Rearrangement of s-phosphorylisothioureas into n-phosphoryl-thioureas: stereochemistry at phosphorus and mechanism

Tcrmhrdron Vol. 42. No. 16. pi. 4591 104601, 1986

oMo-4o20/86 s3.00+ .oo Fqamoa lourmb Ltd.

mntcd inGrtntBtitain.

REARRANGEMENTOF S-PHOSPHORYLISOTHIOUREAS

INTO N-PHOSPHORYL-

THIOUREAS: STEREOCHEMISTRY AT PHOSPHORUS AN0 MECHANISM

MARIAN MIKOtAJCZYK+,

Centre

of Molecular and of Sciences, Department t6df, Boczna 5, Poland

PIOTR KIEtBASINSKI

and

ANNA SIJT

Macromolecular Studies, Polish of Organic Sulphur Compounds,

Academy 90-362

(Receioed in UK 9 June 1986)

Abstract - Stereochemistry of the rearrangement of S-phosphorylisothioureas into N-phosphorylthioureas has been investigated using two chiralphosphorothioic acid: c clic 4-methyl-2-oxo-2-mercapto-1,3,2-dioxaphosphorinane (1 5 and acyclic, optically active 0-methyl-0-1-naphthyl phosphorothioic acid (2). Configuration at phosphorus in N-phosphorylthioureas 4 aEd 9, obtained in the reaction of these thioacids with various carbodiimides, has been established by means of chemical correlation and CO spectra. The title rearrangement has been shown to proceed with full retention of configuration at phosphorus. The stereochemistry of the rearrangement under discussion, as well as the different reactivity of various types of phosphorus thioacids towards carbodiimides have been explained in terms of the mechanism involving pseudorotation of a pentacovalent phosphorus intermediate.

INTRODUCTION As a part and

of 1

phosphorothioic, first

step

Scheme

program recently

phosphorodithroic

on the found and

reactions that

the

to

the

stable

and

(A)

isolable

I

R’N=C=NR’

X

-

(R012P-~-~-~~~* !

carbodiimides

!R'

X = S, Se Y = 0, s

4591

=-

of acids

which

N-phosphorylthiokeleno)

I).

+ (R0)2i-YH

of reaction

phosphoroselenoic

S-(Se)-phosphorylisothio(seleno)-ureas

rearrangement (Scheme

a general

, we have

selenoacids

with

thio-

carbodiimides affords

undergo

with in

the

facile ureas

(El2

4592

M. we have

Moreover, are

strongly

the

nature

tuents

of

force

possible acting

also

shown that

dependent the

on their

their

geometry

reverse

as real

R’

to

react

des,

those with

prepared a second

shown in Scheme II

with

properties is,

of

in turn,

the nitrogen

these

atom.

by

Bulky

(1)

substi-

which

makes

to S(Se)-phosphorylisothio(seleno)ureas

agents.

Therefore,

(DCC) and diisopropylcarbodiimide of

thioacid

(A)

N-phosphorylthioureas,(IJ)obtai-

from dibenzylcarbodiimide molecule

adducts

determined

N-phosphorylthio(seleno)ureas

rearrangement

ned from dicyclohexylcarbodiimide contrast

which

connected

of

phosphorylating

ef al.

the phosphorylating

conformation

substituents

a special

MIKOLNCZYK

in

(DP’C),

(LlBC) and diarylcarbodiimi-

yielding

a mixture

of

the

products

3.

Scheme II R’

(RO)&-NHR’ 0

_

s

s

0

In contrast reactions phorus

of

In these the

to

the complex

containing

cases

phorylated

the

ureas

course

with

of

+ R’NHCNHR’ J

the

phosphoric

directly and ureas

described

and all

occur

intermediates

but react

anhydrides

reactions

acids

one or two C-P bonds

isourea-type

(0)

corresponding

+ II S

i-Pr

carbodiimides

acids

+ (Ro13p

I 0

= c-Hex,

R’

(RO)~PSR

+

(Ro)~;-o-[(oR)~

kinds

the

(Scheme

next

isomerize

acid

the

organophos-

in a much simpler

CC) do not

with

above, of

way. to N-phos-

molecule

to give

III).

III

Scheme

1 R\

P-OH

+ R3N=C=NR3

-

R2’

itJ IR1R2p(x)oH

R3 “\P-i

R*'

C-NHR3 -11 X

1 0

+

(R’NH)~c=X

0 a) R’=R*=AlkO,

It

b)

R’=Alk,

c)

R’=R*=Alk,

is

quite

R*=AlkO,

Ar,

dependent

acids

X=O,S,Se

X=O,S,Se

reasonable

us organophosphorus partially,

ArO , X=0 Ar,

to assume that towards

on the

ability

the

carbodiimides of

the

differences mentioned

initially

in reactivity above

formed

of

may be,

adducts

i

vario-

at least

and

C to

Rearrangement of Sphosphoryliaotbiourcas undergo

isomerization

(reversible

g and I.This

raises

The present

research

phosphoryl

group

the

or

questions

was undertaken

migration

irreversible)

concerning

4593

to their

N-phosphoryl

the mechanism

to determine

the

of

this

isomers

rearrangement.

stereochemistry

of

the

S-N

acids

in our stu-

in S-phosphorylisothioureas.

RESULTS AN0 DISCUSSION Two types dies.

of

first

The

the

model,

was a cyclic

(1)

which

ble

in the diastereoisomerically

active,

exists

acyclic

guration

of

6

analysis

chiral

phosphorothioic

in two diastereoisomeric pure

forms state4.

cis-l

used

has recently

and trans-l

second

The

II-methyl-O-naphthylphosphorothioic

which

were

4-methyl-2-oxo-2-mercapto-l,3,2-dioxaphosphorinane

acid

been established

easily

availa-

one was an optically (2j5

the

absolute

in our laboratory

confi-

by an X-ray

. SH

SH

I

I O- 9,

H CO*.*P\ 3 0’ O

0’ trans-1

(+)-R-z

0

I

O-P,

A2

o/

SH

H3CO*. .P,

H3C

d

cis-l

In the a series via

the

of

first

set

of

isomerization

0, /SH o/P8o

Some physical collected

This

in Table

each

the

of

the

+

RN=C=NR -

00 (D (-1-S-2 diastereoisomer

corresponding

transiently

properties

formed

of

the

of 1 was reacted

N-phosphorylthioureas

S-phosphorylisothioureas

a,

R = Ph

b,

R = PhCH2

c,

R = p-MeOC6H4

adducts

2 obtained

with 4 1.

in this

way are

I.

important

observation

diastereoisomerically unequivocally

specific

proves

is

pure

adducts

that

the

that

the

reactions

4 as can be seen

rearrangement

afforded from

the

31

of 2 to 3 proceeds

in all P-NMR

cases spectra.

in a stereo-

manner.

To determine 4 and in this of

isomeric

adducts

In the

first

obtained

chemical

configuration stereochemistry transformations

at phosphorus of of

-4a (R=Ph). This chemical step, the two diastereoisomeric

according

trans-

the

way the

a series

from

to give

and spectral

The most the

experiments

carbodiimides

SH

to

the

procedure

of

the

N-phosphorylthioureas

the -3-4 isomerization krown stereochemistry correlation

described

is

for

out

the diastereo-

shown in Scheme IV.

phosphoroanilidates by Stec

we carried

1 have been 7 starting

and topusinski

and cis-4-methyl-2-hydrogen-2-oxo-l,3,2-dioxaphosphorinanes

(2).

4594

M.

Table

I.

Physical

Configuration of 1

and Spectral

MIKO~.ASCZYKer al.

Data of

Adducts

4

N-(4-methyl-Z-oxo-l,3,2-dioxaphosphorinanyl)thiourea

R

Symbol

[wml

31~

4JP-CH~ [Hz]

(CH~~~,H~P~~)

cis

Ph

trans-4ab

trans

Ph

C&F

cis

PhCH2

transGF

trans

PhCti2

cis-4b

cis

p-MeOC6H4

trans-4c cis-2

trans a> for

p-tQgC6H4

all

compounds

*0.3%)

have been

b)

on the

basis

of

the chemical

c>

on the basis

of

X-ray

These net

of

cis-

the

at phosphorus.

conversion (it

place

cis-la-

revealed tion

trans.7 of

of

the

trans-l

of

configuration

lic

phorothioic to

case,

the

the that

the

acid (2) afford

reactions

?a are

shown

into

(z-R-2

(a)

chlorine

(+>-11

with

values

for

C,H,N,P

and S (within

from benzene;

with

in the stereospecific

syn-

of _Z from 2 results

in the

is

change that

diphenylcarbodiimide

assigned facts

on the

basis

discussed

moiety

adduct

an X-ray

lead

transformed

thioacids

_

trans-a

in the

forma-

-4b obtained analysis to be

to the

proceeds

the

the physical

gives

results the of

above

phosphoryl

is of

from _Z and from

of

2 by Since

at phosphorus

cis-f

Comparison

diphenylcarbodiimide

the configuration

2 were

isothiocyanate.

obvious

obtained.

obtained

anilidates

N-phosphorylthioureas

by phenyl

it

same stereochemistry active

conclusion

with

with

corresponding

optically

of 2 appeared

to be entirely

of

the primary

data

of

the

as in the case the

will

of

four

that

full

retention

with

an acyc-

configuration

question

of

active

adducts

shift

2.

Also

in the

course

of

This

adducts the

it

(+)-R-z

chlorolysis in Ccl4 aniline

of

the

methyl

the

iodide

phosphorothiolate

and fc)

solution giving

with

required

the

reaction

<+)-lo

phosphoroanilidate

was necessa-

2 solving

in the presence of

II. in

8-Y isomerization. -with the adduct the conversion of

performed to correlate the thioacid (+)-R-z we accomplished in Scheme V and VI.At first, optically active phosphoroanilidate (+>-12 in three of

Some

in Table

from 1,

from

means

stereospecific.

summarized

2 obtained

at phosphorus

in this

as seen

reagent.

8 to 2 is

2 are

phos-

and was

adducts

stereospecific

chiral

adducts

the stereochemical

II-1-naphthyl

carbodiimides

of

adducts the

be observed

(+)-CR)-O-methyl

of _9 taken in the presence

methylation

bicarbonate(b) tal

74-76

configurational

with

optically

rearrangement

way the

2.45

was condensed

and spectral

ry to establish

ving

the

formation

Similarly this

the

grouping,

NMR spectra

physical

142-145

-9.9

two diastereoisomeric

is

cis-l

the cyclic

whether

phosphoryl

found

2.77

at phosphorus.

To check

The

of

lfB-lzg

-6.3

followed

atom),

of

experimental

the S-N migration

105-107

1.75

corresponding

trans-e

cis-4a.Additionally, from cis-l_ and D6C has been All

2.75

-3.5

synthesis

without

of

trans’.

the

the adducts

the reaction

treatment

-1.3

as substrates

the

hydride

at the nitrogen

properties

that

and the

into

4 proceeds

and from

and spectral

also

Then,

sodium

of 1 into

takes

into

with

134-136

crystallization

The two-step

stereospecifically

treatment

149-153

2.5

correlation;

serve

and trans-A.

inversion

converted

3.0

analysis.

dioxaphosphorinanes

thesis

-7.4

analytical

after

p$j

-10.4 c

satisfactory obtained

(2ja

steps

invol-

of

sodium

by means of

alemen-

the phosphorochloridate r+)-12.

Then,

we

4595

Rearrangement of S-phosphorylisothioureas Scheme

IV

O-P. O/

i H

P

Cl2 _ CH2C12

o/p

@

.Cl

“3

H3C

:.~~~CS

1

“F Ph-N-&-NHPh

cis-1

cis-6

trans-5

.

NHPh ii__0

PhNH2 EtJN

!

-0

A:+ H3C

cis-la -

NPh

II

S-C-NHPh

+ PhN=C=NPh

S -

-

N shift

1

trans-3a -

0

I + PhN=C=NPh

S -N

shift

P--S-C-NHPh

-

t!Ph

H3C

7 NHPh

cis-3a -

cis-1

I 0-Q;: O/

AL H3C

trans-4a

trans-1

cis-$

tried

to

addition trast

transform of

to

phosphorus in

due

optically

sequence

(+)-12.

into

the

phenylisothiocyanate

our

expectations (OPC)

carbodiimide bably

-

and (-)-S-z.

i.e. to

the pure

presented

fact state. in

this the

corresponding to

the

reaction

sodium resulted

N-phosphorylthiourea salt in

of the

(+)-12. formation

E However, of

by the in

con-

diphenyl-

starting The partial

thioacid L with inverted configuration at loss of its optical activity is most pro(+)-R-u was not obtained phosphorochloridate

that It Scheme

the should

be noted

V constitutes

that, although the reactions cycle a new Walden inversion

for

45%

M. MIKOLNCZYK

W’J,

P-SH

er al,

NptO,

+ RN=C=NR -

MeO’N

Me0 /P-S-F-NHR 8 NR

0

-

s a, b,

R = PhCHZ

c,

R = c-Hex

d,

R = Cl-C6Hq

II.

Physical

and

Spectral

blfj”

Ph PhCH2

+lEl”

cyclohexyl p-Cl-C6H4

for

-9a satisfactory been obtained measured

in

and

active

that

from

type

(+>-9aenantiomer

does

not

(+)-9aon treatment of

already

the

(+)-R-z

with

cyclic

at

of

the

The results reactions

N-phosphoryl must

be the

-3.8

+bl”

for

well

C,H,N,P

and

S(withinf

to as

ascribe

the

absolute

also

oil 98-103

0.3%)

have

the

form

and

triethylamine

it

has

been

to the

It

was

affords

that

the

under

nitrogen

in

and

OPC.

and

cyc-

basic

fragmentation

configurational (+>-9~ has the & of

found the

synthesized

(+)-S-configuration.

rearrangement of the migration

to

OPC.

assume

Thus,

sulphur

Emmons-

fragmentation

phosphonoanilidates

accompanying

have

thioacid

the

a similar

to

(+)-lo -

the

via

of

due of

that

or of

mainly

of s

perform

reasonable also

is

chlorolysis

(+)-R-z

above and the The fact that

that

from

to

which

is

This the

configuration

configuration

assumption

anionic

reaction

phosphorus.

group

of

from

should

the

isolated.

hydride

quite

(+)-(S)-2. at

be

course

formed

1 from is

establish

to

a reasonable

phosphorus

indicates

phosphoryl

- 9.5O

sodium

thioacid it

retention

a stereoretentive

-0.1

Emmons-Wadsworth

and

is

oil

-9c -9d

obtained

with

the

retention

phosphorus

also

96-97

- 5.1°

we attempted

(+)-9ain (+)-R-z. Hence, (+)-g VI shows the reaction discussed at

+64.ii0

0.0

(+)-11.By making the transiently

phosphoroanilidates9,

between

zob

[aI 0

-3.5

permit

as

fragmentation,

with

conditions

(2)

-9aa -9b

values

involved,

adduct

By analogy lic

of

arises

-Wadsworth

same

2

51~ [ppml (CHC13,H3P04)

not -9a which here could concerning the steric

aminolysis

the

it

compounds

uncertainties

using

analytical

acids,

the

(-)-S-2

Adducts

CHC13

phosphorothioic optically

the

Symbol

+lSO

some

of

N-(0-methyl-0-l-naphthyl)phosphoryl-thiourea

+le”

all

Oata

= 1-naphthyl

R

+lRO

to

2

I

Npt

of the DCHA salt of the thioacid 2

b)

S

R = Ph

Table

a)

R I g-N-;-NHR

NptO\ MeO,

of Scheme

relationship S configuration

in both

(+I-% occurs acyclic and

S-phosphorylisothioureas

process. discussed

above

presented

in

thiourea

E,

(-)-R-enantiomer

allowed

Scheme

whose

us

V. First

fragmentation

of 2

e.g.

its

to

comment of

the

all,

leads absolute

the to

the

stereochemistry transiently thioacid

configuration

formed (-1-S-2, is

opposite

Rearrangement of S-phosphoryli~thiounas

4591

Scheme V SH

SCH,

CH31

I H3CO---.P*0 / NptO

Cl

H3CO---P+0 I NptO

- NaHC03

(+)-R-z

I

Cl2

H3CO*--PN0 I NptO

cc14

(+)-R-10-

[a]~o+lS.~O(~~~~

salt)

[al ;” +48.2O

r

[a] o+lO. 0’

1

H+ H3CO*--P1SH I NptO

(+)-R-l1 -

l.NaH

;I ‘;” H,CO-se“N-C-N-Ph I 2-1 NptO

-DPC

(-1-S-2

P.PhNCS H3CO-Npt

(+)-R-12

(-)-R-9a

[a]~“-10.70(OCHA

salt)

2PhNH2

1 0 II

-

[ oo] 20+19 * 3O

Scheme VI

Ph-N-i-NHPh

SH

NaH

I H3CO---P+0 I NptO

or Et3N

c H3CO-‘- +O I NptO

-0PC

(+)-S-9a-

(+)-R-g

[a] 20 = +64.6 0

to

that

(+I-12above,

of

the

which

starting also

and aminolysis of

it

is

of

have

the

of

(+)-11) -

probable

at phosphorus.

lo

that

and its Therefore,

-f11 In an extension

with

of

as well

the

chlorination

into

of with

R-configuration

one of

the

(chlorolysis while

leading

(+)-lowith in-

the precise

mecha-

carried

by

out

by Inch to

two

of

the other

account

published

(+)-lo-

aniline

+17.6’(0CHAsalt)

=

reasonsdiscussed

phosphorothiolates results

0

phosphoroanilidate

the

means that

retention,

Taking

as the

reaction the

the

for

unknown stereochemistry

chlorolysis

and coworkers

quite

Conseqently,

at phosphorus.

on the

by retention

(+)-R-z.

(-)-R-Vaand (-1-S-2, R-configuration. This

must occur

configuration

studies

Michalski nied

thioacid

a source

shown in Scheme V of

version nistic

[a]

is

should

reactions

0

and Ha1111j12

(+I-11is accompaof configuration

by inversion may be ascribed

to

(+)-phosphoro-

chloridate also

treated

configuration).

with

of

this

benzylamine

However,

set

of

experiments,

to give

our attempts

(+I-phosphorochloridate

N-benzylamide to convert

it

C-1-13 (with inversion into the corresponding

N-phosphorylthiourea

hydride

and benzylisothiocyanate

unsuccessful.

-9b using sodium Similarly, we were not

able

transform

obtained

(+)-R-z

from

and OBC, into

the

to

starting

thioacid

the

adduct 1.

-11 was of

were (-)-9b,

Whereas

with

sodium

hf.

4598 hydride ted

no reaction

in

the

was

formation

observed,

of

the

MIKO~NCZYK

et d.

treatment

of

the

achiral

demethylation

(-)-9b -

with

product

Cl

I

2PhCH2NH2 *

H3CW jp-O

(+)-R-l1 [a];0

resul-

l.NaH 2.PhCH2NCS \r 4 A

P H3CO-’-P-.NHCH2Ph I NptO

NptO

triethylamine

14 -*

-9b

(-1-R-13 zlo

[a]:’

-4.2’

NaH CH30\

P-NCH2Ph

I 0 c=s I

NptO’I

r

no reaction

IjHCH2Ph

0-Npt

-9b

Et3N

Et3iMe

e=s I NHCH2Ph -14

In the

this

situation

enantiomeric

(-1-z.

It

Cotton

effect

effects

at

lar

in

seems

we have

amide

was

found at

structure reasonable

and

and

exhibit

to

have

same

that

the

S-N migration

The

results

circular

from

the

CO-spectrum The adduct

Cotton that

effects

both

configuration

at

both

in -Sb leading

(-)-S-z)

compounds

almost

(+I-13and This result

S.

spectra

(CO)

and

the

for adduct

(+I-13there is a strong positive exhibits two positive Cotton

Since

I).

dichroism thioacid

of (-)-9b-

225 nm (Figure

assume

they

the

220 nm.

258

the

(obtained

that

about

about

the

(+)-13in

measured

identical

(-)-9b -

are

provides

to -9b occurs

are

very

simi-

wavelengths,

homochiral; the

it

that

additional

with

retention

of

that

the

rearrangement

(8)

occurs

is

support

configura-

tion. described

above

-phosphorylisothioureas tally ry

with

retention

results These the

first

thiourea

of

the

VII

the

pseudorotation

forming to

configuration

data the

According

bond

breaking

intermediate,

put

sulphur

in

(F)

formed

should

at

that

In this

addition,

the

rearrangement

that

phosphorus.

can

be explained

a pentacovalent

leading

(E).

bipyramidal

a new phosphorane

kinetics

rearrangement

and

phosphorus.

revealed

involving

phosphorus

intermediate bond

a trigonal

retained

of

attacks

at

of

S-

stereospecifipreliminareaction

.

and

Scheme

step

(1)

phosphorane that

in

indicate

N-phosphorylthioureas

studies 13

kinetics

stereochemical

shown

clearly

into

configuration

kinetic

first-order

chanism In

of

our

of

exhibits

(A)

nitrogen

atom

in

terms

of

the

intermediate.

S-phosphoryliso-

to

the

formation

to

the

commonly

a betaine-type assumption15 accepted

processes occur the phosphorane

only at apical positions (E) should undergo

position. result

in

phosphorus

in

Cleavage

of

of

N-phosphorylthiourea

the

P-S

bond

(El) with

in

me-

4599

(-)-9b

280

CO-spectra

Fig.1.

of

(+I-13-

and

5 nm

(-)-9b -

Scheme VII

RNHC=S

,OR1 I R-N-P-&O

’ 2 OR

’ 2 OR

The pseudorotation ted

for

the

S-phosphoryl

fact

process that

analogues,

N-phosphinylthioureas,

do not

a constraint

rial

in a trigonal

position is

phorus

believed acids

that towards

here

is

essential

because

it

and S-phosphinylisothioureas,

undergo

isomerization

to

can be accounin contrast

N-phosphonyl-

to and

respectively.

bond provides It

postulated

S-phosphonyl-

The main reasons for this is that the C-P 15 by prefering strongly an equato16 . bipyramidal pentacovalent phosphorus intermediate

to pseudorotation

in this

way the

carbodiimides

different

behaviour

of

various

types

of

phos-

may be interpreted.

EXPERIMENTALSECTION ‘H-NMR spectra were measured with a Perkin-Elmer R-12 and 31P-NHR spectra with a FT Jeol FX-60 instrument. Mass spectra were recorded with a LKB 2091 mass spectrometer. Melting points are uncorrected. Cis- and trans-4-methyl-2-oxo-2-mercapto-l,3,2-dioxaphosphorinanes (1) were prepared from the corresponding cyclic phosphites according to the procedure described previously4. Cis- and trans-2-N-phenylamino-2-oxo-4-methyl-l,3,2-dioxaphosphorinanes (7) were prepared according to the method of Stec and topusidski7. Optically active-o-methyl-O-1-naphthyl phosphorothioic acid (2) was obtained according to the procedure described by us3 and 0-methyl-0-1-iiaphthyl-S-methyl by Akintonwal7 phosphorothioate [(+)-R-10]- according to the procedure published

M. MIKOUKZYK

4al

et al.

N-phosphorylthioureas (4 and 9) from carbodiimides and thioacids (1 and 2) procedure. A solution of a thioacid (1 or 2) (0.01 mol) in ether (10 -30 ml) was slowly added dropwise at room temperature to a solution of the corresponding carbodiimide (0.01 mol) in ether (lo-30 ml). After the addition was complete, ether was evaporated to give the desired adduct in a quantitative yield. Physical and spectral properties of the products (A and 2) are collected in Tables I and II. - general

Correlation

of

configuration

Preparation of 0-methyl-0-1-naphthyl phosphorochloridate (11). A solution of chlorine (0 21 2 9 1 ) ' CC1 (15 ml) was added slowly to a solution of O-methyl-O-i-na~~th~l-~~~e~hy~nphos~horothioate (10) (0.78~. 2.9 mmole; in CC14 (15 ml). The resulted mixture was stikred at room temoeratu[a] il”+4R. 2’) re ?or 0.5 h and then aportted under reduced ressure to give the crude product !! 1P NMR (CC1 ,H3PG4): (11) (0.6Sg; 90%). [a] ti +lO 6=0.2 ppm; (CHC13, C=1.59); ~HNMR (COC13,TMSj:6 = .7(d,3HiJp_GCH3=14 Hz); 4.7-5.9 ppm 1!n,7H). This compound was used without further purification to the synthesis of phosphoroamidates m and 13). In a similar manner starting from 10 and SO2C12 phosphorochloridate -II was xtained in 80% yield; [a] z” +4’(CHC13 ,Fl.S). Preparation of 0-methyl-0-1-naphthyl-N-phenyl phosphoroamidate (12). A solution f th f hly prepared (+)-11 (0 9 1)’ b (15 ml) was added ~ropw~ser~~ the solution of Giline ~~“7”mm~?e)“~~“~&zene (15 ml) and the mixture was stirred overnight at room temperature. Aniline hydrochloride formed was filtered off and the filtrate was evaporated to give lg (91%) of a crude oily product, which was purified by preparative t.1.c. on silica gel using etganol-chloroform (1:20) as an eluent. Yield of pure 12: 0.559 (50X);[a]s0 +19.3 (CHC13, c=O.7); 31P NMR (CHC13,H3P04): 6=-0.6 ppm;lH NMR (COC13,TMS): 6=3.9 (d,3H,Jp_GCH3=12Hz); 6.7-8.2 ppm (m,13H). M.S.: m/e=313(M+,lOO). 0-methyl-0-1-napthyl-N-benzyl in a similar way. Yield 31P NMR (COC13, H3P04):

phosphoroamidate (13) was preptred and purified f th e pure product: 55% [ala0 -4.2 (CHCl3, c=l.lS). a” =4.9 ppm; M . s. : m/e=32i(M+,lOO).

Reaction of 12 with phenyl isothiocyanate.NaH (0.24g; 10 mmole) was added to the solution of ti (3.13g; 10 mmole) in freshly distilled from sodium dioxane (40 ml). The suspension obtained was stirred for 0.5 h and phenyl isothiocyanate (1.37g; 10.2 mmole) was added. Stirring was continued overnight. The solvent was removed under reduced pressure and the residue was dissolved in water. The aqueous solution was acidified with 10% CH3COOH and extracted with CHC13. The organic solution was dried over MgSOq and evaporated to give 0.15g (59%) of the crude acid @).,The crude,acid was dissolved in ether and dicyclohexylamine was added. The salt of 2 was filtered off and dried: pre bpitated dicyclohexylammonium [alI - 10.7 (CHC13,c=l). milne &O.?3g; 2.2 mmole) was Basic Cleavage of 9a to OPC and 2. +64.6 ) in benzene (15 ml) to the solution of a (0.52g;1.2 mmole [a Water was added and mixture was stirred overnight at acidified with a diluted solution were separated. The aqueous layer was and extracted with ether. The etheral solution was dried over MgSO4 and the acid (L), which was transformed into its +17.6’(CHC13, c=l).

added and the the layers of HCl evaporadicyc-

NaH (0.24g; 10 mmole) was added Reaction of trans-7 with phenyl isothiocyanate. 2-N-phenylamino-2-oxo-4-methyl-l,3,2-dioxaphosphorinane t th 1 ti f t The resulted suspension was (yrani-yy y2.iyg” 10r~~~~e) in dioxane (40 ml) stirred-for 0.5h’and phenyl isothiocyanate (1.37g; 10.2 mmole) was added. StirrThe solvent was removed and water was added. The ing was continued overnight. The chloroform solution was acidified with 10% CH COOH and extracted with CHCl was removed to gi.J’ e trans-4a in a solution was dried over MgSO and 3 he solvent 6=-7.4 ppm. In a similar manner 66% yield; m.p.=149-153O. 318 NMR (CHC13,H3P04): cis-4a was obtained from cis-1 and phenyl isothiocyanate in a 60% yield; m.p.= =134q360.3lP NMR (CHC13,H3PG4): 6=-10.4 ppm. REFERENCES 1.

M.Mikolajczyk

and

M.Mikolajczyk, (1976); Chem.,

P.Kielbasinski,

P.Kielbasinski

M.Mikolajczyk, 42 _,

2345

37,

H.M.Schiebel,

P.Kielbasinski,

233

(1981);

J.Chem.Soc.,Perkin

J.H.Barlow

and

I,

O.R.Russell,

564

J.GrQ.

(1977).

2.

M.Mikokajczyk,

P.Kielbasinski

3.

H.Mikolajczyk,

P.Kiekbasinski

J.Karolak-Wojciechowska, M.Mikolajczyk,

Tetrahedron, and

P.Kielbasinski

and

Z.Goszczynska,

and

W.Basinski,

H.W.Wieczorek, and

A.Sut,

J.Org.Chem., J.Org.Chem.,

Y.T.Struchkov, Phosphorus

42, 49,

3629

899

(1977).

(1984);

M.Y.Antipin, Sulfur,

l7,

141

(1983).

Rearrangement of S-phosphorylisothiou 4.

M.Mikolajczyk

5.

C.Oonninger

and and

P.Kiekbasifiski,

Tetrahedron,

2El,

O.H.Hutson,

Tetrahedron

Letters,

J.Michalski,

Tetrahedron, 6.

J.tuczak,

3l,

M.Miko1ajczyk,

2809

and

W.J.Stec

and

8.

J.Karolak-Wojeciechowska,

9.

W.J.Stec, 2,

10. 11.

and

(1976);

According

to with

guration

at

Hall

+4 ’

and

with

sulphuryl

12.

C.R.Hall

13.

For

Inch 12

case

and

T.O.Inch,

example,

the is

et

al.

found,

obtained

exhibits

k=2.6.10s5 for

the

and

this

rate

the

it type

s-l.

the

6584

that same

(1980).

by chlorine

with

retention with

sign

(+)-R-g,

I,

temperature O.A.A.Akintonwa,

FT

1104

constant

of

[a];'

of

both

confi-

reagents

optical

the

rotation

+lEl" (OCHA

salt)

of

(1979).

for

at

Se-(O,O-dineopentyl)phospho-

-43’C

order

by means kinetics

of was

FT 31P NMR also

observed

S-thiophosphorylisothioureas

J.-J.Perie, II,

to

Tetrahedron, should E or 1

36,

be noted in

the

R.Roques,

31 P NMR

2059

that

Tetrahedron,

our

reaction

2,

and

were 959

(1980). attempts

between and

spectroscopy

J.P.Oeclerq

7 (1982).

-thioxo-Z-mercapto-1,3,2-dioxaphospholane

17.

102,

a phosphorothiolate

of

The first

A.Klaebe,

T.O.Inch,

reagrd, of

J.Org.Chem.,

(1983).

.

J.Chem.Soc.Perkin

mediate

P.Kielbasifiski,

(1983).

J.Michalski,

however,

reaction

rearrangement 14

M.-B.Gasc,

With

(1983).

A.Sut,

587

chloride

measured

G.Germain,

16.

of

. We have

isomerisation

C.Blonski,

C.R.Hall

and

by sulphuryl

the

M.W.Wieczorek,

105

J.Am.Chem.Soc.,

J.Chem.Soc.Perkin

- thiophosphorylthioureas

15.

A.Skowrofiska,

chloride).

spectroscopy

14.

J.Omelaficzuk,

and

(1973).

l6;411

chlorolysis

of

l5,

C 39,

B.lJznarlski

ryl-N,N’-diphenyl-isoselenourea by Perie

(1968);

M.Mikolajczyk,

Cryst.,

E.Tadeusiak,

while (2)

the

Acta

and

phosphorus in

547

Acc.Chem.Res.,

inversion

phosphorochloridate ([cl];0

2,

K.Lesiak,

J.Michalski

proceeds

Sulfur,

M.W.Wieczorek,

W.J.Stec,

B.Krawiecka,

4871

J.Karolak-Wojciechowska,

Phosphorus

M.Y.Antipin,

A.Okruszek,

227

A.Sut,

A.topusifiski,Tetrahedron,

Y.T.Struchkov

(1972).

(1975).

M.Y.Antipin,

7.

5411

M.Mikolajczyk

J.Mikolajczak,

P.Kie%basifiski,

Y.T.Struchkov

4601

OCC or

negative.

(1978).

to

catch

the

inter-

4,4,5,5-tetramethyl-2Of3C by means

of

low

N-