A new route to azocines

Tetrahedron Letters No.21, pp. lSj7-1840,1970.

Pergmmn

Press.

A NEW ROUTE TO AZOCINES

Printed in Great EPitain.

(1)

J.A. Elix, W.S. Wilson and R.N. Warrener, Department Australian

of Chemistry,

National

University,

School of General Studies, Canberra,

A.C.T.

2600.

Australia

(Received in UK 19 March 1970; accepted for publication 3 April 1970) It has

recently been reported

(4+2)ncycloaddition

reactions

the reaction.

(nitrogen elimination

to form a pyridazine).

of this diene necessitated

can participate

and two modes of addition were observed

on the nature of the dienophile nitrile elimination

(2) that 1,2,4-triazines

the use of electron

rich dienophiles

Our own experience with such electron deficient

ested that efficient

cycloadditions

activated by ring strain.

to facilitate dienes

Consistent with this premise was the observation

(refluxing benzene

for 3 days) to form ultimately

lined in Scheme 1. way was preferred

(3) sugg-

could also be obtained with dienophiles

(Ia,b) reacted with bicyclo[2.2.l]hepta-2,5-diene

via the sequence

or

requirement

that the triazines

presumably

depending

to form a pyridine

The reverse electronic

of cycloaddition/retro

This also established

the pyridines Diels-Alder

that the nitrogen

in the reaction with ring-strained

(II)

(III a,b)*, reactions out-

elimination

path-

olefins.

SCHEME 1

COOR

COOR 0’1)

a) R-Me

*

in

;

b)R=Et

This result has been fully confirmed

(Illa)

m.p.

IOP

(Illb)

m.~..

92’

recently in an independent

W. Dittmar, J. Sauer and A. Steigel, Tetrahedron

Letters,

5171

study by

(1969).

No.21

&ocN,

&OCH,

(VIII)

Application reactions

of

(Scheme

the

of

triazine

(Ia)

and the yellow

315.

‘4 x 10 ) together

with

rather

isomer

the

cycloaddition/fragmentation

(IV)

The i.r.

an a,8-unsaturated

than

(4+2)n

tricyclo[4.2.2.02y5]deca-3,7,9-triene-

(VII),

m/e

of

dimethyl

azocine

Found

yield.

sequence

2) utilising

7,8-dicarboxylate formed

a similar

(VII)

coloured

prisms

spectrum

(uCG’l715

ester

and the

tailing

up to

spectrum,

the ABMX vinylic

structure

(VII)

and is

proton

portion

shown in Figure

of

for m.p.

which

the

is

(60%

the presence

EtOH (Amax 254 nm, E 2.62

spectrum

confirmed

7 days) 125’

-1 cm ) indicated

360 nm) supported was fully

toluene

from hexane,

ultraviolet

This

(VIII).

(refluxing

azocine

isomer

by the

only

(VII)

100 MHz p.m.r.

consistent

with

1.

x

M

A IS

FIGURE 1. 100 MHz p.m.r. Scale

is

No direct

spectrum

of

in ppm,

zero

evidence

for

ed either

by p.m.r.

dienophiles

like

the

behaviour

of

and may reflect a coplanar

azocine at TMS.

any of

spectroscopy

2-methoxyazocine

or eclipsed

reluctance

the bicyclic

(as

N-phenylmaleimide

the

(VII).

of

configuration.

or

valence

low as -60’)

isomers

or by reactions

tetracyanoethylene. 3,8_disubstituted

the

phenyl

Indirect

groups

evidence

for

of

be detect-

with

This

and related vicinal

could

contrasts

with

analogues

(4,s)

(VII)

the

standard

to

assume

bridgehead

1839

No.21

nitrogen

valence

ethyl ester

isomer may be reflected

(VII;

ponds to tolan

m/e 329.1412,

(m/e 178.0779,

in the mass spectrum of the azocine

talc. 329.1416) in which

the base peak corres-

talc. 178.0783).

*/\ * ’ N’ f?

CooC*H, (VIIP)

In order to gain some insight into the flexibility system towards conformational (VII) was prepared. eotropic

inversion,

the related ethyl ester of the azocine

In this compound the ester methylene

(6,7) and thus their p;m.r.

ring (either tub or chair).

VIIe*VIIf) attained become

the A and B protons

sistent with a degenerate migration.

this temperature

interchange

The higher temperature

(ring inversion)

and not with bond

required to effect rapid ring inversion

transition state

if the reverse Diels-Alder

(X) reacts with the triazine

in

(8,9) (IX, t = 70of the adjacent phenyl

(VIIp) required for ring inversion.

Stable 1:l adducts of the triazines philes

reson-

range and this is only con-

reflects the increased steric interaction

groups in the planar

of one conformer

The vinylic proton

this case, in comparison with the related cyclooctatetraenes 100°) presumably

(VIIc=VIId;

of each state has been

the B and A protons of the second conformer). throughout

proton resonances

that ring inversion

and that equal population

(in the ring inversion process

antes remain unchanged

are diaster-

due to the chiralty of the azocine

At 150' and above the methylene

(A2X3 system) indicating

is occurring

protons

(60 MHz) signal appears as the AB portion

of an ABX3 spin system at room temperature

became equivalent

of the azocine ring

can be obtained with ring-strain

reaction is precluded.

(Ib) to form two adducts

(XIII) m.p. 228-230", separated by preparative

dieno-

Thus the cyclobutene

(XII), m.p. 208-209' and

t.1.c. on silica/ether.

The

No. 21

1840

@

(XIII)

p.m.r.

spectrum of the 1:l adduct

3.20 m, 6H, bridgehead

(CDC13, 6.p.p.m:

3.57 s, 6H, ester methyl;

methine;

6.11, t, ZH, olefinic;

m, SH, aromatic;

7.80-8.00, m, ZH aromatic)

described

in the monocyclic

dihydroazocines

The stereochemistry separate

formation

for the valence

of

adduct

isomer

7.15-7.50,

confirms that the dihydroazocine This contrasts with the previously

(10) and with similar cyclooctatriene

systems

(XIII) was assigned after consideration

from the 1:l adduct

1.40, t, 3H, methyl;

(XII), (which provides

(XI)), and from its p.m.r. spectrum

4.40, 9, 2H, ester methylene;

(11). of its

indirect evidence

(CDC13 6 p.p.m.:

2.20-2.50, m, 8H and 2.75-3.20, m, SH, bridgehead

3.62, s, 12H, ester methyl; olefinic;

form (XII).

2.80-

3.90-4.50, m, ZH,

645-6.65, m, ZH, olefinic;

ester methylene;

exists entireZy

1.21 t, 3H, methyl;

methine;

6.55, m, 4H,

7.24, m, lOH, aromatic).

References Part III in series "Cyclobutenes as Dienophiles". the following references are considered as part I and part 11 resp.: C.M. Anderson, .J.B. Bremner, I.W. McCay and R.N. Warrener, Tetrahedron Letters, 1255 (1968); C.M. Anderson, J.B. Bremner, H.H. Westberg, and R.N. Warrener,Tetrahedron Letters, 1585 (1969). 2. H. Neunhoeffer and N-H. Fruhauf, Tetrahedron Letters, 3151 (1969). W.S. Wilson and R.N. Warrener, unpublished results. 43: L.A. Paquette and T. Kakihana, J.Amer.Chem.'oc., 211, 3897 (1968) 5. L.A. Paquette and J.C. Phillips, J..4mer.Chem.Soc., 2, 3898 (1968). 6. J.W. Pavlik, N. Filipescu and R.S. Egan, TetrahedrTon Letters 4631 (1969). 7. K. Mislow and M. Raban, in N.L. Allinger and E.L. Eliel, ed. "Topics in Stereochemistry", Vol I, Wiley. N.Y. 8. F.A.L. Anet and B. Gregorovich, Tetrahedron Letters, 5961 (1966) 9. F.A.L. Anet and L.A. Bock, J.ACWF.C~~V.SOC., 90, 7130 (1968) 10. L.A. Paquette, T. Kakihana, %J.F. Kelly and J.R. Malpass, Tetrahedron Letters, 1455 (1969). 11. R. Huisgen, G. Boche, A. Dahmen and W. Hechtl, Tetraizedron Letter.s , 5215 (1968). 1.