Studies of some 7 substituted pinane monoterpenes

SlJ.'\JDilUS OF SQ11f'E SUJ3STITDTED PINANE MONOTl!lRPENlUS

A th("'sis sented for the degree of Doctm:· of Philosophy in Chemistry in the University of Cante1~1)Ury₁

Christchurch, Nevl Zealand.,

by

P.A,.E. Cant

:;::;.

INDEX

The T'nermal Reactions of Pinane

7 -Substituted Pinanos Nomonclatul'e DT Preparations.: Ver1Jenone Chrysanthenone Ghrysantho11ol

7-liffo thyl chry san th eno 1

Chrysanthenyl Acetate cis-Ghrysanthanol

cis-Chrysanthanyl Acetate ci_~-Chr;y· san thanone

Verbenone Cl:n:ysanthenol

7-Methylchrysanthenol Ghrysan-thenyl Acetate cis-Chrysanthanol

_£is-Ghrysanthanyl Acetate cis-Chry santhanon e

COJITCLUSIO:NS

APPENDIX I

The Pyrolysis of a -Pinene

APPENDIX II

Hydrogenation of Chrysanthonone ₁₁₄

EX:PERIMEN'11_AL

Pyrolysis Apparatus 118

Preparations 121

ryrolyses ₁₃₇

Appendix I

₁₅₄

Appendix II ₁₃₅

REFEREt\ C F.:S

₁₅₅

Abstract

-A number of pinane derivatives, o:xygena-l;ed at ·the ?-position, have been p;)rrolysed and the resulting product mixtures analysed. Nowhere in the extensive literature concerned 'l'li th the pyrolyses of pinanG derivatives has there been a report of the cyolobutane ring opening initially by vmy of either 1,7~ 01'

5;7-

el0avage,

although there are examples of both 1

,6-

and

5

96- bond cleavage. r[he present study has shovn1 that it is }')OSsible to induce cleavage of the 1/{- and

5,7-

bonds by inserting suitable sub-sti tuents a·l;

07.

Cleavage of the 1₉6- and 1, 7- bonds occurs ·to a simHar extent in the p;'rrolysis of ci s-chrysanthenol (.38) (28% and 25% respectively)., whereas in that of 7--methylchry·santhenol (54)~

1,

7- cleavage becomes the more favoured mode -

43%

compared to 3~; o:7fO

/

.

When the hydroxyl group of cis-chrysanthenol 'vas aceJcy1ated₉ the -resulting compount proved very unstuble under the pyrolysis conditions, giving a large number of products, only t\fO of which

(29% in all) l·rere present in identifiable quanti ties.

The pyrolyses of the three ?-oxygenated derivatives of

a -pinene displayed one feature in common. 1'-lhen 1,6- cleavage occurred and monocyclic products were formed, the major product in each case was formed by migration of a hydrogen from the

R

₁

0~

--

R

₁

0

..

R2

R1 H, CH3 CO

1

R

~

2 H, CH3

R

1

0

+

R

₁

0

Neither .::d.s-chrysa.nthanol (48) nor cis-~chrysanthanyl acetate

(49)

gave any cyclic :products on pyrolysis. Both compounds

rearranged to give the aldehydes citronellal and 5₉7-dimethyl-6-·~

octenal but, in addition, cis-chrysanthanyl acetate gave the cis- (3%) ancl j;r~'2_- (28%) enol acetates of oi tronellal.

~

A cO

+

CHO

Verbenone

(5)

tn:.s p;yro1ysl~cl at 425° and. fow~ compounds no-t mentioned in previous reports v~ere identified. as 2,6 ,6-trimeth;yl-bioyolo [ 3. 2. 0] hepten·-7-one (45), 1~formyl-2, 6 ,6-.t.rimeth;y-lcycJ.o-hexa-1~3-cliene (57), and. the trienals 3,7-·dime-thyl-2.-ciS-₉ 4-cis-, 6-octatri enal (60) and 3, 7 -clirnethyl-2--_gj s-,

4-·

t:r.'a.ns-6-octa trienal

(59)

I-t 1vas also olJserved that the unsatura-ted pinene derivatives

IN'l'RODUCTION

From the time when man was first moved to improve the

quality of his surroundings, he has made use of the

sweet-smelling substances that are to be obtained from herbs and trees.

Today, in a vastly more populous and sophisticated world

enjoying greatly improved ~tandards of liv , the demand for

the perfumery chemicals used in most household products has

far outstripped the supply of the essential oils that can be

obtained from natural resources. The supply of these natural

oils is not only inadequate; it varies widely in volume and

quality, and therefore in price, from season to season - all

good reasons to encourage science and industry to look for new

and more reliable sources of perfume chemicals. Th they have

done with a good deal of success.

Many of the main components giving rise to the fragrances

of the essential oils are oxygenated

c

10 compounds belonging to

the class known as monoterpenoid. Monoterpeno were

oonsidered1 to be formed by the fusion of two isoprene units in

a "head to ta 11 _{orientation. Isoprene has the formula}

c

5

H

8

,

with the isopropenyl end bf the molecule as the

11_head11_•

(Scheme 1)

ieoprene monoterpenoid

Many naturally occurrin~ compounds of up to 30 carbon atoms can be v wed as comprising numerous isoprene units

linked in a regular way to form an ordered sequence.

The most commonly occurring monoterpenoids are the

pinenes, a-(1) and ~-(2), which are major constituents of

wood turpentine. Turpentine is the mixture of volatile

hydrocarbons present in the wood of coniferous trees; 70?6 of

( 8 7 -1 )'

the world's current production x 10 gallon annum is

obtained as a by-product of the Kraft pulping process. ~1uch industrial research has been directed towards oxygenating the

pinenes and isomerising the derivatives by pyrolysis or

hydro-lysis to give the fragrant monocyclic and acyclic

monoter-penoids. At present 0-pinene is utilised more fully in the

fine-chemical industry, and thus more valuable than its

isomer a-pinene.

The c~mposition ot wood turpedtine varies markedly from

country to country. New Zealand, supplying as it does some

0.57.6 of the world's production, but with a potential of

6

-1

>

00,000 gallon annum , has an unusually high percentage of

~-pinene in its turpentine -65?0, compared with the 277{, m 1ximum

found elsewhere. a-Pinene and ~-pinene are, respectively, the

2,3- and 2,10-olefinic derivatives of the parent compound

pinane

(3).

With a structural formula of

2,6,6-bicyclo-[3,1,1] heptane, the monoterpenoid nature of the pinane skeleton

is easily recognised (Fig. 1).

pinane (+)a-pinene (+)-[3-pinene

3.

The absolute configuration of (+) a-pinene and (+) ~-pinene

are as shown, with the e~erl]_-dimethyl functions above the plane of the paper.

Although (-) a-pinene was used to synthesise the

7- substituted pinanes studied in this work, the photolysis step

in which chrysanthenone (4) is obtained from verbenone (5) by

a [1,3] sigmatropic shift, also reverses the configuration.

The compounds concerned are thus 7- substituted (+) - pinanes,

As noted

b~

Teisseire et al2 the optical rotation of

chrysanthenone (4) depends upon both the irradiation time and

distillation conditions, varying between 0° and 40°.

The rhermal ~eactions of Finane Deriv~tives

Although the thermolysis of pinane derivatives was first

reported in 1841, when turpentine was heated to give oils of

7.

different volatilitiesJ, it was not until the 1950's that any

real understanding of the reaction was gained. From the early

work some of the pyrolysis products from pinane (3) itself,

and from its unsaturated analogues4'5 a-pinene (1), and

~-pinene (2), were identified, but these pyrolyses continued

to be studied up to 1970.6' 7 It was noted also that a-pinene

recovered from the pyrolysate was racemised, and this loss of

optical activity enabled Smith4 in 1927 to calculate the

activation energy for the pyrolysis of a-pinene to be

184 kJ mol-1•

The most significant result of this work has been the

commercial exploitation of the pyrolysis of both ~-pinene (2)

and pinane (3) in the production of a variety of perfumery

and flavouring materials.

Myrcene

(6)

is produced in a continuous process by

4.

time. A yield of up to 85~ can be achieved in this way.

From myrcene (Scheme 2) nerol

(7),

geraniol

(8),

citronellol

(9)

and linaloBl (10),compounds used extensively in the perfume

industry, are synthesised by relatively simple transformations.

Citral, the oxidation product of nerol and geraniol, is widely

employed as a substitute for essential oils such as lemon grass,

and is used extensively as a perfume base in toiletries, soaps,

and disinfectants. It is utilised als0 as a precursor in the

~-pinene

OHC

+

(a)

Citral

Scheme 2

(b)

l.inalool

HCl

~ CuCl 2

Cl

Oxidise

4

-HO

HO

"--Saponify

Geraniol

l

i

AcOH

Cu ,,Cl...,

C L

Ct

+

I

NaOAc

~

Amine

!

Saponify

+

HO

nerol

6.

Pinane

(3)

is also pyrolysed commercially in a

continuous process to give dihydromyrcene (11), from which

the valuable 1- menthol (12) can be produced. (Scheme

3).

OH

( 11) .Scheme ( 12)

Although commercially exploited, the pyrolysis of

pinane derivatives was but poorly understood until 1951, when

Burwe118 proposed a mechanism to explain the kinetic and product

data available for the pyrolyses of a-pinene (1) and a-pinene

(2). Earlier workers had shown that vapour or liquid phase

0 0

pyrolysis of a-pinene at temperatures of 200 - 500 resulted

initially in three simultaneous9 reactions, all first order?

racemisation of a-pinene, isomerisation to alloocimine (13), and

isomerisation to almost inactive limonene (14), The pyrolysis

. f f t d b tl d d . t . f b . . d t . . d t 1 0

1s una ec e y 1e a 1 1on o enzo1c ac1 , an 1ox1 an s,

or dipentene (d,l-limonene), implying that it cannot occur by

way of an ionic intermediate.

Burwell expanded an idea first mooted by Rice and Rice11

in 1935: that a-pinene could undergo homolytic scission of the

1,6- bond to form a biradical intermediate (1a) (Scheme

4),

one of the radicals being allylic and thus stabilised as a

resonance hybrid. Recombination of the radicals forms

d,l-o:-pinene; scission of the

3,4-

or

4,5-

bonds forms

ocimine (15), which rearranges to give the more stable

allo~cimine (13); and intramolecular hydrogen transfe~ from

7.

d,l-limonene (14).

(d)-(1)

(1a)

_(d,l)-(1)

Scheme

4

( 15) (13)

Rice and Rice11 had predicted the formation of ocimine in the reaction, and this was subsequently confirmed, but they did

not consider the stereochemical consequences of their

biradical termediate, nor all the reactions i t could undergo.

8

By a similar mechanism, Burwell was able to explain the known

pyrolysis products of ~-pinene, including the formation of limonene (14) of high optical purity (Scheme

5).

(2a) - (1)-(2)

+ +

(l)-(1L~)

(6)

8.

He also demonstrated that the activation energy of a·-pinene

was explicable in terms of the biradical intermediate. The

formation of an allylic radical from the thermolysis of

1-butene had been shown12 to involve an activation energy of

259 kJ. mol-1•

CH

=

CH - CH - CH

2 2 3

L\E* - 259 kJ mol -1

CH 2

This value would be reduced to about the 171 kJ mol-1 calculated

for the pyrolysis of a-pinene if allowance is made for the bond

strain in a cyclobutane ring, some 109 kJ mol-1• 13

Burwell's diradical mechanism for the nyrolysis of

pinane derivatives remains the one which best explains the

products obtained from these reactions, although the possibility

of a concerted cycloreversion mechanism operating to give some

acyclic products has been considered.

In terms of a concerted mechanism14 the formation of

ocimine (15) from a-pinene can be envisaged as either a

[o2s + o2a] (allowed) or a [a2s + o2s] (non-allowed) process. To accommodate the allowed cycloreversion, the cyclobutane

ring must deform substantially to allow the ethylenic components

to become mutually orthogonal, as the [o2s + a2a] mechanism

requires inversion at one (or three) of the four ring carbona

for the formation of the new bonds with conservation of orbital

tl I I I 1\ l - - - f l l 1 1 \ l l l l l

A

\ l ' \ ,,-~,~,~===:::,"';, .~.·

...

*

-

~

~

-..

::

...

8''

II! I•

-p

-..

....

B

B

/

~

"' =

inversion Scheme 6

Although the four-membered ring in pinane derivatives

is more puckered than cyclobutane itself by up to 20° (Fig. 2),

0

the dihedral angle is far removed from the

75

required for two

of the bonds to be orthogonal to each o~her.

\

\

+D

[o2s + o2a]

transition state

l f \

V\ ~ bond to be broken

2

cyclobutane

\

'

10.

The operation of the [o2s + process cau be~ seen

clearly in the diagram in which the incipient double bonds are

vertical and horizontal. Formation of the n-bond along the

horizontal a-bond occurs on the same face ( s.Y:.!.-) while a

n-bond is formed by orbital lobes on opposite faces (~nti) of

the vertical a-bond. It is likely that the [o2s + o2a]

cycle-reversion contribution to the pyrolysis mechanism will be small

because of the prohibitively large distortion required of the

molecule.

The [o2s + n2s] concerted 'non-allowed' reaction pathway

is so described because, where able, a molecule will react by

the lower energy [o2s + o2a] process. If, as has been observed recently15, steric factors prevent the allowed reaction,

molecular reorganisation can occur by the non-allowed route.

Huckel M.O. calculations show that for [1,3] sigmatropic shifts

(an example of a [2 + 2] process), the energy of the [n2s + o2s]

path is lower than for a diradical mechanism. Application of

this hypothesis to the [2 + 2] pinane cycloreversion awaits the

necessary calculations,

In a recent report of the thermolysis of cyclobutane

derivatives in the bicyclo[2,2,0]hexane system, an alternative

to the [a2s +a2a] process is suggested16 that conserves orbital

symmetry. Pyrolysis of all-end_~-hexamethylbicyclo[2, 2, O]hexane

0

at 153 was found to give only the all-exo·-isomer and the ring

opened erythro-3,4,5,6-tetramethylocta-2~6E,-diene (Scheme

7).

11.

The allowed [o2s + o2a] cycloreversion could account for the

observed diane, but is rejected since it would involve

unreasonable distortion of the bicyclic system. A two-step

mechanism is proposed, involving the conversion of the

C(1)-C(4) a-bond into an-bond, followed by conrotatory

open-ing of the C(2)-C(3) bond; this satisfies the ~oodward-Hoffmann

selection rules14 (Scheme

8).

The inverted bicycle- product is also accounted for

by this means. In the diagram, the two methyl groups at the

rear of the molecule have been omitted for clarity.

Ill

H

ant:i.clockwise con rotation

H

Ill

Scheme

8

Although the bicyclic isomers are in equilibrium, it is found

that the more stable all-exo- compound is favoured to·the

exclusion of the other. Concerted ring opening must be

12.

occur both clockwise and a.nticlockwise, lea<'l.ing to the formation

of the two optical isomers of the acyclic product. In th

ce 1 -!.:he1·e appears to be no steric factor to favour rotation

in one sense, and a racemic mixture should result. Unfortunately

the optical purity of the diene is not reported.16

It is unlikely, however, that this attractive alternative

to the [a2s + a2a] mechanism can be applied to the pyr s of derivatives, as models show that the constraint of the

e ring across 0(1) and C(5) s the inversion at

C(6)

C(7) necessary to form the n-bond between them.

In attempts to utilise the more r ly available

isomer, ~-pinene (1), work since the mid-19401_{s has centred on}

the pyrolysis of its oxygenated deri which are produced

by autoxidation of a-pinene.1

7

These studies have been

made po~sible by tho advent of such techniques as gas

chroma-tography and n.m.r. spectroscopy, for the isolation and

ident cation of the pyrolysis products.

In spite of recent suggestions that the opening of the

cyclobutane ring during the pyrslysis of pinane derivatives

cou:d involve a concerted rearrangement, the mechanism which

is most widely accepted is that of Burwe11.

8

In terms

·of Burwell 1_{s mechanism, homolytic cleavage of one of the bonds}

in the cyclobutane rise to a b cal intermediate,

so that substituents which can either affect the stability of

the radical centres, or which can interact with them becaube of

a particular stereochemistry, will influence markedly the type

of products initially produced in the reaction. Some primary

reaction products undergo further intramolecular rearrangements,

13.

Pyrolysis of the pinanes involves, initially, homolytic

scission of either the 1,6- or the 5,6- bond to give a biradical

species always containing an isopropenyl radical. The relative

stability of this teridr.vc;y· radical precludes cleavage of either the 1,7- or 5,7- bonds, both of which would lead to a

primary radical at C(7). Cleavage of the 1,6- and 5,6- bonds

is affected by substituents at the C(2) and C(ll) positions

particularly, as these may stabilise an adjacent radical by

allylic or inductive delocalisation. Substituents can be placed

in order of their ability to cause bond cleavage at the

neighbouring bridgehead position.18 An examination of the

pro-duct composition from the pyrolysis of verbenene (16)19 allows

a comparison of the influence exerted on the initial cleavage

by an endocyclic and by an exocyclic double bond. Two biradical

intermediates can be envisaged for this reaction - one (16a)

stabilised by the exocyclic methylene and the other (16b) by

the endocyclic olefin (Scheme 9).

( 16)

( 16a) ( 16b)

Since all the products isolated from the pyrolysate arise

from biradical (16b), the endocyclic double bond appears to be

more effective than its exocyclic counterpart in stabilising

( 16)

(18a)

l

C~pe

Rearrangement

(18), 39?-h

Ill

(19), 14?6 Scheme 10

14.

1

H transfer

( 17)! 29%

(trace)

( 20) t 9%

The biradical can undergo a [1,5-J hydrogen transfer to give

the E-menthatriene (17), some of which rearranges and is

dehydrogenated to produce a trace of O-isopropenyltoluene.

Alternatively, the 1,6-bond can break, an intermediate

tetraene (18a) that suffers a [3,3](Cope) rearran~ement to give

a triene (18). Successive [1,5] thermal sigmatropic hydrogen

shifts account for the other two triene~, (19) and (20), found in lower yields.

From the product analyses of the pyrolyses of ~-pinene (2)

8

an d noplnone . (2 ) 20, 20a -1 , an exocyc 1' lC me· y ene can th 1 b e

adjudged to induce more cleavage at the adjacent bridgehead

exclusively from 1,6- bond cleavage (p.7), nopinone (21)

on pyrolysis is observed to produce

2-methyl-2,7-octadien-4-one (22) as a result of scission of the 5,6- bond (Scheme 11).

-(21)

(22)

Lt. 5%

+

24.576

9%

·Scheme 11

This ketone (22) is, however, a minor component,

and the majority of products are derived from 1,6- bond cleavage.

Similar consideration of the pyr0lysis product compositions for

cis-verbanone (23)20, neo-isoverbanol (24)21 and nopinol ( )22'. 22a

allows a comparison.to be made of the relative ability of the

substituents carbonyl and methyl, methyl and hydroxyl, and

hydroxyl and hydrogen respectively to induce cleavage of a·bond

to the adjacent bridgehead position. The order deduced from

the foregoing observations endo- C:::C

>

exo-C=O >CH

3

>

OH >H.

Substituents on C(10) have been found not to influence

the course of the pyrolysis reaction, giving products with 27,

R =

R :::

R :::

R ₌ R ::::

R ::::

16.

+

t

H

2 (o:,-pinene) 0 (myrtenal)

OH,H (myrtenol)

OAc,H (myrtenyl acetate)

CH

20H,H (nopol)

CH

₂

0Ac~H (llopyl acetate)

Scheme 12

Although substituents at C(3) are remote from the possible

radical centres at C(1) and C(5), interaction with the radical

is ~ften possible. Pyrolysis of cis- and trans-24 2l~a

pinocarveol (26) (27) ' produce, as well as products with

skeletons sim to those obtained from thermolysis of a-pinene,

a symmetric diene and an aldehyde (32), both of which involve

a drastic reorganisation of the carbon skeleton. The two

rearranged products arise by participation of the hydroxyl

group in a cleavage, which is initiated on the opposite side

of the ring, to produce two discrete allylic radicals (32a), (32b)

(Scheme 13). A difference in the ~eld of the aldehyde (32)

from the cis- and trans- pinocarveols is due to the difference

inter-17.

+

( 26) -} 9/~

CHO

(27) ~~ 3. 5/S

1 L~?6 (- ( 2 6 ) 4.

7?6

<- ( 27)

(32)

~

+

MHO

_.

'

(32b)

/

"

H--o

(32a)

~~

)

₍

(27a~· ~

(26a)

I!> Ill •

Ill

Ill

HO'GJ

HO

HQ,,

,,

HQ.,

'•

_.,

_4--·

510° 510°

(26) ₍₂₇₎

!

_!

HO

HO

HQ.,

_,,

HO·,

_,,

HQ,,, .

I

+

+ +

62.2%

-18.

mediates (26a) and ( ). The biradical snecies (27a),

arising from tran_~~pinocarveol (27), has an axial isopropenyl

radical and is1 therefore, less favoured energetically than

the biradical (26a) in which the isopropenyl group is

equatorial. cis-Pinocarveol (26) gives rise to 14% of aldehyde

(32)1 while trans-pinocarveol (27) produces only 4.7% when

pyrolysed at 510°.

Another trend in the products formed on pyrolysis of

pinane derivatives becomes evident if the pinane substrates are

divided into

two~pes:

2

5

those with an hybridised carbon, and those with sp3 hybridisation adjacent to a ring junction.

Isopropenylcyclohexane derivatives are formed only in the

pyrolyses of the with an sp2 carbon adjacent to a r

junction.

Pyrolysis of nopinone (21)20 at 600° gives the following

compounds: (Scheme 14).

(21)

S.M

6.

5";6

Lower b.p. compounds (??b) and five unknowns (5.576)

constitute the remainder.

19.

from 1, and from

5,6-

bond cleavage respectively (Scheme

15).

Ill

3

0

Q

~

₄

8-2~

-H

0

H

1 7 (21b)

/

H

H

/

_~

_;Y~

\ I

cyclopentanones

staggered.

/~

almost eclipsed

1t<\

H

5

4---t

H

H

( 21a) . (21b)

20.

Bond cleavage will not occur unless the radical orbital lies

in the same plane as the bond to be broken. If this alignment

is not present, there will be a degres of orthogonality in the

developing double bond (5,7-) which may prevent its formation.

I t can be seen (Scheme 15) that the radical at C(5) is

eclipsed with the bot,d, C(1)-C(7), to be broken in biradical

(21b), and no isopropenylcyclohexane is found (Scheme 15).

In contrast, biradical (21a) gives rise to more

isopropenylcyclohexane than it does to the dienone (28).

Here the radical orbital does not easily overlap with the

breaking 5,7- bond, thus making the formation of a double bond

at C(5)-C(7) more difficult. This effect has also been noted in

the products isolated from the pyrolysis of cis- verbanone (23)20•

Cyclopentane derivatives occur frequently among the products of

pyrolysis of pinanes, and are derived from the cyclisation26

of 1,6- octadienes by an 'ene' reaction, The relative yields

of the four stereoisomeric cyclisation products are in the

order of the expected relative energies of the possible transition

states leading to them. The isomer in the highest yield arises

from the transition state in ~~ich non-bonded interactions are minimised, as shown below for linaloB127 (Scheme 16).

H

Scheme 16

:CH

~:

3

'

•, _,

..

r-21.

The other trend which pinane pyrolyses appear to follow is

the production of carbonyl compounds from those pinanols in

which a hydroxyl group is adjacent to a ring junction.28 A

1,6-octadiene (30) formed by scission of the 1,7- and

5,6-nopinol (25) bonds2,2 can cyclise to give cyclopentanols (31), in which the hydroxyl function is adjacent to the isopropenyl

group. A re!:.££-ene reaction can then occur, leading to the

14~:,~ of 4, 6-dime thylhept-6-enal ('105) which is found in the

pyrolysis of nopinol at 630° (Scheme 17).

OH

+

7

(30)

(29)

(31) (33)

( lt isomers)

II

!

Scheme 17

The four cyclopentanols (33), formed from the other dienol (29),

cannot undergo this type of rearrangement.

An example of the commercial exploitation of the pyrolyses

22.

synthesis of the a- and

a-

irones (34) (35), extremely valuable perfumery compounds found in the essential oil of

violets. Pyrolysis of verbenol (36), produced from the

aut-oxidation of a-pinene, was achieved by introducing the chemical

dropwise at a rate of 1 ml min -1 through a

1/L~tr

i. d. stainless

steel tube maintained at 450° - 470°. After distillation of

the pyrolysate at reduced pressure, the fractions were assayed

by g.l.c., and the pyrolysis was found to give the products as

follows (Scheme 18):

~OH

Hydrocarbons

450° - Unknowns

Residue

Unchanged verb enol

Verb enol _Loss

HO

_HO

limonen-3-ol limonen-5-ol

+

~-

a-Scheme 18

pseudotagetones

OHCU

(37)

11%

4%

13e5% 10%

9.5%

23.

To obtain"o:.- and ~- irene, pseudocyclocitral (37) is reduced~ by a Wolff-Kischner process, to the hydrocarbon before being

condensed with formaldehyde and oxidised to give the

6-methylcyclocitrals. These are readily condensed with a ketone

to produce the perfumery materials (Scheme 19):

( 1)

(2)

Oxidation

•

Reduction

~OH

OHCD

---~'

I

...

a-pinene verb enol

~~

H

6-methylcyclogeraniols

l

oxidise

~CHO

~

+

HO

a- _{+ base}

6-methylcyclocitrals

Scheme 19

pseudocyclocitral

Wolf-Kischner reduction

l

( 1) AcOH/ Ac ~;0

«a-Paraf

orma~deh;yd

saponify

n

1,3,3,4-tetramethy cyclohexene

o:.-irone

~-irene

At the time, and according to the patent,2

9

this process was more efficient than existing methods of synthesising the irones

and had the added adv~ntage that, if optically active a-pinene was used, the irone8 produced would also be optically active.

This product is commercially more valuable than the racemic irene

24.

- Substituted Pinanes

Although pinane derivatives substituted in tl1e 2,3,4

and 10 positions occur frequently in oils derived from plants,

7- substituted pinanes have seldom been observed. The first

such compound reported was chrysan then one ( 2--pinen-7-one) ( 4),

which was isolated30 by Kotake and Nonaka in 1957 from the oil

of Chrysanthemum sinense (sabin). Blanchard31 however, pointed

out that the compound which Simonsen32 in 1939 obtained from the

oil of Zieria smithii and designated 11

i~

3

-caren-5,6-epoxide"

(39)

exhibited the same properties as Kotake and Nonaka's compound,

and thus must rank as the first example of a 7- substituted

pinene to be discovered. More recently, ci~.:-7-acetoxy-2-pinene (LJO)

has been isolated both from oil of 'Chrysanthemum vulgare' grown

in Finland33, and in 45% yield from the oil extract of Centipeda

cunninghamii, a small perennial plant, native to Australia34•

Chry8anthenone ( 4 ) was synthesised in 1959 by Hurst and

Whitham,35, 3

6

who subjected verbenone (5) to ultra-violet

irradiation in the expectation that this system would rearrange

to give the cyclobutanone derivative. The photolysis was studied

in great detail by Erman,37' 38 who isolated a number of other

. primary and secondary products from the reaction when it was

carried out under a variety of conditions. He confirmed the

finding of Hurst and Whitham that racemisation of chrysanthenone

occurs during prolonged irradiation, and thus was led to propose

two pathways by which verbenone (5) isomerises, both of which

involve an unspecified optically active intermediate (5a)

(-)·-(5) (42)

/

_Jr

slow

--(-)-(4)

( 5a)

ROH

---..

R := 1'1e

R == Et

ROO

( 44)

ROOC

( 43)

Scheme 20

+

The schem& shows only the primary reaction products, some

of which underwent secondary reactions.

Racemised chrysanthenone was formed by the cyclisation

of the second intermediate, ketene (42), while reaction of the first intermediate ( 5a) gave directly the optically active

product. The presenoo of the ketene (42) was demonstrated by the isolation of the methyl esters

(43, 44),

when the photolysis

was performed in methanol.

In the light of the rules proposed for photochemical

reactions by '1/oodward and

Hoffmann~

4

the formation of

chrysanthenone from verbenone can be explained by a [1,3]

sigmatropic shi~t with retention 0f configuration cf the

26.

that both the [1,3] sigmatropic shift and the ring cleavage

to give the intermediate ketene must take place from the same

excited triplet state or from thermally equilibrated excited

triplet states, From experiments utilising different triplet

sensitizers the triplet state energy was found to be at least

293

kJ mol-1and its lifetime of the order of 10-

9

sec. They concluded that, in verbenone and similar compounds, intersystem

crossing to triplet states is much mor~ rapid than a [1,3]

sigmatropic shift from the excited s et state, the state

usually associated with retention of configuration.

Chrysanthenone (4) has not been pyrolysed in a carrier

gas stream1 but has been found to be unstable at temperatures

as low as 65°, This author has observed that even when stored

at 0° in a coldroom, the compound polymerised noticeably over

a period of four weeks, and it proved impossible to purify

chrysanthenone by preparative gas chromatography.2

3q 25 0

Wenkert "'heated (-)-chrysanthenone([cx]D - 36.6 )

under a nitrogen atmosphere and in a sealed tube at 250° for

20 min. Three products were obtained3

9

and identified a8

(+)-2,6,6-trimethylbicyclo[3.2.0]hept-2-en-7-one (45)

([aJD25 + 1.8°) (16'::6), isopiperitenone (46) (Y6), and pipedtenone

( 47) ( 187&); the remainder ( 6y~) was presumably starting material.

A mechanism was proposed in which (-)-chrysanthenone (4) was

in equilibrium with the ketene (42), a system which could

cyclise to both the [3.2.0] bicycloheptenone (45) and the

isomeric (+)-chrysanthenone (4). Wenkert39 did not suggest a

mechanism for the production of the piperitenones in the

pyro-lysis but considered them to arise from a series of acid-induced

1,2-alkyl shifts when chrysanthenone is heated in acidic media

0~)-(4)

---!\>

A,

____.,

tit

-.:---"

)(g

...--(+)-Ut)

'-'0

t

H+

(42)

HO

(46)

!

( 45)

( 47) .Scheme

The incomplete racemisation of

2,6,6-trimethylbicyclo-[3.2.0]hept-2-en-7-one (45) is seen as a consequence of the rapid

isomerisation of chrysanthenone and the ketene (42), together with

.a slower, but still competitive, ionic pathway between

chrysanthenone and the isomeric cyclobutane (45).

Pyrolysis of chrysanthenone (4) in the absence of acid,

could ~roceed via a biradical intermediate (4a), which can give

isopiperitenone (46) by a [1,5] transfer of hydrogen, or can

undergo

5,7-

bond cleavage to give the ketene (42) (Scheme 22).

The bicyclic product would again be produced by cyclisation of

the ketene, the

1%

optical activity probably arising from some

28.

chrysanthenone

(4),

or of iso-pineritenone

(46)

recovered from

the pyrolysis are reported, but both should be racemic if the

biradical mechanism is operative.

5,7

o~c

::--.

cleavage.

~ ~

-=:--(4a) (42)

I

1,

5

~ H shift

(47)

(46)

( 45)

In the pyfolyses of the substituted pinanes examined

to date, the biradical intermediates f0rmed initially are

generated by cleavage of the

1,6-

or

5,6-

bonds. In the Jresent

work, pinanes with substituents in the cyclohutane ring have been

pyrolysed, in order to investigate the possibility of inducing

.NOl·l 'Gl'~CLA'J.'UHE

Throughout this work, the 7-substituted-pin-2-enes will

be considered as derivatives of chrysanthenol

(38).

The name

'chrysanthenol'

(38)

itself, will imply a - relationship

between the C(?)- hydrox;:r (!;roup and the }l~E_-dimethyl moiety on

0(6). The other isomer, which has an ~}];_ti- relationship between the~orementioned functional groups, will be referred to as

( L~1)

epichrysanthenol

(41),

following the nomenclature of Rouessac •

Thus the structure cis etoxypin-2-ene

(40)

will be referred

to as chrysanthenyl acetate. Similarly, the saturated

?-substituted analogues are named as derivat of

cis-chrysanthanol (Lf8), where "cis-" rtders to a - relationship

between the C(1) methyl and the C(6) - methyls. The

relationship between the hydr and the methyls is

implied by 11_{chrysanthanoln (F'ig. 3).} ~'hus, _cis

-acetoxy·~£iE;_-pinane ( 11·9) will be called cit?.-chrysanthanyl acetate, and

trans etoxy-E_Js-pimme (50), £i:E,-epichrysanthanyl acetate.

Verbenone

·---~.;;..

The is of compound relies upon the autoxidation

of a-pinene (1), a singularlJ inefficient reaction requiring that

air be bubbled through the neat starting mater for periods

of up to a week. This reaction has been studied in detail by

industrial chemists, since pinane der ves oxygenated in the

2-,

3-,

~-, and 10- positions are formed and these chemicals

find extensive employment in perfumery • . The reaction of air

w a-pinene produces various hydroperoxides. If these are

reduced with basic sodium thiosulfate ( 1+2),

th~

main product is

tra~·-verbenol (51). Oxidation of the alcohol vii th sodium

dichromate in acetic acid verbenone

(5),

but the yield

30.

HO

_H

(38)

OH

Epiohrysanthenol (4·1)

HO

H

trans-Chrysanthanol ( 106) I

H

.

\H

.

cis-Chrysanthanol (48)

HO

A cO

H

_?is-Chrysanthanyl Acetate (49)

A cO

~-Epiohrysanthanyl Acetate (50)

Fie:ure 3

Whitham<43) reacted a.-pinene (1) with lead tetra-acetate

in benzene to produce trans-2-acetoxypin-3-ene (52), which

rearranges in acetic acid to t~-verbenyl acetate (53).

Alkaline hydrolysis of the acetate and subsequent oxidation of

the resulting verbenol forms verbenone. The first two steps led

to the recovery of only 47% of the ~-verbenyl acetate.

However, it was noted that on a scale larger than the

5

g employed

in this instance, the rearrangement of the

trans-2-acetoxypin-3-ene (52) in acetic acid could lead to the formation of verbtrans-2-acetoxypin-3-enene

(16), by the elimination of acetic acid.

The most promising synthetic routes to verbenone from

a.-pinene involve the use of catalysts1 and in particular chromium

trioxide, in the aerial oxidation reaction. This reaction was

reported by Badoche(44) in 1953 and reinvestigated by Klein(45)

and Schmidt in 1969. The later study showed that at least 28

compounds are produced by the oxidation, and that verbenone is

formed, under optimum conditions, in up to 30% yield. Under

other conditions the yield can be as low as

5%.

In the present work, the preparation in which the oxidation

was catalysed by chromium trioxide was used after earlier attempts,

using the two-step synthesis, had given verbenone in 16% overall

yield.

Chrlsanthenone (4)

Chrysanthenone is formed by the photochemical rearrangement

of verbenone (5). As noted earlier, much work has been carried

out on this reactiont and it has been observed that the optical

purity of chrysanthenone is dependent upon both the photolysis

conditions and the distillation conditions. Erman(37) has

was photolysed in glacial acetic acid, but this is not the

most convenient of solvents. Although resulting in significant

racemisation( 37 ), the solvent used in the present work was

pentane, from which chrysanthenone can be separated readily.

32.

The pentane solution of verbenone was purged with dry, oxygen-free

nitrogen for an hour before photolysis began. Using g.l.c.

analysis, it was found that at least 90% of the verbenone had

reacted after 6~ hours of photolysis, and

95%

after 8 hours.

The ch~ysanthenone was not usually purified before being

used in the syntheses of 7-methylchrysanthenol

(54)

and

chrysanth0nol (38), as it was found that large losses of the

material due to decomposition were incurred when either

spinning-band distillation or column chromatography, even on 10% deactivated

alumina, was employed as a purification technique.

Spinning-band .distillation always gave chrysanthenone which

contained from five to ten percent of impurity. When the

chrysanthenone, so isolated, was kept in a cold room (3°) for

four weeks, the ~aterial became viscous, probably due to a

s~ow polymerisation.

Attempts to purify chrysanthenone by preparative g.l.c.

also gave a material which showed signs of polymerisation.

It was found, however, that chrysanthenol (38) was stable

indefinitely at room temperature, and this was used as the

starting material in the preparations of the other 7- substituted

pinane derivatives examined in this work.

Small amounts of chrysanthenone were purified by column

chromatography on deactivated alumina and identified from infrared

and n.m.r. spectra.

A~

absorption in the infrared at 1780 cm-1

is characteristic of a cyclobutanone, while ban~s typical of a

-1)

moiety

(1355

em were observed also.

The n.m.r. spectrum contained a vinyl proton multiplet

h

( 65.34;

w

₂

=

6Hz;

C (3 )H), a four-proton multiplet at 6 2.

60

comprising signals due to the·C(1) ru1d C(5) brideehead protons,

and the C(4) methylene. The C(2) methyl gave rise to a multiplet

(W~

=6Hz)

at 61.70, while the C(8) and C(9) methyl signals 2

partially overlapped at 61.19.

Chrysanthenol (38)

Reduction of chrysanthenone by lithium aluminium hydride

in dry ether afforded chrysanthenol in high yield, although the

course of this reaction was influenced markedly by the temperature

at which the excess reducing agent was quenched. Best results

were obtained when the reaction was carried out at -70°, and

subsequently was stirred at this temperature for two hours. If

the reaction was then brought up to room temperature before being

quenched with either water or sodium sulfate decahydrate, the

yield of chrysanthenol was variable but seldom exceeded

60%,

although no starting material remained. Analysis of the product

mixture by gol.c. showed there to be three other compounds present.

Two of these, ~- and trans-verbenol (55) (5'1) were isolated

by preparative g.l.c., but the third compound decomposed on the

column and was not identified. The cis- and trans-verbenols

were charactel"•ised by their infrared and n.m.r. spectra, which

were identical to those of authentic samples. Chrysanthenol (38)

was also isolated from the reaction mixture by preparative g.l.c.

Oxidation of a small sample, by chromium trioxide in pyridine,

gave chrysanthenone (4).

The stereochemistry of chrysanthenol at C(7) was deduced

appeared as a sharp singlet at 63.97. From Dreiding models,

the dihedral angle between the anti- C(7) proton and the C(1)

and C(5) protons is close to 90°, and no coupling of the

anti-C(7) proton would be observed. The 2-pinene derivative

containing a '1-~l'lt~- hydroxyl group (epichrysanthenol (41))

has been synthesised recently by Joulain and Rouessac(41), and

34.

they report that the syn- C(7) proton signal in the n.m.r. appears

at 62.7 as a multiplet. The yield of chrysanthenol was some

90% (g.l.c.), when the reduction of chrysanthenone (4) was quenched

0 '

at -70 by the addition of powdered sodium sulfate decahydrate,

and stirred at this temperature for at least two hours before

being worked up at room temperature.

Although the crude chrysanthenol was of adequate purity

for subsequent reaction to form chrysanthenyl acetate (40) and

cis-chrysanthanol (48), spinning-band distillation afforded the

material sufficiently pure for pyrolysis. The infrared spectrum

of chrysanthenol (38) contained bands at 790 cm-1 and 3450 cm-1

characteristic of a trisubstituted olefin and an alcoholic

function respectively. Leas distinctive were absorptions at

6 '

-1

6

-1

1 55 em and 13 0 em indicative of olefinic stretch and a

~em- dimethyl moiety respectively.

A vinyl proton multiplet in the n.m.r. spectrum(S5~22)

was assigned to the C(3) proton. Three methyl signals appeared,

h

at 61.66 (W2 ==4Hz; C(2)CH

3), at 61.56 (C(8)H3) and at 60.89 (C(9)H

3). The C(4) methylene and the two bridgehead protons at C(1) and C(5) appeared as two multiplets, each of two protons,

at 6 2.11 and 61.99 respectively. The C(7) proton gave a singlet

7-Methylchrysanthenol (54)

Chrysanthenone (4) was reacted with methylmagnesium iodide

in ether to obtain 7-methylchrysanthenol in 70% (g.l.c.) yield.

Purification of the alcohol was effected by chromatography on an

active alumina column, to give a colourless, low-melting,

crystalline material (m.p. 53° - 54°). The infrared spectrum

of this compound exhibited bands at 795 cm-1 and 3225 qm-1

consistent with the presence in the molecule of a trisubstituted

olefin and a hydroxyl function respectively.

The syn- relationship of the C(7) hydroxyl to the

,g~-dimethyl moiety was assigned on the following bases. First, the

Grignard reagent should attack chrysanthenone (4) from the least

hindered side, analogous to the reduction of that ketone by

35.

lithium aluminium hydride. Secondly, the positions of the methyl

signals in the n.m.r. spectrum are consistent with a C(7)0H ~~­

to the C(8) methyl. 7-Methylchrysanthenol (54) shows a broad

6-proton singlet at 61.66, and two three-proton singlets at 61.27

and 00.93. One methyl contributing to the 61.66 signal will be

the vinyl C(2) methyl, and the other the C(8)H

3• Evidence for the assignment of the C(8) methyl comes from the compound

chrysanthenol (38) where the C(8)H

3 ( 61.46) is deshielded, by the hydroxyl

!El.E..-

to it, relative to the C(8) methyl of a-pinene

(61.27). Both 'the C(9)H

3 and the C(7)CH3 are shielded by the 2,3- double bond, but the C(7)CH

3 will be deshielded by its

proximity to the C(7) hydroxyl. Thus, the 61.27 and 60.93 singlets

can be assigned to the C(7) and C(9) methyl groups respectively.

Multiplets at 05.25, 02.22, and 62.00 were assigned to the

C(3) vinyl proton, allylic C(4) methylene, and bridgehead

"

Acetylation of chrysanthenol (38) by reaction with .acetic

anhydride in pyridine afforded chrysanthenyl acetate (40). The

product showed bonds due to the acetate at 1735 cm-1 and 1230 cm-1

in the infrared spectrum. The vinyl 0(2) proton and the 0(7)

h

proton nppeared as a multiplet (W2 ::: 6Hz) at 05.27 and a singlet

at 04.54, resnectively in the n.m.r. Double irradiation

experiments demonstrated the broad singlet of the 0(2) methyl

at 61.68 to be coupled to the 0(3) vinyl multiplet. S ets

at 01. Lf6 and

6o.

were assigned to the 0(8) and 0(9) (JI~-)

methyls respectively. Confirmation of the stereochemistry at

0(7) is gained from the deshielding of the 0(3) methyl ( 61.27)

relative to the position of the 0(8) methyl resonance for

a-pinene, by the ~yn-7-acetoxy, and from the singlet nature of

the 0(7) proton signal.

The mass spectrum of the compound did not give the expected

-1

parent ion at mass 194 g mol • The highest mass peak found was

1 g mol ..;1 , which could be accounted for by losci of ketene -1

(CH

2CO; mass 42 g mol ) from the parent ion (Scheme ).

Confirmation of the structure of chrysanthenyl acetate was

~+

HO)((J

§_chem~ 23

obtained when it was reduced, by lithium aluminium hydride

37.

The synthesis of ?-oxygenated derivatives of ~-pinane

While catalytic hydrogenation of chrysanthenone (4) gave

a mixture of cis- and l£~- pinane derivatives (Appendix

II),

lt

did not prove to be a practical synthetic route to the

series, because it would have necessitated their purification

by preparative g.l.c. Hydrogenation of chrysanthenol (38),

however, yielded only cis-chrysanthanol (1+8). Oxidation and

acetylation of the latter compound gave, respectively, ci

-chrysanthanone (56) and cis-chrysanthanyl acetate (49).

c:Ls-Chrysanthanol (48).

~==--~~---~

~is-Chrysanthanol was prepared from chrysanthenol (38) by

catalytic hydrogenation. Chrysanthenol was shaken with a suspension

of 10% Pd/C in dry ethanol under 1600 p.s.i. H

2 pressure for

eight hours. If the ratio of catalyit to substrate was less than

100 mg/1 g~ hydrogenation was incomplete, and had to be continued

after the addition of more catalyst. Following filtration through

celite, the ethanol was distilled off, leaving an oil containing

almost pure cis-chrysanthanol (48). Final purification by

preparative g.l.c. afforded the product as a white, low-melting

The infrared spectrum contained a bond due to hydroxyl

( -1)

stretch 3350 em and a doublet from gem-dimethyl stretching

modes at 1365 cm-1 and 1354 cm-1• Methyl sinE;lets in the n.m.r.

spectrum appeared at 01.48 (C(8)H

3) and 61.07 (C(9)H3). The C(?) proton gave a singlet at 63.66 and the 0(2) methyl a doublet

(J

=

7Hz) at 01.05. The syn- relationship between the C(?)OH

and the C(6)(CH

3)2 was confirmed by the appearance of the C(?)H signal (singlet).

38.

basis that hydrogenation should occur from the least hindered side. If hyclrogena·tion had taken place on both faces ₉ the JI'.Sll§.- pinane derivative i·Jould have been ol)served by g.J..c. as a minor product. No such minor product was found.

ciE\-Chrysawl:;hanyJ. Acetate·

(49)

"" -·-

---AcotyJ.a-tion of ili~chrysanthano:!_ (48) to form cis-ehrysanthanyl acetate was achieverl by stirring the alcohol in an acetic anh;y·dridejpyridine soJ.uUon. Column chromatography afforded tho acetate 95% (g.l. c.) pure.

AbsorptionB d1.te to the ester group appeared in the infra~

. ~1 -1 -1

red spectrum at

1745

em ,

1350

em and

1230

em •

In the n.m.r. spectrum, the

0(7)

proton gave a singlet at

o

4.23,

confirming the assigned stereochemistry at

0(7)

because ·there is no apparent coupling of the

0(7)

proton to the briclgehead protons. The acetoxy methyl appeared as a singlet at & 2.08 and the C(2) methyl as a doublet at & 1.06 (J ::: 6.5Rz)~ Singlets at

o

1.35 and &

1.07

vrere Rssignecl to the C(8) and 0(9) methyl protons respectively.

The mass spectrum of the compound did not contain a peak at 196 g mo 1-1 corresponding to the parent ion, but a peak of

154 -1 was present. A loss of ketene mass

42,

in a mass g mol

manner similar to that suggested for chrysanthenyJ. acetate

(40)

would account for the observed spectrum.

39.

generate(l ~by the method of Rateoliff and Rod(~hur (46) and the product purified by propm•ati ve ga.s chromatography. SingletB in the n. m.r. spectrum fol' san than one &1.42 and. & 1.18 ~~ere assigned to the C(8) and 0(9)

(56) at

)

methylH respectively. The G(2) methyl appeared as a doublet at

o

1 ~ 13

(.T "'

6Hz)., A broad absorption in the infr•ared npectrum at 1785 cro'-1 :i.s characteristic of a cyclobutanone. fJ'he stretching modes of the l';';.~IJ.l-dimethyl moiety gave :.t'ise to a doublet at

1 1

1375 em and 1360 ern •

VeJ~s:_J22.

Although verbenone has been pyrolysed previously

(47),

th0 only products identified vTere p:iperitenone

(47)

and i sopiperibenone

(46), together amounting to 4Tfn of the pyrolysate. Th:iB pyrolyBis was performed in an iron pipe at 400°

In the presen·~ reinvestigation of Ulis reactimr, the pyrolysis of verbenon0 at 425° vras found to give, in addi t:i.on to the two piperitenones₉ six other major products, four of which were identified from their spectra (Table

1).

Isopiperitenone

(46) v1as pl~esent in 34~0 and show·ed. bands in the infrared n..t

866

om-

1

and

872

cm-

1

₁ character:i.s-tic of trisubsti tute(1 double bonds. An absorption at 1650 cm-1 indioatecl the presence of

the conjuga·l;ed ketone function, l'Thich also exhi b:i. ted an absorption in the ultraviolet at 226 n.m. ( 1:. = 8, 345); this value is similar to that expected at 228 n.m. for a {J ~P-disubstituted conjuga,tocl enone in cyclohexane. T.he n.m.r. spectrum of the compound

contained three single-proton vinyl mul tiplets, each 1vith a

Table 1

Yields (~) of products formed in the pyrolysis

of Verbenone (5) at 425°

Low boiling point compounds

Unknown I

2, 6, 6-'t,r imethylb icyclo[3. 2.

O]hept-2-en-7-one

(45)

1-Ii'ormyl-2, 6,

6-trimethylcyclohexa-1 ,3-diene (57)

Unknown II

5%

7%

Verbenone (5) 1096

Isopiperitenone (46)

Piperitenone (47)

3, 7-Jlimethyl-2-~is-,

4-c

is-,

6-octatrienal (60)

3,7-Dimethyl-2-cis-,4-trans-,6-octatrienal (59)

other compounds (10 of)

2%

3%

'+1 •

at 62.95 (J

=

?.5Hz) arose from the C(4) proton. Methyl singlets at 61.96 and 61.76 were due to the C(8)cH

3 and C(1)CH3 respectively.

Piperitenone (47) was found to be present in the

pyrolysis mixture to the extent of only 2?& at lt25°. However,

when a mixture of isopiperitenone and piperitenone was pyrolysed

6 0 . -1

at 00 , with a N

2 flow rate of 30 ml m~n , g.l. c. analysis showed that the piperitenone peak had increased at the expense

of isopiperitenone. No other product was noted in this

pyro-lysate. Piperitenone was identified from its infrared, n.m.r.,

and ultraviolet spectra. Absorptions in the infrared spectrum

at 875 cm-1 and 1660 cm-1 indicated the presence of

tri-substituted olefin ru1d a conjugated ketone respectively. A

h

vinyl proton multiplet (\V2

=

3.5Hz) in the n.m.r. spectrum at 65.85, was assigned to the C(2)H, and two singlets at

62.08 and 61.92 arose from the exocyclic vinyl methyl groups

at C(8). The C(1) vinyl methyl protons gave rise to a broad

singlet at 61.84.

The structure of a compound, present in the pyrolysate in

7% yield, was tentatively identified from consideratioh of its

spectra as 1-formyl-2,6,6-trimethylcyclohexa-1,3-diene (57).

6 4

-1 -1

Absorptions at 1 7 em and 2730 em were respectively due

to the C=O and C-H stretching frequencies of an aldehyde group.

A

~em-dimethyl

moiety was indicated by two bands at 1367 cm-1

-1

and 1390 em , while a cis-dlsubstituted double bond gave an

absorption at 680 cm-1• The n.m.r. spectrum displayed a singlet

at 69.37 and a doublet (J = 5.5Hz) at 66.59, which were

assigned to the aldehyde and C(3) vinyl protons respectively.

A vinyl

multi~let (W~

=

8Hz) at 65.93 arose from the C(4) proton.

by a conjugated diene system, while a chemical shift of 05.93

corresponds to that of a proton at the end of a conjugated

diene system. A two-proton multiplet at 02.12 was assi~ned to th~

1

0(5) methylene. The two thyls gave a six-proton singlet

at 61.03 and the vinyl methyl a broad singlet at 61.90.

An absorption in the ultraviolet region (cyclohexane) at 305 n.m.

(E

=

10,265) implied that the aldehyde was conjugated, but

differed from the calculated (cyclohexane) ~max (313 n.m.) for

a dienone with a homoannular diene component. Other structures

were considered but were eliminated on various grounds. The

two vinyl protons are mutually coupled by 5.5Hz, of the right

order for a cis- relationship, and the terminal proton is also

coupled to at least one other proton. These data, together

with the knowledge that the aldehyde is conjugated and not

coupled to an a-proton, and that is present a vinylic

methyl group, restrict the structure as is seen; (Fig.

4).

CHO

e

4

As the measured mass of the molecular ion indicated a formula

o1

c

10H1l•O' only a C(CH3)2 moiety remained to be placed into the

partial structure above. In

1-formyl-2,6,6-trimethylcyclohexa-1,3-diene (57) the gem- methyls are in a symmetrical

environment and would as is observed, give rise to a single

1-Formyl-2,6,6-trimethylcyclohexa-1,3-diene (57)

·---~·---H---~

4

H

H

HO

A bicyclic cyclobutanone,

2,6,6-trimethylbicyclo[3.2.0]hept-2-en-7-one (45) comprising 14% of the pyrolysate, was identified

from its spectra • . An absorption in the infrared spectrum at

-1

1778 em indicated the presence of a cyclobutanone moiety, while

a doublet (1365 cm-1 and 1347 cm-1)

~rose

from a gem- dimethyl

8

-1

group. A trisubstituted double bond gave a band at 10 em •

Two single-proton multiplets appeared in the n.m.r. spectrum at

h h

65.43

(W2

=

5Hz) and 64.07

(W2

=

11Hz). The former was

assigned to the C(3) vinyl proton, and double irradiation

experiments demonstrated that it was coupled to the C(2) vinyl

methyl signal at 61.77, to a three-proton multiplet at 6 2. 55,

and to the multiplet at 64.07. Assignment of t:ne 6 4.07 signal

to the C(1) bridgehead proton followed from its positiori in the

n.m.r. spectrum,deshielded by both the carbonyl and olefinic

groups adjacent to it. Coupling was also demonstrated between

the C(1) proton and the multiplet at 62.55, which arose from the

combined C(5)H and C(4) methylene signals. Two singlets, at

44.

The data above compared well with those reported for this

. . ( 48) ( 49)

compound(45) by P.Te1sse1re and J. Beereboom •

An alternative structure, 2,7,7-trimethylbicyclo[3.2.0]

hept-2-en-6-one (58) was eliminated, because the signals

reported( 39 ) for its bridgehead protons differ considerably from

those above. In this compound(58) the C(1) proton gives a

doublet at 62.95 coupled by 8Hz to the C(5)H sextet at 63.87.

The C(5) bridgehead proton and the allylic C(4) methylene

( 62.5) are coupled by 3Hz.

Two other compounds, present in 3% and 4%, were tentatively

identified as the 2-£is-, 4-tra~..E..:. and the 2-ci~-,

4·~cis-isomers respectively of 3,7-dimethyl-2,4,6-octatrienal (59), (60).

Each compound was isola ted only rv40?0 pure, with both samples

containing the other isomer and piperitenone (47) as the major

:i.mpuri ties. The 2-·cis-, 4-cis- isomer had a slightly lower

g.l.c. retention time, and contained the larger amount of

low-boiling impurities. Aldehyde doublets in the n.m.r. spectra

appeared at 610.08 and 610.18. Although these two aldehydes

have not been report0d previously, the four isomers of

2,4,6-heptatrienal were characterised by Schiess and Wisson( 5

o>.

Chemical shifts of 69.51, 69.56, 610.11, and 010.16 were

assigned to the aldehyde proton doublets of the isomers

2-trans-, 4-trans- (61), 2-trans-, 4-cis- (62), 2-cis-,

1+-trans-(63), and 2-cis-, 4-cis- (64) 2,L~,6-heptatrienal respectively.

The authors noted that when treated with dilute acid, or during

attempted preparative gas chromatographic separation of the

isomers, all isomerised to give the most stable 2-trans-,

4-trans-compound (61). This isomer has two absorptions in the

u.v.

spectrum at 298 n.m. (~

=

31,000) and 288 n.m. (~

=

32,000).