Convenient synthesis of crown ethers containing a hydrazine moiety

Tetrahedron Letters,Vol.29,No.44,pp Printed in Great Britain

5589-5592,1988

0040-4039/88 $3.00 Pergamon Press plc

+ .oo

CONVENIENT SYNTHESIS OF CROWN ETHERS CONTAINING A HYDRAZINE MOIETY Jerald

S. Bradsha"*,

Department

Krzysztof

of Chemistry,

E. Krakowiakt,

Geng Wu and Reed M. Izatt

Brigham Young University,

Provo, Utah

84602 U.S.A.

Abstract: A new class of crown ethers containing a hydrazine moiety was synthesized in only 2, 3, or 4 steps starting from 1,2_diacetylhydrazine or 1,2_diethylhydrazine. Hydrazino-crown ethers with 2 or 4 nitrogen atoms in the ring were obtained by reacting the hydrazine derivatives with l,ll-diiodo-(or dichloro)-3,6,9_trioxaundecane, 4-allyloxymethyl-1,8-diiodo3,6-dioxaoctane, 3-chloro-2-chloromethyl-l-propene, l,lO-dibenzyl-l,lO-diaza-3,7-dioxadecane or diglycolyl dichloride (followed by reduction). The diazahydrazino-19-crown-6 compound formed a complex with methylammonium chloride.

The

aza-crown

ability have

ethylene

carbon form

compounds

of complex

bridges

between

with

moiety

the

ability built

crown ethers A

6).

few

these to

compounds metal could

a hydrazine

convenient

of nitrogen

readily

available

7

sodium

carbonate.

convenient reaction using

mixture

2-propanol,

reduced18, reaction

was

sequence

tPermanent address Lodz, Poland.

the

by

K.E.K.,

Some

believe

reported.

crown

of hydrazino-crown

starting

from hydrazine

by first

reacting

one

which

containing

the

A few small

ring

and 1,5,6-

hydrazine

ethers

abilities.

ethers

with

moieties,

ethers

compounds

with

hydrazine

We have prepared

one of the ring nitrogen

1,2_diacetylhydrazine the

use

of

the

triazaand

and methanol

atoms

ethers

aza-

(compounds

with

derivatives

the

above and

residue

Department

mentioned

tetraaza-crown was

7 (55% overall);

1,2_diethylhydrazine

of

5589

Chemical

2.1 equivalents

in DMF at 120°C

l-

differing which

are

bp

acetamide

A

on

The tetraamide

product

yield

of the The

silica

115-117"/0.01mmHg.

School

for

compounds.1'

gave only a marginal

Technology,

of N-[2-(2-

in the presence

chromatographed

to give the tetraamide.

to give

using

or thiourea

open-chain

that

of their

1 and 2.

evaporated

distillation

and conditions

for

and

because

Most aza-crown

1,4,5-oxadiazepine12*13

complexing

preparation

1) was prepared

reported

filtered,

We

years

a few aza-crowns

crown

not been

cavity.

important

N-alkyl-substituted

then ethanol

followed

a small

been

urea

including

has replaced

(A) with

have

of

have

Saturated

have

prepared

ions.15116 have

for

(Scheme

We

synthesis

atoms)

in the macroring

chloroethoxy)ethyl]acetamide

in recent

and anions. l-8

There

amines.g-ll

have

are shown in Schemes

intermediate

atoms.

nitrogen

moiety

methods

atoms

and

have,been

complex

numbers

Key

between

into the ring

where

interest cations

in the form of the guanidinum, anions

compounds

oxadiazocyne l4 but

moieties

atoms

(no atoms

considerable and organic

the nitrogen

cations,

hydrazine-containing

have

received of metal

between

nitrogen

complexes

hydrazine

have

a variety

The

gel was same

of 7.

of Medicine,

90145,

5590

Compound

7 was

carbonate

at

reaction yield

reacted

reflux

mixture

of crown

1, (6) 0.90

with

B or C in acetonitrilelg

temperature

was

to effect

filtered,

evaporated

121 and a 50% yield

(t, 6 H), 0.95

H); and for 2,

(6) 0.95

ring

to form

and the residue

of crown

(t, 6 H), 2.55

(t, 6 H), 1.00

in the presence

closure

221.

was

(t, 6 H), 2.6

2,

signals

The

to give a 48%

are as follows:

(s, 4 H), 3.55

(m, 20 H), 3.55

or potassium

respectively.

chromatographed20

The NME spectral

(m, 16, H), 3.05

of sodium

1 and

for

(m, 8 H), 5.05 (s, 2 (m,

(m, 17 H), 4.0

2 H),

5.2 (m, 2 H), 5.9 (m, 1 H). Compound

7

was

also

reacted

simultaneously

added

equivalents

triethylamine

of

temperature,

over

filtered

several at

as

follows.

period

The

to

toluene

The residue

The cyclic diamide

of 321 as an oil; NME

Dig

hour

5°C.

and evaporated.

the cyclic diamide. 71% yield

a

with

reactant

(well

stirred)

was

stirred

and purified

(t, 6 H), 1.00

in

toluene

was

containing

for

was chromatographed2'

was reduced18

(6): 0.95

toluene

solution

Each

24 hours

three at room

to give a 65% yield of

by chromatography20

to give a

(t, 6 H), 2.6 (m, 20 H), 3.55 (m, 12

H). The

starting

trioxaundecane solution give

was

two

1,2_diacethylhydrazine

in

DMF1'

stirred

ring

from by

2.45

2.65

synthesized

in

crown

(t, 4 H),

one

step

5 was

chloroform

by

during

the addition

dried over anhydrous to

temperature

yield

with

chromatography2'

78%

compound

and

also

(Scheme

because reacted

of

sulfate

compound

Hlg

mixture

of

8,

reducedl'

sodium

ion

chloroacetyl

Crown with

template

4 was also l,ll-diiodo-

The residue

This

diamide

in the presence

and evaporated

effect.

was

of sodium

washed

and an stirred

twice with

was crystallized condensed carbonate

of

in water

in chloroform

and the crude product

6 2l (45%), NME

1,2-

in a mixture

was vigorously

layer was separated,

66°C.

at reflux

of crown 4.

of 1,2_diethylhydrazine chloride

to

a 26-

(t, 6 H),

carbonate

chloride

The mixture

The

followed

(6): 0.95

of sodium

of chloroacetyl

reduced l8 to give crown

then was

the

and evaporated.

in acetonitrile was filtered

NMB

and

to give a 41% or 36% yield

with

2).

chromatographed20

dihydrochloride

carbonate.

m.p.

Scheme

(8% overall).

To 1 equivalent

2).

was

separately

in the presence

3 h, the chloroform

magnesium

were

S21

(see

cyclocondensation

(35% overall);

as above

of potassium

After

process.

The reaction

period.

reaction

of 3 equivalents

a 1:l

products 421

l,ll-dichloro-3,6,9-

carbonate

The residue

from

1,2_diethylhydrazine

at O'C, 3 equivalents

water,

2-propanol

These

or ethanollg

was

as follows

ring

was purified

this

sodium

and evaporated.

crown

with

condensed

of

(m, 12 H), and crown

reacting

in

simultaneously

solution

presence

13-membered

3.65

dihydrochloride

also

was

the

to give

mixture

observed

and water

were dropped

a

in acetonitrile

The reaction

Diethylhydrazine

aqueous

products,

chromatography20

3,6,9-trioxaundecane temperature.

in

a 2:2 cyclocondensation.

by purification (q, 4 H),

130°C

for 48 h, filtered

cycloaddition

membered

No

at

at

from reflux

over a 24-h

was purified

(6): 1.00

by

(t, 6 H), 2.70

(m, 12 H), 3.00 (m, 4 H), 3.55 (m, 8 H), 3.60 (s, 4 H), 7.30 (m, 10 H). This

work

substituents

on

substituents

have

crowns A

are being study

complexation alkylammonium interaction

reports

only

the

hydrazine

also

been

the

synthetic

nitrogen

prepared

pathway

atoms.

and other

to

form

hydrazino-crowns

Hydrazino-crown

synthetic

pathways

compounds

for

the

with

ethyl

with

formation

benzyl of these

investigated.

of work

the is

salts.

complexation not The

of

complete,

these it

hydrazino-crowns

has

log K and AH values

of 3 with methylammonium

chloride

been

found

has

that

in methanol-water

been

crown

Although

started. 3

forms

(9/l) solvent

a

complex

mixture

the with

for the

are 1.52 f 0.04 and -23.7 IL 3.5, respectively,

as

5591

Scheme 1. Preparation

of Compounds

C, K&O3

/

NHC(O)CH,

PON-Et

Et-N L-0

B

03

1-3.

K

Cl

Cl

D=

Scheme 2. Preparation

of Compounds

4-6

Et. + Et

(‘

Y

o-o-o7

.N

L

ouo_oJ‘Et

5

Et-HN-NH-Et.2

1) H, Na2C03 * 2) LIAIH,

HCI

8

F=

E= .+04, Cl G=

u

l~of31

Cl H = CeHsCH2HN 0

6

A/-K

0

NHCH2CbH,

/Et

F

5592

determined crown-6

by

a calorimetric

(compound

3 with

are 4.15 f 0.01

and

forms

complex

a weaker

Triaza-18-crown-6

-33.3 + 0.3, with

hydrogen

nitrogen not be

atom

bonding

and

of

ethyl substituents thereby

reducing

complete

results

of

ability this

study

will be reported The

supporting

9. 10. 11. 12. 13. 14. 15. 16. 17. 18.

19. 20. 21. 22. 23.

side but hydrogen

moiety bond

atoms hinder

bond.

the approach

nitrogen

that compound

to accept

of these compounds

3

for an optimum

interferes

well

the other

moiety)

triaza-18-crown-6.

the macroring

It is also possible

hydrazine

with this

to one hydrazine

amino nitrogen

This that

would

reduce

the

the two neighboring

of the ammonium a hydrogen with

would

both

hydrogen,

bond.

More

alkylammonium

when the study is finished.

thank

the Centers

of Excellence

Program

of the State

of Utah

for

this work. References

1. 2. 3. 4. 5. 6. 7. 8.

comparable

would

for triaza-18-

the hydrazine

from these data

the

The hydrazine hydrogen

the third

on the complexation

and metal cations

does

spaced around

on the same

cation.

nitrogen

of either

Acknowledgement:

authors

than

cation.23

to receive

an alkylammonium

on the hydrazine the

atom

log K and AH values atom replacing

It is evident

salts

One ammonium

nitrogen

position

nitrogen

atoms evenly

of the ammonium

the amino

3 with

comparable

respectively.

arrangement.

in a symmetrical

interaction

The

alkylammonium

has the three nitrogen

fit for the three hydrogens optimum

technique.22

an N-benzyl-substituted

and Notes

E. Graf and J.M. Lehn, Helv. Chim. Acta, 64, 1040 (1981). B. Dietrich, M.W. Hosseini, J.M. Lehn and R.B. Session, Helv. Chim. Acta, 66, 1262 (1983). A. Kumar, S. Mageswaran and 1.0. Sutherland, Tetrahedron, 42, 3291 (1986). F.P. Schmidtchen, J. Org. Chem., 51, 5161 (1986). V.M. Ostravska and I.A. Dyakonova, Khim. Geterotsikl. Soedin., 867 (1987). M.W. Hosseini, H.M. Lehn, S.R. Duff, K. Gu and M.P. Mertes, J. Org. Chem., 52, 1662 (1987). K.E. Krakowiak and J.S. Bradshaw, J. Org. Chem., 53, 1808 (1988). J.S. Bradshaw, K.E. Krakowiak, R.L. Bruening, B.J. Tarbet, P.B. Savage and R.M. Izatt, JOrg. Chem., in press. B. Dietrich, T.M. Fyles, J. M. Lehn, L.G. Pease and D.L. Fyles, J. Chem. Sot.. Chem. Commun. 934 (1978). -7 N.G. Lukyanenko, A.V. Bogatski, T.I. Kirichenko, S.V. Shcherbakov, Zh. Org. Khim.. 17, 1279 (1981). N.G. Lukyanenko, T.I. Kirichenko and V.V. Limich, Synthesis, 928 (1986). D. Tkaczyrska and A. Kotelko, Dissert. Pharm. Pharmacol., 24, 379 (1972). K.E. Krakowiak and B. Kotelko, Acta Polon. Pharm., 38, 673 (1981). R. Glinka and B. Kotelko, Acta Polon. Pharm., 32, 667, (1975). M. Sieprawski, J. Said and R. Cohen-Ahad, J. Chim. Phvs., 70, 1417 (1973). G. Schniarzenback and A. Zobrist, Helv. Chim. Acta, 35, 1291 (1952). K.E. Krakowiak, J.S. Bradshaw and R.M. Izatt, Tetrahedron Lett., in press. Reduction was by lithium aluminum hydride in THF at 0-5°C using one equivalent of the hydride per amide group. After the amide was added, the mixture was refluxed for 24 h, The resulting mixture cooled and water, 10% aqueous sodium hydroxide and water were added. were was filtered, the residue was washed with THF and the combined THF mixtures evaporated. Equimolar amounts of each reactant was used. Chromatography was on neutral alumina using toluene/ethanol:lOO/l as eluant. Satisfactory elemental analyses, molecular weights by MS, and IR spectra were obtained. R.B. Davidson, J.S. Bradshaw, B.A. Jones, N.K. Dailey, J.J. Christensen, R.M. Izatt, F.G. Morin and D.M. Grant, J. Ore. Chem., 49, 353 (1984). J.M. Lehn and P. Vierling, Tetrahedron Lett., 21, 1323 (1980). (Received

in

USA

3 June

1988)