Insertion of isoprene units into indole systems.

TetrahedronLetters N0.2y, PP. 2485-2487,l!J@. PergemonPress. Printed in Greet Britain.

INSERTION

OF

ISOPRENE

UNITS

G .Casmti, M.Fmncioni,

INTO

INDOLE

SYSTEM.

A .Guoreschl and A .Pochini

lstituto di Chimico Orgonica dell’lJniversit&

di Parma

43100 - PARMA (Italy)

(Receivedin UK 20 April 1969; acceptedfor publioation23 May We wish to report prelimimry system simuloti~ -

biological

dimethylallyl

resulk of work dim&d

conditions.

1969)

to insert on isoprene unit into an indole

We hove investigated the reaction between indoles and

bromide (I) in acetic acid-water

y ,y

-

medium buffeted with sodium acetote’ at room kmpemture

under nitrogen. The m&n produck from indole and 3-methyl-2-y

, y

(Ila) and rkatole (Ilb) wem 3-

-dimethylallyndole

y ,y

-dirnethylallylindole

()lb)

(Illb).

R”

II

III Ill0

lb

:

R=H

Ilb

:

R

=

lllb

CH3

R’= H;

:

R’=

R”=y

/ 7

;

R”=CH3

The experimental results are summarized in toble I. The reaction products Ilk n-hexane/ethyl

acetate 9:l

spectrum in CDC13 at 5 triplet,

en-H),

3.41

and lllb were sepomted by absorption chromotogmphy (silicagel,

in vol.). 6.72

(lH,

Illa,

o white solid,

brood singlet,

(2H, brood doublet,

maxim0 in the uv (95% ethanol) at 223.5

mp 43-5

ti -H),

02

6.9-7.7

, shows resomnces in the pnmr (SH,z-H

and H on N),

methylene H, J=7 cps) and 1 .73 (6H,singlet, (log E =4.59),

282 (3.76) and 290.5

air serrsitive oil whose pnmr spectrum in CDC13 exhibits resonances at 6 7.CL7.6 5.21‘(1H,

brood triplet,.en-H),

3.29

(2M, doublet,

methyl H) and 2.19 (3H, singlet, ring methyl). by toking ik pnmr spectrum in trifluoroocetic

methylene H, Jz7.5

cp),

5.41 (lH,brood

methyl H)

mF(3.69). (SH,%-H

lllb

and is on

and H on N),

1 .7 (6H,brwd

singlet,

The position of the methyl group in Illb was ascertained

acid3 which causes protomtion

2485

of the I-position

of the ring

No.29

24a6

with

the appeamnce

group

of a new quartet

on the ring whose signal

are also

influenced

ethanol

exhibits

at

5 4.32

shows up at

by the protonation

(1H)

3 1.87

and the shielding (3H,

moving to 3 3.96.

maxima at 228 (log E 4.41),

285

Reaction

of I with

Relative

:

1 hr.

Jz7.5

cps.).

uv spectrum

and 291

The

of Illb

methylene

m k (3.37).

lndole and Skatole

(a)

Composition4 Moncalkylated

Unidentified

lndole

43.3

55.8

0.9

28.3

61.5

10.2

The relative

0.05

compositions

hydrogens

recorded in 95%

Skatole mol -Ila or*,

of the methyl

I

Unreacted

time

The

(3.80)

Table

(a) 0.042

doublet,

and the splitting

mall,

100 ml

were established

acetic acid

(13N)

and log

by glc using 20%

sodium ocetote;

SE 30 on 60-80

reaction

mesh Chromosorb

W at 205’.

The any

intemction

of r

with

tryptophane , its cupric complex and N-acetyltryptophane5

new compound in the same experimental

white The

solid,

separated

uv spectrum

290.4

m TA, (3.69).

elemental

amlysis

of hydrogen 159 (less

by two successive

is suggestive Molecular agree with

bromide.

The

- CH2 = CO)

prepamtive

of an indoline weight

structure:

determined

N-acetyl-tryptamine,

tic’s,

mp 94-5’,

(EtOH

which

ions in the moss spectrum

and 130 (less CH2=NH).

95%)

This

though,

229.5

(log c = 4.59),

(molec.

corresponds

pattern

282

I

with

201

adduct

with

(elimination

is analogous

with

that

toa

product.

(3.76),

ion at 270 mass units)

to o 1:l

showed up at 270,

fmgmentation

did not yield

reacted

which was the main reaction

by mass spectrometry

C ,7H22N20,

the formula

main

conditions.

and

elimination of C5H9), of

physostigmine6. The In particular, 5

5.23

pnmr spectrum

from a deuterochloroform

the espected singlet

for

the proton

solution

provided a definitive

on the carbon attuched

7’8.

IV

5.28

. . ..-.

H

t

I

C’CCH3...

.

, -98’ 5.23’

evidence

to two nitrogen

for structure

atoms falls

ot

IV.

A byproduct N-acetyltryptamine 287

(3.85),

was isolated was assigned

295

rnb

to which

the structure

on the basis

of its

V_ corresponding

(y

to 1,2

, y -dimethylallyl)-

: uv max.at

uv and pnmr spectra

230

(log E = 4.48),

(3.84).

5.6

1.ad 2.82t

(J=6.Ocp)

3 .45d 3.48 (J=6.5cps)

V

5.13t

The formation position

of the indole

and b,

V) or cyclize

recently

uncovered

of the above ring9:

on the nucleophilic

with

are mtionalized

the intermediary

indolenine

site

with

a primary

electrophilic

thus farmed may either

of a suitably

located

rearmngs

ring substituent

(Iv),

attack

ot the 3

to indoles

(Illa -

a phenomenon

7,8,10

other substrates.

- We wish

Ackowledgements

products

to thank Mr.A.Arnone

for

the NM

spectm and Dr.A.Selva

for the mass

spectm. This

work

was supported

in part by the Canbiglio

Nazionale

delle

Ricerche.

References

1) -

Positive

2) -

A.H.Jacbon

3) - R.L.

results

Hinmanand

results

6) - R.Rcbinson Press,

relative

Vol .X ,

Motonori

Smith,

ore obtained

Ohno,

989 (1964).

J.Chem.Soc.

with

2534

(Suppl.I)

5510,1964.

only to gaschromotagmphabile

N-acetyltryptophane

and H .L.Holmes.

(1962).

esters;

The Alkaloids:

fraction.

the research Chemistry

in this field

are in progress.

and Physiology,Academic

Fag .383.

MC Farland,

9) - A.H.Jackson, 10) -

11,

percentages are referred

M.Wilchek

8) - B.Gaffney

solvents.

J.Am.Chem.Soc.84,

in R.H .E .hnske

7) - T.E.Spande,

in oprotic

Tetmhedron

E.B.Whipple,

0ndA.E.

4) - The reported Positive

obtained

andA.E.Smith,

A.H.Jackson

5) -

ore also

B.Naidov T.F.

and B.Witkop, Jasuo

Jnoue

and P.Smith,

J ;Am.Chem.Soc.E, and

Koji

Nakanishi,

Tetrahedron

Spande and B.Witkop,

3256

(1968).

Tetrahedron

2,6119

J.Am.Chem.Soc.,

Letters

857,

(1968). 90,

6521

(1968).

1969.