Tautomerism in 2-ketomethyl quinolines

by

khc

v. CrrrNII*,-todmrrC10#ad School o!

Ptwnueutloll

Chtmlsuy

School of Ormlstry md Chtmial Tatmo@y UnAvutity of Bradfad, Brdfad, BD7 IDP, E!n@uJ

(&dvrd

VI

LX4 14 Dw&r

1987)

The Lr. $olutlal spectra of l suka of 2ScetomethylqulnouMY hmn betn Rdkd. Tmstomuic tatlos hwt bttn detumhd by n.m.r. sptctroscopy. Vkh au c~ctptioc\ the amwere 8ubstMtLJly a txck3slveiy in rht enamInom fams. Tht by c~mpotmd acry@ an 0-mtthyi g~o44 (18) pm~od to bt 90hdy In the kctooe fOm.

0 3319

3320

\ \ R’

R2

R3

R’

Me

H

H

H

2

Et

H

H

Ii

3

Pd

H

H

H

0

But

n

H

H

5

c-t

H

H

H

b

CN

H

H

H

7

Ph

H

H

H

8

But

H

Me

H

9

COOEt

H

h4e

H

10

Ptl

H

Me

H

II

Ph

H

Me

Ph

12

Ph

Ii

P?l

Prl

16

Me

cooEt

H

H

I7

Me

CN

H

H

1

There

ue

sever4

Compound I vu

reports

A over B with p)<~-

Other wakers

19

in the literature

(DMSO-d6)

or

compktciy

These and other publiutlons Thrzr

for the ccupied C=O/Cd ahow its prmncrl

lht resulta

that the enol form

cnolked.~

u

of

thu

groyr

of compounds.

Compound

tetruhlakk.~

4 vu

A was ccxMdere4 to be the main tautomer, mixed tiwn3

by potcntiomctric

l

Slmtluly,

titrrtiar

to fevour

compowd

7 vu

band, but

UC rstabfe for rhe lack of infra-rd

syxtem.

Oomirwt.

One nport

wed

of l methylm reported6

bromine

lssigned l

66.38

sIgna end caKluded

to have 94%

UCXC at 1618 cm-l.

titration

S&MI at

of form C in

In ccmrcquen~r the

form 0.’

is ample cvkknce~~0

urbonyl

of our infr+red

C vu

They found Im trm

said to show no orbany

drawn in the en01 zvltteria,

region.

in urban

Another group studled the n. m.r, spear& and

6 6.60 tCOC13) to W! en01 vinyl prvton.

The 1.r. spectrum of 19 vu

1600 cm-l

fam

solution compound 7 vu

suggested far compound 5

that the compound vu

structure vu

~1 the tautorndsm

of A:B by n.m.r.

‘0

1.09.

in dry rnethhnol and u.v. spectrWoPy.’

CDCIJ.

6cp N

4

reported to show an 85:15 ratio

11.3 to S8.896 of form 8. 2 In ~MWS

f,

“0

14 nzl 15 nz2

by U.V. and n.m.r. in 25 solvents. In most cues

lumind with

cdlfcting

k

%

Furthermore,

data releting to UN-H or uO-H or to the lxx)-

that efuminone8 JIov any comwnd

stmq

conulning

band above 1700 cm-l.

study of compounds I to 19 ue givm in Table 1.

ban& ~1 either ride of I600 cm-l the simple ketone tautomer B vould

3321

w

OoIoc

C-CIW

A?

axlct

1720 (60)

1639 (SO01

I sar (200)

i SS6 (590)

2

17lgoo)

1637 (440,

I S90 (210)

15% (SIO)

3

1712 (lOOf

1636 WOI

IS93 (240)

IS55 060)

4

I712 (90)

f636 030)

1592 (2eO1

I SH WOl

5

1636 (630)

1593 UOO)

1174 030)

6

16% (9200)

ISPS (3x1)

1572 (lotO)

16% (630)

IS90 fW0)

15% (730)

1636 000)

1592 (3gO)

1940wo)

1

7 a

I710 Uoo)

1726 (300)

9

16% (3901

1595 (2601

1575 WOf

10

163) (600)

1595 (440)

I S63 (9201

II

1616 WO)

I602 (6SOo)

1550 (730)

I2

1613 (210)

1590 (730)

16311 0)

IS% hh)

I sbs (alof 1S62 (1)

I3

2

I3

E

1)

13

1603 (m)

1S75 (sh)

1516 Ivd

I740 (SO)

16Q4 (SSO)

159g1210)

I Set WOH))

1747 (70)

1646 010)

I S96 090)

1 H9 (2SOP

171s iv)

162S (sh)

1607 (rf

I UQ (11

1719 (120)

1642 (92)

1604 (330)

1551 (140P*

1633 (4901

1591090)

I6

I7

1636 (1260)

I9

l

1602 (170) 1609 @60)

* Dloxuu * Dioxur

solutica. solution.

(2401

1530wo10)

I S93 (SSO)

16g7 (2SOK))

l6g2 (210)

I%2 (ISO) fsfg

I8

1722 (320)

CHCl3 CHCI3

1sa2 (960)

spectrum

hd

spstrum

I ss3 090)

M extra

band

at 1573 040).

not welt redvcd.

20 a R-H b R=p-toiyi Typic&

*pi

162s cm-l Another

crvminunt (C A 6ZkO) an4

group10

gave

UC=0 uxf uC=C 1534 cm- l (CA

the relevant

dominance

of tautometric form

significant

pnrportion

An intaesting

computi

of tautomcr

band

vhratitxkt

!a

660) and for 20, !a

A b cleufy

at

solutlarr

hove ken

I61 t cm- l k5A

7400) and

21 at 164@ and ISgS cm-l.

For most of

shown

dme

by cornpuira,

8, weak unconiyl@ted

is provided1

chlorofam

1 by compournf

urbonyl

with

examph

reported9 I%6

cm-’

for ZCb

at

tEA

MO).

the mtries in Table

I the

&I dKnc

CIyI

with a

bands were vets.

22.

@G&J

Qyp 22

3322

8 I

A

x32

b 6.62

d

R8tiohlB

11.9b

4.13

a0:20

0.05

?6:2b

C

0

5.3b

6.7 I

15.00

A

5.32

6.6 I

15.00

b.10

?6:2b

0

5.u

6.74

IS.06

b&b

70:30

3

A

5.30

6.5b

IS.05

4.13

a:12

0

A

J.52

6.70

f 5.27

0.26

tKI:iz

0

5.12

6.82

15.b4

b.20

15:ilS

A

6.13

7.05

0

6.311

I.15

1x36 I S,OI

2

5 6

A

5.71

6.97

7

A

6.07

6.80

lOO!o fOOdI IOOFO b.73

97:3

0

6.16

6.95

15.13

b.67

%:b

8

A

5.53

2.20 (Me)

15.76

b.29

9o:lO

9

A

6.40

2.37 (Me)

10

A

6.08

2.31 (Me)

II

A

6.20

I2

A

S.7)

13

A

x90

lb 115

lOOI 16.20

IOOZO

16.Sb

lOOI iOo&

16.62 9.07

3.3

A

6.61

I ,.a0

0

6.66

lb.13

A

t.Oa

it.00

100.9

we) 3.52

aot20

a2:tr b.07

SOGO

B

16.53

17:13

A

17.11

1oO:o

I7

A

I5.90

IS

A

I9

A

14

lOOr 5.15 (HI

s.sa

12.$b

OIIOO LOOtO

3323

Twtomerism in 2.ketomcthyl quinohcs

a

‘b

C

d

l

f

I

191.71

92.36

152.75

205.30

53.96

155.1b

2

195.68

95.16

152.93

207.15

52s

156.96

3

191.41

90.16

153.31

210.77

5o.71

I 55.a5

0

200.52

aa.

l53.ao

212.bO

97.09

156.19

5

170.b2

93.59

155.13

6

157.07

96.62

154.15

7

lab.22

19.15

15b.15

8

201.65

a4.07

I 53.11

C-0 161.97 C-N 116.52 212.30

09.41

157.u)

b5.6a

153.al

9

172.15

19.09

I 55.22

IO

1a5.31

a6.10

15b.16

II

I a5.09

16.04

154.26

I2

1aXb9

a9.64

1H.62

I3

I a6197

90.95

153.56

16

199.71

99.21

147.2a

2ol.a2

57.80

159.76

I5

17a.17

91.91

156.23

210.19

57.aa

160.43

I6

195.10

9a.3b

159.59

I7

195.60

7a.52

15b.62

ia9.53

92.41

isas

ma5

C-0 169.39 C-N 12035 199.ba

I8 I9

cd

51.77

161.10

Here, than

the thermodyrumic la

enol

cost of diu\gtian

the quinolinea.

uCK

between

The

rf d.

1. V. GMEN~KL

3324

1646 cm-l

there

mly

example

with UC-C

wlth

lo

-&+-cc

n

sp3

lnfra-red

(2) and

hryl)

system

to give an enaminone

ahours it to be l mixture

1600 cm-

to tiw

tatlary

spectrum

planar

coefflcknts.

the extlnctJ~ Is rrpatcd9

(d

of the aromatic

spearurn

of ketone,

1 and only

two very

compound

13,

weak

form would be greater

K-0

1712 cm-l

bands at

1575 and

fd

and

155s cm-*

and 1300 cm-l.

confamatlon. twisted

The infra-red

nltrqen,

Is more complex

trms+cc

Evldena?

C=O 1621 cm-l

than the rest

(E) forms. 8

la

cannot

and probably

adopt

of bud

form is provided

by comparison

CK

IS28 cm-l

a

cis-s+zir --

planu

made it impossible

born

of

shows the presaa

The multiplicity

the truw-s-cc

(c A 230) and

clearly

to estimate

with compound

tf

which

((L A 1280) in chloroform.

23

Most compounds other

show a do&M

uomatic

protons

absent and

Is replaced

Compounds

luvlry

in the

whkh

both C3-H

of the ketone

steric

Interwztlon

Conwquently uutomeric put

lam

compounds

derivative,

C3-H

8 was asentially

agalnn

form

to the 0vefaJl

Flnrlly,

able to hydrogenate

reflect

Small

effects re-an

effat

the stqth

differences

tautomeric

see Table

for the pnrvlous,

deutaochloroform

that, fams

*wed

with

of the ring in farm

59.07

the

studlcd

5 7.1 cleuly

A.

for

the

from

the

13 this ¶lRNI

truu-s-cc

Is

form.1’

for the two sigMls.

The

parent, compound

to be 100% In form 8. structure

I&

7, showd

Our flrn

only a

idea VU

had dcstabillsed

that

this form.

0fthexallexcept~werelOO%famA8ndthe

prepared.

Is exerted

separated

For compound

be expected

the same as the unsubstltuted

2.

compound

between

7 to obtain

compound

the phenyl and methyl

4.

arorgr

We conclude

with C3-H

to rev-1

any clear

ratios

The t-butyl

exctytion

UN-H bad

(or uO-H)

that

probably

prompted

ratios

4 was by far the most mrltive l

solution

As

Thb mwt

in a weak dipole.

va~uesl*2*6

m tautomalc

19.

In spite

1ob.

ln any compound.

which results

here and literature

study. 2 Howevef,

of compound

contrlbutlons

band fa

Small c-e,

derivative

detaIled,

bands close to those of compound

hydrwcn

reported

on the results.

very

a small sample of the 3,b-dihydroderivative

form with the Infra-red

no change in the Wtornefic

A with rtrcq

as would

I8 vas a surprise.

of the intra-molcculr

and concentration

In dloxane~~,

a happy choice

We CaKlude

symmetry

between

of solvent

enamlmne

we were unable vd

I&

and

intaaction.

this gave l single tautomeric

of considerable

66.5

group in the erumim

8 to 12, I6 and 17 were

pressure

we were

at

cornpud

and the methyl

also contrlbutlng

expected,

to the C3-H doublet

between

and a vinyl proton showed equal integrals

for compound

of the stale

spectrum

8, but 18 was the only compound

between

ratio

luigned

is

by l downfield

The structure of the c-methyl t~wx

lH n.m.r.

were

us to check em

fa

to thls change,

of compound

2 diluted

the

ample, so It vu

1 to 100 in

ratlo.

II,

the

tautomeric

from the mesomeric

forms D.

systems

rtudied

were

essentially

In

Tau~ommsm

Infra-red

spectra

magnetic

re4uunce

calculated with

half

a,

signal

was taken

tautomers

wry

The followmg 1620,

For compounds

(d) of farm

8.

the

by the

13C n.m.r.

confirmed

I-4,

were

For compouW

stirring

mixture

Tht

using a combinrtion

methodr:

by literature via silica columns

all

and nuclear ratfor

of thr vinyl rlgnl

the

of broad

sfgM

other

bud

were

(a) of form

at

6.61

canpatndr

proton

313, 0,

112, 213,

followed,

under

refluxed

nitrogen. 4g hr*

Methyl The

(3 x 50 ml).

k

tthanol).

ud

were

decoupled

A

7,Oll tingk

and DEPT

515, 616,

717,

13”.

for the sollds, by recrystallintkm

1411,

to connant

solution

txtract column

C, 79.9;

((MI

H, 7.9;

Cl6Hl9NO

require,:

S.g5; N, 4.00.

(IO).

requlro:

Ud the OOhnt

CVa&WAted.

dllutt

with ether The rWiduc

C,

79.7:

Ii,

7.91 N,

1.1%.

By similar

61%.

(3-mtthylquinolylidencn-2-yl)

(12).

Pyruvate

lthoxide

added to potanium

solution

of 2,3-dimtthylquinoline

(0.01

The pr=ipitate

VU

precipitate

collected

skohol).

Found:

wu

C, 70.2; Ii, 5.75: N, S.30.

l-~~1-2-~puin01-2-y1~~~-1~n (0.24 g, 0.01

(3 x SO ml).

to give the propanone

hydrochloride

m.p.

tthuml).

112.

(from

Found:

C, g2.2; H, 5.6; N,

ethanol).

Ig4*

(from ethuml).

wu

(I.9

Found C, gS,

Found: C, g7.f;

11H,

H, MO:

and immcdlattly

requires:

used to raise

added

extracts

(from

m.p.

the mixture acetk

ethanol).

vim

ud

dilute

a-3

,

22 m.p.

CjgHl6ClNO

(SO ml) WAS wlth

the whok

a

acid (3 x

added btfort

wu

fllttred

nirrtng

refluxed

hydrochloric

urbonate

(MgSO4)

Literature

N,4.4S.

undtr nitrogen

product

potauium

were drkd

After

(from

N, 5.45%.

rtfkxtd

the cooled

A

allowed

wid.

129-130.

(IO

(20 ml)).

7 (2.> g. 0.01 mot) in dry THF

(SO ml) and extracted

Found: C, 72.3; Ii, 5.R

uxl

to dilutt

C, 70.0; H,J.gS;

the pH to 6-7 ud

org&c

(1.g ml) In ether

(0.35 g, 27%)

of comwnd

wlth ether

(0.7s g, O.OOJ mol) in dry ether

added dropwiw

(20 ml) and the mixture

g, 72%) m-p. 94.

(from ethanol).

(IO ml1 wu

(20 ml) was added to

The combined

oxalatc

(0.4 gl and ethanol

the keto-esta

A solution

mol) in THF

was diluted

sodium hydroxide

with ether

rapidly

Cl5Hl5N03

(1.4 g, 0.01 mol) in THF

The cooled solution

of diethyl

mol) in ether

to give

(18).

added to sodium hydride

25%, m.p. 207.

A solution

collected

5 day3. the new

Aqueous

(9).

0.005

to st4nd

5 hrs.

(from

12%, m.y.

mol from potassium

(0.7%.

stirring,

lodomethane

m.p. 100.

C, g7.2; H, 11.2s; N, 3.50%.

ml) vu

removed

with

urd txtrrtnl

&quirtr: C, 8S.R H, 5.6% N, 4.15%.

C24Hl9NO

C27H2lNO

SO ml).

extrticd

AIM the

to give the buunorw? (0.31 g, 26%) m.p. 111’

requireu

(I I).

2-(3,4-Diphenylquinolyliden-2-yI)-I-phenylethuwm

txtrsction

and

(20 ml)

ddcd

C, S2.7; H, S.g; N, 3.4%.

2-~3-Mt~yl-4-~ylquinilyti~-2-yl~I-~ylethmom

further

(20 ml) vu

with 4c4lum arbavte

ttusat

mol) in THF

were obtained:

ClgHllNO

3.S hr.

mol) in THF

fikmd

u

(0.79 g, 0.00s

(Q.6 g, 0.021

tthec (SO ml)

with

dried (h@l+),

N, 5.h

hydride

g, 0.007

was diluted

with chl~oform

2-(3-Mcthylqumolyliden-2-yl)-I-phenylttMume

N, 3.35.

to 4alium

was made buic

wu

of 2,3~i~~yl~~I~

A solution

10 minr

trlmethyl~etatc

coaled

on l silica

Found:

over

The acid solution

ffgmic

combined

was chromatographed

procedurts

(8).

(80 ml) was added dropwiw

acid (3 x 40 ml).

Ethyl

A.

ttatlan

Tautomerk

point.

hydrochloric

5.3.

Qta

probe.

14 and 15 the C3-H

tam

l-~3-~tthyl~~~lyli~-2-yI~-3~3~i~~ylbut~2~

(from

to a 3500

7 and 8 by compulstn

en4nminorwz

pl)rued

They were purified

mol) in dry THF with

linked

with l 5 mm C/H

fitted

carbon atom type.

compounds

1721.

instrument,

to rwesent

to determine

PE GM) instrument

a 3eol CX270

integrals.

the mrthykne

experiment3

melting

run on a Perkin-Elma

wtr4

from ‘H n.m.r.

respectively

1519,

were

3325

In 2-kctomethyl qwnoliocs

and the solvent

IOO-lOl.S*.

requires

It gave the

C,72.6;

ttJ.401

N, 4.70%. 2-0,4-DLhyCapu~ly1da7-Z-yl)-I-~~lethnOnC charcoal filtration

(0.5 g) in met-1 the

(b.p. OO-GO*) u 6.20; N, S.60.

residue cluent Cl7Hl

00

wu

(19).

ml) was hydrogenated

chromatogr*phed

on 4 riliu

to give the enaminone 5~~

requires:

C, 11.9,

A mixture at

room column

(0.19 g, 19%) my.

H, 6.00,

N, 5.60%.

of compound temperature using 102106*

I:1

7 (I g) ud

and preuure

10% Palladium fa

II

dichlaometfune/petrokum

(from

tolume).

Fard:

hrs.

on

After ether

C, 11.6;

H,

3326

1. V. G -LL

1.

R. Mcdelll

and L. Malinl,

2.

R. Ra~llcl,

M. Oteyu

3. Hetaocycl. 3.

de

Tetrahdron, CWCICTO,

1966,22,

r~ d.

3213

P. Spegt and 3. C. Cdin,

Chem., 1912, 19, 7:s

A. R. E. Cuey,

C. F&u,

R. A. M. O’Far4ll

and M. C. Murphy,

3. Chem. Sot., Perkln Tram 2, 198S, I71 I 4.

A. M. StocJc, V. E. Dmahue 3. Orb Chem,

5.

8. Gofankkvier Mm.,

ud

K.

GoluJde~ic~,

BulL Acad. Palm. Sci.. Ser. Sci.

Chim.,

1966,

14, 199; w

65, 10466c

6.

P. L. Compagnon, F. Guquz,

7.

M. Hwnana and H. Nod,

a.

3. V. GwenhIll,

9.

D. Smith and P. 3. Taylor, s

IO.

J. [kkovskl,

II.

and E. D. Amstarz

l9XI, 23, 1140

Chem. Sot. Revs., 1977,6,

Specvochlmla

P. 3. Teyla,

persod

Tautomerlrm R. hi. Achem

13.

N. N.

14.

R. Road,

I Y.

N. 3. L-d

COidbW6

931

277. 1976,X&

1477

3. Elguero, C. Muzin,

A. R.

Katritzky

and P. Linda, “The

Academic Press, 1976, p. I88

ud C. Procter, 3. Chem. Sot., Pakin-Tranr ad

1982.91,

Acta, 1963, 19,475

commvllution;

of Heterocydaa,

12.

0.. Compqnon and T. Kinny, Bull. Sot. Chim. &I&.,

Chem. Phwm. Bull., 1966, I@, 762

I, 1979, 2171

R. Lcvlne, 3. Amer. Chem. Sac., 19S2.70, 5217

M. 0. de Cuerrero UKI 3. C. Gdln, s

1986, 19, 291

and 3. H. Bayer, 3. Amer. Chem. Sot., 19x),72,2910

16.

M. H4mat-a and M. Yamuaki,

17.

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