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
