Reaction of alcohols containing vicinal ether
subsituents with mercury(II) oxide and iodine
Andre Goosen, Jennifer Jones, Hugh A.H. Laue, Antoine P.B. Maasdorp, and
Cedric W. McCleland
Irradiation of aliphatic vicinal hydroxy-ethers in the presence of
mercury(ll) oxide and iodine gives rise to the formation of
dioxolans and carbonyl compounds, through closure or
fragmentation of the appropriate intermediates generated after
intramolecular y-hydrogen abstraction. Phenyl substituents on
the vicinal carbons of vicinal hydroxy ethers promote exclusive
α-fission under the reaction conditions.
S Atr
J. Chem.,
1979, 32,182-186
Bestraling van alifatiese visinale hidroksi-eters in die
teenwoordigheid van kwik(ll)oksied en jodium lei tot die
vorming van dioksolane en karbonielverbindings deur
ringsluiting of splyting van die geskikte tussenproduk, wat
gevorm is na y-waterstofonttrekking. Fenielsubstituente op die
visinale koolstofatome bevorder uitsluitlik α-splitsing onder die
reaksietoestande.
S.-Alr.
Tydskr.
Chem.,
1979,32,182-166
Andre Goosen.* Jennifer Jones, Hugh A.H. Laue,
Antoine P.B, Maasdorp. and Cedric W. McCleland
Department of Chemistry, University of Port Elizabeth,
P.O. Box 1600, Port Elizabeth 6000.
•To whom all correspondence should be addressed
Rcwived 18 June 1979
Continuing the study 1 of the effect of vicinal substituents on
the reactions of alkoxy-radicals, this paper reports the effect
of vicinal ether substituents. The major competing processes of alkoxy-radicals with vicinal ether substituents
would be either the fragmentation reaction (Scheme 1,
path a), or 1,3-dioxolan formation via a 1,5 hydrogen atom
transfer process (Scheme 1, path b).
Mihailovic and his coworkers 2 found that 1,3-dioxolans
are the major products when acyclic vicinal ethers are
heated with lead tetraacetate, whereas hydrogen abstraction, to form the 1,3-dioxolan, and fission processes occur
to approximately the same extent with 2-hydroxymethyltetrahydropyran. Utilizing the same reagent, Morand and
Kaufmann 3 rationalized their products derived from 5amethoxy-6/i-hydroxy- and 5a-hydroxy-6/?-methoxysteroids
as arising from the C - C bond cleavage reaction. Ultraviolet photolysis4 of methoxyethanol in the liquid phase
gave mainly products arising from C - O H and C - O C H 3
fission and very little as a result of the fragmentation process. It has recently been reported 5 that 2-phenoxyethanols
react with mercury(II) oxide and iodine to form A r , - 5 and
A r 2 - 6 products.
In this study, the alkoxy-radicals were generated by
irradiating the alcohols in the presence of mercury(II) oxide
and iodine. Excess iodine in the reaction mixture functioned as a free radical trap. 6 The use of t-butyl hypoiodite
as a 'positive' iodinating reagent was not considered since it
has been shown that this reagent promotes ester formation.7
Prior to undertaking the photolytic reactions of vicinal
hydroxy-ethers with mercury(II) oxide and iodine, the stability of possible reaction products towards the reagent was
investigated. It has been established8 that aldehydes in
aprotic solvents are stable to mercury(II) oxide and iodine
in the dark and, upon irradiation, they are slowly converted
to complex mixtures. The stability of dioxolans is dependent upon the nature of the substituent on the 2-position.
With an alkyl group on the 2-position, the dioxolans are
relatively stable to mercury(II) oxide and iodine in the dark
below 40 °C. Above 40 °C they react completely with
mercury(II) oxide and iodine within a few hours. Since
water could be produced in the reaction mixtures, an equivalent of water was added to the dioxolan reaction mixtures
and shown to enhance their rate of decomposition slightly.
183
S. Afr. J. Chem., 1979,32 (4)
S c h e m e 1 Competing alkoxy-radical processes in
vicinal hydroxy-ethers
OH
R
R
Ο
0
S c h e m e 2 F o r m a t i o n o f v i c i n a l h y d r o x y - e s t e r s from
dioxolans
Ϊ'
J — L
• CH,
path b
I
o ^ o
|
I
R
2
-J
CH2
+
path a
B1
0
R2
Γ
OH
C" "
,CH
Rl
R
CH — R
R2
'
CH^
Ο
+
3
R
C H 0
OH
RJ
R
7
R ' - CHI— R
,R
-o
-CO — R 2
?
,"
A .= Η
R 3 : Η"
R- Pr" R?
• PJ
: R = R"= Η
3
R - R - CH } , R τ R"r Η
R^
= R 3 - R"= Η
Ρ :C 6 H 5 CH 2
R
C H
?
3
R = R = Η , ' R= " = 6 5
4
R = Pr", R ? = ΗR ' = R = C T H T
R = PR" R ;
3
R" - CCΗ C
R = R" =CH,, R
R1 : R 3 : R 4 ϊ c Η
R? = Μ
R
c=o
1
6^
=H3 - C 6 H 5 ,
RJ - R4 = Η
Several 2-alkoxy-alcohols ( l a — l j ) were stirred in the
dark for a period and then irradiated. Aliquots were withdrawn at intervals and analysed (g.l.c.). The respective intermediate radicals (3) and (5) generated from the hydroxyethers (la and lb) by paths (a) and (b) (Scheme 1) would be
expected to exhibit similar stabilities. The reaction mixture
from 2-methoxyethanol (la) gave, after work-up, 1,3dioxolan. All efforts to detect formaldehyde were unsuccessful. Similarly, 2-butoxypentan-l-ol (lb) was converted into the dioxolan more readily than it underwent
fission. However, both butanal and dioxolan were slowly
formed in the dark, and irradiation rapidly increased the
yields of both products. Hence, it is proposed that both products were formed in the dark from the alkoxy-radical
generated by thermal homolysis of the hypoiodite. Prolonged irradiation caused the yield of 2,4-di-n-propyl-l,3dioxolan (6, R 1 = R 3 = nPr, R 2 = R 4 = H) to decrease, and
2-hydroxypentyl butanoate was formed. In a separate
experiment, the dioxolan was also converted into the ester
upon irradiation in the presence of excess mercury(II) oxide
J
'
CH,
OH
I
0
"'2
and iodine, possibly via the route (path a) outlined in
Scheme 2.
2-Butoxyethanol (lc), upon treatment with mercury(II)
oxide and iodine, slowly produced butanal and 2-n-propyl1,3-dioxolan in the dark; the relative rates of formation
varied from reaction to reaction. However, when the reaction mixture was irradiated, the dioxolan was produced
much more rapidly. Since this dioxolan is stable in the dark
and decomposes slowly upon irradiation, it cannot be the
source of the butanal. Thus it seems more likely in this case
that both the butanal and dioxolan are formed from a common intermediate (7) after the abstraction reaction. The
reaction of 2-isopropoxyethanol (Id) produced qualitatively similar results when anhydrous calcium sulphate was
added, since the dioxolan (6, R 1 = R 2 = CH 3 , R 3 = R 4 = H)
was shown to be unstable when water was present in the
reaction mixture. 2-Benzyloxyethanol (le) behaved similarly, but prolonged reaction converted the rapidly formed
dioxolan (6, R 1 = C 6 H 5 C H 2 , R 2 = R 3 = R 4 = H) into 1,2ethanediol monobenzoate. Since this rearrangement occurred in the dark with mercury(II) oxide and iodine when
water was present, it is suggested to be a heterolytic process (Scheme 2, path b). A similar mechanism has been proposed 10 for the rearrangement of dioxolans to diol
monoesters with iodine monochloride.
These results thus show that the abstraction reaction
(Scheme 1, path b) to form the dioxolan occurs more
readily than α-cleavage (Scheme 1, path a) with aliphatic
systems. Since the dioxolans are stable under the reaction
conditions in the dark and, under irradiation, decompose
slowly to afford esters, it is concluded that the carbonyl
compounds must form from a competitive fragmentation of
the iodo-intermediate (7) generated by abstraction; iodoproducts (R 1 R 2 CHI) would be expected from the acleavage process.
In order to assess the effect of phenyl groups on the reaction, several l,2-diphenyl-2-alkoxyethanols (If—li) were
synthesized. All these compounds except li were synthesized from stilbene oxide. l,2-Diphenyl-2-benzyloxyethanol (li) was synthesized from benzoin (Scheme 3).
These hydroxy-ethers (If—li) react slowly in the dark
with mercury(II) oxide and iodine, to produce benzaldehyde, and the rate of benzaldehyde formation was accelerated when the reaction mixture was irradiated. Prolonged irradiation oxidized the benzaldehyde to benzoic
184
S.-Afr.
Scheme 3 Synthesis of 1,2-diphenyl-2-benzyloxyethanol
ydskr. Chem., 1979, 32 (4)
Table 1 G.l.c. operating conditions 8
Temperatures/°C
Column
A
Condition
Injection port
Detector
A1
100—185"
200
230
A2
200
250
250
A3
40—100"
130
200
A4
230
250
B1
45 — 180"
8 0 — 125 b
180
230
B2
80
180
200
CI
150
200
230
C2
100—135"
250
250
C3
125 — 2 1 5 b
250
250
Β
C
Oven
• Ν, carrier gas at 25 — 35 ml/min.
b
Programmed at 10 °C/min.
acid. No dioxolans were produced. Furthermore, no
dihydrobenzofurans (8), which could have formed by an
intramolecular cyclization process, were detected in the
CΗ R| R2
Θ
In order to assess the role of a single phenyl substituent,
2-phenyl-2-benzyloxyethanol (lj) was synthesized from
styrene oxide and benzyl alcohol. Its structure was confirmed by its failure to undergo oxidation with manganese
dioxide and by the double proton lowfield n.m.r. shift of the
acetate derivate. Upon reaction with mercury(II) oxide and
iodine, the hydroxy-ether (lj) produced mainly benzaldehyde, indicating that even one phenyl group on the 2-position promotes the cleavage reaction (Scheme 1, path a) at
the expense of the abstraction process (Scheme 1, path b).
It has been shown that the C - C fragmentation reaction
of alkoxy-radicals is facilitated by the presence of vicinal
hydroxy,8 carbonyl, 11 and Λ'-acyl substituents, 12 whereas
vicinal acetoxy-groups 13 impede the fragmentation. With
substrates which contain a vicinal ether group and in which
there is free rotation about all the bonds, intramolecular
hydrogen abstraction is the dominant process. This demonstrates that, even though there is a smaller probability of
attaining a favourable configuration for hydrogen abstraction, this process is nevertheless favoured over the C - C
bond fragmentation process. The role of the phenyl substituents on the 1,2- or 2-positions of 2-alkoxyethanols in promoting C - C bond fragmentation, is being investigated.
Experimental
M.p.s were determined with a Kofler hot-stage apparatus. G.l.c. analyses were carried out with a Becker Packard 420 gas chromatograph
with flame ionization detector. Column A (130 X 0,3 cm) contained 10%
SP 1200/1% H j P 0 4 on Chromosorb W A W 8 0 — 1 0 0 mesh, column Β
(145X0,3 cm) Carbowax 20M on Chromosorb Μ 8 0 — 1 0 0 mesh
(15:85), column C (127 X 0,3 cm) Apiezon L on Chromosorb Ρ 8 0 —
100 mesh (15:85), and column D (136 X 0,3 cm) 4% Ethofat/2% isophthalic acid on Chromosorb T. Quantitative analyses were carried out
with internal standards and the relative peak areas obtained with an
Autolab 6300 digital integrator. I.r. and n.m.r. spectra were determined
with Unicam SP 1000 and Perkin Elmer R12A spectrometers respectively.
1,2-Diphenyl-2-benzyloxyethanol
(1 i)
l,2-Diphenyl-l-oxo-2-chloroethane (7 g: 0,03 mol) was added to silver
nitrate (10 g; 0.058 mol) in benzyl alcohol and the mixture was stirred
for 24 h. The filtered reaction mixture was concentrated, taken up in
ether, washed (HC1, N a , C 0 3 ) and dried, to give an oil (4,2 g) which was
reduced (LAH). Chromatography of the resultant product gave a solid
which crystallized from petroleum ether (60 — 80 °C) as needles of 1,2diphenyl l benzyloxyethanol,
m.p. 6 3 — 6 5 °C, <S(CDC13) 7,17 (m,
15H), 4,82 (m, 1H), 4.39 (m, 3H), and 2,35 (d, 1H, OH), v ^ (CHCL,)
3 600 cm" 1 (Found: C, 82.7; H. 6,65%; [ A / - C 6 H 5 C H 2 J + , 213. Calc.
for C 2 1 H 2 0 O 2 ; C. 82,85;H, 6,62%; M. 304.)
2-Alkoxyethanols
The alkoxyethanols prepared by standard procedures were 2-phenyl-2benzyloxyethanol,
b.p. 1 6 8 — 1 7 0 ° C / 3 mm., <5(CDC13) 7,3 (d. 10H),
4,45 (m, 3H). 3,65 (m, 2H), and 2,5 (s, OH) (Found: C, 79,0; H, 6,65%;
M \ 228. Calc. for C 1 5 H 1 6 0 2 : C, 78,9; H, 8,1%; M, 228); 2-butoxypentan-l-ol. b.p. 72 °C/2,5 mm, t5(CCl4) 3,4 (m, 5H), 2,7 (s, OH), and
1,15 (m, 14H); \,2-diphenyl-2-methoxyethanol,
m.p. 97 °C, <5(CDClj)
7,15 (m, 10H), 4,88 (d, H), 4,3 (m, H), 3,2 (m, 3H), and 2,4 (s, OH), v m i i i
(CHClj) 3 600 cm"' (Found: C, 78,35 ; H , 7,0%; [ M - O H 1 + , 211. Calc.
for C 1 S H ] 6 0 2 : C. 78,9; H, 7,1%; M, 228);
\2-diphenyl-2-butoxyethanol, m.p. 3 6 — 3 8 °C, <5(CC14) 7,15 (s, 10H), 4,7 (d, H), 4,25 (d, H),
3,25 (m, 2H), 2,2 (s, OH), and 1.2 (m, 7H),
(CHC1 3 ) 3 600 c m " 1
(Found: [ J W - n B u O ] + , 197. Calc. for C l s H 1 2 0 2 : M, 270); and 1,2diphenyl-2-isopropoxyethanol,
m.p. 5 4 — 5 6 °C, <5(CC14) 7,15 (m, 10H),
4,45 (m, 2H), 3,4 (m, H), 2,7 (s, OH), and 0,95 (m, 6H). P m n i (CHC1 3 )
3 6 0 0 c m " 1 (Found: C, 79,5; H, 7,85%; [ J W - i P r O ] + , 197. Calc. for
C 1 7 H M 0 3 : C, 79,65: H, 7,86%; M, 256).
Table 2 Reaction of 2-benzyloxyethanoi (1e) a
Yield/%
Time/h
Benzaldehyde
Dioxolan
Ethanediol
monobenzoate
Starting
material
0
0
0
100
4
11
0
80
5
12
0
78
16
32
0
60
21
50
0
55
1.25
25
53
0
46
2.0
36
47
8
36
2.75
34
44
10
23
8.25
30
33
39
5
8
69
0
0b
0,25"
0,50"
0,75
1.0
11.75
31
* G.l.c. on column A1 (retention times in parantheses): starting material
(510 s), 1,2-ethanediol monobenzoate (805 s), internal standard [nix)
(136 s), and on column C1:2-phenyl-1,3-dioxolan (750 s),
benzaldehyde (223 s), internal standard (mi) (141 s).
b
In the dark.
S. Afr. J. Chem., 1979, 32 (4)
185
Reaction of vicinal hydroxy-ethers with mercury (ίΓ) oxide and iodine
General procedure
The hydroxy-ether (ca 3 mmol) in CC1 4 (50 ml), contained in a Pyrex
flask, was treated with red mercury(II) oxide (5 mmol) and iodine
(10 mmol), stirred in the dark ( 1 — 3 h) and irradiated (3 — 24 h) with a
Table 3 Reaction of 2-isopropoxyethanol ( i d ) in the
presence of calcium sulphate 3
125 W mercury vapour lamp through water maintained at room temperature ( < 3 0 -C). A liquid ( 1 — 5 ml) withdrawn at intervals, were
quenched with aqueous 20% sodium thiosulphate (10 ml) and added to
the g.l.c. internal standard ( 1 — 5 ml). The g.l.c. internal standards were
10—20% solutions of either m-xylene (nix) or nitrobenzene (nb) in
CC1 4 . The concentration of starting materials or products was obtained
from standard curves of relative peak areas. The results are summarized
in Tables 2 — 9 .
2-Methoxyethanol
Yield/%
Quantitative g.l.c. analysis on column B2 I (retention times in paren-
Time/h
Acetone
Dioxolan
Starting material
0
0
0
0
23
30
100
93
78
72
37
12
4
0b
l,0 b
2,0 b
2,25
2,75
13
27
21
32
53
3,25
3,75
4,75
8
b
55
66
67
48
61
Table 6 Reaction of 1,2-diphenyl-2-methoxyethanol (1f) a
Yield/%
Time/h
b
Starting material
0
9
23
31
34
(24)
50
46
34
0
1
33
52
100
91
44
15
50
59
39
41
9
6
5
5
2
4
0b
0,5 b
0,75
1,0
1,25
1,50
1,75
2,25
3,75
5,75
48
35
38
• G.l.c. on column A3 (retention times in parentheses): starting materia!
(762 s), butanal (209 s), 2-propy 1-1,3-dioxolan (551 s), internal
standard (mx) (580 s).
b
In the dark.
Time/h
Starting
material
0b
1"
1,125
100
93
21
1,25
1,75
4,25
11
9
7
7
7
7,25
24,0
48,0
a
b
0
Dioxolan
0
0
2,0
15
17
19
18
8
74
78
19
18
0
71
46
31
6
0
Ester
0
0
0
G.l.c. on column A2 (retention times in parentheses): starting material
(888 s), 4,5-diphenyl-l ,3-dioxolan (750 s), benzaldehyde (44 s),
internal standard (nb) (69 s).
In the dark.
Time/h
0b
0,5 b
1,0"
l,5 b
1,75
2,0
2,5
a
Benzaldehyde
Starting material
0
11
20
27
100
75
65
58
78
75
69
7
5
2
G.l.c. on column A2 (retention times in parentheses): starting material
(944 s), benzaldehyde (45 s)14,5-diphenyl-2,2-dimethyl-l,3-dioxolan
(750 s), internal standard (nb) (69 s).
In the dark.
Table 8 Reaction of 1,2-diphenyl-2-butoxyethanol (1g) a
Yield/%
0
0
0
6
Time/h
0"
0,5 b
17
48
65
72
1,5"
1,75
2,0
2,25
2,75
89
G.l.c. on column A4 (retention times in parentheses): starting material
(921 s), 2,4-di-n-propyl-1,3-dioxolan (749 s), butanal (228 s), 2hydroxy pentyl butanoate (1041 s), internal standard (mx) (574 s).
In the dark.
0
Yield/%
b
Butanol
63
60
Table 7 Reaction of 1,2-diphenyl-2-isopropoxyethanol
(1h) a
Table 5 Reaction of 2-butoxypentanol (1b) 3
Yield/%
85
83
1,5"
2,5 b
Yield/%
Dioxolan
3,25
4,0
1,0"
a
Butanal
100
88
66
2,75
3,0
0
9
16
19
25
89
87
0
G.l.c. on column B1 (retention times in parantheses): starting material
(650 s), 2,2-dimethy!-l,3-dioxolan (291 s), acetone (146 s), internal
standard (TO) (551 s).
In the dark.
Time/h
Starting material
0,5"
0
Table 4 Reaction of 2-butoxyethanol (1c) a
Benzaldehyde
b
0
b
Benzaldehyde
Starting material
0
13
34
100
68
64
89
89
84
0
0
0
78
0
G.l.c. on column A2 (retention times in parentheses): starting material
(1775 s), benzaldehyde (45 s), internal standard (nb) (69 s).
In the dark.
186
S.-Afr.
Table 9 Reaction of 2-phenyl-2-benzyloxyethanol (1j) a
Time/h
0»
0,5"
l,0 b
1,5"
1,75
2,0
3,5
5,0
6,5
Benzaldehyde/%
References
1
0
17
30
36
49
51
60
67
61
• G.l.c. on column C2 (retention times in parentheses): starting material
(500 s), benzaldehyde (426 s) and the internal standard (mx) (331 s).
b
In the dark.
theses): starting material (474 s), 1,3-dioxolan (149 s), internal standard
(mx) (420 s)] confirmed the formation of 1,3-dioxolan (27%).
Acknowledgement
The authors thank the Council for Scientific and Industrial
Research for financial support.
ydskr. Chem., 1979, 32 (4)
2
3
4
5
6
7
8
9
10
11
12
13
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