Organic Syntheses, Vol. 78, pp. 123-134
Checked by Brian Haney, Brian Bucher, and Dennis P. Curran.
1. Procedure
2. Notes
1.
D-Glucose
(BioChemika, = 99.5%) was obtained from Fluka Feinchemikalien
GmbH, Neu-Ulm, Germany or Aldrich Chemical Company, Inc.
2.
Paraldehyde (=
97%) was obtained from Fluka Feinchemikalien GmbH, Neu-Ulm,
Germany or Acros Chemical Company, and
was used without distillation.
3. If the
sulfuric acid is added too fast, the
reaction mixture becomes brown, probably from charring of the
glucose.
4. The submitters used a
shaking machine (IKA
Labortechnik KS 250 basic, ca. 500/min). The checkers used a shaking machine from
Lab Line Instruments (Model number 4600).
6. The pH was checked with Merck Universal-Indikatorpapier, range
1-14.
8. Charcoal (powdered) was obtained from E. Merck KGaA, Darmstadt,
Germany or J. T. Baker Chemical Company.
9. The solids are dissolved in hot
ethanol and
then kept overnight in the freezer at −30°C. The checkers found that standing
overnight at −5°C gave similar results.
10. In
deuterium oxide (D
2O) the
product is a 34/66-mixture of α/β-anomers. The spectral properties of
(−)-4,6-O-ethylidene-D-glucose
are as follows:
1H
NMR (250 MHz, D
2O) δ: 1.22 (d, 3 H, J = 5.0, CHCH
3),
3.03-3.78 (m, 5 H, 2-H, 3-H, 4-H, 5-H, 6-H
a), 3.90-4.12
(m, 1 H, 6-H
b), 4.40-5.13 (m, 5 H, 1-H, 3 OH, CHCH
3);
2a
[α]D20 −2.3°
(H2O, 2 d, c 19.7),
2a
[α]D20 −2.37°
(H2O, equilibrium, c 19.7).
3
11.
Sodium periodate
(NaIO4) (98%) was obtained from Fluka Feinchemikalien
GmbH, Neu-Ulm, Germany or Aldrich Chemical Company, Inc.
12. In several experiments it was found that the yield of
2,4-O-ethylidene-D-erythrose
generally is somewhat lower when the reaction is performed on a larger scale.
14. The pH was checked every 30 min and, if necessary, more aqueous
sodium hydroxide was added to keep the pH at 4.
16.
Caution: The evaporation of the solvent must be done
slowly and carefully because the product shows a strong tendency to foam.
17. It is difficult to give exact spectral properties of
(−)-2,4-O-ethylidene-D-erythrose
because of rapid di- and/or oligomerization. The melting points given in the literature
differ from 65-80°C
4
to 150-151°C,
5 depending on the degree
of oligomerization of the product. With the present procedure, mainly the dimer is
obtained. In order to check the optical purity of the product, it is convenient to
compare the equilibrium value of specific rotation, as obtained after 2 days in aqueous
solution at room temperature:
[α]D20
−39.5° (H2O, 2 d, c 1.00),
6 [α]D20 −36.8° (H2O, equilibrium,
c 8.25),
3 [α]D25 −36.2° (H2O, equilibrium,
c 8.2).
5 The analytical data of the
product were as follows:
2a Calcd for C
6H
10O
4
(146.14): C, 49.31; H, 6.90. Found: C, 49.18; H, 7.07;
1H NMR (200.1 MHz, D
2O) δ:
1.38 (d, 3 H, J = 5.0, CHCH
3), 3.39-3.99 (m,1 H, OCH),
4.06-4.31 (m, 2 H, OCH
2), 4.75-5.63 (m, 1 H, OH, CHCH
3);
13C NMR (50.3
MHz, D
2O/dioxane) δ: 20.1 (CHCH
3), 61.2
(CHOH), 67.1, 67.9, 68.4 (CH
2O),
70.3, 71.5, 76.0, 78.5, 80.8,
90.6, 91.6 (CHO), 95.6, 97.4,
100.3, 101.2 (O
2CHCH
3).
18. According to ref.
5,
monomeric
(−)-2,4-O-ethylidene-D-erythrose may
be obtained by heating a solution of the dimer in
ethyl acetate
with a catalytic amount of
glacial acetic acid
or
100% phosphoric acid
for 20 min at 90°C.
19.
Nitrogen was dried by means of a Sicapent
(r)
(E. Merck) drying tube. The checkers used dry
argon.
20.
Sodium hydride
(60% sodium hydride in paraffin) was obtained
from Fluka Feinchemikalien GmbH, Neu-Ulm, Germany or Aldrich
Chemical Company, Inc.
21.
Pentane (technical
grade) was purified by distillation from
sodium.
24. Crude product contains
triethyl phosphonacetate;
the isomeric purity (E/Z) of
ethyl 4,6-O-ethylidene-(4S,5R,1'R)-4,5,6-trihydroxy-2-hexenoate
was > 95 : 5 according to
13C NMR.
25. A 20 cm × 5 cm column packed with 200 g of Kieselgel 60, (E.
Merck, 0.040-0.063 mm, 250-400 mesh) was used. The checkers used a 40 cm × 10 cm column
packed with silica gel (Bowman Chemical Co., 60Å) and eluted with
1/1
hexane/ethyl acetate with similar
results.
26.
Ethyl acetate and
petroleum ether (technical grade; boiling range 40-80°C)
were purified by distillation.
27.
Hexane (technical
grade) was distilled before use.
28.
Hexane was added
to the solid in 5-mL portions (ca. 35 mL were needed)
until a single phase was formed. On slowly cooling to room temperature, the liquid
again separates into two phases before crystallization starts.
29. The analytical data (after chromatography) were as follows:
6 Calcd for C
10H
16O
5 (216.23):
C, 55.55; H, 7.46. Found: C, 55.40; H, 7.43. The E/Z ratio was found to be > 99:1
(determined by HPLC): t
E = 4.50 min; t
z =
3.40 min,
eluent
hexane/
ethyl acetate 60/40 [LiChrosorb
Si 60 column, E. Merck]. (The Z-diastereomer reference sample was prepared as described
in Ref.
7).
TLC: R
f = 0.38 (petroleum ether/
ethyl acetate 60/40).
[α]D20 −41.3°
(CHCl3; E/Z > 99:1, c 0.500),
mp 62-63°C, ref.
7:
[α]D25 −35.2°
(CHCl3, c 1.21),
mp
59-60°C.
13C
NMR (75.5 MHz, CDCl
3) δ: 14.2 (OCH
2CH
3),
20.4 (O
2CHCH
3), 60.8 (OCH
2CH
3),
65.1 (C-5), 70.7 (C-6), 79.9 (C-4), 98.8
(O
2CHCH
3), 122.2 (C-2), 143.7 (C-3),
166.7 (C-1);
1H
NMR (300 MHz, CDCl
3) δ: 1.30 (t, 3 H, J = 7.1, OCH
2CH
3),
1.36 (d, 3 H, J = 5.1, O
2CHCH
3), 2.85 (bs,
1 H, OH), 3.44 (t, 1 H, J = 9.5, 6-H
a), 3.52
(dt, 1 H, J = 4.4, J = 9.5, 5-H), 4.01 (ddd, 1 H,
4J = 1.7,
J = 4.5, J = 9.5, 4-H), 4.14 (dd, 1 H, J = 4.4, J = 9.9, 6-H
b),
4.20 (q, 2 H, J = 7.1, OCH
2CH
3), 4.74 (q,
1 H, J = 5.1, O
2CHCH
3), 6.16 (dd, 1 H,
4J
= 1.7, J = 15.8, 2-H), 7.09 (dd, 1 H, J = 4.5, J = 15.8, 3-H).
30. In various runs,
20 to 100 mmol
of D-erythrose acetal were used, with yields
ranging from
65 to 73%.
All toxic materials were disposed of in accordance with "Prudent Practices in the
Laboratory"; National Academy Press; Washington, DC, 1995 and "Neue Datenblätter für
gefährliche Arbeitsstoffe nach der Gefahrstoffverordnung", Welzbacher, U. (Ed.); WEKA
Fachverlage, Kissing, 1991.
3. Discussion
Both enantiomers of
2,4-O-ethylideneerythose have been used
as intermediates in the preparation of free
D- and
L-erythrose.
12,13,15,16,17 In some reactions
it proved advantageous to promote monomer formation of
2 from the dimer/oligomers
by addition of 2-pyridone.
2,19
The N-benzylimine
20 and some hydrazones
20,21
of
2 have been described earlier in the literature. Imines, nitrones, oximes,
and nitrile oxides derived from
2 were recently employed in a variety of additions
and cycloadditions.
2,22,23
Aldehyde
2 has been transformed in various other Wittig reactions
24,25,26
and in an Abramov reaction with dimethyl phosphite.
27
Formation of the diethyldithioacetal,
28 the dimethyl phosphonate,
29 or the condensation with
nitromethane4,12,30
represent other uses of
2. 2,3-Epoxyamides were prepared by treating
2
with stabilized sulfur ylides generated in situ.
31 (−)-2,4-O-Ethylidene-D-erythrose
2 has been used for the preparation of
2-deoxy-D-ribose
via addition of stabilized ylides and subsequent hydrolysis in the presence of mercuric
ion.
5 Further, diastereoselective propargyl addition
to the aldehyde
2 was recently performed with
propargyl bromide
and
zinc.
32
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