3-Bromo-2,5-dihydrofuran-2-one and 4-bromo-2,5-dihydrofuran-2-one

Article abstract of DOI:10.1135/cccc19991154

Although 3-bromo-2,5-dihydrofuran-2-one and 4-bromo-2,5-dihydrofuran-2-one were first reported in 1894, considerable ambiguity still exists about the correct structure assignment of the two compounds. The present article gives a brief overview on the varying assignments of constitution and describes a novel method for the formation of 3-bromo-2,5-dihydrofuran-2-one. A comparison is made of the experimental ¹³C NMR chemical shifts with values predicted by increment calculations and experimental ¹/_C-C coupling constants are given for both compounds. Secure structural assignments are now available for both isomers.

Full text of DOI:10.1135/cccc19991154

1
154
Brecker, Kreiser, Ernst, Hopf:
3
-BROMO-2,5-DIHYDROFURAN-2-ONE AND 4-BROMO-2,5-DIHYDRO-
FURAN-2-ONE
Lothar BRECKER * , Wolfgang KREISERa2,*, Ludger ERNSTb1 and
a1, ,+
b2
Henning HOPF
a
Naturstoffchemie, Universität Dortmund, D-44221 Dortmund, Germany; e-mail:
brecker@orgc.tu-graz.ac.at, kreiser@citrin.chemie.uni-dortmund.de
Institut für Organische Chemie, Technische Universität Braunschweig, Hagenring 30, D-38106
1
2
b
1
2
Braunschweig, Germany; e-mail: l.ernst@tu-bs.de, h.hopf@tu-bs.de
Received March 15, 1999
Accepted April 30, 1999
Alth ough 3-brom o-2,5-dih ydrofuran -2-on e an d 4-brom o-2,5-dih ydrofuran -2-on e were first
reported in 1894, con siderable am biguity still exists about th e correct structure assign m en t
of th e two com poun ds. Th e presen t article gives a brief overview on th e varyin g assign m en ts
of con stitution an d describes a n ovel m eth od for th e form ation of 3-brom o-2,5-dih ydro-
1
3
furan -2-on e. A com parison is m ade of th e experim en tal C NMR ch em ical sh ifts with values
predicted by in crem en t calculation s an d experim en tal 1J
couplin g con stan ts are given for
C–C
both com poun ds. Secure structural assign m en ts are n ow available for both isom ers.
Key w ord s: Revision ; Brom o-2,5-dih ydrofuran -2-on es; Buten olides; Structure assign m en ts;
NMR spectroscopy; Lacton es.
Th e two title com poun ds were first reported in 1894 by Hill an d
1
Corn elison . Th e 3-brom o-2,5-dih ydrofuran -2-on e (1), described by th em
form ed colourless crystals ch aracterized by a m eltin g poin t of 77 °C. Th ese
auth ors also reported 4-brom o-2,5-dih ydrofuran -2-on e (2) as colourless
crystals displayin g a m eltin g poin t of 58 °C. However, th eir assign m en t of
th e structures to th e isolated com poun ds turn ed out to be wron g. We h ere
sh ow th at th e attribution of th e structures to th e above m eltin g poin ts h as
to be reversed. Sin ce th en , both substan ces h ave been syn th esized by in de-
pen den t procedures an d various ph ysical ch aracteristics h ave been pub-
lish ed. But th e first in correct determ in ation of th e two structures created
con fusion in th e literature th at persists un til th e presen t tim e, alth ough
+
Present address: Institut für Organische Chemie, Technische Universität Graz, Stremayrgasse 16,
A-8010 Graz, Austria.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Bromo-2,5-dihydrofuran-2-ones
1155
som e attem pts h ave been m ade to solve th e in con sisten cies of th e an alyti-
2
,3
cal data (refs ). We h ave n ow resolved th ese.
RESULTS AND DISCUSSION
For th e first tim e, 3-brom o-2,5-dih ydrofuran -2-on e (1) was correctly de-
4
5a
5b
scribed by Owen an d Sultan bawa an d by Sukigara et al. an d Hata . With
referen ce to Hill an d Corn elison 1 an d Wh itin g , Hopf an d Natsias also
2
6
reported the analytical data of 1 but erroneously assigned them to structure 2.
4
-Brom o-2,5-dih ydrofuran -2-on e (2) was described an d iden tified correctly
5
,7–9
) but Wh itin g2 an d in depen den tly Lespieau an d
four tim es (refs
1
0
1
Viguier also described it an d referrin g to Hill an d Corn elison , wron gly as-
sign ed it to structure 1.
With
a
differen t purpose in m in d, we acciden tally prepared
3
3
-brom o-2,5-dih ydrofuran -2-on e (1) by elim in ation of water from (3S,4S)-
-brom o-4-h ydroxytetrah ydrofuran -2-on e (3) (ref. ) ( Sch em e 1). Sin ce th e
1
1
an alytical data of our product did n ot agree with th e values given by Hopf
6
an d Natsias , we un dertook a directed syn th esis of 4-brom o-2,5-dih ydro-
furan -2-on e (2) from tetrah ydrofuran -2,4-dion e (4) usin g th e m eth od of
8
Jas (Sch em e 1). Th e an alytical data of th is m aterial agreed exactly with th e
6
substan ce reported by Hopf an d Natsias .
Br
OH
Br
(i)
O
O
O
O
O
3
1
O
Br
(ii)
O
O
O
4
2
(i) OH ; (ii) (COBr)2
SCHEME 1
Havin g both com poun ds in h an ds an d com parin g ch em ical sh ifts values
1
for th e vin yl H atom s in th e H NMR spectrum with δ 7.58 (1) an d 6.33 (2)
ppm , we suggest a revision of structure assign m en t on th e basis of th e
6
desh ieldin g effect in 1 (relative to ref. ). In order n ot to rely solely on th at
em pirical rule, we determ in ed an d assign ed th e structures of th e two com -
1
3
poun ds by C NMR spectroscopy. Th e ch em ical sh ifts were com pared with
th e sh ifts calculated by th e in crem en t m eth od. Th e sh ifts for th e paren t
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1
156
Brecker, Kreiser, Ernst, Hopf:
m olecule, 2,5-dih ydrofuran -2-on e are 121.0 ppm (C-3) an d 153.2 ppm
1
2
(
(
C-4) (ref. ). Th e in crem en t values for th e brom o substituen ts are –8.6 ppm
1
3
α-position) and –0.9 ppm (β-position ) (ref. ). In addition , we m easured
on e-dim en sion al C-INADEQUATE spectra of both com poun ds an d were
1
3
able to determ in e th e exact position s of th e carbon atom s in th e correspon d-
1
in g furan on e rin gs from th e J
couplin g con stan ts, wh ich con firm ed th e
C-C
results of th e in crem en t m eth od.
Th e 13C NMR m easurem en t on 3-brom o-2,5-dih ydrofuran -2-on e (1)
sh ows ch em ical sh ifts of 110.9 ppm for C-3 an d 150.5 ppm for th e
m eth yn e (CH) carbon atom , an d th e proper sign al m ultiplicities in th e
DEPT spectrum . Th e in crem en t m eth od predicts values of 112.4 an d 152.3
1
ppm , respectively. Th e J
couplin g con stan ts of com poun d 1 taken from
C–C
th e INADEQUATE m easurem en t are given in Fig. 1. For 4-brom o-
,5-dih ydrofuran -2-on e (2) we foun d ch em ical sh ift values of 121.1 ppm
2
for th e m eth yn e carbon in th e C=C double bon d an d 146.0 ppm for th e
quatern ary carbon atom . Th e values calculated by th e in crem en t m eth od
1
are 120.1 an d 144.6 ppm , respectively. Figure 1 also sh ows th e J
plin g con stan ts determ in ed for com poun d 2.
cou-
C–C
Eviden tly, th ere is good agreem en t between th e calculated an d experi-
m en tal sh ifts for th e carbon atom s of th e C=C double bon d in both
1
com pounds. In addition, the JC–C coupling constants verify that this assign-
m ent of the structures to the substances is correct. The different coupling con-
stants between the carbonyl and the CH carbon atom s and their respective
2
neighbours are significantly different and allow unam biguous assignm ents.
To sum m arize, we h ave proved th at th e structural assign m en t of Hill an d
Corn elison 1 is not correct. Th e isom er with th e m eltin g poin t of 58 °C is
3
-brom o-2,5-dihydrofuran-2-one (1) and 4-brom o-2,5-dihydrofuran-2-one (2)
is th e isom er with th e m eltin g poin t of 77 °C. Com plete sets of an alytical
data for both substan ces are given in th e Experim en tal.
Br 76.5
75.3
Br
74.5
66.5
35.8
39.7
O
O
O
O
1
2
FIG. 1
Couplin g con stan ts of 3-brom o-2,5-dih ydrofuran -2-on e (1) an d 4-brom o-2,5-
dih ydrofuran -2-on e (2)
1J
C–C
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Bromo-2,5-dihydrofuran-2-ones
1157
EXPERIMENTAL
All com m ercial startin g m aterials were used with out purification . TLC plates were prepared
with silica gel 60 F254 (Merck) an d th e spots were observed un der UV ligh t. Meltin g poin ts
h ave been m easured on a Büch i 510 an d are un corrected. NMR spectra were recorded of
CDCl3 solution s on a Bruker DPX-300. Ch em ical sh ift referen ces (δ-scale in ppm ) were
1
13
–1
CHCl3 (7.24) for H an d CDCl3 (77.05) for C NMR. Th e IR spectra (waven um bers in cm
)
of th e com poun ds were taken in KBr on a Nicolet Im pact 400D an d th e MS spectra were
m easured on a Fin n igan MAT 8200.
3
-Brom o-2,5-dih ydrofuran -2-on e (1)
(
(
(
3S,4S)-3-Brom o-4-h ydroxytetrah ydrofuran -2-on e11 (3; 2.7 g, 15 m m ol) was dissolved in THF
20 m l) an d aqueous 2 M NaOH (5 m l) was added to th e solution . After stirrin g for 4 h , eth er
75 m l) was added an d th e m ixture was extracted with aqueous 5% Na CO . After dryin g
2
3
th e organ ic layer over Na SO th e solven t was rem oved in vacuo an d th e product purified by
2
4
ch rom atograph y (silica gel, eth yl acetate–cycloh exan e 1 : 1). Crystallization from eth er gave
colourless crystals (1.8 g, 72%), m .p. 58 °C. IR: 3 100, 2 954, 1 767, 1 606, 1 188, 1 052, 988,
1
3
3
13
7
(
(
1
–
17. H NMR: 4.69 (2 H, d,
J
= 1.9, CH ); 7.58 (1 H, t, JH–H = 1.9, CH). C NMR: 168.6
H–H 2
s, 1J
= 74.5, C2), 150.5 (d, JC–C = 76.5, 35.8, C4), 110.9 (s, 1J
1
= 76.5, 74.5, C3), 71.5
C–C
C–C
t, 1JC–C = 35.8, C5). MS, m/z: 164/162 (1 : 1, 63%; M ), 136/134 (1 : 1, 42%; M – CO),
+
+
35/133 (1 : 1, 100%; M+ – CO – H), 107/105 (1 : 1, 38%; M – COOCH2 + H), 53 (33%; M
+
+
+
OCH2 – Br), 39 (36%; M – CO2 – Br).
4
-Brom o-2,5-dih ydrofuran -2-on e (2)
N,N-Dim eth ylform am ide (2.25 m l, 29 m m ol) was added to a suspen sion of tetrah ydrofuran -
2
,4-dion e (4; 2.25 g, 22.5 m m ol ) in CH Cl (50 m l). Oxalyl dibrom ide (5.8 g, 27 m m ol) was
2 2
added at 0 °C over a period of 15 m in . Th e reaction m ixture was allowed to reach room
tem perature an d th en stirred for 3 h . After addition of water (60 m l) th e organ ic layer was
separated an d th e aqueous layer wash ed with eth er (4 × 30 m l). Th e com bin ed organ ic lay-
ers were dried over Na SO , th e solven t was rem oved in vacuo, an d th e product purified by
2
4
ch rom atograph y (silica gel, eth yl acetate–cycloh exan e 1 : 1). Crystallization from eth er gave
8
colourless crystals (2.5 g, 66%), m .p. 77 °C. IR: 3 187, 3 104, 3 095, 1 742, 1 701, 1 599,
1
4
4
1
263, 1 151, 1 012, 865, 698. H NMR: 4.84 (2 H, d, JH–H = 1.9, CH ); 6.33 (1 H, t, JH–H =
2
1
1
.9, CH). 13C NMR: 170.3 (s, 1J
= 66.5, C2), 146.0 (s, 1J
= 39.7, C5). MS, m/z: 164/162 (1 : 1, 52%; M ), 135/133
= 75.3, 39.7, C4), 121.1 (d,
C–C
C–C
JC–C = 75.3, 66.5, C3), 74.4 (t, 1J
+
C–C
1 : 1, 28%; M+ – CO – H), 83 (100%; M – Br), 53 (20%; M – OCH2 – Br), 39 (26%; M
+
+
+
–
(
CO2 –Br).
REFERENCES
1
. a) Hill H. B., Cornelison R. W.: Am. Chem. J. 1894, 16, 188; b) Hill H. B., Cornelison
R. W.: Am. Chem. J. 1894, 16, 277.
2
3
4
. Whiting M. C.: J. Am. Chem. Soc. 1949, 71, 2946.
. Beilstein 17, E III/IV, p. 4296.
. Owen L. N., Sultanbawa M. U. S.: J. Chem. Soc. 1949, 3105.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

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Brecker, Kreiser, Ernst, Hopf:
5
. a) Sukigara K., Hata Y., Kurita Y., Kubo M.: Tetrahedron 1958, 4, 337; b) Hata Y.: Nippon
Kagaku Zasshi 1958, 79, 1528; Chem. Abstr. 1960, 54, 24620.
. Hopf H., Natsias K.: Liebigs Ann. Chem. 1988, 705.
6
7
8
9
. Marby T. J.: J. Org. Chem. 1963, 28, 1699.
. Jas G.: Synthesis 1991, 11, 965.
. Hollingworth G. J., Knight J. R., Sweeney J. B.: Synth. Commun. 1994, 24, 755.
1
1
1
0. Lespieau R., Viguier P. L.: C. R. Hebd. Séances Acad. Sci. 1909, 148, 419.
1. Bols M., Lundt I.: Acta Chem. Scand., Ser. B 1988, 42, 67.
2. Bremser W., Ernst L., Fachinger W., Gerhards R., Hardt A., Lewis P. M. E.: Carbon-13
NMR Spectral Data, 4th ed., Spectrum No. 35366. Verlag Chemie, Weinheim 1987.
3. Pretsch E., Clerc T., Seibl J., Simon W.: Tabellen zur Strukturaufklärung organischer
Verbindungen mit spektroskopischen Methoden, 3rd ed., p. C90. Springer, Berlin 1986.
1
Collect. Czech. Chem. Commun. (Vol. 64) (1999)