Synthesis of some benzimidazoles containing 2-perfluoro substituents

Journal of Fluorine Chemistry, 18 (1981) 243-251 0 Ekevier Sequoia S.A., Lausanne Received:

February

SYNTHESIS

3, 198 1

OF SOME BENZIMIDAZOLES

KALATHIL

C.

243

- Printed in The Netherlands

EAPEN;? and

Air Force Wright Wright-Patterson

CHRIST

Aeronautical Air Force

CONTAINING

Z-PERFLUORO

SUBSTITUENTS

TAMBORSKI

Laboratories, Base, Ohio 45433

Materials (U.S.A.)

Laboratory

SUMMARY A new method benzimidazoles

is

described

through

the

for

2-Pentafluorophenylbenzimidazole o-phenylenediamine phoric

acid.

yields

by

and

the

N-monoacyl

preparation

has

been

pentafluorobenzoic

direct

condensation

acids

derivatives

of

in

the

these

of

absence

compounds

of

obtained acid

2-Perfluoroalkylbenzimidazoles

carboxylic

of

derivatives

by

in

are

also

solvent

reaction

presence

been

o-phenylenediamine any

the

the

have

of

2-perfluoroalkylether-

o-phenylenediamine.

prepared

with or

of

of

polyphos-

in

excellent

perfluoroalkane-

added

reagent.

Some

described.

INTRODUCTION A number They

were

of

2-perfluoroalkylbenzimidazoles

prepared

by a)

perfluorocarboxylic the

nitro

CF3C02H

C2F5C02H

acids In

our

compounds, perfluoroalkyl, zoles.

of

Our

N-substituted

*University 300 College

in

the

of

presence

N-(o-nitrophenyl)

cyclization or

mineral

acids

group

concurrent

condensation

to with

the

have substituted of

been

previously

strong

acids

[l],

perfluoroalkylamides

benzimidazole

substituted

[I],

reported.

o-phenylenediamines

to

and

c)

b) the

amine

condensation

o-phenylenediamines

in

the

with

reduction and

of

absence

[2]. continuing

we have

studies

examined

on

the

fluoroalkyl

synthesis

perfluoroalkylether, findings

are

as

described

here

and well along

2-perfluoroalkylbenzimidazoles.

of Dayton Research Park, Dayton, Ohio

Institute 45463 (U.S.A.)

substituted reactions as

heterocyclic of

2-substituted

perfluoroaryl

with

the

synthesis

benzimidaof

some

of

of

244 RESULTS

AND DISCUSSION

Reaction

of

equimolar

amounts

C3F70CF(CF3)CF,0CF(CF3)C(0)F gave

a misture

of

of.o-phenylenediamine

(Ila)

products

(.see

in

benzene

Scheme

at

(I)

and

room temperature

for

4 h

1).

Rf

19 C - F

-

(Ila)

(LLf) (a)

Rf

(Da)

1

Nearly

50mole

HF salt

h)

a 2:l

product

pure

of

molar

on

ratio

of

of

11% of reaction. Ya

purification was

aa,

was

tedious

low.

mixture.

this

and

diamine ya

and

and

thus

the

for to

Pa

16% of it

yield

ma

was

of

the

possible

the

(YXa);

of

time

due

of

gave

the

diamide

a period

when

repeated

soluble

18% of the

Repetition fluoride

and

water

apparently

hydrofluoride,

reaction,

chromatography

LYa

acid

the

48% of

temperature

reaction

the

to

approximately and

of

73% of

From column

room

diamine

to

by

at

of (Pa)

cyclization

the

the

converted

consisted

standing

in

was

benzimidazole

complete

In addition

4 h of

sample

diamine

products the

HF present

ratio.

benzimidazole

other

almost

approximately

end

its

to of

starting

34% of

mixture,

led

traces

with

48%”

only

the

The

(ma),

reaction

the

of

% of

(m).

monoamide

GLC/MS

by

SCHEME

(~18

ma)

= -CF(CF3)OCF2CF(CF3)OC3F7

A Identified

The

(Pa)34%

18%

the

to

reaction

a different product

analyzed to

consisted at

isolate

crystallization; 2-perfluoroalkylether-

the a but

245 The yield

Z-perfluoroalkyletherbenzimidazoles

by a new

two-step

procedure

could

shown

in

Scheme

be

prepared

in

excellent

2.

N”2 + NH2

n-f3uLi

I

a-

N”2 Cgijl

NHLi Qzz

ld\ ‘%

6 (l/2

CO

N”2

y

H PPA

(b) Rf = -CF(CF,I[OCF,

-CO-(CF,),

CO-Y Nx3 H (XI

-H,O

= -CFKF,)OCF,

“2

H

@I

PPA

1;1

SCHEME 2

EQUW

-LiOEt

“20

(a) Rf

MOLAR

OEr

\

CF(CF,)OC,F, CFKF,)]2

OC,F,

- H,O

246 This

method

had

monoamides

of

reported in

methods.

diethyl

fast

while

ture

for

the complete

after

analysis.

XI

by

During

the

amounts

of

reaction

mixture,

ethoxide

generated

and

lithium

reaction amide

could

day

heating

after

slow

was

during

3 days

Involves

ion

giving

the

was

not

that

of

XIX

as

chracterized,

the

XII?.

9

olefin

r

f

C-$-OCFz--y-O&F,

Ii

CFs

good

was

same

isolated

from of

shown

the

in

its

be

formed

In

order

from

-&OC

the

room

SCHEME 3

is

ter-

GLC

yields

to

the

Though

spectrum

____L

as

the

and

the well

volatile

in the

lithium ma The

starting as

The

reaction a

GO -

fluoride

component

corresponded

to

OH

-

A

-I

-Xiii

of

further,

eliminates

analysis

N’

ef;OC+CXrF,

formation

mixture. which

3.

lF,

m

be

and

temperature.

75% of

reaction

k

[

Tpb

by

amide this

product

anion=

Li OEt

the

about

volatile

CF,

s F ,-

to

tempera-

reaction

the

study

at

of

F

CF,=&OCF,

and

GLC analysis

+ F

alkyl-

room

noticed

IJb,

by

to

ether

Scheme mass

the

75-97%

l_!Ja and

observed

recovery

The

at

ma

was in

an

appeared

days

if

amide

isolating by other

acid.

diethyl

the

5-7

cyclized

to

with

metallation

yields

of

prepare

o-phenylenediamine

monoamides

of

monoamides

in by

formation

completely

NH2 y--

olefin

in

to

reaction

took

The

amount

reaction.

reacted

were the

The and

ester.

sujpected

reaction.

2-hydroxybenzimidazole apparently

the

the

indicated

of

slow

product

the

were as

was

capability

of

by

polyphosphoric of

a new volatile which

acid.

conveniently

with

preparation

ic

optimum

be

the difficult

followed

isolated

the

could

ethoxide

was

be

when

amides

benzimidazoles

of

was

monolithiation

O“C,

ester

utilization

one The

with

at

provided

which

involves

n-C

reaction

bis-monoamide

small

method

with

and (m

H Li 49 perfluoroalkylethercarboxyl

of

minated

applicability

The

ether

ester

the

general

o-phenylenediamine

1

241

esters

This

decomposition

with

NaOR [3]

general

mode of

perfluoroalkyl

is

and

analogous

decomposition or

to

LiOC2H5[4].

It

exhibited

the

decomposition

would

appear

by many

perfluoroalkylethercarboxylic

of

that

different acids

fluorinated

this

may be a

derivatives in

the

of

presence

of

bases. 2-Pentafluorophenylbenzimidazole by

heating

acid in

at

o-phenylenediamine 190-200°C

the

for

synthesis

o-phenylenediamine phoric

acid

this

120°C

by

heating

was

lOO-105°C

for

be

4 h gave

about

as

in

data

at

than

sealed

115-120°C

are

polyphosphoric

presented

together

for

only

4 h. as

about

the

[C2F5C(0)]20

with

was

omitted

tubes

Table

and using

at

the

THERHAL

DECOWOSITION*OF

Z-SUBSTITUENT

Z-SUBSTITUTED

the

anhydrides at

the

new benzimidazoles

determined

by

estimating

the

n-dodecane

heating

undecomposed

as

an

internal

for

AMOUNT DECOWOSED

H.P.(*C)

(%)

zoo*c

25O’C

325°C

-_

6.4

28.3

-OH

310-Z

__

NIL

__

H

300-l

__

4.0

9.0

F

226

__

116

36.8

__

““I00

__

45.8

CF

__

* Estimated by determining amount recovered by GLC using n-dodecane after heating sample in an evacuated sealed pyrex glass tube for

NIL

as internal IV h.

under amounts standard.

I.

BENZIHIDAZOLES

312-4

could

prepared

them

170

d;“;o

at

88% yield.

XI

-(c:l/l

the

out

IlO-120°C

Q

CF

which

benzimidazole.

-H

-FFOCF2tFOC3F7

from

obtained

carried

acid,

some of

were

was

reaction

of

helpful

polyphos-

temperature

same

not

when

2-heptafluoropropyl-

o-phenylenediamine in

of

chromatography in

was

excess

acid

The

>30% yield

instance,

with of

15% yield

perfluoroalkanecarboxylic

glass

acid

For

10% yield

critical

benzimidazoles

Pyrex

in

polyphosphoric

and

2-heptafluoropropylbenzimidazole

decomposition

gas

prepared acid

1

TABLE

I

the

known

best

When polyphosphoric

appeared

Heating

quantitative

The

of

6 h gave

thermal

some

vacuum by

of

less

2-pentafluoroethylbenzimidazole

The well

12 h,

reactants

used.

of

heated

2

be obtained.

conducted

Instead also

37

a 90% yield the

reaction

presence

C F CO H were

for

could

reaction,

The

was

pentafluorobenzoic

2-perfluoroalkylbenzimidazole. and

at

benzimidazole

4 h.

of

m

with

al DO

standard

as

248 Though

the

clusions at

data

can

the

is

be

insufficient

of

It

stability. greater

and while

zinc

[5,61.

copper the

when

of

analysis

corresponds copper

The

free

alkyl

any

initially

and be

medium

entially

isolated

periodide

a.

m,

periodides methyl

salt formed

its

perfluorinated

thermal

substituent

has

substituent. salts

with

with to

various

form

copper,

metals.

silver

cadmium,

ethanol

with

was

determined,

not

by

con-

substituent

decrease

and

mercury

cobalt

or

2-pentafluoroethylbenzimidazole

anhydrous

reflux

forms

cuprous

displacement

give

further

alternate

of

a

Though

oxide.

be

Heating

the

its

elemental

the

amino

These

hydrogen

m

with

gave

excess n-C4HgBr

a complex in

the

excess

absence

(See

Scheme

of 4)

derivative

liberated be

ally1

m

in

could

With

N-ally1

the

prefer-

iodide,

derivative

XXI

XXI

was

also

N-allyl-o-phenylenediamine with

CH2 = CHCH21 or

n-C7H15f

mixture

reaction

I,

an

the

the

49

o-phenylenediamine

conditions

with

in

products

time.

by heating

H I,

the

49

The

reacted

products n-C

H 1 and

reaction

isolated.

of

reported

n-C (xx).

procedure

salt

CH2 = CHCH2x

With

with

by alkylation

these

copper and

well-defined

a periodide

could

the

characterized.

controlling

been

as

n-C4Hgf

to

and

yield by

have

of

of

CH2 = CHCH2Br) also

did

gave not

products.

the

react Format

periowith ion

2-methylbenzimidazole

analytical

The

thermal

data

of

all

decomposition

thermal

analysis.

CH2 = CHCH21

with

and

were

I,

new compounds of

The released

consistent

with

the

prepared

periodide

volatile between

m

products 73°C

and

are was

given

identified 135°C.

fragmentation

of

prepared

characterized

in

studied were Most

Table

by mass

of

composed the

N-allylbenzimidazole

other m.

EXPER IHENTAL Most

of

of

[7].

The

peaks

that

as well

CH2 = CHCH2Br

iodide

spectral

ion

to

Under while

to

reported

noticed

copper

reacted

[C,F5C(O)],O.

dide

of

under

(obtained

with

a perfluorinated

tend

N-metal were

was

C6H5CH2Br,

(m)

by an

(m

that

aliphatic

form

a specie

isolated

formed,

prepared

to

like

reaction

the

to

in the

benzimidazole

could

an

some

atom.

halides

solvents

which

known

refluxed

with

of

ring

generalizations,

a perfluorophenyl

observed

structure

one

that than

formation

We have

accurate

indicate

2-methylbenzimidazoles no salt

salt

exact

results

suggests

are

make

benzimidazole

stability

Benzimidazoles

salts

the

also

thermal

2-Phenyl

The

made.

f-position

to

the

new compounds

(chemical

ionization),

performed

on

a

infrared

Perkin-Elmer

and

Sigma

were

elemental

1 or

analysis.

Hewlett-Packard

by mass GLC analysis Model

700

spectral were

instrument

2.

and

249

NN\)CF,CF, d”

H

(XVII)

im) /-

Excess CH3=CH-C&I \

\

LH,Ph

CH,CH =CH,

n-au

;H2CH=CH2

(XIX) (XVIII)

(Eg)

n-&I

CH,=CH

t

n-Bu

aN”

CH,I

>CFzCF3

I

AH,CH=

n- Bu

cki,

(xx) -

NH3

7o” , 3hr , Toluene

NH2

+

CH, = CH -CH20r

No H Co3

y-CH,CH=

NH3 (1)

(XXIII) +Polyolkylalion

using or

a 6’

or

Apiezon

recorded

12’

L on in

Acylation

stainless

Table

of

and

5 min.

for

solvents

of

rapid

X

(I)

(1.089;

stirring

was

precipitate

which

low

(l/4”

I.D.)

Details

o-phenylenediamine

hydrofluoride and

W.

of

column

the

packed

new compounds

with

products

10% SE30

prepared

are

2.

A white

4 h after

amine

steel

Chromosorb

To a solution nitrogen of

CH,

H

ether

(m).

The

boiling

C3F70CF(CF3)CF20CF(CF3)C(0)F(17a)

O.Olmole)

dissolved

added

at

was

diethyl

with

Da

slowly (6Omi)

formed. was

precipitate

components

room

removed

The

added m on a

in

benzene

temperature

which

(0.509) rotary

(60ml) over

mixture

was

precipitated was

filtered

vacuum

under

a period stirred the and

evaporator.

the

’m-

m-

a

TABLE

6”

N’

N

x

N

HzN

D

cF*cF3

CF(CF,lOCF,CFKF,)OC,F,

NHClO)(CFz),ClO)HN

NH2

NHC(O)CF(CF,)OCF,CF(CF,)OC,F,

2

mm

IX31

tXY1

[IhI

i&l

El1

[ITal

’

’ 2

36.18 35.8T

1.34 -1.25

14.58 -13.84

2.60 T.is a.13 53.x $t

312-314

__

9.86 -T.E

1.76 -i.x 54.93 3G.z 284 -sG

225-226

-3

3.81 -T-;92

_!!ze;F 4.87

13ra 12.85

0.68 T.v

0?!8 0.86

_& 33 3.31

29.43 29.T

i.!l.! e! 31.85

48.57 7K4r

4.78

1. 19 ix9

30.70 3o.E

4.80

N

H

C

Elemental analysis

734 734-

%

%

586 586

talc MS L found

89-90

116

-

78-79

m.p.(b.p.)'C

found

talc.

3

1 2

Shows IR carbonyl absorption Cyclizes to a on heating. Does not have a sharp m.p.

A

N-CH,CH=CHz

NH,

CH,CH=CH,

W,l,CH,

(CH,), CH,

CH,CH=CH,

CF, CF,

Wi,l,CH,

b-i,Ph

at

17OOcm

mJ31

Dxm

txx1

[XXII

Dlxl

cPL.rIrl

lmn

-1

.

74-75/0.08min

90-91(dec.)

114(dec.)

70-71/0.09mm

64/o.

101-102

I, I21

5

4

148 i-G

tt4+-c3t15

Copper Iodine

I ) I21

698 2;J6

[M+-C4Hg

%

%

292

292

%

*

4.45 4.59

3.00

.&a

analysis analysis.

-E%

-W

8.11 8.15

I.90

2.00

%f&+ +%

Tix

52.17

53.42 53.72

58.89 -iTsi

%$+.

4.01 3.91

3.77

3.84

10.15 -Ex

9.59 8.99

I:+

54.5a5 53.70

51.03

52.195

252 The

remaining

indicated !Ua

brown

the

in

The

same

the

higher

crude

reaction when

of

Preparation

20

(400ml)

reaction C(O)OC

H 25

ma)

G.L.C.

to

the

night.

was

the

LiOC2H5.

follow

ether diethyl

solvent

low

was

layer

Xb

0C2H5 time

ized

(see

h,

the

of

monoamide

to

I:na,

Pa.

gave

procedure

is

anhydrous

diethyl

a

difficult.

The

the

yield

was and

of

benzene

ma.

the

the

amide

(33.79;

produced

a total of

24

(see

as

amide

of

of

h.

of

5 days, that

with

water,

the the

with

dried

a brown

the

Beyond

once

Da

min.

over-

later)

combined,

96%)

the

the

analyzed

addition

extracted

were

20

and

temperature

addition

layer

layers

end

reaction

aqueous

ether

After

for

by

of

of

water

continued at

of

color

a period

with

room

IXa

a period the

C3F70CF(CF3)CF20CF(CF3)

up to

by a side

the

crude

from

was

hydrolyzed

diethyl

the

warm

and

over

monoamide

reaction

consumed

ester

mixture

to

over

noted

hydrolyzed

allowed

the

0.07mole) (4’C)

reaction

maximum

The yield

(4.489;

in

addi-

and

the

solid.

(27.19;

66%)

as

a

Ipb

was

and

prepared

as

attempts

The

to

crude

Ipb

bis-monoamide

prepare was

above

a pure

(86%

sample

by

used

for

cyclization

by

the

method

It

yield).

was a

recrystallization to

the

benzimi-

XI

bis-monoamide

Xl

0.12mole)

n-C4HgLi

off

described

later).

(17.769;

by

24

and

diamide

IXb

solid

a thick

filtered

G.L.C.

the

converted

synthesis

rise

of

was

mixture

(2x)

of

The (12.99;

of

ratio

dissolved

blue.

the

formation

separated

to

amide

Preparation

I

this

periodically,

slowly

ether.

unsuccessful.

dazole

n-C4HgLi

to

of

reaction

of

melting

were

molar

by

and

a period

completely

a 2:1 by

(34%)

solid.

Preparation The

Ya

a deep

added

stirring

removed

cream

into

the

Recrystallization pale

almost

temperature

indicated

The

tional

immediately Ia

for

0.07mole)

added

mixture

amide

diethyl

of

removed

reaction

analysis

period,

was using

(7.569;

was

were

Although

G.L.C.

mixture

a slight

turned

samples

ester,

analyzed

temperature

repeated

1

0°C

was

mixture

Al iquot by

of

at

There

min.

was

benzimidazole

TYa

To a solution ether

room

Isolation

Ya.

of

(18%),

at

reaction,

yield

semisolid

aa

On standing

(48%).

Ha

viscous

monoamide

and

The

0.06mole). yellow and

passing

was

prepared (7.689; reaction

precipitate

quickly

formed.

dissolved

CO2 through

the

in aqueous

0.12mole) was The

and

terminated

described

after

precipitate

a minimum solution.

amount

above

using

C2H50C(0)(CF2)3C(O) 20

h during

(hygroscopic) of

A cream

water

solid

and

which was

neutral-

formed,

was

253 filtered The

and

compound

product. to

ring. extracted

at

with

the

amide

reaction

was

separated

130°C

samples

were

diethyl

ether

yield

component

dil.

the

ethanol

to

melting

crude

purified

by

mation.

By this

heated

for

a period

the

under of

mixture

by

a white

crystalline

since

was

it

83%).

began

to

The from pb

The

added with

again

crude

reaction

ether were

was

When to

ice,

It

water.

with

water

the

white

was

then

solid

finally

were or

in

stopped

the

and

(40-60”~)

obtained

stir-

in water,

benzimidazoles

petroleum and Xn:

polyphosphoric efficient

dissolved

GLC.

slowly

washed

with

4 h with

disappeared.

repeatedly

benzimidazole.

procedureza,

(17.59;

point.

nitrogen 3 to

removed,

analyzed

washed

recrystallization

XI

point

melting

GLC analysis

solution,

3

its

yield

product

procedure)

and

and

NaHCO

near

was

the

the

a sharp

periodically

in

yield

from

XII

(12.5g)

to

have

not

about

filtration

with

dried

(general

terminated,

by

stirred

did

monoamides

Aliquot

when

and

recrystallized

monoamide

(%15Og)

water

bis-benzimidazole

of

The

with

bis-amide

the

Cyclization

acid

was

The

cyclize

to

washed

further by

93%,

dried

subli-

74% and

70% respectively.

Reaction

of

To was

aa

LiOC2H5

added

the

Aliquot

gen.

extracted

of

flask

diethyl

into

diethyl

two

in

reaction

the

filtered was

432

and

acidified

ether identical

to

to

and

traps

From

which flask

of

the

HCI, amount

the with

unreacted

saturated of

an authentic

a pale sample

had

f

rst

trap

le

the

most

of

by

the

XTIY.

water

(20ml).

monoamide. NaCl

yellow of

water,

the

amide

was

and

solid.

noted. The

trap

dlethyl

(25ml) nitro-

concenAt

the

reaction

separated

contained second

olefin

with

with

time

products

GLC/MS

ether under

reacted.

he volatile

residue

to

With product

de Da

wh

trap

the

stirred

as

The

first

of

GLC.

a volatile aa

diethyl stirring

hydrolyzed

by

and

product

the

was

dil.

a small that

line

corresponds

identified

of the

-78°C.

at

volatile

anhydrous vigorous

periodically,

25% of

a vacuum

in

with

analyzed

formation

Analysis

with

yield

the

the

suspended O.Olmole)

removed

ether

to

ether.

by distillation. of

were

and

and

weight

(5.869;

approximately

connected

ether

O.Olmole)

=a

diethyl

decreased

condensed

the

(0.529;

samples

3 days was

LiOC2H5

amide

with

tration end

with

and

a mixture

of

contained

mostly

ether

was

removed

indicated

a molecular

The

residue

left

solid

was

brown

The The

brown yellow

extracted The

aqueous with

IR spectrum

2-hydroxybenzimidazole.

layer

diethyl was

254 Preparation

of

The

XzI

diamine

I

phosphoric

acid

(2009)

was

between

heated

effervescence into

ice

was

noted.

with

filtered,

washed

to

the

lized

from

of

The heated was

under

as

a

I

Preparation To (6.159; for

slurried After

with

solid NaHCO

dil. It

m,

m.p.

became to

was

3

poly-

reaction dark

and

100°C

and

which

separated

solution

further

poured

and

recrystal-

225”-226°C.

orange

and for

and

n-C3F7C02H The

4 h. boiled

solid

(25.79;

to

to

violet

water It

yield

0.20mole)

was

mixture

charcoal

and

precipitated

a pure

were

reaction

activated

90%).

ethanol/water

dark

with

on addition

(42.89;

the

further

benzi-

purified

product,

m.p.

by

22O’C

220°C).

the

2-Pentafluoroethylbenzimidazole

diamine

I

The

(2.169;

The

contents

the

solid

with

dil.

from

the

and

NaHCO crude

3

(BpI)

O.OZmole)

reaction

of

mass

the

drying,

lization

pink

91.5%).

product

12O’C

ethanol

solution

0.022mole).

to

stirred

(52.09;

a pure

about

from

of

4 h.

added

and

light

cooled

and The

mixture

was

The

O.lOmole)

in

ethanol pale

m.p.

water product

O.ZOmole) nitrogen.

reaction

mixture

stirring.

(10.89; at

recrystallization (lit.111,

The

4 h.

reaction

(42.49; under

2-(n-Heptafluoropropyl)benzimidazole

reflux

The

stirred

for

yield

dissolved

filtered. midazole

with

to

diamine

cooled,

C6F5C02H

vigorously

The

crude

ethanol

Preparation

O.ZOmole),

vigorous

dried

yield

were

190”-200°C

was

water

(21.69;

mixture

flask

stirred

was

to

and

(4.159;

a violet

reflux

was

m.p.

at

mass.

sol id was

washed

88%)

needles,

[C2F5C(0)120

under

The

filtered

white

added

heated

solidified

benzimidazole gave

slowly

vigorously.

solution,

ethanol/water

was

with

fi

Water

was

I tered

and

water

repeatedly.

obtained.

213OC

%120°C

Recrystal-

(lit.[ll,

m.p.

212-214°C).

Preparation

of

m

2-Pentafluoroethylbenzimidazole oxide

(5.439;

under

nitrogen.

The

reaction

unreacted mixture

As was

as was

benzimidazole.

0.038mole)

were

the

indicated

The

heated

reaction

continued

filtered,

(m)

by wash residue

for the

under

(11.09; reflux a pale

proceeded, Even

5 days. deeper

repeatedly suspended

color with in

then

of

diethyl

in

some

to ether

solid

began

curpous

The

and

the the

(IOOml)

to

oxide

oxide. remove

cuprous

C2H50H

anhydrous

grey

cuprous

ethanol

and

0.047mole)

react excess

heavier

form.

remained ion

255 cuprous

oxide

(8.59)

was

tive

separated

dried

represented

Preparation

by

and

the

repeated

analysis

N-derivatives

(general

used

for

the

heat

the

benzimidazole

volatile to

tected

from

the

the

solved

in

sol id,

were

refluxed

even

was

experimental in

Preparation

and the

number and

was

The

solvent

sol id.

This

was

un reacted

f .

additional

1

leum

ether

solution

left

a

graphy

(21.69;

by

remove

halides

the

copper or

still

of

the

was

Most

the

ether

After vacuum

was

of

product

or

various

pro-

under residue

iodide.

petroleum

with

apparent.

The

when

to

were

flask

by distillation

fractionated of

was halide

Reactions

reaction

was

was

alkyl

time.

temperature.

preparation

ally1

and

was added

liquid

gel;

enediamine

XXIII.

(30%

on

by

with

to

dis-

the

ethanol

was

a

hexane.

The

N-derivatives

(4.29)

are

and

filtered left

(lOOm1)

and

still was

eluent) pureXXlX,

obtained.

a period

the

to

remove

to

petroleum

ether.

to

vacuum

contained

some

separated to

yield b.p.

di

resinous

remove

about

20ml The

and

pet ro-

distillation unreacted

by column crude

mono,

a

inorganic

to

evaporated

were of

terminated

brown

filtered

of

formation

was

a dark

and

samples

indicated

reaction

which

subjected

mixture

ether

was

and

of

over Aliquot

products The

was

(350ml)

indicated

these

addition

toluene

70°C.

formed.

vacuum

which The

On distillation,

to

solution

the

separated

CH2=CHCH2Br)

0.040mole)

ether

ether

petroleum

(5.09;

of

by

in

heated

ethanol

diethyl

by

dissolved

GLC which

being

removed

diethyl

was

then

analysis

were

GLC analysis.

(silica

bromide was

analyzed

diluted

The

O.ZOmole)

mixture

precipitated

red-brown

based

1

GLC/MS

cooled,

salts.

indicated

reaction

to

the

derivatives

2 h,

the

I,

removed

(a)

procedure the

volatile the

of

was

of

less

used

liberation

halide

product

for

of

was

by addition

added

products.

polyallyl

after

of

removed

of

deriva-

3.

reaction

periodically

solid

XXlIt

(lO.Og) The

the

filtered

liquid

Table

of

10 min.

grey N-copper

salt

of

a period

those

iodide

alkyl

precipitated

To a mixture NaHC03

copper

its

an excess

for

while

below

details

indicated

the

A typical

with

solvent

though

excess

temperature

and

any

When an alkyl

ethanol

it

or

N-derivatives. (2.09)

of

the

removed

the

absence

light

the

of

m)

or=

Q~l00’C.

reaction,

keeping

was

preparation

halides

heated

with

method)

2-Pentafluoroethylbenzimidazole

in

pale

agreed

by m.

of

(slO.Og)

The

centrifugation.

elemental

which f

as

chromato-

N-allyl-o-phenyl-

74”-75”C/O.O8mm,

1.89

3

2

1

__

l.Og

__

__

l.Og

__

Xzi

solvent

Productm

The

2.09

--

5.09

2.09

--

2.09

m

also

10% EtOH

orxwas

was

(10.09)

n-BuI

(5.og)

n-BuI

(15.09)

CH2=CH-CH21

(lO.Og)

CH2=CH-CH21

(5.09)

PhCH2B r

(10.09)

PhCH2Br

Alkyl Halide

in present

Et20

to

70-80”

70-80”

60-70”

60-70”

90”

%100°

(“C)

Temp.

in

these

which

but

not

added was

was

XIX2

Xx2

XKI

xxll

Product

hexane reaction,

excess

7 Days

11 Days

1 Day

3 Days

28 h

1 Day

Time

N-substitutedEk?nzimidam~es

AIImnts/~ctants

Preparationof

TABLE

precipitate isolated.

to

__

EtOH-Et20-Hexane’

__

EtOH-Et20-Hexane’

pet-ether

pet-ether

Sol vent for Crystal1 ization

the

product.

24

10

50

30

58

53

Yield(%)

257 Cyclization

of

n

The XXIII heated

in

indicated

heated

under

diethyl

layer

and

above

yellow ally1

to

This

iodide

(see

dil. to

compound

Table

for

was

3,

1 day

E.

G.

reaction

The

XXI b.p.

identical

tom

and GLC

mixture was

was

dissolved

diethyl

(1,8g;

m,

reaction

which

residue

water.

crude

yield

(3ml) time

the

and

yield to

[C,F5C(O)l,O 2 h at

crude

anhydride, NaHCO

vacuum

with

100°C The

excess

removed under

liquid.

mixed

at

cyclization.

with

solvent

distilled

was

nitrogen

remove

washed

dried,

was

(1.29)

of

complete

vacuum ether,

was

.product pale

from

an atmosphere

analysis

in

to m

ether The

80%).

70°-71”C/0.09mm obtained

crude as

from

m

time).

ACKNOWLEDGEMENT The Inc.,

authors

Dayton,

thank

Ohio

for

Or. the

mass

Jones

of

spectral

Systems

thermal

Research analysis

Laboratories, of

the

compound

xxll.

REFERENCES 1

B.

C.

2

Fisons 18lOlh]

3

D.

Bishop,

A.

Pest

Control

W. Wiley,

4

L.

S.

5

S.

Skraup,

6

F.

Feigl

7

C.

K.

S.

U.S.

Chen,

G.

Tinkler,

H.

and

Ltd.,

Belgian

Pat.

J.

Ann., and

Jones

and

(1919)

Gleich, J.

C.

3,091,643

Chen 419

J.

Chem.

C.

J.

Pat.

659,384

(1963)

[CA.

Tamborski,

J.

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(1912)

(1928) 1245

Chem Sot., (1965)

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(1963)

Fluorine

70

Montash, Sot.

Tatlow,

385

(1964)

[CA.

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3076 (1965)

11266el Chem.,

in

press

a