloheptatriene (112.5:6

In 24 hours at 1400 5 should be completely converted

to 9 and would also be expected to isomerize considerably

12
to 12” but very little if any of 11 should be formed in this
time, so it would not be expected to be an intermediate in
the formation of Z.

A sample of 9 was prepared,5:6 and reacted with dimethyl
acetylenedicarboxylate in xylene at 140°. The starting
material was gone in one hour and the reaction was stopped
and worked up. The 3:1 adduct Z was obtained in a 10 per-
cent yield.

A sample containing 45 percent of 9 and 55 percent of
12 was also prepared 5'5 and reacted with dimethyl acetylene-
dicarboxylate in xylene at 1400 for one hour as above. The
3:1 adduct 1 was again obtained but only in a 3 percent
yield. If 19.had been an intermediate in the formation of
1 then an enriched sample of 12 should have given a much
greater yield of Z than would be obtained when starting with
5 or 9. Compound 12 should not, therefore, be an intermedi-
ate in the formation of 2, Since 9 is formed nonreversibly
from 21 then 9 must be an intermediate in the formation of 1.

It should be noted that 9 has a pair of geminal protons
and Z does not. The remainder of the reaction pathway must
then involve at least one hydrogen migration.

Cycloheptatrienes normally yield substituted tricyclo-
[3.2.2.02:4]nona-6,8—dienes as a major reaction product
from their thermal addition to dimethyl acetylenedicarboxyl-
ate. In this case one would expect to obtain 6,7-dicarbo-
methoxy—B-methoxy—tricyclo[3.2.2.02I4]nona-6,8-diene (12)

as the major product from the reaction of 9 with

13
dimethyl acetylenedicarboxylate. No evidence of this com-

pound was found in the reaction mixture, however.

__ —. ,.... —-

+ E-CEC-E ————a~ ’//\\\. E

if

OCH3 ‘E

9 12
~ E = COZCH3 rvv

Attempts to prepare 12 in order to prove that it is an
intermediate in the formation of Z all proved unsuccessful,
but are briefly described below.

The reaction of 9 with dimethyl acetylenedicarboxylate
in refluxing benzene or toluene gave very little reaction
even after several days and showed no indication of the

desired product. The reaction products were not identified.

Benzene //\\\\E

+ E-C?C-E-——jjf——o- .//
Toluene | “~‘47/
OCH3 H CO E
3

9 12,
E = C02CH3

6,7-Dicarbomethoxy—tricyclo[3.2.2.02:4]nona-6,8-diene
(2) was prepared1 from cycloheptatriene (L) and dimethyl
acetylenedicarboxylate. It was then oxidized with 40 per—

cent peracetic acid in an attempt to prepare

14
8,9-epoxy—6,7—dicarbomethoxy—tricyclo[3.2.2.02'4]nona-6-ene
(13). The structure of the crude reaction product could

not be verified. This crude product was reacted with sodium

 

3H
2m

.31.
CH3OH % CH30-

‘E
H3CO’

/ <73
new < w

12 H3CO'
rvv E = COZCHB ,VV

methoxide in refluxing methanol in an attempt to prepare
6,7—dicarbomethoxy-8-hydroxy—9—methoxy—tricyclo[3.2.2.02r4]—
nona—6—ene (14)'but no reaction occurred.

Since bromo-methoxy compounds can be formed by bromina-
tion of a carbon—carbon double bond in methanol, this was
tried with 2“ but a bad mixture resulted and none of the

products could be isolated or identified.

15

 

Finally attempts were made to react g with chloro-
maleic anhydride in refluxing xylene. A black, tarry mix—

ture resulted from which none of the products were identi—

fied.

O

I

+
l O +>
Cl
O
OCH3 H3CO

.9.

 

E 2 C02CH3

Even though 12 could not be prepared it is still assumed
to be an intermediate in the formation of Z;

Dimethyl acetylenedicarboxylate has been reported to
react with bicyclo[2.2.2.]octa—2,5,7—triene (barrelene) (L5)
to yield 7,8—dicarbomethoxy—tetracyclo[4.4.0.02'1°.05'9]—
deca-3,7-diene (16). With continued heating 16 will rear-

range to 1,2—dicarbomethoxy—dehydronaphthylene (ll).7

16

 

 

// //
E
/ 4/ A E
// > ——>
I / r’
“L ____.
E-C:C'E E E
ii Lg 17

If 12 reacted similarly it would yield a 2:1 adduct,
1(7)-methoxy-8,9,10,11—tetracarbomethoxy-pentacyclo[5.4.0.
0911.03r5.06c1°]undeca—8—ene (18). This 2:1 adduct 18'
could then rearrange in a similar manner to l-methoxy—8,9,
10,11-tetracarbomethoxy-bicyclo[5.4.0]undeca—2,5,8,10-

tetraene (12).

 

\ E
E E-
.// 7// > //
H3CO ~%<:_ E: \\
(f; ‘E
‘;V E OCH3
E‘CZC-E
12 19

 

If the mechanism proposed by Goldstein3 for the prepa-
ration of 3,4-dicarbomethoxy-bicyclo[3.2.2]nona—2,6,8-triene

(4) from 1 and dimethyl acetylenedicarboxylate is applied

17

—-—->- -—->- \N

 

(H

to 19 then the 3:1 adduct Z would result. It should be

noted that this final sequence also contains a hydrogen

E E
E ~\\ H E
__”>
E O ,5) (H E O H
E U R__ E L)
:1? E-C:C-E £1
19 E E
El
E
E
E H
0E
E
E : COzCH3

 

migration which was found necessary earlier in the paper.

The entire proposed mechanism is given in Figure 3.

18

OCH3 v

E
E-CEC-E
___> ————-—————_—__> I
E
OCH3

E, 2' H3CO 12

1 E-CEC-E

 

 

 

E
E
y E-CEC-E
E
OCH3 Idrgi
E E
l
E E H
E // <5?\\ E\
HSCO /lj > 47/
E \f/)\\,
E H E/
’§§i\E E
E 1.
E = COZCH3

Figure 3. Proposed mechanism for formation of 7 from 5.

EXPERIMENTAL

 

General Procedures

 

Nmr spectra were run on Varian A—60 or T—60 spectrom-
eters. Dr. M. Gross of Michigan State University did de—
coupling and variable temperature nmr experiments on 1.
Dr. R. T. Iwamasa of the Chemical Physics Research Labora—
tory of the Dow Chemical Company redetermined the coupling
constants of Z and confirmed the prOposed structure of Z,
by using the shift reagent Eu(fod)3. Mass spectral analysis
of Z was determined by J. H. Mark of the Chemical Physics
Research Laboratory of the Dow Chemical Company.

Elemental and ultraviolet analyses were determined by
the Analytical Laboratory of the Dow Chemical Company.

Infrared spectra were obtained on an InfracordR or
Perkin Elmer Model 237 spectrometer.

Gas Chromatography was carried out on an F & M Model
500 gas chromatograph with a 2' x 1/4" ID glass column
packed with 5% DC—410 on Gas Crom Q, 60-80 mesh, helium
carrier (40 ml/min), programmed at 50—3000 at 110 per
minute.

Thin layer chromatography was carried out on Brinkman

Instruments F—254, 5 x 20 cm silica gel covered glass plates

19

20
eluted with chloroform and acetone (v/v 19:1) except where

the solvent system is stated to be different.

7-Methoxygycloheptatriene (5)

 

7-Methoxycycloheptatriene (5) was prepared by the meth-
od of Dauben.8,9 Starting with 70 g of cycloheptatriene,
50 g of 5 (49%) was obtained: b.p. 45—60 (4.5 mm); nmr

(neat) 5 6.53 (t, 2, 3.5 Hz), 6.03 (m, 2), 5.37 (d of

IL:
u

d, 2, g_= 3.5 Hz and 10 Hz), 3.28 (s, 3, -OCH3) and

IC-c
u

3.23 ppm (m, 1).

3.4.5.6,10,11—Hexacarbomethoxyf7—methoxyftricycloL6.3.2.02I7]-
trideca-3,5,9,12—tetraene (Z); 3:1 adduct 1

 

7-Methoxycycloheptatriene8 (7 g, 57.4 mmol) and di-
methyl acetylenedicarboxylate (28.4 g, 200 mmol) were dis—
solved in xylene (75 ml) and heated at 140-1450 for 24 hours.
The resulting dark solution was mixed with hexane. The
hexane was decanted and the remaining oily residue was
triturated with methanol to give Z'as a white crystalline
solid; 1.2 g, 3.8%; mp 222—2230; uv max (CH3OH) 234 mu
(5 = 10750), 305 mu (5 = 500); ir (CHCl3) 3.3 (c-H), 5.87
(0:0), 6.02 (c=c),6.23 (cIc), 7.7 and 7.85 0; ms m/e 516;
nmr (c9013) 0 7.23 (d of d, 1, 51’, = 8.5 Hz and 91,5 = 1.3
Hz, CH = c, H1), 6.28 (t, 1, g2,3 = 8 Hz, Q”; = 7 Hz and

£2” = 1 Hz, CH = c, Hz), 5.90 (t, 1, 513,2 = 8 Hz, g3”; -

€3.5 Hz and J3,4 = 1 Hz, CH_= C, H3), 4-28 (tr 1' 24,1 =

83.5 Hz, JA,2 = 7 Hz and 24,3 = 1 Hz, bridgehead, H4), 3.88

21

(d of d, 1, £5” = 3 Hz and 11,5 = 1.3 Hz, CHCOZCHa, H5),
3.86 (5, 1, bridgehead, H6), 3.79 (m, 1, £73 = 1 Hz, 17,3
3 6.5 Hz and £7,5 = 3 Hz, bridgehead, H7), 3.78 (s, 9,
cochB), 3.72 (s, 3, cozcgj), 3.71 (s, 3, cochB), 3.62
(s, 3, C02C§3)r and 3.30 ppm (5, 3, OCH3)7 tlc Rf 0.61.

Anal. Calcd for C26H28013: C, 56.93; H, 5.15.

Found: C, 57.11; H, 5.42.
An additional sample (0.6 g) of Z was obtained from

the methanol mother liquor: mp 214-70. Total yield 5.7%.

3-Me£hoxy—cycloheptatgiene (9)

AN

 

The procedure of Nozoe and Takahashi5 was used to
prepare 9. Starting with 5 g of 7—methoxycycloheptatriene,
2 g (40%) of 9 was obtained: bp 860 (33 mm); nmr (neat)

0 6.23—4.90 (m, 5, CH = C), 3.50 (s, 3, OCH3), and 2.23 ppm

(t, 2, J = 6.5 Hz, -CH2-).

Reaction of 3—methoxycycloheptatriene (9) with dimethyl

 

acetylenedicarboxylate

7-Methoxycycloheptatriene (5) (3.5 g, 28.7 mmol) was
heated at 1500 for 1 hour. Nmr analysis of the peaks at
3.50, 3.57, and 3.35 ppm, respectively, indicated that the
product was composed of 11% 10, 84% 9, and 5% 5; A solu-
tion of this crude product and dimethyl acetylenedicarboxyl-
ate (12.8 g, 90 mmol) in xylene (8 ml) was heated at 140-
1450 for 1 hour. Gas chromatographic analysis showed that

9 had completely reacted. The reaction solution was mixed

22
with hexane. The hexane was decanted and the remaining
oily residue triturated with methanol to yield 7 as a white

crystalline solid; 1.61 g, mp 222-30, 10.2% yield.

 

lfMethoxycycloheptatriene (12)

Following the procedure of Nozoe and Takahashi5
3-methoxycycloheptatriene (9) (4 g, 32.8 mmol) was heated
at 145° for 21 hours. CompariSon of the peak areas in the
nmr at 2.45 and 2.23 ppm showed that the crude product was
composed of 55% 12 and 45% 93 The product was used without

further purification.

Reaction of 1—methoxycycloheptatriene (12) with dimethyl

 

acetylenedicarboxylate

 

1-Methoxycycloheptatriene (30) (15.8 mmol) and dimethyl
acetylenedicarboxylate (17 g, 120 mmol) were dissolved in
xylene (10 ml) and heated at 140—1450 for 1 hour. The re—
action solution was cooled and mixed with hexane. The
hexane was decanted and the remaining oily residue was
triturated with methanol to give Z’as a white crystalline

solid; 0.63 9, mp 219-2200, 3.5% yield.

3,4—Dicarbomethoxy-6,7(2',3',4',5'—tetracarbomethoxybenzo)—
bicyclo[3.2.2]nona-2,6,8-triene (fi)

 

 

(A) Attempted high pressure hydrogenation of Z.

The 3:1 adduct 7 (1 g) platinum oxide (0.2 g) and
methanol (150 ml) were placed in a stainless steel bomb.

This was pressurized to 500 psi with hydrogen and heated

23
at 100° with rocking for 24 hours. The reaction mixture
was filtered and the bomb and filter cake washed well with
chloroform and acetone. The solvents were evaporated and
the residue crystallized from methanol to yield 8’as a
white crystalline solid: 0.5 g; mp 164-50; tlc, Rf 0.75;
uv (CH30H) 219 m0 (6 = 33,300), 287 mu (6 = 1,450); ir (mull)
5.75 (c=o), 6.05 (c=c), 7.85, 8.05 and 8.2 u) nmr (CDC13)
0 7.45 (d of d, 1, l1,5 = 1.6 Hz and g1’4 = 9 Hz, cg;c, H1),

6.38 (t, 1, 52,3 = 7.5 Hz and £2 4 = 7.5 Hz, cgéc, Hz), 5.95

(t, 1, 53,2 = 7.5 Hz and 53,5 = 7.5 Hz, cgsc, H3), 4.33 (m,

2, bridgehead protons, H4 and H5), 4.00 (s, 3, C02CH3), 3.93
(s, 3, cochB), 3.87 (s, 6, cozcfl3). 3-77 (S: 3: cozcg3)

and 3.65 ppm (5, 3, COZCH3). The entire e5ter region inte-

grates for 19 protons so H6 must be found in this region.

Anal. Calcd for C25H24012: C, 58.14; H, 4.68.

Found: C, 57.93; H, 4.97.

(B) Effect of acid on 1

 

A xylene solution (20 ml) of Z (0.3 g), concentrated
sulfuric acid (5 drops), and acetic anhydride (3 ml) was
allowed to stand at room temperature until tlc analysis
indicated that all of Z had reacted. Sodium bicarbonate
was added and the mixture filtered. The cake was rinsed
well with chloroform. The solvents were evaporated and the
residue crystallized from methanol to give 8’as a white

crystalline solid; 0.2 g, mp 164—50.

24

(C) Effect of heating Zlaboveits melting point.

 

A sample of Z’in a melting point capillary was heated
at 300° for a few minutes. The capillary was crushed and
the contents extracted with methanol. Tlc analysis cor-

re5ponded to a mixture of Z and 8.

Attempted bromination of Z

 

(A) Bromine (100 01) was added to solutions of Z (50 mg)
in carbon tetrachloride, N,N—dimethylforamide and ethyl
acetate. These solutions were allowed to stand at room
temperature for two months. Tlc analysis indicated no re-

action in any of the solutions.

(B) A solution of 7 (50 mg) and bromine (0.5 g) in carbon
tetrachloride was refluxed for 2 hours. Tlc analysis indi-

cated no reaction.

Attempted hydrogenation of 1

 

(A) A methanolic (25 ml) solution of Z (212 mg, 0.386 mmol)
and 5% palladium on carbon (100 mg) were mixed in a micro-
hydrogenation apparatus at atmospheric pressure for two days.
No hydrogen was absorbed and tlc analysis indicated no

reaction.

Using platinum oxide or 5% rhodium on carbon catalysts
under the same conditions also showed no indication of re—

action by tlc analysis.

25
(B) An ethyl acetate (50 ml) solution of Z (300 mg), con—
centrated hydrochloric acid (1 ml), and the mixed catalysts
platinum oxide (100 mg), 5% palladium on carbon (100 mg),
5% rhodium on carbon (100 mg) were shaken on a Parr hydro-
genation apparatus at 50 psi of hydrogen for five days.

Tlc analysis indicated no reaction.

Ruthenium dioxide oxidation of Z

 

A solution of sodium metaperiodate (590 mg) in water
(10 ml) was added to a mixture of Z (300 mg, 0.548 mmol)
and ruthenium dioxide (15 mg) in carbon tetrachloride (10 ml).
After the mixture was stirred for one day it was filtered
and the aqueous layer extracted with chloroform. The com-
bined organic layers were evaporated and the residue
chromatographed through silicic acid (20 gm) eluted with
chloroform and acetone (V/V 1:1). The main fraction was
eluted as a dark band. The nmr Spectrum was very compli—

cated and was not evaluated.

Potassium permanganate oxidation of 1

 

A solution of potassium permanganate (7 g, 44 mmol) in
water (400 ml) was added quickly to an acetone (300 ml) solu-
tion of‘Z (1 g, 1.82 mmol). The temperature rose from 25°
to 40°. In 5 minutes the permanganate had been consumed.
Sulfur dioxide was added to give a clear solution to which
concentrated hydrochloric acid (5 ml) was added. The

solution was extracted with chloroform and the extract

26

evaporated. The residue was eluted with chloroform through
silicic acid (20 g). The first seven 50 ml fractions
contained a mixture of four compounds. The eighth fraction
was evaporated and the residue dissolved in benzene (50 ml).
Hexane (1 l) was quickly added to give a powdery solid: 0.2
9: mp 102-50; Tlc (CC14:CH30H, v/v 10:4) Rf 0.33, (EtOAc)
Rf 0.64. .

The nmr spectrum was very complicated and could not

be evaluated.

BIBLIOGRAPHY

BIBLIOGRAPHY

 

J. A. Berson and M. R. Willcott, III, J. Amer. Chem. E
Soc., 88, 2494 (1966). g

 

K. Alder and G. Jacobs, Chem. Ber., 88, 1528 (1953). E

 

 

M. J. Goldstein and A. H. Gevirtz, Tetrahgdron Letters, (
4413 (1965). )

J. P. Szendry, Master's Thesis, Michigan State University
(1967).

T. Nozoe and K. Takahashi, Bull. Chem. Soc. Japan, 88/
665 (1965).

 

E. Weth and A. S. Dreiding, Proc. Chem. Soc. 1964, 59.

 

H. E. Zimmerman and G. L. Grunewald, J. Amer. Chem. Soc.
§§x 1434 (1964).

 

A. G. Harrison, L. R. Honnen, H. J. Dauben, F. P.
Lossing, J. Amer. Chem. Soc., §Zx 5593 (1960).

 

H. J. Dauben, L. R. Honnen, K. M. Harmon, J. Org. Chem.,
22v 1442 (1960).

 

27

APPENDIX

28

I0.0 ".0

 

Figure 4. Infrared spectrum of 7-methoxycycloheptatriene (8).

 
  

TIANSMITANCE ('ial

 

3500 3000 2500 2000

Ila-Inn mm; m. nfi

Figure 5. Infrared spectrum of 3-methoxycycloheptatriene (8).

29

mm (fl

 

Figure 6. Infrared Spectrum of 3:1 adduct 1.

4000 3000 2000 1500 CM" 1000 900 800 700

ABSORBANCE

 

' WAVELENGTH (MICRONS)

Figure 7. Infrared spectrum of 3:1 adduct 1.

30

ow"

700

.....

800

900

1000

1500

2000

4000 3000

 

WAVELENGTH (MICRONS)

~

Infrared spectrum of derivative 8,

Figure 8.

9..

I..-

530

4.0

”111

 

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Nmr spectrum of 7-methoxycycloheptatriene (8).

Figure 9.

 

 

 

 

 

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31
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Nmr Spectrum of 3:1 adduct 7

l

 

 

 

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1
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Figure 10.
4.9
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Figure 11.

 

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32

 

 

v

1.1.41. 11
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'
v r u
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Nmr spectrum of derivative 8.

Figure 12.

 

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