Journal of Labelled Compounds and Radiopharmaceuticals - Vol. XIII, NO.

4 53 5

THE SMALL-SCALE SYNTHESIS OF 13C-18ARELLED DICHLOROMETHV, PHOSPHIXE

(METHYLPHOPPHONOUS DICHLORIDE)

I a J.Colqutboun and :I .Plck’arlane,

Department of Chemistry,
C i t y o f London Polytechnic,
London 5X3N 2EY, Received August 24, 1976
tingland. Revised September 20, 1976

Dichloromethylphosphine (methylohosphonous d i c h l o r i d e ) i s a v a l u a h l e

s t a r t i n g m a t e r i a l f o r many s y n t h e s e s , b u t published for

i t s p r e o a r a t i o n a r e not w e l l s u i t e d t o l a b e l l i n p with I3C. We have

found t h a t t h e r o u t e o f equations (1) - ( 4 ) which s t a r t s f r o n t h e

r e a d i l y a v a i l a b l e 13C-labelled metkvl i o d i d e and relies upon t h e

p r o t e c t i n g e f f e c t of N,I-diethylamino groups t o prevent d i - o r tri-

methylation o f phosphorus works s a t i s f a c t o r L l y on a smal.3 s c a l e ,

althoiich it, is a l s o s u i t e b l e when l a r g e r m o u n t s of Froduct 8 r e

wanted.

F+ ?”
PC1 +?Et NH+2E+. N
3 - 2 3
4(Et2N)2PC1+2Et3NH’CI-

EX 2O
13CH31+!4g 13CH3M, I

Et20
13CH3MgT+(EtTN )2PC1 +( E t 2 N ) 13CH3+1.1cICl
-70’

(Et2Nl2P13CH3+PhPC12 13CH3PC12+(Et.2N),PPh
(4)

All p r e p a r a t i o n s were c a r r i e d out and p r o d u r t s were handled under

sn atmoPohrtre of d r y nitroKen, and e s p e c i a l c a r e should be e x e r c i s e d

with (Et3N)2PC1 which r e a c t s e x p l o s i v e l y v i t h water.

0 1977 by John Wiley & Sons, Ltd.

536 I. J . CoZquhoun and W. McFarZane

I?:?- ( : I T . E ~ 3 ~ I L 9op ~ ~ i i ~ o ~ o ~ ~ o ~ ~ r ~ l ~ y
Diet.hylmine (2.92 c;.; 40 m m o l ) i n e t h e r (10 ml.) was added

dropwise o v e r 0.5 h t o a s t i r r e d m i x t u r e of nhosphoriis t r i c h l o r i d e

(2.76 c. ; ?0 m aol) arid t r i e t h y l m i n e (4.04 A . ; 40 m m o l ) i n

s o d i m - d r i e d e t h e r ( 2 5 ml.). When t h e r e a c t i o n was complete t h e

bulky p r e c i p i t a t e ol' t r i e t h y l z m i r e h y d r o c h l o r i d e was f i l t e r e d o f f

and washed w'th two 15 m l . p o r t i o n s o f d r y e t h e r ; t h e f i l t r a t e and

rrashings wrre combinpd and most of t h e e t h e r was removed u n d e r

vscuum. When t h e bulk had b e m redTved t c l La 8 ml. t h e r e s i d u e

was d p r a n t e d i n t o a small d i s t i l l a t i o n n o t f i t t e d w i t h a s h o r t

Vigreux column and d i 5 t i l l a t i o n pave 2.96 g. of (Gt2N)2PC1 as a

c l e w colourl-ss ! i $ u i d , b.p. t;o-6eo/0.1 F'F Fir.

RIS- (DICTHYLAMINO-__
----__I _-.--
) -P-METYYL - ---I
( 13C ) -PHOSPHIIE
-
-- ----
A se'lution of t h e met.hyl Gripnard r e a r e n t e n r i c h e d i n 13C WRS

rreoxred f m m w t h y i ;ndid- (2.0 c. ; I1 7 mol, e n r i c h e d t o 9Oq

i n 13C) and magnesium (0.34 R . ; 14 m moll i n d r y e t h e r (10 ml.).

Tbe y i e l d war, zssumed t o b e 85'1;. It. was f i l t e r e d t h r o u g h glsss

wool Rnd Rddrd d r m v i s e over 0.5 h o u r t o 8 s t i r r e 4 and cooled

( d r y i c e - a c c t o o e ) s3liitior o f (1':+2'i)7PC1 (2.52 r . ; 12 m mol) i n

d ~ ey t h e r ( 1 5 ml. 1. T h e r e a c t i o r m i x t u r e vas allowed t o v-irm

t o r3oT trmppratT:-*, and '?as thO.1 r e f l w e d fcr 0.5 hour when s o l i d

matter vas fowid t o have b e c o w runny an? t o have Rdhered t o t h e

wall. OF t h e f!%sk. T b snlutjor. WRS t h e n c o o l e d t o roo?

1 ~ - - r a t i i r e ~911rkcar f e d , t h e c.thrr wz.? renov-d by d i s t i l l a t i o n

rt a.lpos,)l e - i c n r - ' . ~ w i r - w ? +h= i-*?idw= k*zs d ; s t < l l r d thrnuch 9

s n o r t VipreiLu coliwn i n t o a 10 111. r o u d - h o t t o m flask t o y i e l d

1.72 fz. (755) o f !Ct2iV)q?CH3 as a c l e a r colnii-1-ss liquid.

b.?. 85°/1cI vr.Pp.

13C-DCP (for Dich loromethy lpkosphine) 537

t h e f l a s k c o n t a i n i n g t h e product from t h e previous s t e p . Heat

w a s evolved, a small teflon-coated magnetic s t i r r e r b a r was added,

and t h e f l a s k was made t h e pot of an apparatus s e t up f o r d i s t i l l a t i o n

under n i t r o g e n a t atmospheric pressure. The c o n t e n t s o f t h e f l a s k

were s t i r r e d g e n t l y and heated i n a s i l i c o n e - f l u i d b a t h ; a t a b a t h

temperature of 2OC-22O0 MeFCl

2
(0.8 g., 767; d i s t i l l e d as a c l e a r
c o l o u r l e s s l i q u i d , b.p, 8lo/7j0 mm.Hg. Comparison of t h e proton nmr

s p e c t r a o f t h e i n i t i a l enriched methyl i o d i d e and. t h e product

showed that no i s o t o p i c d i l u t i o n of t h e 13C c o n t e n t had occurred.

References

1 7..i.Iioffnann, i).H..ladsworth and H.D.';eics, J .Amer.Chem&,

20, 7945 (1958) 0

2 . B.J.Ferry, 2.3.Reesor and Z.L.Ferron, Canad.Journ.Chen., 9,

2299 (1963)a
3. L.:'aier, J.Inorg.Nuclear Chem., 24, 1073 (1362).

4. LJlaier, lIelv.Chim.Acta, & 2026 (1963); 47, 2137 (1964).