A convenient synthesis of fluorinated α, β-unsaturated amides

Journal of Fluorine Chemistry, 53 (1991)429-436

429

Received: May 17,1991;accepted: June 7, 1991

A CONVENIENT

SYNTHESIS

YANCHANG

SHEN*

and

Shanghai

Institute

OF FLUORINATED

of Organic

of fluorinated

amides

fluorobenzene, E-isomer

generated

Ilexafluorob~~nzPI1P

amides

undergoing

from or

in good

in

methylene-

chloro-pentagiving

yields

especially

fluorinated

Ishihara

a tllljni>:?r (>I?natural

to

compounds,

reported

tcansF0rmations

their il?~r

a

capable [2].

formation

attrdcted

much

atten-

fluorillo ion-catalyzed

1-ptrosphonyloxy-F-I-dlkenephosphonates

0022-1139/91/$3.50

of

products

l'!leyare also

ory,+nic

ladcling

et al.

class

an important

activities[l].

tnariy Iuseful

rc?Act ions

oE

constitute

~1ide 1 y

Tllerefore

reaction

by the reaction

exclusively.

show biologically

tion.

in situ

with d-bromoacetamides

compoun~ls occurring

of

Sinica,

(China]

br synth+
could

and

d$-Unsaturated

which

Academia

p-chloro-tetrafluorophenylated

or

arsorane,

triphenylarsorane

Chemistry,

200032

Pentafluorophenylated d,p-unsaturated

AMIDES

YIJEJUtlXIANG

Lu, Shanghai

345 Lingling

d,g-UNSATURATED

with

01991 - Elsevier Sequoia, Lausanne

430

amines ‘but

to

the

give

In~th0il

Recently olefincs

I10-d

porflljoci

for

their

we found via

gation

t’le

*is:1

fluorinated

synthr>tic

r-~ll,~,r-‘:

t_,

a

‘1t-

with

ides.

d-brom?acetam

c:tilL of

util

amides

Limited.

pentafluorophenyl

T,I O~.II-colltinuiny

ihy

ci)nv~?ni~?u t

d,g-unsaturate:1

~lll:~r(~,pil~rl~latl~~

is

synthe:;is

yl ides [31 .

the

amides[3],

d,B-~~lsatt_~r.~~r?~l

preparation

a facile

.arsoniilm

exploit

to

natei

by

of

this

,n’-l’u the

t

investireagent

we.

synthesis

reaction

of

of penta-

ci1l.~,r~,-l~,~I~r~~~l.I~.,r~.,p:1~~llyl~~t~d arsorane

RESULTS AND DISCUSSION Pentafluc~r~~pl~enylmott~yl~~ri~~tripiir~r~ylars~~rar~~~ tetr~~luor~,l,;~~?rlyl nerated

from

benzene

or

reacted

with

4 in in

52-808

Scheme

‘nl?tllyll,rll?tci~~:~

~:1~l.,~r:;oranc

mnetliyl~nrtript~enylars~~ra~rls

chloro-pl~nta

yields(3

to

steps).

The

give

p-chloro-

wh ich and

Cl.llorobenzent?,

d-bromoacetamides

or

was ge-

hexaEluoro-

w i th0u t

isolation,

fluorinated

rg?nctiorl

products

squence

is

1.

PhLi Ph3As+CH3

I-

-

Ph3As=CH2

H

p-XC6F4 \ 1 H

/

C=C \ 4

Scheme

1.

3

2

1

BrCH CONR1R2 2 c

-Ph3As=CH-C6F4X-p

CONR1R2

shown

4a: X=F,

RL&C

2H 5

4e:

X=Cl;

12 =R

R

=C2H5

4b: X=F;

Rl=R2=C3H7-i

4f: X=Cl;

R1=R2=C3H,-i

4c: X=F;

12 R =R =C4Hg-n

49: X=Cl;

R1=R2=C4Hg-n

4d: X=F;

R1,R2=-(CH2)5-

4h. X=Cl;

R1,R2=-(CH2)5-

The mechanism It

is

initiated

arsorane

salt

6 which

5.

be

nut 1WiJh

of

charge

RrCH

2

attack

i I ic

with

7 is more

stable

to

transfer,

4CCording than

2.

fluorinated

molecule

to 7 via hydrogen

that

in Scheme

of

another

triphcnylarsine

explained

negative

be rationalized

atom of bromoacetamide

5 reacted

converted

by elimination may

by

3 on the d-carbon

arsonium g&e

of 3 to 4 may

give

of 3 to followed

product

4.

6 because

can ijt?~;t~bilizeii by the CO!JR12 9

It the

yroup.

CONR1R2

3 *

3

Ph3&-CH-CH2CONR1R2

Br-

-

I C6F4X-p

5

Ph As=C-CH 3

I

Scheme

giving

-

eh A+~-CH-CHC~~JR~R~ 3.

-4

I

C6F4X-P

C6F4X-p

6

7

-Ph3As

2.

This rated

CONRlR2

2

one-pot

amides

is

E-isomer

synthesis quite

Of

convenient

exclusively

Fluorinated under

as judged

on

mild

d

,g-unsatuconditions

the basis

of

NMR

432

TABLE 1 Synthesis

of Fluorinated

x

Compound

d,p-Unsaturatr:rl amill-s 4

R

1

Yicl.d(%)a

r?

45

F

C 2115

c2:i5

65

4b

F

C3H7-i

C3H7-i

75

4C

F

C4Hg-n

C4Q9-n

80

4d

F

4e

Cl

C2H5

(IzH5

52

4f

C1

CjH,-i

r:jl17-i

74

4g

Cl

C4H9-n

C 4 H 9 -n

79

4h

Cl

62

-(ClI&-

75

-(CH&

a Isolated yields.

spectroscopy Eluorinated

and

lnay be

natural

useful

iII the

preparation

of

products.

ZXPERIHENTAL

melting points and boiling points were uncorrected.

All Infrared

spectra

Qf

disks

and

IR-443

spectrometer.

solid

of liquid

products

products WIR

ipectra

from TMS

for

'H NMR

and

positive

Eor

upfield

shiEts)

EM-360

spectrometer

on a Finnigan

from

at 60 MHz.

2C-MC-4021

were

Yass

were

obtained

as films

(chemical external

werp Maqs

TFA

obtained spectra

spectrometer.

as KC1

on a Shimadzu shifts

in ppm

for lgF NMR, on

a Varian

were recorded

d,@-unsaturated

Phenyllithium was

?dfled

arsonium under

(4 mmol)

( 4 mmol)

iodide

to O"C,

benzene

min at O°C,

in

Then at 20°C

column

chromatography

for 3h.

46'C;

m.p.

c,

for

53.24:

H, 4.05;

cm

;

‘tl

TFA): MS

for

was

added

and

was

isolated

light

1668(s),

by

petroleum

1620(s)

3.25(4H,q,J=6Hz), "F

NMR(CC14/TFA):

221(M+-NEt2,

100%);

H, 4.09;

13%),

IR(film):

cm

-1

7.26(1H,d,J=l6Hz):

6.85 62.3-

Analysis:

N, 4.78:

Found:

76.3-77.4(1F,m), 278(M+-Pr,

12%),

1612(s)

3.82(2H,hepta, "F

;

MS m/z:

1656(s),

1.28(12H,d,J=6Hz),

NMK(CC14/TMS):

321(M+,

stirred

m)ppm;

105°C/2mmHg;

63.3-65.0(2F,m),

m/z:

for 15

and

84.6-87.0(2F,

C, 53.26:

6.87(1H,d,J=16Hz),

J=6Hz),

stirring

N, 4.45%.

4b: 75% yield,; b.p. -1

22%),

C13H12F5NO:

4

gel with

IR(KC~):

7.37(1H,d,J=16Hz);

278(M+-Me,

for lh and

(8:2) as eluent.

75.3-77.0(1F,m),

293(M+,45%),

to 20°C

l.O2(6H,t,J=6Hz),

'H NMR(CC14/TMS):

(6 ml)

(25 ml) at 20°C

at 20°C

After

product

on silica

4a:

ether

or chloro-pentaEluoro-

all
The

ether

64.6(2F,m),

stirred

was warmed

(b.p. 60-90°C)-ethyl

65% yield;

Et20

d -I,r[~lnl~;lceta'nidl~ (I mmol)

stirred

Calcd

was

slowly

the,mixturo

(lH,d,J=16Hz),

absolute

the hexafluorohenzeno

was

diethyl

~s;!)r~rlsi )I);>r mrttllyltriphenyl

Tile mixture

(2 mmol)

30 min.

in absolute

('1 cop~ri'it> to tile

nitroyen.

cooled

4

amides

NMR(CCl$/

84.0-86.3(2F,m)PPm: 221(M+-NPr2,

77%);

434

Analysis: Found:

Calcd

for Cl5Hl6F5NO:

C, 56.33;

4c: 80% yield: cm

-1

;

H, 4.88;

b.p.

c_,

59.17;

MS m/z:

14,

349(M+,O%),

5.91;

N,

m.p.

H NMR(CC14/T!4S):

(lH,d,J=16Hz), 64.6(2F,

m),

55.66; 4e: cm

-1

H, 3.61;

52% yield; 1

;

TFA): 42%),

Analysis:

H, 5.73:

IR(KC1):

62*C;

1.4?)-1.73(6H,

N, 4.01;

'3, 55.LO:

1660(s),

m),

Found:

1620(s)

3.30-3,65(4H,

m),

lgF Nr4R(CC14/TFA):

84.0-86.4(2F,

305(M +,379,), 221(M

t

m)ppmn;

7.01 62.6-

MS m/z: Analysis

-I~C51110, 13%);

H, 3.93:

cm-';

Found:

N, 4.59;

C,

N, 4.06%.

b.p.

l10°C/2mmHg;

J=l6Hz),

62.0-63,3(2F,m), 237(M+-NEt2,100%);

C, 50.43;

22l(M+-NBu2,100%):

3.83%.

H NMR(CC14/TYS):

7.OO(lH,d,

Hz);

lgF

84.4-86.3

C, 58.47;

75.9-77.2(1F,m),

C14H12F5WQ:

for

1.13-1.80(8H,m),

75.7-77.2(1F,m),

7.43(1H,d,J=16Hz);

306(M++l,lOO%),

1660(s)., 1618(s)

0.95(6H,t,J=6Hz),

c 17H20F5NO:

4d: 62% yield; 1

IR(film):

62.3-64.7(2F,m).

NMR(CC14/TFA):

for

N, 4.36;

7.06(1FI,d,.l=16tlz), 7.56(1il,d,J=16Hz);

3.33(4H,t,J=6Hz),

Calcd

H, 4.98:

N, 4.02%.

122°C/2mmHg;

‘11 NMR(CCl/TMS):

(2F,m)ppm;

C, 56.10;

H, 3.88;

IR(film):

i.lr,(r,N,t,

1660(s),

J=fiHz), 3.30(4H,q,

7.49(1H,d,

J=16Hz);

63.3-65.0(2F,m)ppm; Analysis:

N, 4.52;

1622(s)

Calcd

Found:

"F

J=6

NMR(CC14/

MS m/z:

309(M+,

for C13H12ClF4NO:

C, 50.38;

H, 3.80; N,

4.34%. 4f:

74% yield;

cm-'; J=6Hz),

b.p.

10R°C/2mmHg;

'H NMR(CC14/TMS): 6.94(1H,d,J=16Hz),

IR(film):

1.32(12H,d,

1650(s),

1610(s)

UJ=6Hz), 3.87(2H,hepta,

7.49(1H,d,J=16Hz);

"F

NMR(CC14/

435 TFA): 15%),

62.3~63.5(2F,m), 237(Y

C, 53.36:

t

63.5-65.3(2F,m)ppv;

69%);

-NPr2,

H, 4.74:

Analysis:

N, 4.15;

C*tcd

Found:

MS m/z:

337(M+,

for C15!116C1F4NO:

C, 53.90;

H, 4.78:

N,

3.78%.

49: 79% yield; cm

-1

;

b.p.

1H NMR(CC14/TMS):

3.30(4H,t,J=6Hz), NMR(CC14/TFA): 365(M+,

9%),

H, 5.61

IR(film):

0.92(6H,t,J=6Hz),

7,07(1H,d,J=l6Hz), 62.5-64.0(2F,m),

237(M+-NBu2,

C17H20ClF4NO:

16 18(s)

1660(s),

1.12-1.75(8H,m),

MS m/z:

64.-65.0(2F,m)ppm;

H, 5.47;

19F

7.50(1H,d,J=16Hz);

100%);

C, 55.84;

Analysis: N, 3.83;

Calcd

Found:

for

C, 55.87;

N, 3.78%.

4h: 75% yield;

m.p.

'H NMR(CC14/TMS):

64.0(2F,m),

IR(KC1):

1.40-1.90(6H,

237(M

C14H12C1F4NO:

m), "F

+

73%);

-NC5H10,

C, 52,28;

1656(s),

H, 3.73;

1616(s)

NMR(CC14/TFA): 321(M+,

Analysis:

N, 4.36:

cm

-1

62.7-

74%), Calcd

320 for

Found:

C, 52.16;

Natural

Science

N, 4.20.

ACKNOWLEDGEMENT

The

authors

Foundation support.

of

wish Ch ina

to thank and

the National

Academia

;

m) , 7.17

3.40-3.70(4H,

MS m/z:

64.0-65.0(2F,m)ppm;

loo%),

H, 3.42:

60°C;

7,59(1H,d,J=16Hz);

(lH,d,J=16Hz),

(M+-1,

1.16"C/2mmHg:

Sinica

for financial

436

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D.

[lassan-Gonzales,

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C. Moore

Trans

T.,

J. Chum.

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