A simplified procedure for the preparation of triphenylmethylethers

Tetrahedron Letters No. 2, PP 95 - 98. Pergamon Press Ltd. 1979. Printed in Great Britain.

A SIMPLIFIED PROCEDURE

FOR THE PREPARATION

Sunil K. Chaudhary Environmental Institute

Research

Triangle

of Environmental

a synthesis

During the course of our work towards

(3b). -

of the alcohol of pyridine describes agent3.

The classical

substrate

method

the application

ranging

has definite

involved makes

tritylpyridinium

salt from which

of this pyridinium

reaction

proceeds

reaction

as solvent,

triphenylmethylating

procedure,

catalyzed

by initial

although

transfer

the

of acyl

formation

to the alcohol.

and consequently

Ra-CPh,

X=Cl-, BF4-

mono-

for large scale preparations.

the alkyl group is transfered

Ph3CX + aN=

a need

A more recent report

as a potent

over the classical

involves

preferably

up to 1ooo2.

for the pyridine

salt (2_) is rate determining

B2' we developed

(3a) to the corresponding of trityl ethers

fluoroborate

it prohibitive

that the tritylation

USA

in the presence,

advantages

mechanism

Sciences

27709

of thromboxane

from room temperature

In analogy with the established groups4 one can assume

Health

for the preparation

of N-tritylpyridinium

This latter method

Branch

of a-methylglucoside

with triphenylmethylchloride

at temperatures

high cost of reagents

and Chemistry

Park, North Carolina

for a simple way to effect the conversion trityl ether

and Oscar Hernandez*

Biology

National

OF TRIPHENYLMETHYLETHERS

of an N-

The formation

the high reactivity

of N-

X-

j_

R=H, Me2N

tritylpyridinium

fluoroborate

tuents at the para position g4, a finding which

(2, X=BF4) can be explained of the pyridine

has found synthetic

reaction

of tritylchloride

solution

overnight

(0.04 eq) and triethylamine

application

in acylation

(1.1 eq) with a-methylglucoside

at room temperature

By the same procedure

this way.

ring favor formation

in the presence

(1.5 eq) cleanly

tritylethers,

E

produced

and 8b - were

95

Electron

donating

of intermediates reactions5.

to

Accordingly,

(3a) in N,N-dimethylformamide -

of 4-N,N-dimethylaminopyridine 6-0-trityl-a-methylglucoside6,

isolated

substi-

similar

in 75 and 85% yield

(DMF) (DAP)

z

(88%).

after workup7

No.

96

OH

2

RO

CH20R

H

0

OR a,

R=H

&,

3,

R=-CPh3

4b_,R=-CPh3

R=H

;k:.

0

HO 2,

R=H

z,

R=-CPh3

RO &,

R=H

&,

R=-CPh3

.&zYs) 7a_,R=H E, R=-CPh3

R"Y-Yr

&, R=HH 8&, R=-CPh3

This combination of reagents is also effective in solvents other than DMF as shown by formation of 4b (90%) in dichloromethane solution at room temperature. Reaction of secondary alcohols is considerably slower (18-24 hr) and requires higher temperatures (40-45"), thus the trityl ethers 6b and 7b were prepared in refluxing dichloromethane (68% and 70%) and in DMF solution at 45" (7b, 65n.

~Bu~cph3

0

>97%

0

OH

DAP Ph3Cl, CH2C12

*

&Bu

7a -

In the latter case, a unique selectivity was observed in that the tritylether 7b consisted mostly (>97%) of the trans (equatorial) isomer for the reaction carried out in dichloromethane 7b containing solution8. The reaction in DMF solution was slightly less selective affording 95% of the equatorial isomer. This rather unexpected event suggests a large steric requirement of 2 (X=Cl) for reaction with alcohols, and consequently the selectivity observed with primary

No.

97

2

alcohols

would

preference

be largely

of equatorial

rates of equatorial the tosylation

drate2

our immediate

will stimulate

tion conditions,

chloride-pyridine

procedure

work-up

Analysis

and a compound

tentatively

Following

-3b in 61% yield

of the hydroxyl

product with pyridine simple crystallization. The preparation

procedure

as protective

for the

groups

in carbohyprocedure

Definite

chemistry.

wider choice

tool.

advantages

of solvents,

milder

reac-

a preparation of 2 by the 6,12 the reaction procedures,

literature

(lit.6 60%) after purification

liquid chromatography

(HPLC) on a reverse

a substantial

and triphenylmethanol,

(see experiphase

amount of pyridine

as a bis-trityl ether (see experimental). Based on the 14 this compound is probably the HO-6 and HO-2 bisin 3a

groups

was carried

at 25" the bis-trityl

These experiments

(36%).

cases with the pyridine

to product

synthetic

identified

When the reaction

-3b was much lower

into a practical

organic

reaction

with a large preference

For comparison,

operations.

of crude -3b by high-pressure

in addition

proceeds

and we feel that the present

selectivity,

was included.

out at 100" and afforded

ratio of acetylation

a simpler and more efficient

is well documented,

to the large

is 3.8'" and in a related

The role of tritylethers

are increased

and simplified

showed,

reactivity

chemistry'

applies

Similarly,,;he

may be developed

need was to develop

procedure

pyridine-as-solvent was carried

ether.

potentially

in &.

anhydride-pyridine

their use in other areas of synthetic

over the classical

column13

acetic

of the title compounds.

and nucleoside

mental).

axial as observed

by p-toluensulfonyl 11 hydroxyl groups.

selectivity

This same argument

factor.

of inositol

This kinetic

preparation

versus

and axial &by

for the equatorial

However,

due to a kinetic

solvent

illustrate namely

procedure,

and other trityl ethers 2

ether was absent

the difficulties

the formation

of addition

both of which contaminants

of triphenylmethylethers

by the DAP procedure

but the yield of

encountered

in some

complexes

of the

are not removed

is illustrated

by

by the fol-

lowing examples: 1-O-Methyl-6-trityl-glucopyranoside chloride

(18.4 g, 0.066 mol),

stirred overnight solution

at room temperature

was poured

into ice-water

were washed with saturated After removal

liquors

Preparation tritylchloride

tritY1

ether

work-up

acetate.

the yellowish

After 12 hr stirring,

water,

raising

solvent.

isolated,

-3b and some pyridine.

61%) of white crystals,

After 20 hr at room temperature,

from ethanol

mp 154-155"

an experiment

extracts

to give

to 88%.

Reaction

of 3a (10 mmol) with by conven-

on silica gel' using 20%

the least polar consisted 3.3 (-0CH3), and 7.1-7.7

mostly

Recrystallization

from ethanol 60% yield).

above afforded

of a bis-

(aromatic).

(lit.6 mp 151-152O, as described

cloudy

of the mother

(20 ml) on a steam bath for 1 hr followed

gave a syrup which was chromatographed were

The organic

Concentration

the total yield (a) At 100":

the yellow

and dried with sodium sulfate.

solid was recrystallized

(lit.6 mp 151-152').

in dry pyridine

Two fractions

contained

of 3a (11.64 g, 0.06 mol), trityl-

with dichloromethane.

solution,

(0.68 g, 10%); proton nmr (6, CDC13),

second fraction (two crops,

chloride

of 3b using pyridine

tional extractive

under nitrogen.

4.1 g of product

(11 mmol)

A solution

(15 ml), and DAP (0.003 mol, 582 mg) in DMF was

and extracted

mp 154.5-155.5"

gave additional

CHC13/ethyl

ammonium

of the solvents,

(18.7 g, 71%) pure 3&

(3b):

triethylamine

The

gave 2.65 g (b) At 25':

1.68 g (37%) of _* 3b

No. 2

98

Triphenylmethylbenzylether (11 mmol), overnight

triethylamine afforded

(4b):

Reaction

of benzylalcohol

(2.5 ml) and DAP (0.4 mmol)

after work-up

(10 mmol) with tritylchloride

in dichloromethane

as above and recrystallization

at room temperature

from hot ethanol,

3.2 g (91%)

of pure 4&, mp 950. References 1.

0. Hernandez,

Tetrahedron

2.

B. Helferich,

Advan.

3.

(a) S. Hanessian Staub, Methods

4.

5.

Lett., 219 (1978).

Carbohyd.

Chem., 3, 79 (1978).

and P.A. Staub, Tetrahedron

Carbohydr.

(b) S. Hanessian

and P.A.

J. Am. Chem. Sot.,

92, 5432 (1970); (b) A.R. Fersht and

ibid., 92, 5442 (1970).

(a) W. Steglich

and G. Hofle, Angew.

B. Meyer, and P. Hofmann, ibid., 619 (1972);

Lett., 3555 (1973);

Chem., 7, 63 (1976).

(a) A.R. Fersht and W.P. Jencks, W.P. Jencks,

and Notes

(d) E. Guibe-Jampel

6.

B. Helferich

7.

New compounds

11 _,

Chem.

Internat.

423 (1972);

Synthesis,

Chem. Comm., 267 (1971).

1 (1924).

Spectral

had C,H analyses.

(b) H. Hofmann,

(c) G. Hofle and W. Steglich,

and M. Waukselman,

and J. Becker, Ann., 440,

Edit., i& 981 (1969);

data obtained

on samples were consistent

with

the structure. 8.

Purification

of the reaction mixture

liquid chromatograph analyzed

by gas liquid chromatography

at 4O/min.

Under these conditions,

Relative yields sample

(Aldrich)

were calculated

magnetic 9.

above.

out on a Waters Associates

base line separation

gwas

from 70" to 95'

For comparison,

and the resulting

of the individual

Prep 500

Unchanged

of the two isomers was achieved.

peak heights.

as above gave 69.7% equatorial

(dry HCl, CH2C12)

The identity

eluent mixtures.

(glc) on a OV-225 column programmed

by measuring

of 7a analyzed

trityl group was cleaved described

was carried

using hexane-dichloromethane

a commercial

and 30.3 axial

alcohol

analyzed

isomers was confirmed

isomer.

The

by glc as

by proton nuclear

resonance.

K.L. Agarwal,

A. Yamazaki,

P.L. Cashion,

and H.G. Khorana,

Angew.

Chem. Internat.

Edit.,

11, 451 (1972). 10.

E.L. Eliel and C.A. Lukach, J. Am. Chem. Sot., 79, 5986 (1957).

11.

T. Suami,

S. Ogawa, and S. Oki, Bull. Chem. Sot. Japan, 44, 2820 (1971).

12.

U.D. Reynolds

13.

Analytical

and W.L. Evans, Org. Syn. Coll. Vol. 3, 432 (1955).

HPLC analysis

using a C-8 Chromega water

in 15 min at 1 ml/min.

were as follows: 14.

were performed

column

A.H. Haines,

pyridine,

(Received in USA 21 September

from 70 to 90% methanol/

at UV 254 nm and retention

6.5; triphenylmethanol,

Chem., 33, 11 (1976).

1978)

ALC 244 liquid chromatograph

and a linear gradient

Peaks were detected 3; a,

Adv. Carbohydr.

on a Waters Associates

(ES Industries)

7; bis-ether,

11.

times

(minutes)