CHEMISTRY OF HETEROCYCLIC COMPOUNDS 5

SYNTttES1S AND REACTIONS OF t tALOGEN-CONTAINING COMPOUNDS OF THE

FURAN SERIES

I. Synthes is of a -Subs t i t u t ed T e t r a h y d r o f u r a n s

N. A. Ryabinin and I. P. Kolenko

Khimiya G e t e r o t s i k l i c h e s k i k h Soedineni i , Vol. 4, No. 1, pp. 8 - 1 0 , 1968

UDC 547. 722.3 '727:542. 958.2

A study of the interaction of a-chlorotetrahydrofuran with Grignard reagents and with secondary amines.

The fundamenta l methods for obtaining t e t r a h y d r o - furan and i ts homologs a r e the hydrogena t ion of furan compounds [1-31 and the cye l i za t i on of 1 , 4 - d i o l s and of

1 , 4 - h a l o h y d r i n s [4]. Not long ago Bel ' ski i and Shuikin [5] d e s c r i b e d a method for the ca ta ly t i c syn thes i s of t e t r a h y d r o f u r a n h o m o l o g s , which c o n s i s t e d of the hydrogena t ion of 1 - f u r y l - 3 - a l k a n o l s in the vapor phase . In addit ion to these me thods , a - s u b s t i t u t e d t e t r a h y -

d r o f u r a n s may also be obtained by the i n t e r ac t i on of

c~ -eh lo ro te t r ahydro fu ran (I) with nue leophi l i e r e -

agents .

The a im of the p r e s e n t inves t iga t ion was to study

the i n t e r ac t i on of I with a l k y l ( a r y l ) m a g n e s i u m ha l ides and s e c o n d a r y amines . The G r i g n a r d r e a g e n t s w e r e

p r e p a r e d by the usual method , and pen ta f luo ropheny l - m a g n e s i u m ch lo r ide by the p r o c e d u r e d e s c r i b e d in

the l i t e r a t u r e [61. The r e a c t i o n of I with G r i g n a r d r e a g e n t s p r o c e e d e d acco rd ing to the usual pa t t e rn .

ether Q']/N RMgX * ~ + MRCIX,

C~ R

X = Br; C1; R = propyl, butyl, amyl, hexyl, phenyl, o-tolyl, m-trifluoromethylpbenylene, pentafluoro- phenyl.

The speed of the i n t e r ac t i on of I with a lkylmagne~ s lum ha l ides depends on the nuc l eoph i l i c i t y of the r e a g e n t , and on the t e m p e r a t u r e and concen t r a t i on of the r e a c t i n g subs tances . Thus , I r e a c t s v e r y v io -

len t ly with p r o p y l - and bu ty lmagnes ium b r o m i d e s , and it is n e c e s s a r y to conduct the r e a c t i o n with in- t ens ive s t i r r i n g and good cool ing. The r e a c t i o n p r o -

c eeds m o r e smooth ly when di lu ted e t h e r e a l so lu t ions a r e employed . The i n t e r a c t i o n s of a m y l - and hyxy l - m a g n e s i u m b r o m i d e s , and of a r y l m a g n e s i u m ha l ides , with I p r o c e e d m o r e smooth ly and do not r e q u i r e i n -

t ens ive cool ing. The r e a c t i o n m i x t u r e s w e r e p r o c e s s e d a c c o r d i n g

to the usual methods . The s epa ra t i on of pure a lky l - t e t r a h y d r o f u r a n s was a c c o m p l i s h e d by r ec t i f i c a t i on under n o r m a l or r educed p r e s s u r e , depending on the

boi l ing point of the subs tance . The tab le s u m m a r i z e s the data on the y i e ld s of alkyl d e r i v a t i v e s of t e t r a h y -

d ro fu ran and t h e i r e l e m e n t a r y ana lyses .

F r o m the i n t e r ac t i on of I with pyr id ine , a q u a t e r - nary sa l t m e l t i n g at 219 ~ ~ C (deeomp. ) is obtained. With m o r p h o l i n e , I f o r m s the c o r r e s p o n d i n g amine

with an 80% yield. With an e x c e s s of d i e thy l amine , I r e a c t s to fo rm c~-(N, N - d i e t h y l ) - a m i n o t e t r a h y d r o f u r a n , but the y ie ld is lower .

It is known f r o m the l i t e r a t u r e [7,8] that o~,f l-di- c h l o r o t e t r a h y d r o f u r a n r e a c t s with nuc leoph i l i c r e -

agents., such as a l c o h o l a t e s , a l k y l ( a r y l ) m a g n e s i u m - ha l ides , and s e c o n d a r y a m i n e s , to f o r m the c o r r e - sponding c r - s u b s t i t u t e d - f i - c h l o r o t e t r a h y d r o f u r a n s with

m o r e than 80% yield. In this c a se , the s ide r e a c t i o n leading to the s e p a r a t i o n of a m o l e c u l e of hydrogen ch lo r ide is p r a c t i c a l l y s u p p r e s s e d .

As may be seen f r o m the table , the y ie ld of a - s u b -

s t i tu ted t e t r a h y d r o f u r a n s , obta ined by the i n t e r ac t i on

of I with a l k y l ( a r y l ) m a g n e s i u m ha l ides and s e c o n d a r y am ines , is s ign i f i can t ly lower . Th is is e s p e c i a l l y

no t i ceab le when the r e a c t i o n is conducted with s t r o n g nuc leophi l i c r e a g e n t s . Evident ly , th is may be ex - p la ined by the p r e s e n c e of compe t ing r e a c t i o n s , such

as the s e p a r a t i o n of a m o l e c u l e of hydrogen c h l o r i d e , which leads to the f o r m a t i o n of 2 , 3 - d i h y d r o f u r a n .

EXPERIMENTAL

a-Propylter.rahydrofutan (II). 106.5 g (1 mole) of I in 250 ml ab- solute ether was added at 0~ ~ C and under vigorous stirring in the course of 1-1 1/2 hr to a Grignard reagent prepared from 24 g (lg-at) of Mg and 122 g (1.1 mole) of ptopyl bromide in 300 ml of absolute ether. After adding the total quantity of I, the reaction temperature was gradually raised to room conditions, and then the reaction mix- ture was boiled for 1/2-1 hr, thus eliminating 5% of HCL Yield 66.7%.

a-Butyletrahydrofuran was obtained by an analogous method. Compounds IV-IX were synthesized under somewhat different condi- tions. After adding the ethereal solution of I to the Grignard reagent, the temperature was raised to boiling, most of the ether distilled off, and the reaction mixture maintained for 1 3./2-2 hr at 800-90 ~ C. This was followed by treatment in the usual way.

a-(N, N-Diethyl)aminotetrahydrofutan (X). 82 g (1.8 mole) of diethylamine in 160 ml of absolute ether was poured into a t~ee- necked reaction vessel provided with a dropping funnel, a stirrer, and a reflux condenser. Through the dropping funnel and under vigorous stirring and cooling by ice-water, 60 g of I in 150 ml of absolute ether was added drop by drop in the course of 1 hr. The reactionmass was allowed to stand overnight. The precipitated crystals were fil- tered-off, washed twice with ether, and the ethereal solution distilled off. Yield 40%.

By an analogous procedure, a-(N-morpholyl) tetrahydrofuran (XI) is obtained with an 80% yield.

Cr~

No.

of

Bp,

*C (p

ress

ure,

pr

oduc

t C

ompo

und

mm

)

III

~fl-

-c~N

9

IV

~'c

aH

n

V

~--~

-- C

6Hla

cNa

F F

X

~-'~_

NlC~X

O 2

F--

] ,.p

-c,.

Xi

-N

o

Yie

lds

and

Pro

pert

ies

of ~

-Sub

stit

uted

Tet

rahy

drof

uran

s

131-

-131

.5 (7

57

158-

-159

(75

4)

62--

63 (

12)

73.5

--74

(7)

69.5

--70

(3)

82--

83 (

3)

96.5

--97

(12

)

90--

91 (

ll)

0.86

28

0.86

26

0.86

20

0.86

77

1.031

0

1,03

29

1.23

70

1.45

14

2O

n D

.425

0

A31

5

.436

0

.438

5

,532

0

1,536

2

1.46

76

1.45

08

MRD

Foun

d C

alcu

- ta

red

33.8

0 34

.32

38.4

4 38

.97

43.0

8 43

.62

47.2

4 47

.27

44.4

8 44

.77

48,9

1 ~4

9,22

i 48

.4~

48.7

1

4~.1

2 43

.59

Em

piri

cal

form

ula

C17H

140

C8H

160

C9H

,80

CloH

2oO

CIo

H20

Cl1

H1

40

CnH

.FsO

CmH

zFsO

Found, 9

o

7753

.09~

_ 7 iio

76

.19

12.6

0 I

--

76.0

a

76.9

2 12

.80

[ --

76

,91

80.9

9 8.

26 /

--

] 81.

08

81,5

8 8,

77 ]

--

81,4

2

61.2

6 4.

98 t

--

26.3

9 61

.11

/ 50

.3

2.83

[

--

/39.

83 5

0.4

67.0

5 I 1

.73

9.60

67

.13

60.5

9,

30 I

8.7

9 61

.15

61--

62

(12)

97--

98 (

12)

0.93

94

1.46

98 4

2.46

1.04

28

1.47

52 4

2.20

42.7

6 C

aHI7

NO

~249

Ca

H15

NO

2

Cal

cula

ted,

%

" '

"

12.2

8 /

12.5

0 [

12.0

7 l

7,1j ~

26.1

9.79

I

--

Yie

ld,

%

66.7

64.2

58.0

72.4

69.9

72.6

60.6

37.1

40

80.5

> 0 O

r~

CHEMISTRY OF HETEROCYCLIC COMPOUNDS 7

REFERENCES

I. J. Cloke and O. Ayers, J. Am. Chem. Soc., 56, 2144, 1934.

2. A. A. Ponomarev, Synthesis and Reactions of Furanoid Compounds [in Russian], Izd-vo SGU, Sara- tov, 101, 1960.

3. A. A. Ponomarev , Z. B. Til and V. A. Seda- vkina, ZhOKh, 33, 3951, 1963.

4. A. Gipp, B e r . , 18, 3275, 1885. 5. I. F. B e l ' s k i i and N. I. Shuikin, DAN, 128,

945, 1959.

6. N. N. Vorzhtsov J r . , V. A. Barkhash , N. G. Ivanova, S. A. Anichkina, and O. I. Andreevskaya , DAN, 159, 125~ 1964.

7. H~ Normant, C. r . , 226, 185, 1948. 8. L. Crombie and S. Harpe r , J . Chem. Soc . ,

1714, 1950.

29 March 1966 Chemical Insti tute of the Ura l Branch AS USSR, Sverdlovsk