Ozone Reactions with Organic Compounds

8 Ozonation of p-Nitro-N,N-Dimethylaniline

Downloaded by UNIV MASSACHUSETTS AMHERST on August 28, 2013 | http://pubs.acs.org Publication Date: June 1, 1972 | doi: 10.1021/ba-1972-0112.ch008

PER

KOLSAKER

Universitetets Kjemiske Institutt, Blindern/Oslo BRITA

3, Norway

TEIGE

Odontologisk Institutt for Fysiologi og Biokjemi, Blindern/Oslo

The reaction studied.

of p - n i t r o - N , N - d i m e t h y l a n i l i n e with ozone

Only

side-chain

oxidation

oxide,

No N-oxide

could

be

dimeric per-

obtained.

2-carboxy-4-nitro-N,N-dimethylaniline,

- N , N - d i m e t h y l a n i l i n e , and ized.

a

di-[(N-methyl-N-p-nitrophenyl)aminomethyl]

were formed.

comparison

was

p-nitro-N-

products,

- m e t h y l a n i l i n e , p - n i t r o - N - m e t h y l f o r m a n i l i d e , and peroxide,

3, Norway

A mechanism

is

N,N-dimethylaniline

For

p-chlorowere

ozon-

proposed.

^ V z o n a t i o n of t e r t i a r y a l i p h a t i c amines has r e c e i v e d some a t t e n t i o n i n recent years. A m i n e oxide f o r m a t i o n was e s t a b l i s h e d l o n g ago ( 1 ). O x i d a t i o n of a l k y l groups w a s r e p o r t e d b y H e n b e s t a n d S t r a t f o r d S h u l m a n ( 3 ) , a n d B a i l e y et al. (4, 5 ) .

(2),

F o r m a t i o n of a m i n e h y d r o c h l o -

rides w a s e s t a b l i s h e d w h e n c h l o r i n a t e d solvents w e r e u s e d ( 2 - 5 ) .

De-

a l k y l a t e d p r o d u c t s w e r e f o r m e d (2, 4, 5 ) , a n d amides w e r e f o u n d b y the same authors (2-^5). I n a p r e v i o u s p a p e r ( 6 ) w e r e p o r t e d o n the o z o n a t i o n of 2-carboxy4-nitro-N,N-dimethylaniline (I)

and p-nitro-N,N-dimethylaniline

(IVc).

N - o x i d e s w e r e n o t f o u n d i n these cases, a n d the p r o d u c t s f o r m e d i n d i c a t e d o n l y s i d e - c h a i n o x i d a t i o n . T h e i n t e r m e d i a c y of a c a r b i n o l a m i n e I I is i n d i c a t e d b y t h e f o r m a t i o n of the lactone I I I . C H

3\

^

C H

3

C

H

3 \

M

/

C

H

2

O

H

C H

3\

K I

/ «ÎÎ2 C

C

H

3\

M

/

C

H

3

a:X = H b:X = Cl c:X=N0 N0

2

II

III

IV

101 In Ozone Reactions with Organic Compounds; Bailey, P.; Advances in Chemistry; American Chemical Society: Washington, DC, 1972.

2

102

OZONE REACTIONS W I T H ORGANIC COMPOUNDS

Table I.

Ozonation of 2-Carboxy-4-nitro-2V,N-dimethylaniline Demethylated Starting Material,

Solvent CH C1 EtOAc MeOH 2

%

Lactone (III),

81 71 64

2

%

18 28 32

D e m e t h y l a t e d s t a r t i n g m a t e r i a l was also a p r o d u c t of the Downloaded by UNIV MASSACHUSETTS AMHERST on August 28, 2013 | http://pubs.acs.org Publication Date: June 1, 1972 | doi: 10.1021/ba-1972-0112.ch008

(I)

ozonation.

P r o d u c t c o m p o s i t i o n v a r i e d w i t h solvent as s h o w n i n T a b l e I. W h e n p-nitro-N,N-dimethylaniline (IVc)

w a s o z o n i z e d at 0 ° C i n

e t h y l acetate, m e t h y l e n e c h l o r i d e , or m e t h a n o l , a m i x t u r e of resulted.

products

I n a d d i t i o n to the e x p e c t e d s i d e - c h a i n o x i d a t i o n p r o d u c t s —

p-nitro-N-methylaniline

( V c ),

p-nitro-N-methyl formanilide

peroxide compound was formed.

(Vic ) —a

T h i s p e r o x i d e , w h i c h is n o t

u n t i l the solvents are r e m o v e d , w a s s h o w n b y a series of

formed

experiments

( d e s c r i b e d b e l o w ) to b e i d e n t i c a l w i t h d i - [ ( N - m e t h y l - p - n i t r o p h e n y l ) aminomethyl] peroxide ( V I I ) .

D e o x y g e n a t i o n of V I I w i t h t r i e t h y l p h o s

p h i t e ( 7 ) y i e l d e d the ether V I I I , w h i c h i n t u r n d e c o m p o s e d at its m e l t i n g p o i n t to t h e a m i n e I X .

Χ

X

V

VI

N0

N0

2

VIII

2

VII

α:Χ = Η , b:X = CI , c : X = N 0

N0

N0

2

2

2

N0

N0

2

2

IX

W e n o w r e p o r t o u r results w h e n the e x p e r i m e n t a l c o n d i t i o n s are s y s t e m a t i c a l l y v a r i e d . O z o n a t i o n s of some other Ν,Ν-dimethylanilines are also i n c l u d e d . T h e results are g i v e n i n T a b l e I I . Experimental General. T h e o z o n a t i o n p r o c e d u r e s are those d e s c r i b e d i n t h e l i t e r a ture, b o t h u s i n g ozone—oxygen a n d o z o n e - n i t r o g e n . O x y g e n analyses

In Ozone Reactions with Organic Compounds; Bailey, P.; Advances in Chemistry; American Chemical Society: Washington, DC, 1972.


8.

KOLSAKER AND T E i G E

Ozonation

of p-Nitro-N,Ν-Dimethy

laniline

103

w e r e p e r f o r m e d u s i n g a B e c k m a n F 3 o x y g e n a n a l y z e r as d e s c r i b e d p r e v i ously ( 8 ) . Gas l i q u i d chromatographic ( G L C ) determinations were c a r r i e d out w i t h a n A e r o g r a p h m o d e l A 700, u s i n g a n 8.5-ft X 0.25-inch c o l u m n of p o l y e t h y l e n e g l y c o l 2 0 M ( 3 0 % o n C h r o m o s o r b W H M D S , 6 0 / 8 0 m e s h ) f o r E x p e r i m e n t s 1 a n d 2. P r o t o n m a g n e t i c resonance ( P M R ) s p e c t r a w e r e r e c o r d e d o n a V a r i a n A 6 0 A spectrometer u s i n g o r d i n a r y c h l o r o f o r m as solvent a n d t e t r a m e t h y l s i l a n e as i n t e r n a l reference. M e l t i n g points w e r e not c o r r e c t e d . Materials. 2 - C a r b o x y - 4 - n i t r o - N , N - d i m e t h y l a n i l i n e ( I ) w a s s y n t h e s i z e d f r o m its c h l o r o a n a l o g w i t h d i m e t h y l a m i n e ( a q u e o u s s o l u t i o n ) , mp 164°-166°C. p-Chloro-N,IV-dimethylaniline ( I V b ) and N,N-dim e t h y l a n i l i n e ( I V a ) w e r e c o m m e r c i a l l y a v a i l a b l e i n the p u r e state a n d w e r e u s e d as s u p p l i e d . p - N i t r o - N , N - d i m e t h y l a n i l i n e ( I V c ) w a s p r e p a r e d from p-nitrochlorobenzene a n d dimethylamine ( 9 ) ; m p 166°C. Ozonation of 2-Carboxy-4-nitro-N,N-dimethylaniline (I)· The a m i n e (2.10 grams, 10 m m o l e s ) was d i s s o l v e d i n the a p p r o p r i a t e solvents ( 200 m l m e t h a n o l , e t h y l acetate, or m e t h y l e n e c h l o r i d e ) a n d o z o n i z e d at 0 ° C w i t h e q u i m o l a r amounts of o z o n e ; q u a n t i t a t i v e a b s o r p t i o n o c c u r r e d . N e a r the e n d of t h e o z o n a t i o n t i m e , a p r e c i p i t a t e f o r m e d . I n ozonations i n m e t h a n o l this substance was i d e n t i c a l w i t h l a c t o n e I I I ; m p 1 7 6 ° - 1 7 7 ° C . , p r e p a r e d a c c o r d i n g to V i l l i g e r (10). I n the other solvents the i n s o l u b l e p r o d u c t w a s the d e m e t h y l a t e d s t a r t i n g m a t e r i a l , m p 2 6 5 ° - 2 6 8 ° C ( d e c ) ; r e p o r t e d m p 2 6 3 ° - 2 6 4 ° C (11). T h e m o t h e r l i q u o r was e v a p o r a t e d , a n d the t w o c o m p o u n d s w e r e s e p a r a t e d b y f r a c t i o n a l c r y s t a l l i z a t i o n . T h e results are s h o w n i n T a b l e I. Ozonation of N,N-dimethylaniline (IVa). T h e amine (10 mmoles) was d i s s o l v e d i n m e t h y l e n e c h l o r i d e (150 m l ) a n d o z o n i z e d at — 7 8 ° C w i t h 10 m m o l e s of o z o n e ( n i t r o g e n as c a r r i e r gas) (12); q u a n t i t a t i v e a b s o r p t i o n o c c u r r e d . T h e s o l u t i o n b e c a m e d a r k b r o w n , a n d finally a t a r r y substance s e p a r a t e d out. T h i s substance, w h i c h a d h e r e d to the w a l l s of the o z o n a t i o n vessel, w a s r e p e a t e d l y d i g e s t e d w i t h m e t h y l e n e c h l o r i d e . T h e c o m b i n e d m e t h y l e n e c h l o r i d e extracts, after w a s h i n g w i t h w a t e r , w e r e c o n c e n t r a t e d a n d a n a l y z e d b y G L C . T h e results are s h o w n in Table II. Ozonation of £-Chloro-N,N-dimethylaniline ( I V b ) . T h e a m i n e ( 1 0 m m o l e s ) w a s d i s s o l v e d i n m e t h y l e n e c h l o r i d e (100 m l ) a n d o z o n i z e d at —78 ° C w i t h 10 m m o l e s of ozone. Q u a n t i t a t i v e a b s o r p t i o n o c c u r r e d . T h e solution was carefully washed w i t h water a n d then analyzed b y G L C . F o r the results see T a b l e I I . Ozonation of ^-Nitro-2V,2V-dimethylaniline ( I V c ) . C o n c e n t r a t i o n , t e m p e r a t u r e , a n d solvents w e r e v a r i e d as s h o w n i n T a b l e I I . I n a t y p i c a l r u n , 5 m m o l e s of a m i n e w e r e d i s s o l v e d i n 200 m l of e t h y l acetate a n d o z o n i z e d at 0 ° C w i t h 5 m m o l e s ozone, u s i n g n i t r o g e n as c a r r i e r gas; q u a n t i t a t i v e a b s o r p t i o n o c c u r r e d . T h e exit gas w a s a n a l y z e d for m o l e c u l a r o x y g e n . A f t e r the s o l u t i o n h a d c o m e to r o o m t e m p e r a t u r e , i t was still clear a n d h o m o g e n e o u s . T h e solvent was e v a p o r a t e d , a n d the r e s i d u e was d r i e d a n d w e i g h e d . E t h y l acetate (200 m l ) was a d d e d . A y e l l o w c o m p o u n d ( V I I ) was n o w i n s o l u b l e a n d was r e m o v e d b y filtration. T h e filtrate was e v a p o r a t e d , a n d the r e s i d u e was e x a m i n e d b y P M R . T h e amounts of p - n i t r o - I V , N - d i m e t h y l a n i l i n e ( I V c , s t a r t i n g m a t e r i a l ) , p - n i t r o N - m e t h y l a n i l i n e ( V ) , a n d p - n i t r o - N - m e t h y l f o r m a n i l i d e ( V I ) w e r e esti-


104


Table II.


Expt.

Compound

Amine, mmoles

O /0 mmoles s

2

Ozonation

O /N mmoles

Solvent (ml)

Temp., °C

10

CH C1 (150) CH C1 (100) EtOAC(200) EtOAc(200)

-78 -78 -78 -78

5 5 5 10

MeOAc(200) CH C1 (200) EtOAc(200) EtOAc(lOO) EtOAc(200) MeOAc(200) CH C1 (200) EtOAc(lOO) EtOAc(200) EtOAc(200) EtOAc(200) MeOAc(200) CH C1 (200) EtOAc(200) EtOAc(200) MeOAc(200) CH C1 (200) EtOAc(200)

-78 -78 -40 -40 -40 -40 -40 0 0 0 0 0 0 25 25 25 25 -78 -40

s

2

1 2 3 4

IV IV IV IV

a b c c

10 10 10 5

5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV

c c c c c c c c c c c c c c c c c c

5 5 10 10 5 5 5 10 10 5 5 5 5 10 5 5 5 5

23

IV c

5

10

EtOAc(200)

24

IV c

5

10

EtOAc(200)

0

25

IV c

5

10

EtOAc(200)

25

26 27 28 29

IV IV IV IV

5 5 5 5

2.5 2.5 2.5 2.5

EtOAc(200) EtOAc(200) EtOAc(200) EtOAc(200)

-78 -40 0 25

c c c c

10 10 5 5 5 10 10 5 5 5 10 10 5 5 5 5 10

2

2

2

2

2

2

2

2

2

2

2

2

m a t e d b y m e a s u r i n g the i n t e g r a t e d areas for the N - m e t h y l protons. T h e l i m i t of error i n s u c h a d e t e r m i n a t i o n is p r o b a b l y a r o u n d 5 % . Insoluble Compound VII. T h i s c o m p o u n d m e l t e d at 1 7 6 ° - 1 7 7 ° C ( a c e t o n i t r i l e - w a t e r ) . It w a s i d e n t i c a l ( b y i n f r a r e d ) w i t h t h e p r o d u c t obtained when p-nitro-N-methylaniline, formaldehyde, and hydrogen peroxide were heated i n ethanol ( 7 ) . ACTIVE OXYGEN CONTENT.

A

t o t a l of

181.2

mg

(0.5

mmole)

of

VII

w e r e d i s s o l v e d i n 7 5 m l of a c e t o n i t r i l e ; 1 g r a m of s o d i u m i o d i d e i n 2 5 m l a c e t o n i t r i l e w a s a d d e d , a n d n i t r o g e n w a s p a s s e d t h r o u g h the s o l u t i o n . N o r e a c t i o n o c c u r r e d ; w h e n 2 m l p e r c h l o r i c a c i d ( 6 0 % ) w e r e a d d e d , the


8.


Ozonation

105

of p-Nitro-N,N-Dimethylaniline

Experiments


Products 02, mmoles

V, mmoles (%)

VI, mmoles (%)

VII, mmoles (%)

Rec. IV, mmoles (%)

7.9 — 6.5 4.0-4.7

1.0(10) 1.7(17) 0 0

0 0 0 0

4.4 4.5 6.9 — 4.1 4.1 3.9 n.c. 9.0 — 4.1 4.0 3.4 — 4.0 4.3 3.3 7.9

0 2.6(52) 1.7(17) 0.6(6) 0.7(14) 0.9(18) 2.1(42) 0.8(8) 1.1(11) 1.0(20) 0.8(16) 0.6(12) 1.5(30) 0.3(3) 0 traces 1.3(26) 0

2.0(20) 2.6(26) 1.3(13) 0.5-1.0 (10-20) 1.3(26) 1.2(24) 2.5(25) 2.7(27) 1.8(36) 1.7(34) 1.2(24) 2.7(27) 3.3(33) 1.4(28) 1.5(30) 1.6(32) 1.2(24) 3.5(35) 1.8(36) 1.2(24) 1.3(26) 2.3(46)

0.1(4) 0.6(24) 1.6(32) 1.5(30) 0.8(32) 0.7(28) 0.7(28) 1.9(38) 2.2(44) 0.9(36) 1.0(40) 0.9(36) 0.7(28) 2.2(44) 1.0(40) 0.7(28) 0.8(32) 0

2.4(24) 2.0(20) 8.7(87) 4.0^.5 (80-90) 3.5(70) 0 2.7(27) 4.4(44) 0.8(16) 0.9(18) 0.2(4) 2.7(27) 1.3(13) 0.8(16) 0.7(14) 0.9(18) 0.7(14) 1.6(16) 1.2(24) 2.2(44) 0.8(16) 2.5(50)

8.4

0

3.3(66)

0

traces

6.1

0

3.7(74)

0

0

6.9

0

4.3(86)

0

0

2.1 1.9 1.5 1.3

0 0 0 0

0 0.6(12) 0.6(12) 0.5(10)

0 0.4(16) 0.5(20) 0.3(12)

5.0(100) 3.6(72) 3.3(66) 3.9(78)

Remarks tar f o r m a t i o n tar f o r m a t i o n several r u n s

no o x y g e n a n a l y s i s

0.3 m m o l e s (12%) 0.9 m m o l e s (36%) 0.7 m m o l e s (28%) 0.4 m m o l e s (16%)

diperoxide diperoxide diperoxide diperoxide

b r o w n c o l o r of i o d i n e a p p e a r e d i m m e d i a t e l y . A f t e r 20 m i n u t e s at r o o m t e m p e r a t u r e t h e s o l u t i o n w a s t i t r a t e d w i t h 0 . 1 N s o d i u m thiosulfate. T h e e n d p o i n t w a s difficult to observe, b u t a p p r o x i m a t e l y 1 0 - 1 1 m l of titer s o l u t i o n w e r e u s e d , c o r r e s p o n d i n g to a b o u t 1 0 0 % a c t i v e oxygen. S o l i d sodium bicarbonate was then added, a n d the acetonitrile was evaporated. Y e l l o w crystals w e r e filtered off, m e l t i n g at 1 5 0 ° - 1 5 2 ° C . I n f r a r e d s p e c t r a ( K B r p e l l e t ) c o n f i r m e d the i d e n t i t y of t h e substance as p - n i t r o - N - m e t h y l a n i l i n e ( V ) ; the y i e l d w a s 133 m g ( 8 7 . 5 % ). T H E R M A L D E C O M P O S I T I O N : C o m p o u n d V I I (101.7 m g ) w a s h e a t e d neat at 1 5 5 ° C ( b o i l i n g a n i s o l e ) . A n i n f r a r e d s p e c t r u m ( K B r p e l l e t ) of


106


the r e s i d u e s h o w e d it to be i d e n t i c a l w i t h p - n i t r o - N - m e t h y l f o r m a n i l i d e ( V I ) ; the y i e l d w a s 96 m g ( 9 5 % ). REACTION WITH T R I E T H Y L PHOSPHITE (7).

Refluxing V I I

6

1 6


in

triethyl

p h o s p h i t e y i e l d e d a v e r y i n s o l u b l e c o m p o u n d ( V I I I ) m e l t i n g at 1 7 7 ° 1 7 8 ° C . ( F o u n d : C 55.4, H 5.3, Ν 26.4. C a l e . ( C i H N 0 ) : C 55.5, Η 5.2, Ν 16.2). D E C O M P O S I T I O N O F V I I I . H e a t i n g V I I I neat at its m e l t i n g p o i n t y i e l d e d I X ; m p 2 7 6 ° - 2 7 8 ° C ( F o u n d : C 56.9, Η 5.1, Ν 17.3. C a l e . ( C i 5 H N 0 ) : C 57.0, H 5.1, Ν 17.7). C o m p o u n d I X c o u l d also b e synthesized from p-nitro-N-methylaniline and formaldehyde. Ozonation of £-Nitro-N,N-dimethylaniline with T w o Mole E q u i v a lents of Ozone. T h e p r o d u c t s f r o m this o z o n a t i o n w e r e o b t a i n e d a n d a n a l y z e d b y the same p r o c e d u r e as for the e q u i m o l a r runs. T h e i n s o l u b l e c o m p o u n d ( X V I I I ) m e l t e d at 1 5 0 ° C . ( F o u n d : C 49.0, Η 4.4, Ν 14.3. C a l e . ( C i H N 0 ) : C 49.0, H 4.1, Ν 14.3). 4

6

1 8

4

5

4

1 6

4

8

Results ( 1 ) T h e r e seems to b e no significant difference i n p r o d u c t y i e l d s u s i n g either o z o n e - o x y g e n or ozone—nitrogen (e.g., E x p e r i m e n t s 14 a n d 1 5 ) . T h e s m a l l differences m a y b e the result of different rates of o z o n e delivery. ( 2 ) U s e of m e t h y l e n e c h l o r i d e as solvent consistently leads to h i g h e r y i e l d s of d e m e t h y l a t e d p r o d u c t ( V ) , a c c o m p a n i e d m o s t l y b y a decrease i n r e c o v e r e d s t a r t i n g m a t e r i a l . L o w e r o x y g e n y i e l d s are also o b s e r v e d at a l l temperatures except at — 7 8 ° C . ( 3 ) O z o n e appears to b e décomposée! b y p - n i t r o - N , N - d i m e t h y l a n i l i n e i n e t h y l a n d m e t h y l acetate at — 7 8 ° C (cf. E x p e r i m e n t s 3, 4, 5, a n d especially 26). ( 4 ) T h e o n l y t e m p e r a t u r e effect of a n y significance is o b s e r v e d i n e t h y l or m e t h y l acetate i n g o i n g f r o m — 4 0 ° to — 8 0 ° C ( E x p e r i m e n t s 4 and 9). ( 5 ) T h e h i g h e r y i e l d s of the f o r m a n i l i d e V I are a c c o m p a n i e d b y h i g h e r y i e l d s of the p e r o x i d e V I I . ( 6 ) S i n c e s t a r t i n g m a t e r i a l a l w a y s is r e c o v e r e d i n the e q u i m o l a r r u n s , the i n i t i a l attack of o z o n e m u s t b e s o m e w h a t s l o w e r t h a n one ( o r s e v e r a l ) of the subsequent steps i n v o l v i n g o z o n e a n d the p r i m a r y r e a c t i o n product(s). Discussion S e v e r a l authors ( I , 3, 4)

p r o p o s e t h a t o z o n e attacks amines electro-

p h i l i c a l l y at the n i t r o g e n lone p a i r . A d d i t i o n a l s u p p o r t for this comes f r o m the f o l l o w i n g o b s e r v a t i o n .

O z o n e passes u n c h a n g e d t h r o u g h s o l u -

t i o n of p - n i t r o - A ^ N - d i m e t h y l a n i l i n e ( I V c ) [or Ν,Ν-dimethylaniline ( I V a ) ] i n 7 0 % p e r c h l o r i c a c i d . D i l u t i n g the a c i d to about 2 0 - 2 5 % p r o d u c e s the y e l l o w color of u n p r o t o n a t e d a m i n e , a n d o z o n e is n o w a b s o r b e d q u a n t i tatively.

S i n c e the y e l l o w c o l o r of the free a m i n e ( I V c )

disappears i n


8.

K O L S A K E R AND T E i G E

Ozonation


107

c o n c e n t r a t e d a c i d s o l u t i o n , the a m i n e n i t r o g e n ( a n d not another p o i n t of the m o l e c u l e ) m u s t b e p r o t o n a t e d . NMR

studies s h o w that a m i d e s are p r o t o n a t e d at the o x y g e n a t o m ,

i n d i c a t i n g a l o w e r electron d e n s i t y at the n i t r o g e n a t o m i n a m i d e s t h a n e v e n i n p - n i t r o - N , N - d i m e t h y l a n i l i n e . A b o u t 5 0 % excess o z o n e h a d to be passed t h r o u g h a s o l u t i o n of Ν,Ν-dimethylbenzamide a n d as m u c h as 1 2 5 % excess t h r o u g h p - n i t r o - N , I V - d i m e t h y l b e n z a m i d e to ensure a c o m Downloaded by UNIV MASSACHUSETTS AMHERST on August 28, 2013 | http://pubs.acs.org Publication Date: June 1, 1972 | doi: 10.1021/ba-1972-0112.ch008

plete r e a c t i o n . S i n c e the p r o d u c t s of the o z o n a t i o n of I V o n l y i n d i c a t e s i d e - c h a i n o x i d a t i o n , i t is possible t h a t o z o n e i n s e r t i o n i n the

carbon—hydrogen

b o n d is the s t a r t i n g p o i n t of the m e c h a n i s m . A g a i n the a n s w e r m a y b e f o u n d i n N M R spectroscopy, b e a r i n g i n m i n d that the v a r i o u s resonance positions reflect the e l e c t r o n d e n s i t y near the h y d r o g e n a t o m i n a c a r b o n h y d r o g e n b o n d ( i n the absence of s t r o n g a n i s o t r o p i c g r o u p i n g s ) . c h e m i c a l shift difference for the m e t h y l protons i n g o i n g f r o m

The

N,N-di-

m e t h y l a n i l i n e to its conjugate a c i d is 0.45 p p m , i n d i c a t i n g a s o m e w h a t l o w e r e l e c t r o n d e n s i t y i n the c a r b o n - h y d r o g e n b o n d . T h e c h e m i c a l shift difference for t h e m e t h y l e n e g r o u p protons g o i n g f r o m t r i e t h y l a m i n e to d i e t h y l ether is a b o u t 1 p p m (12).

F o r b o t h these c o m p o u n d s s i d e - c h a i n

o x i d a t i o n takes p l a c e a l t h o u g h a m u c h l a r g e r e l e c t r o n d e n s i t y than i n amine-conjugate

change

a c i d p a i r is i n d i c a t e d b y N M R . T h u s , the

i n a b i l i t y of o z o n e to react w i t h the conjugate a c i d m u s t b e l i n k e d to the absence of the lone p a i r o n the a m i n e n i t r o g e n . F r o m these considerations i t seems safe to c o n c l u d e t h a t the

initial

attack of ozone o n amines takes p l a c e at the n i t r o g e n atom. T h i s is also l o g i c a l since the e l e c t r o p h i l i c o z o n e m o l e c u l e m u s t i n t e r a c t w i t h

the

center of highest n u c l e o p h i l i c i t y i n the substrate—viz., the lone p a i r of the n i t r o g e n a t o m . T h e secondary reactions w i l l t h e n b e d e t e r m i n e d b y the rest of the molecule. W h e t h e r amine oxide formation w i l l be competitive w i t h sidec h a i n o x i d a t i o n or not d e p e n d s o n the s t r e n g t h of the nitrogen—oxygen b o n d i n the p r i m a r y a d d u c t .

T h i s a g a i n is d e t e r m i n e d m a i n l y b y the

electron d e n s i t y at the n i t r o g e n a t o m of the substrate—viz., the s t r e n g t h of the base.

A l i p h a t i c amines are stronger bases t h a n t h e a r o m a t i c ( t r i -

m e t h y l a m i n e , pK

h

are f o r m e d

=

4.2, Ν,Ν-dimethylaniline, p K = 6

9.6).

A m i n e oxides

f r o m a l i p h a t i c a m i n e s , i n d i c a t i n g that t h e b o n d

between

n i t r o g e n a n d o x y g e n i n the p r i m a r y a d d u c t is covalent a n d stronger t h a n the o x y g e n - o x y g e n

b o n d , w h i c h breaks d o w n to f o r m a m i n e oxide a n d

m o l e c u l a r oxygen.

I n the a r o m a t i c amines s t u d i e d here the n i t r o g e n -

o x y g e n b o n d is w e a k e r t h a n a n o r m a l c o v a l e n t b o n d a n d p r o b a b l y is m o r e l i k e a c h a r g e transfer b o n d , a n d s e c o n d a r y attack o n a c a r b o n h y d r o g e n b o n d of the side c h a i n takes p l a c e as i n d i c a t e d i n R e a c t i o n s 1 a n d 3.


108


Table III.

Expt.


Solvent 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

CH2CI2 CH2CI2 EtOAc EtOAc MeOAc

CH2CI2 EtOAc EtOAc EtOAc MeOAc

CH2CI2 EtOAc EtOAc EtOAc EtOAc MeOAc

CH2CI2 EtOAc EtOAc MeOAc

CH2CI2 EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc

Ozonation Experiments Consumed IV

Temp., °C -78 -78 -78 -78 -78 -78 -40 -40 -40 -40 -40 0 0 0 0 0 0 25 25 25 25 -78 -40 0 25 -78 -40 0 25

a

Consumed 03

a

Produced" 02

Calcd.

Found

Calcd.

Found

Calcd.

3.0 4.3 1.3 0.51.0 1.5 5.0 7.4 6.3 4.1 4.0 4.7 7.3 8.8 4.2 4.3 4.0 4.1 8.2 3.8 2.6 4.2 2.9 5.1 5.1 5.1 0 1.4 1.6 1.1

7.6 8.0 1.3 0.51.0 1.5 5.0 7.3 5.6 4.2 4.1 4.8 7.3 8.7 4.2 4.3 4.1 4.3 8.4 3.8 2.8 4.2 2.5 5.0 5.0 5.0 0 1.4 1.7 1.1

5.0 6.9 2.6 1.02.0 2.7 5.6 8.3 7.5 5.1 5.0 5.2 8.1 9.9 4.7 4.8 4.7 4.6 9.5 4.6 3.1 4.7 5.2 8.4 8.8 9.4 0 1.6 1.7 1.3

10.0 10.0 10.0

5.0 6.9 2.6 1.02.0 2.7 5.0 6.7 6.0 4.3 4.3 4.5 6.2 7.7 3.8 3.8 3.8 3.9 7.3 3.6 2.4 3.9 4.6 6.6 7.4 8.4 0 1.2 1.2 1.0

a

Y i e l d s are g i v e n i n mmoles.

b

N o entry i n c o l u m n means v a l u e not

5.0 5.0 5.0 10.0 10.0 5.0 5.0 5.0 10.0 10.0 5.0 5.0 5.0 5.0 10.0 5.0 5.0 5.0 10.0 10.0 10.0 10.0 2.5 2.5 2.5 2.5

>

b

Found 7.9 6.5 4.04.7 4.4 4.5 6.9 4.1 4.1 3.9 9.0 4.1 4.0 3.4 4.0 4.3 3.3 7.9 8.4 6.1 6.9 2.1 1.9 1.5 1.3

checked.

A t t a c k other t h a n o n the a m i n o g r o u p a p p a r e n t l y does represent a c o m p e t i t i v e r e a c t i o n course w h e n the substituents o n t h e a r o m a t i c r i n g are less electronegative t h a n the n i t r o g r o u p .

T h i s is d e m o n s t r a t e d b y

the s t r o n g c o l o r a t i o n a n d tar f o r m a t i o n o b s e r v e d w h e n

A/,N-dimethyl-

a n i l i n e a n d p - c h l o r o - N , A - d i m e t h y l a n i l i n e are o z o n i z e d a n d b y the fact 7

that m o r e o z o n e is c o n s u m e d b y these c o m p o u n d s t h a n c a n b e a c c o u n t e d for b y side c h a i n o x i d a t i o n ( T a b l e I I I , E x p e r i m e n t s 1 a n d 2 ) .


8.


CH

J

+

r u

of p-A/itro-N,Ν-Dimethy'foniline

Ar-N

J

109

CH,

CH,

3

δ / δ _ Ar-N—0-0-0] • +

Ozonation

Ar-N

+ 000H"

+ OH"

•

0 (1) 2

CH,

XH,

V ι i*

XI

XII

A t t a c k of a s e c o n d m o l e of o z o n e o n X I I I , s i m i l a r to R e a c t i o n 1, w i l l Downloaded by UNIV MASSACHUSETTS AMHERST on August 28, 2013 | http://pubs.acs.org Publication Date: June 1, 1972 | doi: 10.1021/ba-1972-0112.ch008

t h e n l e a d to t h e N - m e t h y l f o r m a n i l i d e s V I ( R e a c t i o n 3 ) :

+

/

CH

Ar-N

3

+ OH"

Ar-N

V

XII

/

/ Ν

V

(2)

XIII

/ 3

,

3

C H

δ /δ _ / N---0-0-07 — •— — •• Ar-N — • Ar-N---0-0-0j —• Ar-N +

XIII + 0

CH,

+

3 3

+ 0 •H0 2

2

(3)

\HO

I OH

XIV

VI

A c c o r d i n g to R i e c h e et al. ( 13 ) a l i p h a t i c c a r b i n o l a m i n e s m a y react w i t h h y d r o p e r o x i d e s to f o r m α - a m i n o a l k y l p e r o x i d e s . H o r n e r a n d K n a p p ( 7 ) prepared di-a-aminoalkylperoxides from N-alkylanilines,

formaldehyde,

a n d h y d r o g e n p e r o x i d e s . I f t h e r e a c t i o n sequences l e a d i n g to these p e r oxides are those o u t l i n e d b e l o w , a s i m i l a r α - a m i n o h y d r o p e r o x i d e ( X V ) p r o b a b l y also is t h e p r e c u r s o r i n t h e f o r m a t i o n of t h e d i - a - a m i n o a l k y l p e r o x i d e o b t a i n e d i n t h e o z o n a t i o n of p-nitro-IVjIV-dimethylaniline.

+ /

CH

3

Ar-N

• OH"

Η00Η

"CH,

Ar-N

/

CH

q

\CH 00H 2

XII

XII

/

Ar-N

C

H

\C H

XV

CH,

3

\ N-Ar Ν

2

(A)

/ - 00- CH, VII

T h e p r o b l e m t h e n is t h e r o u t e to h y d r o g e n p e r o x i d e i n t h e present case. I n s e r t i o n of o z o n e i n t o a c a r b o n - h y d r o g e n b o n d has b e e n p o s t u l a t e d b y W h i t e a n d B a i l e y (14)

to e x p l a i n t h e o z o n a t i o n of b e n z a l d e h y d e s , b y

P r i c e a n d T u m o l o (15) i n t h e o z o n a t i o n studies of ethers, a n d b y B a t t e r bee a n d B a i l e y (16)

i n t h e i r studies o n t h e o z o n a t i o n o f a n t h r o n e . W e

postulate a s i m i l a r i n t e r m e d i a t e to e x p l a i n t h e f o r m a t i o n o f h y d r o g e n peroxide a n d subsequently the diaminoperoxide V I I .


110


/ Ar-N

ChU

3

C H

+

V

67

Oo

/

3

C H

3

Ar-NΝ

Ar-N—0-0-0,

\H OOOH 2

XVI (5) /

H

3

/ H


Ar-N I

• C ρ Η

3

Ar-N

+ Η00Η CH0

0-0-0Η VI

XVI

A s seen a b o v e , N - m e t h y l f o r m a n i l i d e is also p r o d u c e d b y this route.

The

r e a c t i o n routes p e r t i n e n t to o u r studies a r e s u m m a r i z e d i n S c h e m e 1.

N = CH \

+ OH'

2

χ + 2y•(z-y)

N Ν - C H , • 0,

/ N—CH 000H 2

N=CH

2

N—CHO + 0 + Γ

• OH

\

\

N-CH 000H

Y

2

2

z-y

z-y

N=CH

H0

2

2

N-CHO + H 0

I

2

2

/

\l —CH 00CH -N^ + 2 /

• OH'

2

2

H0 2

2y N = C H * OH' 2

N —CH,0H

N-H

+

CH 0 2

Scheme 1

F r o m these sequences the f o l l o w i n g c a n b e o b t a i n e d : C o n s u m e d s t a r t i n g m a t e r i a l : a = χ -\- y -\- 2y -\- (z — y) = χ C o n s u m e d o z o n e : b = χ + 2y + ζ +

(ζ — y) = χ + y +

2ζ,


2y

z,

8.

KOLSAKER AND

Ozonation

TEiGE

of

111

p-Nitro-N,N-Dimethylaniline

P r o d u c t i o n of o x y g e n : c = χ + 2y + (z — y) + (z — y) = χ -\- 2z, H e r e χ is the y i e l d o f d e m t h y l a t e d s t a r t i n g m a t e r i a l ( V ), y is the y i e l d o f the d i a m i n o p e r o x i d e V I I , ζ is the y i e l d o f N - m e t h y l f o r m a n i l i d e s ( V I ) . A c o m p a r i s o n o f the c a l c u l a t e d values for a, b, a n d c w i t h those o b t a i n e d i n the experiments, as seen f r o m T a b l e I I , are s h o w n i n T a b l e I I I . W h e n 2 m o l e e q u i v a l e n t s o f ozone are u s e d , a c o m p o u n d w h i c h a p p a r e n t l y i s a d i p e r o x i d e is f o r m e d Downloaded by UNIV MASSACHUSETTS AMHERST on August 28, 2013 | http://pubs.acs.org Publication Date: June 1, 1972 | doi: 10.1021/ba-1972-0112.ch008

molecular

formula

(see T a b l e I I ) .

of C i 6 H i N 4 0 , 6

E l e m e n t a l analysis indicates a

and

8

amounts o f p - n i t r o - N - m e t h y l a n i l i n e ( V c ) .

acid

hydrolysis

gives

small

F o r m a t i o n o f this d i p e r o x i d e

c a n b e r a t i o n a l i z e d as f o l l o w s :

/

H

C H ,

3

•/ Ar-N

Ar-N

\C H (

2

OOH

3

OH' CHOOH XVII

XV

(6)

C Ηο

/ 2 XVII

Ar-N

\

CΗο

\

3

/ CH

η-0

3

N-Ar \ / C H

+

2 Η,Ο

XVIII

T h e e n t i t y X V I I o f q u e s t i o n a b l e s t a b i l i t y is t h o u g h t t o d i m e r i z e t o the diperoxide X V I I I .

A m o d i f i e d r e a c t i o n m u s t t h e n be a p p l i e d t o E x p e r i

ments 22-25 ( S c h e m e 2 ) ( p .

112).

F r o m Scheme 2: C o n s u m e d s t a r t i n g m a t e r i a l : a = ζ + 2y

f

C o n s u m e d o z o n e : b = (z + 2y') + (z — 2 i / ) + 2y' = 2z + 2y' r

P r o d u c t i o n of o x y g e n : c = ζ + (ζ — 2y') + 2y = 2z, f

T h e v a l u e o f y' is n o w the y i e l d of d i m e r i c d i p e r o x i d e X V I I I . T h e results are e n t e r e d i n T a b l e I I I , E x p e r i m e n t s 22-25. T a b l e I I I s h o w s that the s t a r t i n g m a t e r i a l is a c c o u n t e d for w e l l . I n E x p e r i m e n t s 1 a n d 2 c o n s i d e r a b l e attack o n the a r o m a t i c n u c l e u s m u s t have t a k e n p l a c e since m u c h tar is f o r m e d i n these ozonations.

When

p - c h l o r o - N , N - d i m e t h y l a n i l i n e ( I V b ) is o z o n i z e d , m o r e attack takes p l a c e


112


\+ N = C H + OH 2

Ν—CH, • 0 ,

(z - 2 y ' ) + 2y' 'N—CH 000H

\

Γ

2


/

V

\

N=CH,+ OH"

2y'

N-CHO + 0

V

z'-2y'

+H 0

2

2

ζ -2y' \

ί' N-CH 000H

/

2y*

V.

N=CH + OH' 2

+

H 0 2

N-CH0 • H 0

I

2

/

2

2y*

N = CH,+ 00H"

2

2y'

2y' N=CH + 00H' 2

0

N = CH00H + OH' + 0?

3

2y'

2y* N = CH00H + OH"

2

0-0 \ / \ / N —CH CH-N

o-o

2y'

• 2 H.,0

Scheme 2

o n t h e a m i n e f u n c t i o n t h a n is t h e case w i t h t h e u n s u b s t i t u t e d

N,N-di-

m e t h y l a n i l i n e ( I V a ). T h i s is expected since t h e c h l o r i n e a t o m deactivates the r i n g f o r e l e c t r o p h i l i c attack. T h i s t r e n d is a c c e n t u a t e d i n g o i n g to t h e n i t r o s u b s t i t u t e d d i m e t h y l a n i l i n e ( I V c ) , w h e r e r i n g attack is n o t observed. T h e a m o u n t o f ozone u s e d f o r r i n g attack is n o t a c c o u n t e d f o r i n o u r expressions; therefore t h e values f o r b a n d c i n E x p e r i m e n t s 1 a n d 2 w i l l be erroneous. T h e large d i s c r e p a n c y i n c o n s u m e d o z o n e a n d o z y g e n y i e l d w h e n o z o n i z i n g i n e t h y l o r m e t h y l acetate at — 7 8 ° C ( E x p e r i m e n t s 3-5, 22, a n d 2 6 ) cannot b e a c c o u n t e d f o r b y a n y o f o u r schemes. b i l i t y o f ozone attack o n t h e solvents cannot b e e x c l u d e d .

T h e possi

However, we

h a v e n o t b e e n a b l e to d i s c o v e r a n y p r o d u c t a r i s i n g f r o m o x i d a t i o n o f t h e solvent. O z o n a t i o n of e t h y l acetate w a s s h o w n b y P r i c e a n d T u m o l o to b e n o n q u a n t i t a t i v e w h i l e o z o n e is q u a n t i t a t i v e l y a b s o r b e d at — 78 ° C w h e n p-nitro-N^N-dimethylaniline

( I V c ) is d i s s o l v e d i n e t h y l acetate.

p r o b l e m has to b e left o p e n at this stage o f o u r research.


This

8.

KOLSAKER AND TEIGE

Ozonation


113

Literature Cited 1. 2. 3. 4.

Bailey, P. S., Chem. Rev. (1958) 58, 925. Henbest, H. B., Stratford, J. W.,J.Chem. Soc. (1964) 711. Shulman, G. P., Can. J. Chem. (1965) 43, 3069. Bailey, P. S., Mitchard, D. Α., Khashab, A.-I. Y., J. Org. Chem. (1968) 33, 2675.


5. Bailey, P. S., Keller, J. E., Mitchard, D. Α., White, Η. M., ADVAN. C H E M .

6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.

SER. (1968) 77, 58. Kolsaker, P., Meth-Cohn, O., Chem. Commun. (1965) 423. Horner, L., Knapp, Κ. H., Ann. (1959) 622, 79. Bailey, P. S., Reader, A . M., Chem. Ind. (1961) 1063. Shirley, D. Α., "Preparations of Organic Intermediates," p. 221, Wiley, New York, 1951. Villiger, V., Chem. Ber. (1909) 42, 3534. Morley, J. S., Simpson, J. C. E., J. Chem. Soc. (1948) 360. Spiesecke, H., Schneider, W. G., J. Chem. Phys. (1961) 35, 722. Rieche, Α., Schmitz, E., Beyer, E., Chem. Ber. (1959) 92, 1206. White, Η. M., Bailey, P. S., J. Org. Chem. (1965) 30, 3037. Price, C.C.,Tumolo, A . L., J Amer. Chem. Soc. (1964) 86, 4691. Batterbee, J. E., Bailey, P. S., J. Org. Chem. (1967) 32, 3899.

RECEIVED June 7, 1971. Work supported by a grant from Det Videnskapelige Forskningsfond av 1919.


Ozone Reactions with Organic Compounds

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