Multisite Phase-Transfer Catalysts - ACS Symposium Series (ACS

Chapter 14

Multisite Phase-Transfer Catalysts 1

John P. Idoux and John T. Gupton

2

Downloaded by UNIV OF CALIFORNIA SAN FRANCISCO on February 12, 2015 | http://pubs.acs.org Publication Date: December 19, 1987 | doi: 10.1021/bk-1987-0326.ch014

1

Lamar University, Beaumont, TX 77710 University of Central Florida, Orlando, F L 32816

2

The syntheses of a variety of "multi-site" phase-transfer catalysts (PTCs) and the determination of their catalytic a c t i v i t y toward some simple Sn2 reactions and some weak nucleophile-weak electrophile SnAr reactions are described. In general, at the same molar ratio, the "multi-site" PTCs are as or more effective than similar "single- s i t e " PTCs. Thus, the "multi-site" PTCs offer an economy of scale compared to "single-site" PTCs. Phase t r a n s f e r c a t a l y s i s (1,2) h a s become i n r e c e n t y e a r s a w i d e l y used, w e l l - e s t a b l i s h e d s y n t h e t i c technique a p p l i e d with advantage t o a m u l t i t u d e o f o r g a n i c t r a n s formations. I n a d d i t i o n t o a s t e a d i l y i n c r e a s i n g number of r e p o r t s i n the primary l i t e r a t u r e , there a r e s e v e r a l r e v i e w s ( 3 - 6 ) , c o m p r e h e n s i v e monographs (7-10) a n d a n ACS A u d i o C o u r s e (1JL) w h i c h d e s c r i b e t h e p h a s e t r a n s f e r p r o c e s s and which p r o v i d e e x t e n s i v e c o m p i l a t i o n s o f phase t r a n s f e r agents and r e a c t i o n types. While the l i s t o f a p p l i c a t i o n s a n d i n many c a s e s t h e s y n t h e t i c r e s u l t s a r e i m p r e s s i v e , p h a s e t r a n s f e r c a t a l y s t s (PTCs) s u f f e r some o f t h e same d i s a d v a n t a g e s a s more c o n v e n t i o n a l h e t e r o and homogeneous c a t a l y s t s — ! · £ . , s e p a r a t i o n a n d r e c o v e r y . I n t h e former case, because o f t h e nature o f most PTCs u s e d i n o r g a n i c t r a n s f o r m a t i o n s , c o n t a m i n a t i o n o f t h e d e s i r e d p r o d u c t c a n be a p r o b l e m ( e . g . , t h e r e l a t i v e l y i n e x p e n s i v e q u a t e r n a r y ammonium a n d phosphonium s a l t s o f t e n form s t a b l e emulsions.) In the l a t t e r case, b e c a u s e o f t h e c o s t o f some o f t h e most e f f i c i e n t PTCs (©•£1· » c r y p t a n d s a n d crown e t h e r s ) , economy o f s c a l e c a n be a m a j o r c o n s i d e r a t i o n . I n p r i n c i p l e , t h e s e d i f f i c u l t i e s c o u l d be overcome (9,12) b y a t t a c h i n g t h e PTC t o a n i n s o l u b l e p o l y m e r i c s u p p o r t ; and, i n f a c t , t h e r e has been a c o n s i d e r a b l e amount o f i n t e r e s t i n t h i s a r e a i n c l u d i n g r e p o r t s o n p o l y m e r - b o u n d q u a t e r n a r y s a l t PTCs ( 1 3 , 1 4 ) , p o l y m e r - b o u n d c r y p t a n d a n d crown e t h e r PTCs (15,16) a n d a t l e a s t one r e v i e w o n t h e s u b j e c t (ITi . 0097-6156/87/0326-0169$06.00/0 © 1987 American Chemical Society

In Phase-Transfer Catalysis; Starks, C.; ACS Symposium Series; American Chemical Society: Washington, DC, 1987.


170

PHASE-TRANSFER CATALYSIS

I n a l l c a s e s , p r e v i o u s l y r e p o r t e d p o l y m e r - b o u n d PTCs a r e o n e s w h i c h c o n t a i n one PTC s i t e / f u n c t i o n a l i z e d arm o f polymer. Because of the a b i l i t y to v a r y the n a t u r e of the s u b s t r a t e i n t r o d u c e d o n t o t h e p o l y m e r arm, t h e p r e p a r a t i o n o f a p o l y m e r - b o u n d PTC w i t h more t h a n one PTC site/ f u n c t i o n a l i z e d arm o f p o l y m e r becomes p o s s i b l e . I n t h e o r y , t h e n , t h e number o f grams o f p o l y m e r b a c k b o n e m a t e r i a l needed to c a r r y a p a r t i c u l a r l e v e l of r e q u i r e d PTC a c t i v e - s i t e e q u i v a l e n c y w o u l d be l e s s f o r a " m u l t i s i t e " s u b s t a n c e compared t o p r e v i o u s l y r e p o r t e d p o l y m e r bound " s i n g l e - s i t e " PTCs. S i m i l a r c o n s i d e r a t i o n s a p p l y as w e l l t o n o n p o l y m e r i c " m u l t i - s i t e " PTCs d e r i v e d f r o m simple, polyhalo substrates. Therefore, i n general, " m u l t i - s i t e " PTCs o f f e r t h e p o t e n t i a l ( i ) o f p r o v i d i n g g r e a t e r PTC a c t i v i t y on a PTC s i t e / g o f PTC n e e d e d f o r c a t a l y t i c a c t i v i t y b a s i s and ( i i ) o f e f f e c t i n g a p a r t i c u l a r s y n t h e t i c t r a n s f o r m a t i o n u n d e r m i l d e r a n d / o r more e f f i c i e n t c o n d i t i o n s . Thus, economy o f s c a l e and e f f i c i e n c y a r e i m p o r t a n t c o n s i d e r a t i o n s f o r b o t h p o l y m e r i c and n o n p o l y m e r i c " m u l t i - s i t e " PTCs. M u l t i - S i t e PTC

Activity

I n Some Sn2

Reactions

I n c o n s i d e r a t i o n o f t h e above p o i n t s , we have p r e v i o u s l y r e p o r t e d (18) t h e s y n t h e s e s o f two i n s o l u b l e , p o l y m e r s u p p o r t e d , m u l t i - s i t e PTCs ( I I and I I I , Scheme 1) and a l i m i t e d s t u d y o f t h e i r e f f e c t i v e n e s s i n two s i m p l e Sn2 reactions. The i m p e t u s f o r t h i s i n v e s t i g a t i o n was p r o v i d e d i n p a r t by a r e p o r t by R e e v e s (.13), who i n c o n t r a s t t o r e p o r t s (JJ*) a t t h a t t i m e by o t h e r w o r k e r s , had d e m o n s t r a t e d t h a t i t was n o t n e c e s s a r y t o s e p a r a t e t h e PTC s i t e o f a p o l y m e r - s u p p o r t e d PTC from t h e p o l y m e r b a c k b o n e by l o n g ( i . e . , 8-39 atoms) s p a c e r c h a i n s i n o r d e r to a c h i e v e a c t i v i t y . F o r example, R e e v e s reported (13) t h a t the polystyrene-backbone m a t e r i a l I 1

1

[P]

-

(CH ) 2

3

-

PBu

+ 3

Br~

I was a s o r more a c t i v e t o w a r d a v a r i e t y o f Sn2 reactions t h a n c o n s i d e r a b l y l o n g e r c h a i n , p o l y m e r - s u p p o r t e d PTCs (iâ)· On t h e o t h e r hand, b o t h R e e v e s (13) and Tomoi (20) have a l s o r e p o r t e d t h a t p o l y s t y r e n e - s u p p o r t e d PTCs w i t h ( C H ) s p a c e r c h a i n s o f χ = 3 o r χ = 4-7, r e s p e c t i v e l y , a r e more a c t i v e i n Sn2 r e a c t i o n s t h a n r e l a t e d PTCs where χ « 1-2. Our p r e l i m i n a r y r e p o r t (18) on m u l t i - s i t e PTCs confirmed these observations. We r e p o r t h e r e t h e s y n t h e s i s o f an a d d i t i o n a l p o l y m e r - s u p p o r t e d , m u l t i - s i t e PTC, t h e s y n t h e s e s o f s e v e r a l s o l u b l e , m u l t i - s i t e PTCs and t h e r e s u l t s o f c a t a l y t i c u t i l i t y s t u d i e s o f t h e s e PTCs t o w a r d a number o f s i m p l e Sn2 r e a c t i o n s . The p o l y m e r - s u p p o r t e d , m u l t i - s i t e PTCs shown i n Scheme 1 a r e t h r e e - c a r b o n a n a l o g s o f I and were 2

x


IDOUX AND GUPTON

Multisite Phase- Transfer Catalysts

CHOHCH / - C - CH \ CHOHCH

3

1) C C H . ( C 0 C H ) ~ ~ — > 2 ) BH-/THF q

]-CH Cl 9

2

9

±

A

[Pl-CH


3

3

3

3)

PBr. ± 4) (n-Bu) P

>

II

3

+

CH(CH )P Bu Q

3

/ [P]-CH

- C - CH

2

Q

Br"

3

Br"

3

3

+

CH(CH )P Bu 3

II

CH.P+Bu. B r " 2

/ - c

[P]-CH

3

- CH

\

I CH P B u 2

III [FROM " c C H ( C 0 E t ) 3

2

2

Br

3

AS STARTING MATERIAL]

+

I [P]-CH

CH(CH. ) P B \ i - B r ο ο +

2

- C - CH CH(CH )P Bu 2

3

+

CH(CH )P Bu 3

3

3

Br"

Br~

IV [FROM ~ C ( C O C H ) C H C O C H 3

2

2

3

AS STARTING MATERIAL]

SCHEME 1


172


s y n t h e s i z e d from c o m m e r c i a l l y a v a i l a b l e c h l o r o m e t h y l p o l y s t y r e n e , [ P ] - C H C 1 ( o b t a i n e d f r o m B i o - R a d a s a 2% d i v i n y l b e n z e n e c r o s s - l i n k e d m a t e r i a l c o n t a i n i n g 4.04 meq Cl/g polymer). The f i r s t s t e p i n e a c h s e q u e n c e i s t h e p r e p a r a t i o n of a polymer-supported carbonyl m a t e r i a l o b t a i n e d by r e a c t i o n o f t h e c h l o r o m e t h y l a t e d p o l y m e r w i t h t h e r e q u i s i t e c a r b o n y l a l p h a - c a r b a n l o n . The p o l y m e r supported c a r b o n y l m a t e r i a l i s then reduced to the c o r r e sponding polymer-supported a l c o h o l v i a r e a c t i o n with BH /THF complex, f o l l o w e d by c o n v e r s i o n t o t h e b r o m i d e and f i n a l l y r e a c t i o n with t r i - n - b u t y l phosphine to y i e l d the d e s i r e d m u l t i - s i t e phosphonium PTC. Combustion a n a l y s e s i n d i c a t e d t h a t p o l y m e r s I I , I I I and IV c o n t a i n e d i n e x c e s s o f 90* o f t h e t h e o r e t i c a l number o f meq o f p h o s p h o r u s / g of polymer. Compound V, t h e s o l u b l e , monomeric


2

3

+

PhCH CCH (CH CHPBu Br") 2

3

3

3

2

V e q u i v a l e n t o f I I , was s i m i l a r l y s y n t h e s i z e d p r e v i o u s l y (18) v i a t h e s e q u e n c e shown i n Scheme 1 f r o m b e n z y l c h l o r i d e as s t a r t i n g m a t e r i a l ( A n a l . C a l c d f o r C H Br Ρ : Ρ, 8.40*. Found: Ρ, 8 . 3 1 * ) . I n an e f f o r t to e v a l u a t e the m u l t i - s i t e methodology i n a v a r i e t y of other s t r u c t u r a l types, s e v e r a l a d d i t i o n a l s o l u b l e , m u l t i - s i t e PTCs ( V I - X I I I ) were s y n t h e s i z e d f r o m t h e c o r r e s p o n d i n g p o l y h a l o compounds v i a r e a c t i o n w i t h t r i - n - b u t y l phosphine. The v a r i o u s a l i p h a t i c d i - s i t e (VI-XI), (CH ) 2

(PBu

x

+ 3

Br~)

2

VI-XI x « 3, the aromatic

di-site

4,

5,

6,

9,

12

(XII) Ph[C(CH ) PBu 3

2

+ 3

cr]

2

XII 1,4-Disubstitution and

the aromatic

tetra-site

(XIII)

Ph[C(CH )(PBu 3

+ 3

Br")(CH PBu 2

+ 3

Br")]

2

XIII 1,4 - D i s u b s t i t u t i o n m a t e r i a l s a l l gave a c c e p t a b l e carbon, halogen, hydrogen and p h o s p h o r u s a n a l y s e s . In o r d e r to determine the e f f i c a c y of the c a t a l y t i c a b i l i t i e s o f t h e v a r i o u s m u l t i - s i t e PTCs and t o compare



14.

IDOUX AND GUPTON


173

t h o s e a b i l i t i e s t o t h o s e o f p r e v i o u s l y r e p o r t e d PTCs, we have u s e d t h e same t e s t r e a c t i o n and c o n d i t i o n s r e p o r t e d by R e e v e s (,13) f o r p o l y m e r - s u p p o r t e d PTC I . Thus, t h e r e s u l t s shown i n T a b l e I f o r r e a c t i o n o f 1-bromopentane w i t h aqueous s o l u t i o n s o f v a r i o u s n u c l e o p h i l e s a l l o w c o m p a r i s o n s t o be made among t h e c a t a l y t i c a b i l i t i e s o f t h e m u l t i - s i t e PTCs and t h o s e o f o t h e r m a t e r i a l s . As e x p e c t e d , t h e r e a c t i o n s p r o c e e d o n l y m i n i m a l l y u n d e r "no c a t a l y s t " o r u n d e r DMSO c o - s o l v e n t c o n d i t i o n s . As i n d i c a t e d , e x c e l l e n t y i e l d s of product are obtained v i a c a t a l y s i s by PTCs I I - I V t h r o u g h t h r e e r e a c t i o n c y c l e s and, i n a d d i t i o n , are s u p e r i o r to those obtained v i a c a t a l y s i s by PTC I . In g e n e r a l , c a t a l y s i s v i a the non-polymeric, m u l t i - s i t e PTCs V - X I I I g a v e good y i e l d s o f r e c o v e r e d p r o d u c t s and r e p r e s e n t r e a c t i o n s u n d e r c l a s s i c a l PTC c o n d i t i o n s ( i . e . , one r u n and c a t a l y s t n o t r e c o v e r e d ) . I n a d d i t i o n , t h e a c t i v i t i e s o f t h e v a r i o u s m u l t i - s i t e PTCs compare f a v o r a b l y w i t h t h o s e o f s e v e r a l d i f f e r e n t s o l u b l e PTCs [ a z a - m a c r o b i c y c l i c p o l y e t h e r s (21), hexadecyltributylphosphonium bromide (21-22), b e n z y l t r i b u t y l ammonium h a l i d e s (23) and m e t h y l t r i c a p r y l a m m o n i u m c h l o r i d e (24)1 w e l l as w i t h those o f o t h e r p o l y s t y r e n e - s u p p o r t e d PTCs (13,19(a),(b),(d),25). Thus, t h e v a r i o u s m u l t i - s i t e PTCs a p p e a r t o o f f e r a number o f p a r t i c u l a r l y a t t r a c t i v e c o n s i d e r a t i o n s . They a r e r e l a t i v e l y e a s y t o p r e p a r e (PTCs V I - X I I I f r o m r e a d i l y a v a i l a b l e p o l y h a l i d e s ) and PTCs I I - I V , l i k e o t h e r p o l y m e r - s u p p o r t e d PTCs, c a n be e a s i l y r e c o v e r e d and r e u s e d . Most i m p o r t a n t l y , however, i s t h a t t h e t o t a l w e i g h t o f m u l t i - s i t e PTC r e q u i r e d i n t h e s e r e a c t i o n s i s l e s s compared t o r e l a t e d s i n g l e - s i t e PTCs. T h i s i s a d e c i d e d a d v a n t a g e f o r t h e p o l y m e r - s u p p o r t e d PTCs I I - I V where t h e t o t a l w e i g h t o f b a c k b o n e p o l y m e r c a r r y i n g an e q u i v a l e n t PTC a c t i v i t y was l e s s t h a n t h a t o f p o l y m e r s u p p o r t e d PTC I . In a d d i t i o n , as i n d i c a t e d i n T a b l e I I , m u l t i - s i t e PTCs o f f e r t h e p o t e n t i a l f o r s u b s t r a t e s p e c i f i c d e s i g n i n m u l t i - l e a v i n g group s u b s t i t u t i o n reactions. F o r example, w h i l e t h e d i f f e r e n c e s i n PTC a c t i v i t y among t h e s i n g l e - s i t e PTC tetrabutylphosphonium b r o m i d e (TBPB) and t h e TBPB a n a l o g s V I , IX, X and XI may be due i n p a r t t o d i f f e r e n c e s i n l i p o p h i l i c i t y , t h e r e a l s o a p p e a r s t o be a s u b s t r a t e r e a c t i o n s i t e - PTC s i t e e f f e c t f o r t h i s d i s u b s t i t u t i o n r e a c t i o n . T h a t i s , TBPB and t h e 1 , 3 ( V I ) , 1,9(X) and 1,12(XI) d i - s i t e PTCs p r o v i d e t h e same a p p r o x i m a t e l e v e l o f e f f i c i e n c y w h i l e t h e 1,6(IX) d i - s i t e PTC i s somewhat more a c t i v e u n d e r t h e p a r t i c u l a r r e a c t i o n c o n d i t i o n s . The l a t t e r r e s u l t i n d i c a t e s a more e f f i c i e n t t r a n s f e r o f n u c l e o p h i l e and suggests the p o s s i b i l i t y of a simultaneous, site-specific transfer in this disubstitution reaction. Additional i n v e s t i g a t i o n s r e l a t i v e to t h i s p o s s i b i l i t y are i n progress. a

s


174


T a b l e I . R e a c t i o n o f 1-Bromopentane w i t h N u c l e o p h i l e s u n d e r PTC C o n d i t i o n s

Various

3

PTC


n-C.IT , B r ~~ O i l

+

K

+

>

Nu

YIELD(%),

n-. C ^ N u

+

+

K Br

b

PhO"

n-C.H., ,Nu O i l PhS~

33

7

8

18

5

30

-

22

79

70

—

PTC

Nu~ =

NONE NONE

C

d

I

81

83

II

e

90->99

90-98

f

III

e

85-95

f

80-90

f

IV

e

85

VI

65

IX X

XIII

g

>95

>95

V

xn

f

f

"CN

MeCOO"

86-99

65-70

75-90

65-70

75-80

60-70

80

74

82

39

71

85

92

76

59

79

90

37

73

66-83 70

79

f

68-77

86-93

19

62

60-73 94

A l l r e a c t i o n s were r u n a t 110 C b y s t i r r i n g a m i x t u r e o f s u b s t r a t e , c a t a l y s t ^ w a t e r a n d n u c l e o p h i l e f o r 1.0 h r (PhO ), 0.2 h r (PhS ), 0.5 h r ( CN) o r 8 h r (MeCOO"). The m o l a r r a t i o o f N u / S u b s t r a t e / P T C was 3/1/0.01 (PhO ), 1.5/1/0.01 (PhS ), 5/1/0.01 ( CN) a n d 2/1/0.01 (MeCOO ) . G e n e r a l l y 33 mmoles o f s u b s t r a t e , 0.3 mmoles o f PTC, 25 ml g f HgO a n d t h e r e q u i r e d amount o f n u c l e o p h i l e were u s e d . P r o a u c t i s o l a t e d by e x t r a c t i o n ( E t 0 ) a n d d i s t i l l e d . DMSO u s e d a s c o - s o l v e n t . Y i e l d s f r o m r e f 13. Yields Represent r a n g e from t h r e e r u n s ( c a t a l y s t r e c y c l e d ) . Y i e l d s f r o m r e f 18. ^ Y i e l d s r e p r e s e n t r a n g e from t h r e e r u n s u s i n g d i f f e r e n t amount o f c a t a l y s t f o r e a c h r u n . c

2


14.

IDOUX AND GUPTON

Table

II.

Br(CH

) Br


175

R e a c t i o n o f Sodium P h e n o x i d e w i t h 1,3-Dlbromopropane u n d e r PTC C o n d i t i o n s PhONa, PTC > PhO(CH ) OPh T o l u e n e , Toluene,


PTC

30

PTC

Yield _ [η-Bu Ρ B r ] [(CHj (n-Bu.P+Br" ) ] [ ( CH; ) t ( n - B u ^ B r " ) ; ] [(CH;)l(n-Bu;P Br"i;] [ ( C H ^ ) ^ ( n - B d P B r j^

mole p e r c e n t

Activity

1 hr

a

None TBPB VI IX X XI a

110°C,

+

+

2

equivalent

3

o f Product

(*)

0 45 46 65 47 53

compared t o s u b s t r a t e .

i n a Weak N u c l e o p h i l e

SnAr

Reaction

We h a v e r e c e n t l y r e p o r t e d (26) s e v e r a l s y n t h e t i c s t u d i e s o f weak n u c l e o p h i l e SnAr r e a c t i o n s . In the l a t t e r cases ( 2 6 f - j ) , new s y n t h e t i c m e t h o d o l o g y was r e p o r t e d f o r t h e d i r e c t i n t r o d u c t i o n o f f l u o r o a l k o x y groups i n t o a v a r i e t y of aromatic systems. These r e p o r t s r e p r e s e n t s y n t h e t i c a l l y u s e f u l p r o c e d u r e s f o r o b t a i n i n g some o t h e r w i s e i n a c c e s s i b l e fluoroalkoxy materials but, unfortunately, they r e q u i r e the use o f a d i p o l a r , a p r o t l c s o l v e n t ( u s u a l l y h e x a m e t h y l p h o s p h o r a m i d e , HMPA) a n d , i n some cases, elevated temperatures. However, b e c a u s e o f t h e i r d i v e r s e and important a p p l i c a t i o n s (27), t h e syntheses o f t h e s e a n d o t h e r o r g a n o f l u o r o compounds c o n t i n u e t o be o f interest. F o r example, two r e c e n t r e p o r t s o f u s e f u l fluoroalkoxy materials Include the I n s e c t i c i d e a c t i v i t y e x h i b i t e d by f l u o r o a l k o x y s u b s t i t u t e d 1,3,4-oxadiazoles (28) a n d t h e c o n t r o l o f c a r d i a c a r r y t h m i a a c t i v i t y d i s p l a y e d by N - ( P i p e r i d y l a l k y l ) f l u o r o a l k o x y b e n z a m i d e s (29) . W h i l e t h e e f f i c a c y o f t h e s e new, b i o l o g i c a l l y a c t i v e m a t e r i a l s h a s b e e n a t t r i b u t e d (28,29) p r i m a r i l y t o the presence o f t h e f l u o r o a l k o x y group, i t i s important t o n o t e t h a t t h e need f o r more e f f i c i e n t s y n t h e s e s o f these and r e l a t e d m a t e r i a l s s t i l l e x i s t s . F o r example, t h e s y n t h e s e s o f b o t h t h e above m a t e r i a l s i n v o l v e m u l t i - s t e p , moderate y i e l d p r o c e s s e s i n which t h e f l u o r o a l k o x y group i s Introduced i n t h e i n i t i a l s t e p o f the sequence v i a r e a c t i o n o f a n u c l e o p h i l i c phenolate d e r i v a t i v e w i t h e i t h e r a f l u o r o a l k e n e (30) o r a t r i f l a t e ( M ) * r e s p e c t i v e l y . Thus, t h e s i m p l i c i t y and c o n v e n i e n c e o f t h e d i r e c t , SnAr i n t r o d u c t i o n o f f l u o r o a l k o x y g r o u p s i s an a t t r a c t i v e a l t e r n a t i v e i f c o n d i t i o n s milder than t h o s e o f f e r e d b y e l e v a t e d t e m p e r a t u r e s a n d HMPA a s s o l v e n t c a n be e s t a b l i s h e d . A possible s e t of milder conditions



176


f o r t h e l a t t e r r e a c t i o n i n v o l v e s t h e use o f p h a s e transfer catalysis. While the g r e a t e s t percentage of PTC-aided a n i o n i c s u b s t i t u t i o n s i n v o l v e non-aromatic systems (7-10), a number o f l i q u i d - l i q u i d and s o l i d - l i q u i d , P T C - a i d e d SnAr r e a c t i o n s have been r e p o r t e d (32-38). These r e p o r t s i n v o l v e a v a r i e t y of s u b s t r a t e s [ u n a c t i v a t e d (32,33), s l i g h t l y a c t i v a t e d ( 3 4 ) , a c t i v a t e d ( 3 5 - 3 7 ) , and t r a n s i t i o n m e t a l c o m p l e x e d {32,38)1, n u c l e o p h i l e s £ OMe ( 3 2 , 3 8 ) , "~CN ( 3 3 ) , ~SR ( 3 4 ) * SCN ( 3 5 ) , SO (36)> OR ( 3 7 ) ] and PTCs [ c r o w n e t h e r s ( 3 2 - 3 8 ) , q u a t s (33-35,38) and t e r t i a r y amine s a l t s (36,37)]. I n an a t t e m p t t o e x t e n d t h i s m e t h o d o l o g y t o a weak n u c l e o p h i l e SnAr r e a c t i o n , we have r e p o r t e d (39) a l i m i t e d s t u d y o f t h e e f f e c t o f some w e l l - k n o w n , s i n g l e s i t e , n e u t r a l and i o n i c PTCs on t h e f l u o r o a l k o x y l a t i o n o f a h a l o a r o m a t l c and a h a l o h e t e r o a r o m a t i c substrate. We r e p o r t h e r e an e x t e n d e d s t u d y o f t h e e f f e c t o f s i n g l e - s i t e PTCs a s w e l l a s t h a t o f some m u l t i - s i t e PTCs on a r o m a t i c f l u o r o a l k o x y l a t i o n . The r e s u l t s o f t h e s e s t u d i e s a r e shown i n Tables III-V. As I n d i c a t e d i n T a b l e I I I , n e i t h e r 4 - c h l o r o n i t r o b e n z e n e nor 2 - c h l o r o - 4 - m e t h y l q u i n o l i n e reacts with t h e 2 , 2 , 2 - t r i f l u o r o e t h o x i d e i o n i n t o l u e n e a t 25 C o r a t s o l v e n t r e f l u x i n t h e a b s e n c e o f c a t a l y s t . On t h e o t h e r hand, s e v e r a l d i f f e r e n t crown e t h e r s and a r a n g e o f p o l y ( e t h y l e n e g l y c o l s ) [PEGs o f a v e r a g e m o l e c u l a r w e i g h t 300 t o 14,000] c a t a l y z e t h i s weak n u c l e o p h i l e SnAr r e a c t i o n . The optimum c o n d i t i o n s f o r t h e s e n e u t r a l PTCs a r e p r o v i d e d by u s e o f PEG-8000 a t 5 mole p e r c e n t equiv a l e n t compared t o s u b s t r a t e . As I n d i c a t e d i n F i g u r e s 1 and 2, t h e r e l a t i v e o r d e r s o f r e a c t i v i t y w i t h r e s p e c t t o b o t h t h e p o s i t i o n o f a l e a v i n g g r o u p and t h e n a t u r e o f t h e l e a v i n g g r o u p f o l l o w t h e same p a t t e r n f o r t h e PEG-8000 m e d i a t e d r e a c t i o n a s t h o s e r e p o r t e d p r e v i o u s l y by us (261) and by o t h e r s (40) f o r non-PTC m e d i a t e d c o n d i t i o n s . That i s , p o s i t i o n r e a c t i v i t y ( F i g u r e 1) i s c l e a r l y ο > |> >> m a s I n d i c a t e d by t h e c o m p l e t e c o n v e r s i o n o f t h e o - i s o m e r d u r i n g t h e f i r s t two h o u r s o f r e a c t i o n and t h e a b s e n c e o f r e a c t i o n o f t h e m-isomer d u r i n g t h e same t i m e p e r i o d . However, u n d e r PTC c o n d i t o n s , p o s i t i o n r e a c t i v i t y i s more s e l e c t i v e ( a b s e n c e o f r e a c t i o n o f t h e m e t a - i s o m e r ) where as, under d i p o l a r , a p r o t i c s o l v e n t c o n d i t i o n s , r e a c t i o n of t h e m e t a - l s o m e r i s s l o w e r compared t o t h e o r t h o - and para-Isomers but s t i l l s y n t h e t i c a l l y u s e f u l (26g,261). As shown i n T a b l e IV, a number o f w e l l - k n o w n , s i n g l e - s i t e , i o n i c PTCs a l s o c a t a l y z e t h e a r o m a t i c f l u o r o a l k o x y l a t i o n r e a c t i o n , a l b e i t a t somewhat h i g h e r m o l a r r a t i o s t h a n t h a t r e q u i r e d f o r t h e optimum c o n d i t i o n s u s i n g PEG-8000. The most e f f e c t i v e o f t h e s e i o n i c m a t e r i a l s was t e t r a b u t y l p h o s p h o n i u r a b r o m i d e (TBPB) w h i c h i s i n a g r e e m e n t w i t h a s t u d y by B r u n e i l e (34c) on t h e PTC-mediated r e a c t i o n of t h i o l a t e s w i t h p o l y c h l o r o benzenes. I t i s I n t e r e s t i n g to note that s o l i d - l i q u i d c o n d i t i o n s g e n e r a l l y p r o v i d e d b e t t e r conversions f o r the i o n i c PTCs t h a n l i q u i d - l i q u i d c o n d i t i o n s and t h a t w a t e r


14.

111


IDOUX AND GUPTON

Table I I I . Reaction of 4-Chloronitrobenzene with 2 , 2 , 2 - T r i f l u o r o e t h o x i d e I o n u n d e r N e u t r a l PTC Conditions PTC 4-Cl-Ph-NO

+ CP CH OH


2

3

(1 eq)

2

(1.5 eq)

PTC (eq)

> 4-CF CH 0-Ph-NO N a O H ( s , l . l eq) PhMe, 24h, 110 C CONVERSION (* BY GCj

_b C

18-C-6 (0.10)^ 18-C-6 (0.28) ' 18-C-6 (0.28) 18-C-6(0.44) 15-C-5 (0.44) DB18-C-5 (0.44) PEG-300 (0.44) PEG-600 (0.44) PEG-1000 (0.44) PEG-1500 (0.44) PEG-3400 (0.44) PEG-8000 ( 0 . 4 4 ) PEG-14000(0.44) PEG-8000 (0.66) PEG-8000 ( 0 . 3 0 ) . PEG-8000 ( 0 . 2 0 ) PEG-8000 (0.20) . PEG-8000 ( 0 . 1 0 ) ^ PEG-8000 (0.05) ' α

θ

e

β

g

e

n

e

1

β

YIELD ( *, CRUDE)

0 57 71 51 75 66 74 56 44 54 43 36 52 47 41 44 62 60 59 78

0 43 58 64 98 60 57 13 37 40 50 61 76 63 78 97 92 52 97 97

WITH 2-CHLORO- 4-METHYLQUINOLINE AS SUBSTRATE PEG-8000

(0.05)

1 , 6

>98

100

Α 1 Γ r e a c t i o n s were r u n u n d e r a n i t r o g e n a t m o s p h e r e . I n i t i a l p r o d u c t i s o l a t i o n was a c c o m p l i s h e d by aqueous e x t r a c t i o n o f t h e r e a c t i o n m i x t u r e f o l l o w e d by c o n c e n t r a t i o n o f the o r g a n i c phase. A z e o t r o p i c removal o f water d u r i n g t h e c o u r s e of. t h e r e a c t i o n d i d n o t a f f e c t t h e indicated results. A t 25°C a n d a t 110 C . 18-Crown-6. B a s e u s e d was N a H ( l . l e q u i v ) . ° S f r o m r e f 39. 15-Crown-5. Dibenzo-18-Crown-6. PEG = P o l y ( e t h y l e n e g l y c o l ) of molecular weight i n d i c a t e d . 1.7 e q u i v o f NaOH and 2.0 e q u i v o f CF.CH OH were u s e d , i s o l a t e d y i e l d = 41*. I s o l a t e d y i e l d = 74*. e

a t

f

g

1


178


T a b l e IV.

Reaction of 4-Chloronitrobenzene with 2,2,2-Trifluoroethoxlde Ion under S i n g l e - S i t e , I o n i c PTC C o n d i t i o n s PTC

4-Cl-Ph-No

+ CP CH OH


2

3

(1 eq)

2

(2 eq)

PTC (ea) BTMAC^ BTEAC BTEAC MTCAC* TBAHS AD464 AD464 TBPB TBPB TBPB TBPB TBPB g

TBPB

> 4-CF CH O-PH-NO NaOH(s,1.2 eq) PhMe, 24h, 110 C

(0.1 (0.1 Λ (0.1 (0.1 (0.1 (0.1 (0.1 \ (0.1 ' Λ (0.1 α (0.3 (0.3 \i (0.5 1

CONVERSION (* BY G O

YIELD (*.CRUDE)

16 9 15 9 26 25 11 49 30 99 88 95

14 2 10 5 16 21 9 32 19 84 68 78

WITH 2-CHL0R0-4-METHYLQUIN0LINE (0.3) 98

AS SUBSTRATE

. 75

U n l e s s o t h e r w i s e i n d i c a t e d , a l l r e a c t i o n s were r u n u n d e r s o l i d - l i q u i d c o n d i t i o n s i n a n i t r o g e n atmosphere and w a t e r was a z e o t r o p i c a l l y removed d u r i n g t h e c o u r s e o f t h e r e a c t i o n . I n i t i a l p r o d u c t i s o l a t i o n was a c c o m p l i s h e d b y r a p i d f i l t r a t i o n of the r e a c t i o n mixture through a s i l i c a g e l c o l u m n f o l l o w e d by c o n c e n t r a t i o n o f t h e o r g a n i c p h a s e . D a t a f o r B T E A C . l i q u i d - l i q u i d c o n d i t i o n s a n d f o r TBAHS f r o m r e f 39. Benzyltrimethylammonium c h l o r i d e . Benzyltriethylammonium c h l o r i d e . L i q u i d - l i q u i d condi t i o n s : c a t a l y s t a d d e d a s a 40% (w/w) aqueous s o l u t i o n . A d o g e n 464 ( A s h l a n d C h e m i c a l Company): M e t h y l t r i a l k y l ( C _ ) ammonium c h l o r i d e . tiiquid-liquid. conditions : water added d i r e c t l y t o r e a c t i o n m i x t u r e . Tetrabutylphosphonium b r o m i d e . W a t e r was n o t removed a z e o t r o p i c a l l y during the course of the r e a c t i o n . I s o l a t e d y i e l d f r o m r e f 39. 9

8

1 Q

J



14.

T a b l e V.

179


IDOUX AND GUPTON

Reaction of 4-Chloronitrobenzene with 2,2,2-Trifluoroethoxide Ion under M u l t i - S i t e , I o n i c PTC C o n d i t i o n s PTC(0.3eq)

4-Cl-Ph-N0

o 2

(1 eq)

+ CF CH 0H Q

3

>

o

2

(2 eq)

4-CF CH 0-Ph-NO * 3

NaOH(s,1.2eg) PhMe,2h,110 C

2

YIELD (*,ISOLATED)

PTC

VI VII VIII IX X XI TBPB TBPB PEG-8000

48 . 58 (58) 70 70 . 65 (65) 71 . 12 (g5 a t 2 4 h r ) trace (41 a t 24hr) f

e

a

S e e f o o t n o t e a, T a b l e IV. Water was n o t removed a z e o t r o p i c a l l y d u r i n g the course of the r e a c t i o n . ^ C o r r e s p o n d s t o a p p r o x i m a t e l y 50* c o n v e r s i o n a t 2 h r . C o r r e s p o n d s t o 99* c o n v e r s i o n a t 24hr (See T a b l e I V ) . A p p r o x i m a t e l y 50* c o n v e r s i o n a t 2hr (See F i g u r e 1 ) . C o r r e s p o n d s t o 97* c o n v e r s i o n a t 24hr (See T a b l e I I I ) . f



180


TIME (MIN.)

F i g u r e 1. B e s t - f i t t e d c o n v e r s i o n ( * ) / t i m e (min) c u r v e s f o r t h e PEG-8000 m e d i a t e d f l u o r o a l k o x y l a t i o n o f ο - , m- a n d p - c h l o r o n i t r o b e n z e n e s



IDOUX AND GUPTON


TIME (MIN.)

F i g u r e 2. B e s t - f i t t e d c o n v e r s i o n ( * ) / t i m e (min) c u r v e s f o r t h e PEG-8000 m e d i a t e d f l u o r o a l k o x y l a t i o n of s u b s t i t u t e d nitrobenzenes A = o-NO , Β » o-F, C =• o - C l , D « o - B r , Ε = o - I , F = p - C l , G = m-Cl




182

a p p e a r s t o i n h i b i t t h e i o n i c P T C - c a t a l y z e d r e a c t i o n s but n o t t h e P E G - c a t a l y z e d r e a c t i o n s . I n f a c t , i t was n e c e s s a r y t o remove w a t e r a z e o t r o p i c a l l y f r o m t h e r e a c t i o n s e m p l o y i n g i o n i c PTCs i n o r d e r t o a c h i e v e optimum c o n v e r sion. S u c h b e h a v i o r seems t o be u n u s u a l i n l i g h t o f t h e many r e p o r t e d (9) a p p l i c a t i o n s o f i o n i c PTCs t o l i q u i d l i q u i d t r a n s f e r s but may be i n d i c a t i v e o f "omega-phase c a t a l y s i s " a s m e n t i o n e d i n t h e f o l l o w i n g d i s c u s s i o n and a s d e s c r i b e d i n d e t a i l by L l o t t a (41) e l s e w h e r e i n t h i s volume. The d a t a r e p o r t e d i n T a b l e V p r o v i d e a summary o f t h e r e a c t i o n of 2 , 2 , 2 - t r i f l u o r o e t h o x l d e i o n with 4-chloron l t r o b e n z e n e i n t h e p r e s e n c e o f t h e d i - s i t e phosphonlum PTCs V I - X I . As i n d i c a t e d , optimum c o n d i t i o n s f o r t h e d i - s i t e PTCs a r e o b t a i n e d a f t e r 2 h r o f r e a c t i o n . Under s u c h c o n d i t i o n s , t h e v a r i o u s d i - s i t e PTCs a r e more e f f e c t i v e t h a n e i t h e r TBPB ( a t t h e same m o l a r r a t i o ) o r PEG-8000. I n a d d i t i o n , i n c o n t r a s t t o TBPB, t h e e f f e c t i v e n e s s o f t h e d i - s i t e PTCs a r e n o t i n h i b i t e d by the p r e s e n c e o f w a t e r . The l a t t e r o b s e r v a t i o n may e x p l a i n why t h e s i n g l e s i t e , i o n i c PTCs a r e g e n e r a l l y more e f f e c t i v e u n d e r s o l i d - l i q u i d c o n d i t i o n s than under l i q u i d - l i q u i d c o n d i t i o n s and, i n c o n t r a s t , why t h e d i - s i t e , i o n i c PTCs a r e more e f f e c t i v e . T h a t i s , f o r a P T C - m e d i a t e d r e a c t i o n c a r r i e d out i n the p r e s e n c e of g r a d u a l l y I n c r e a s i n g amounts o f w a t e r , L l o t t a (41.) has p r e s e n t e d e v i d e n c e w h i c h i n d i c a t e s t h a t t h e PTC moves f r o m t h e o r g a n i c p h a s e onto the s u r f a c e of the s a l t n u c l e o p h i l e . Llotta s u g g e s t s t h a t a new p h a s e i s t h u s f o r m e d ( i . e . , t h e "omega-phase") where r e a c t i o n t h e n o c c u r s on t h e s u r f a c e of the s a l t n u c l e o p h i l e . Under n o r m a l l i q u i d l i q u i d PTC c o n d i t i o n s , where o t h e r t h a n t r a c e amounts o f water are i n v o l v e d , there i s a subsequent decrease i n r e a c t i v i t y . In comparing the r e a c t i v i t i e s of the s i n g l e s i t e , i o n i c PTCs t o t h o s e o f t h e m u l t i - s i t e , i o n i c PTCs, "omega-phase" f o r m a t i o n may w e l l be an i n h i b i t i n g f a c t o r i n t h e f o r m e r c a s e b u t a p p e a r s t o be o f l i t t l e s i g n i f i c a n c e i n the l a t t e r case. Summary Thus, PTC m e t h o d o l o g y c a n be e f f e c t i v e l y a p p l i e d t o a weak n u c l e o p h i l e SnAr r e a c t i o n u n d e r a v a r i e t y o f PTC and reaction conditions. T h i s may p r o v e t o be p a r t i c u l a r l y u s e f u l f o r f l u o r o a l k o x y l a t i o n . T h a t i s , we have r e c e n t l y d e m o n s t r a t e d (26h) t h a t 2 , 2 , 2 - t r i f l u o r o e t h o x l d e i o n r e a c t s u n d e r HMPA s o l v e n t c o n d i t i o n s a t o r n e a r room t e m p e r a t u r e w i t h an e x t e n d e d r a n g e o f s u b s t r a t e s w h i c h c o n t a i n a more a c t i v e l e a v i n g group ( n l t r o ) than c h l o r o . The f o r m e r r e a c t i o n o c c u r s u s e f u l l y even f o r s u b s t r a t e s c o n t a i n i n g t h e w e a k l y a c t i v a t i n g amido f u n c t i o n a l i t y . S i r a i l i a r r e a c t i o n s may be p o s s i b l e f o r t h e s e s u b s t r a t e s u n d e r PTC conditions.


14.

IDOUX AND GUPTON


183


Acknowledgment We a r e g r a t e f u l t o t h e P e t r o l e u m R e s e a r c h F u n d , a d m i n i s t e r e d by t h e A m e r i c a n C h e m i c a l S o c i e t y , and t h e R o b e r t A . Welch F o u n d a t i o n f o r p a r t i a l s u p p o r t of t h i s work. We thank the f o l l o w i n g c o - w o r k e r s f o r t h e i r e x p e r i m e n t a l a s s i s t a n c e and e x p e r t i s e : Ronald Wysocki, Sherre Young, J e f f e r y T u r c o t , C h a r l e n e Ohlman, R u s s e l l L e o n a r d , J e f f e r y Dodge, J i l l G a r r i s o n , C r a i g Hughes, J o s e p h C o u r y , M a r t i n Moebus and D e r - L u n C h u .

Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19.

Starks, C. M. J . Am. Chem. Soc. 1971, 93, 195. Starks, C. M. i b i d . 1973, 95, 3613. Sjoberg, K. Aldrichimica Acta 1980, 13, 55. Jones, A. R. ibid. 1976, 9, 35. Gokel, G. W.; Weber, W. P. J . Chem. Educ. 1978, 55, 350 and 429. Reuben, B . ; Sjoberg, K. Chemtech 1981, 315. Dehmlow, Ε. V . ; Dehmlow, S. "Phase Transfer Catalysis," Verlag Chemie, Weinheim and Deerfield Beach, Florida, 1980. Keller, W. E.; E d . , "Compendium of Phase-Transfer Reactions and Related Synthetic Methods," Fluka AG, CH-9470 Buchs, Switzerland, 1979. Liotta, C . ; Starks, C. M. "Phase Transfer Catalysis," Academic Press, New York, 1977. Weber, W. P.; Gokel, G. W. "Phase Transfer Catalysis in Organic Synthesis," Springer-Verlag, New York, 1977. Gokel, G. W.; Jarvis, Β. B. "Medium Effects in Organic Synthesis," ACS Audio Course, 1983. Mathur, N. K . ; Narang, C. K . ; Williams, R. E. "Polymers as Aids in Organic Chemistry," Academic Press, New York, 1980. (a) Chiles, M. S.; Reeves, P. C. Tetrahedron Letters 1979, 3367; (b) Chiles, M. S.; Jackson, D. D.; Reeves, P. C. J . Org. Chem. 1980, 45, 2915. Regen, S. L . ; B o l i k a l , D.; Barcelon, D. J . Org. Chem. 1981, 46, 2511. Fukunishi, K . ; Czech, B . ; Regen, S. L . ibid. 1981, 46, 1218. Montanari, F . ; Tundo, p. i b i d . 1981, 46, 2125. Regen, S. L. Angew. Chem. Int. Ed. Engl. 1979, 18, 421. Idoux, J . P.; Wysocki, R.; Young, S.; Turcot, J . ; Ohlman, C . ; Leonard, R. Synth. Commun. 1983, 13, 139. (a) Brown, J . ; Jenkins, J . J . Chem. Soc., Chem. Commun. 1976, 458; (b) Cinouini, M.; Colonna, S.; Molinari, H . ; Montanari, F . ; Tundo, P. ibid. 1976, 394; (c) Molinari, H . ; Montanari, F . ; Tundo, P.


184

20.


21. 22. 23. 24. 25. 26.

27. 28.

29. 30. 31. 32. 33. 34.

35. 36. 37. 38. 39. 40. 41.


ibid. 1977, 639; (d) Molinari, H . ; Montanari, F . ; Quinci, S.; Tundo, P. J . Am. Chem. Soc. 1979, 101, 3920. (a) Tomoi, M.; Ogama, E . ; Hosokawa, Y . ; Kaiuchi, H. J . Polym. S c i . , Polvm. Chem. Ed. 1982, 20, 3015; (b) Tomoi, M.; Hosokawa, Y . ; Kaiuchi, H. Ibid. 1984, 22, 1243. Cinquini, M.; Montanari, F . ; Tundo, P. J . Chem. Soc. Chem. Commun. 1975, 393. Landini, D.; Rolla, F. Synthesis 1974, 565. McKillop, Α . ; Fiaud, J . C . ; Hug, R. P. Tetrahedron 1974, 30, 1379. Herriott, Α . ; Picker, D. Synthesis 1975, 447. Tundo, P. Synthesis 1978, 315. Idoux, J . P.; Gupton, J . T . ; et al.: (a) Synth. Commun. 1985, 15, 43; (b) i b i d . 1984, 14, 1001; (c) i b i d . 1983, 13, 1083; (d) i b i d . 1982, 12, 907; (e) J. Org. Chem. 1983, 48, 2933; (f) Synth. Commun. 1984, 14, 621; (g) i b i d . 1982, 12, 695; (h) J . Org. Chem. 1985, 50, 1876; (1) i b i d . 1983, 48, 3771; (j) Can. J . Chem. 1985, 63, 3037. Gerstenberger, M.; Haas, A. Angew. Chem. Int. Ed. Engl. 1981, 20, 647. (a) Arrington, J . ; Wade, L . , U.S. Patent 4,215,129, July 29, 1985; (b) Idoux, J . P.; Cunningham, G. N.; Gupton, J . T . , unpublished results reported in part at the 1984 Southeast Regional ACS Meeting. Chem. & Engr. News 1984, September 10, pp. 32-38. Idoux, J . P.; Gibbs-Rein, Κ., unpublished results. Banitt, Ε. H . ; Brown, W. R.; Coyne, W. E.; Schmid, J . R. J . Med. Chem. 1977, 20, 821. Fukui, M.; Endo, Y . ; Oishi, T. Chem. Pharm. B u l l . 1980, 28, 3639. Cassar, L . ; Foa, M.; Montanari, F . ; Marinelli, G. P. J . Organomet. Chem. 1979, 173, 335. (a) Landini, D.; Montanari, F . ; Rolla, F. J . Org. Chem. 1983, 48, 604; (b) Reeves, W.; Bothwell, T . ; Rudis, J . ; McClusky, J . ; Synth. Commun. 1982, 12, 1071; (c) Brunelle, D. J . Org. Chem. 1984, 49, 1309. Reeves, W. P.; Simmons, Α . ; Keller, K. Synth. Commun. 1980, 10, 633. Bunnett, J . F . ; Gisler, M.; Zollinger, H. Helv. Chim. Acta 1982, 65, 63. Paradisi, C . ; Quintily, U . ; Scorrano, G. J . Org. Chem. 1983, 48, 3022. Montanari, F . ; Pelosi, M.; Rolla, F. Chem. Ind. (London) 1982, 412. Gupton, J . T . ; Coury, J . ; Moebus, M.; Idoux, J . P. Synth. Commun. 1985, 15, 431. March, J . "Advanced Organic Chemistry"; 3rd ed.; McGraw-Hill: New York, 1985; Chapter 10. L i o t t a , C. L. "Omega-Phase Catalysis," this volume.

RECEIVED July

26, 1986


Multisite Phase-Transfer Catalysts - ACS Symposium Series (ACS

Recommend Documents