1,3-Diphenylpropane-1,3-diamines XII [1]. A novel approach to stereodefined oximes and oxime ethers of monothioketalized 1,3-diketones and their conversion to 3-aminooximes

Article abstract of DOI:10.1007/PL00013502

Mono-O,O-and mono-S,S-ketals of 1,3-diphenylpropane-1,3-diones react with hydroxylamine hydrochloride and O-methylhydroxylamine hydrochloride affording mixtures of (E/Z) isomers which are hard to separate or are even unseparable. Isomerically pure oximes

Full text of DOI:10.1007/PL00013502

Monatshefte fuÈr Chemie 129, 937±952 (1998)
1,3-Diphenylpropane-1,3-diamines XII [1].
A Novel Approach to Stereode®ned Oximes
and Oxime Ethers of Monothioketalized
1,3-Diketones and their Conversion
to 3-Aminooximesa
Ã
Alexander Kaiser and Wolfgang Wiegrebe
Institute of Pharmacy, University of Regensburg, D-93040 Regensburg, Germany
Summary. Mono-O,O- and mono-S,S-ketals of 1,3-diphenylpropane-1,3-diones react with
hydroxylamine hydrochloride and O-methylhydroxylamine hydrochloride affording mixtures of
(E/Z) isomers which are hard to separate or are even unseparable. Isomerically pure oximes and O-
methyloximes, however, are obtained either from 2-lithiated 1,3-dithianes and ꢀ-halogeno-oximes
and ꢀ-halogeno-oxime ethers, resp., or from lithiated oxime ethers and dithienium salts. Reduction,
acetylation, hydrolysis of the ketal increment, and oximation afford 3-amino-oximes which are
precursors of 1,3-diphenylpropane-1,3-diamines.
Keywords. 1,3-Diphenylpropane-1,3-diamines; Monoketalized 1,3-diones; Lithiated 1,3-dithianes;
ꢀ-Halogeno-oximes; ꢀ-Halogeno-oxime ethers; Dithienium salts; Lithiated oxime ethers.
1,3-Diphenylpropan-1,3-diamine, 12. Mitt. [1]. Ein neuer Zugang zu stereochemisch
einheitlichen Oximen und Oximethern von monothioketalisierten 1,3-Diketonen
und ihre Umsetzung zu 3-Aminooximen
Zusammenfassung. Mono-O,O- und Mono-S,S-ketale von 1,3-Diphenylpropan-1,3-dionen liefern
mit Hydroxylaminhydrochlorid bzw. O-Methylhydroxylaminhydrochlorid (E/Z)-Gemische der
Oxime bzw. der O-Methyloxime, die sich nur schwer oder uÈberhaupt nicht trennen lassen.
Andererseits sind isomerenreine Oxime bzw. O-Methyloxime durch Umsetzung von 2-lithiierten
1,3-Dithianen mit ꢀ-Halogenoximen und ihren O-Methylethern oder durch Reaktion von lithiierten
È
Oximethern mit Dithieniumsalzen zuganglich. Reduktion, Acetylierung, Ketalspaltung und
Oximbildung fuÈhren dann zu 3-Aminooximen. Diese Verbindungen sind Vorstufen fuÈr 1,3-
Diphenylpropan-1,3-diamine.
a
Dedicated with warm regards to Prof. Dr. G. Heinisch, Innsbruck, on the occasion of his 60th
birthday
Ã
Corresponding author

938
A. Kaiser and W. Wiegrebe
Introduction
In part IX of this series [2] we have described the reaction of ꢀ-lithiobenzylamines
with an ꢀ-halogeno-oxime ether affording 3-aminopropan-1-one oxime ethers.
Here we report on the synthesis of stereode®ned oximes and their pertinent O-
methyl ethers of 1,3-diketones, obtained from 2-lithiated 1,3-dithianes and ꢀ-
halogeno-oximes and their O-methyl- and O-silyl derivatives.
Results and Discussion
1,3-Diones, their mono-O,O- and mono-S,S-ketals, and their oximes
and oxime ethers
The starting point of our synthesis of monoketal 2 (Scheme 1) was the formation of
a dimethyl ketal from a 2,3-dibromopropan-1-one with KOH/MeOH as described
in 1904 by Wieland [3]. To the best of our knowledge this is the only report on this
conversion. A forthcoming paper will be concerned with this reaction.
In sharp contrast to the preparation of the dioxolane derivative 2, we could not
prepare the dithiolane 8 and the dithiane 9, resp., when reacting the
dibromopropanone 1 with pertinent alkanedithioles: Although we used various
basic catalysts, we always obtained high yields of bis(4-methoxyphenyl)-2-propen-
1-one (5). Dehalogenations of ꢀ,ꢁ-dibromo compounds with thioles and Na2S,
respectively, are known [4, 5]. A variety of methods has been described for the
synthesis of monoketals of 1,3-diones [6±9]. In our hands, only the twofold
Michael-analogous addition of dithioles [8, 9] to propinone 7 was successful.
Due to the lability of the dioxolane increment, oximation of ketal 2 was
dif®cult. Besides the expected instability in acidic media, the dioxolane ring was
opened also under basic conditions giving rise to 3,5-bis(4-methoxyphenyl)isox-
azole 6 (Scheme 1), probably following an E1cB mechanism. Satisfying results
were obtained only in pyridine under strict control of the procedures used for the
reaction and for work-up: For the reactions with hydroxylamine hydrochloride
without addition of a base, protic solvents turned out to be unsuitable. In water/
EtOH with KOH as a base, the yield of oxime 3 was also poor, and the formation of
the isoxazole was dominant. Moreover, the crude oxime 3 was a 85:15 (E/Z)
mixture (1H NMR) from which (Z)-3 could be removed by ether and subsequent
recrystallization. We tried to obtain pure (Z)-3, but only an enrichment was
possible. The formation of the oxime ether 4 also requires sophisticated handling:
column chromatography (CC) of the 75:25 (E/Z) mixture afforded 41% (E)-4, 7%
(Z)-4, and 26% of (E/Z)-4.
Due to the higher stability of thioketals as compared to their oxygen analogues
[10], no dif®culties arose when the dithiolane (8) or dithiane derivatives (9) were
converted to the pertinent oximes. With hydroxylamine hydrochloride as well as
with its O-methyl ether, the corresponding oximes 10 and 12 or the oxime ethers 11
and 13 were obtained as (E/Z) mixtures. For the dithiane derivatives 12 and 13, the
intensity of the C-2 methylene protons (1H NMR) revealed (E/Z) ratios of 70:30
and 60:40, resp. For the dithiolanes 10 and 11, the (E/Z) ratio could not be
1
determined by H NMR spectroscopy, because the N-methoxy signal of 11

Oximes and Oxime Ethers of Monothioketalized 1,3-Diketones
939
Scheme 1
overlaps with those of the anisole increments, and the S-CH2 groups interfere with
C-2 methylene protons.
The (E/Z) isomers of the oxime ethers 11 and 13 could not be separated. For
the reduction with chiral borane complexes according to Sakito et al. [11],
however, stereochemically homogeneous educts are required. These authors
obtained enantiomerically pure amines by reduction of the (E)- and (Z)-stereomers
of O-methyloximes, using the same enantiomerically pure reducing agent.
Therefore, we established a synthesis of diastereomerically pure oxime derivatives
of monothioketalized 1,3-diketones.
Diastereomerically pure oxime derivatives of 2-(2-(4-methoxyphenyl)-
1,3-dithian-2-yl)-1-(4-methoxyphenyl)ethanone (9) from a 2-lithio-1,3-dithiane
and ꢀ-halogeno-oxime derivatives
a) Oximes
We examined the reaction of the lithiated dithiane 14 with oxime 15 and oxime
ethers 16±19 (Scheme 2). According to Ref. [12], substitution of ꢀ-halogeno-

940
A. Kaiser and W. Wiegrebe
Scheme 2
Scheme 3
oximes with strongly basic nucleophiles follows an elimination-addition mechan-
ism: 1,4-Elimination leads to a nitrosoalkene which is attacked by a second
equivalent of the nucleophile in a Michael-analogous manner. Here, two
disadvantages come up: loss of one equivalent of the nucleophile and the
separation of non-reacted nucleophile, which is probably dif®cult.
In spite of these drawbacks we reacted the diastereomeric mixture (E/Z)-15
with lithiated dithiane 14, because we were interested in the stereochemical result
of this procedure. ꢀ-Halogeno-oximes may react with nucleophiles either by
inversion [13, 14] or possibly by retention [15, 16] of the oxime geometry. In our
1
hands, the reaction led exclusively to (E)-12, as indicated by the H NMR
spectrum of the crude product, but the excess of dithiane 14 could not be removed
by crystallization, because compounds 12 and 14 behaved similarly under the
conditions of recrystallization, and the low solubility of the condensation product
12 impeded puri®cation by CC. Because we expected to obtain (E)-12 by another
route (see below), we did not follow this procedure any longer.
The conversion of lithiated dithiane 14 with (E/Z)-ꢀ-chloro-O-silyloxime
(E/Z)-16 and subsequent in situ desilylation with AcOH/H2O [17] or tetra-
butylammonium ¯uoride (TBAF) [18], resp., led to an (E/Z) mixture of oxime 12
in 80 and 65% yield, resp. Threefold recrystallization afforded 49% of
diastereomerically pure (E)-12.
Use of isomerically pure (Z)-ꢀ-bromo-O-silyloxime (Z)-17 was of no bene®t as
compared to the reaction of 14 with (E/Z)-16, because desilylation with AcOH/
H2O led partially to isomerization; this could be avoided using TBAF. However, the

Oximes and Oxime Ethers of Monothioketalized 1,3-Diketones
941
Scheme 4
crude products in both versions were contaminated by 1,4-bis(4-methoxyphenyl)-
1,4-butanedione dioxime (21a) (Scheme 6). Separation of 21a led to heavy losses
of isomerically pure (E)-12; therefore, this procedure had no favourable effect
when compared with the reaction of (E/Z)-16.
b) Oxime ethers
Reaction of (Z)-ꢀ-chloro-oxime ether (Z)-18, however, led to the desired ketalized
oxime ether (E)-13 in 80% yield after recrystallization. (E/Z)-18 yielded 85% of
(E/Z)-13 after CC puri®cation.
(Z)-ꢀ-Iodo-oxime ether (Z)-19, however, is unsuitable: According to its
1H NMR spectrum, the crude product contained less than 10% of (E)-13; the
main quantity consisted of the dimerization products 20 and 21. Dimerization
of 2-lithiated dithianes under the conditions of electrophilic reactions is known
[10, 19, 20].
Scheme 5
Scheme 6

942
A. Kaiser and W. Wiegrebe
Reaction of 1,3-dithienium salts and lithiated oxime ethers
The reaction of C-lithiated oximes and oxime ethers, resp., with 1,3-dithienium
salts offers a further possibility for the synthesis of isomerically pure oxime
derivatives of monothioketalized 1,3-diketones. The twofold lithiated oxime 22 did
not react with the dithienium salt 24 as expected: (E)-12 could not be detected in
the reaction mixture. The (mono) lithiated oxime ether 23, however, afforded (E)-
13 in 40% yield.
Scheme 7
Assignment of oxime geometries
According to Karabatsos (21], (E)- and (Z)-O-methyloximes can be differentiated
by the chemical shifts of the methoxyimino increments in their H NMR spectra.
1
They show a difference of 0.16±0.18 ppm; the isomer with its O-methyl group anti
to the aromatic ring resonates at lower ®eld strength than the diastereomer with syn
position. For our oxime ethers (E)-4 and (Z)-4, however, these assignments are
impossible, because the methoxyimino moieties absorb near the resonances of the
anisole increments. Assignment after hydrolysis of the dioxolane ring to a 3-
methoxyimino-propanone and comparison with authentic (E)-3-methoxyimino-
propanone 25 also failed (Scheme 8). Both isomers of the oxime ether 4 afforded
the (E)-3-methoxyimino-propanone 25. Under the hydrolytic conditions [22] used
(Z)-4 obviously isomerizes to (E)-4, either at the dioxolane status or as the
corresponding oxime ether ketone. Finally, the stereochemistry of the isomeric
oximes 3 and the oxime ethers 4 was established by comparison with the oxime
derivatives 12 and 13 the stereochemistry of which had been ascertained by
independent ways: Reaction of dithiane 14 with the bromo compound (Z)-17
afforded (E)-12 (cf. also Scheme 5). The isomers of 3 and 4, resp., as well as the
isomers of 12 and 13 exhibit different chemical shifts of their C-2 methylene
increment. In the (E)-isomers of 12 and 13 the resonances of this CH2-moiety are
shifted down®eld as compared with those of the (Z)-isomers. Therefore, we assign
(E)-con®guration to those diastereomers of 3 and 4 with more down®eld chemical
shifts.
The chemical shift value of 3.63 ppm for the methoxyimino group in (E)-13 is
peculiar. Comparison with the H NMR spectrum of (E/Z)-13 indicates that the
1
(Z)-isomer resonates down®eld in the region of the aromatic methoxy groups. In
this case, assignment according to Karabatsos [21] would have led to the wrong
result.

Oximes and Oxime Ethers of Monothioketalized 1,3-Diketones
943
Scheme 8
Scheme 9

944
A. Kaiser and W. Wiegrebe
Conversion of oxime ethers to 3-amino-oxime derivatives
The oxime ethers 4, 11, and 13 were reduced by borane-THF [23] producing the
amines 26, 27, and 28 in 35%, 86%, and 85% yield. These ketalized amines could
not be converted to 1,3-bis(4-methoxyphenyl)-3-aminopropan-1-one. Hydrolysis of
the dioxolane 26 afforded 1,3-bis(4-methoxyphenyl)-2-propen-1-one (5; Scheme
1), treatment of the thioketals 27 and 28 with chloramine T (N-chlorotoluene-
sulfonamide sodium salt) [24] in MeOH/H2O gave useless mixtures, probably due
to the well known sensitivity of 1,3-diphenyl-3-aminopropan-1-ones [25]. After N-
acetylation to the amides 29±31, the ketals could be cleaved, affording the 3-
acetamidopropanone 32. This amide was converted to the oxime 33 and the oxime
ether 34 in isomerically pure status; both of them show (E)-con®guration as
1
established by comparison with the H NMR spectra of known (E)-3-acylamino-
oxime ethers [26].
Experimental
General remarks: see Ref. [2]. CC was performed on silica gel. Compounds 1 [27], 14 [10], (E/Z)-15
[28], (Z)-18, (Z)-19 [2], 22, 23 [26], and 24 [7] were prepared according to the pertinent procedures.
Compound 7 was synthesized according to Ref. [29] by reaction of 4-methoxyphenylethine with the
corresponding benzaldehyde, using the Li-acetylide instead of the Mg-acetylide and PDC/DMF
instead of CrO3/H2SO4 for subsequent oxidation of the secondary carbinol to the ketone.
2-(2-(4-Methoxyphenyl)-1,3-dioxolan-2-yl)-1-(4-methoxyphenyl)ethanone (2)
To a solution of 2.0 g (87 mmol) of Na in 60 ml of dry ethylene glycol, 20 ml of dry dioxane are
added. The ¯ask is placed in oil bath (50±60ꢀC), and a solution of 8.56 g (20 mmol) of 1 in 50 ml of
dry dioxane is added. The temperature is raised to 100ꢀC within 1 h, and stirring is continued for 1 h
at this temperature. After cooling, dioxane is removed in vacuo, and the mixture is extracted with
Et2O (3Â100 ml). The combined Et2O layers are washed with H2O (2Â50 ml) and brine (2Â40 ml),
dried, and evaporated. CC (gradient from CH2Cl2/EtOAc 9.5/0.5 to 9/1) affords 2 as a pale yellow oil
which crystallizes upon drying at the oil pump.
Yield: 3.81 g (58%); m.p.: 66±68 ꢀC; IR (Kbr): ꢂ ˆ 1665 (C ˆ O) cmꢁ1
;
1H NMR (CDCl3):
ꢃ ˆ 3.52 (s, 2H, CH2), 3.63±4.00 (m, 4H, OCH2CH2O, partially overlapped by OCH3), 3.77 (s, 3H,
OCH3), 3.85 (s, 3H, OCH3), 6.77±7.00 (m, 4H, arom), 7.37±7.57 (m, 2H, arom), 7.85±8.07 (m, 2H,
arom) ppm; C19H20O5 (328.4); calcd.: C 69.50, H 6.14; found: C 69.31, H 6.25.
2-(2-(4-Methoxyphenyl)-1,3-dithiolan-2-yl)-1-(4-methoxyphenyl)ethanone (8)
To a solution of 1.15 g (50 mmol) of Na in 40 ml of dry MeOH, a solution of 1.8 g (19 mmol) of 1,2-
ethanedithiol in 10 ml of dry MeOH and a solution of 3.33 g (12.5 mmol) of 7 in 30 ml of dry dioxan
are added successively at 0ꢀC under N2 within 5 min. After stirring for 1.5 h at 0ꢀC, the mixture is
poured into 350 ml of H2O and extracted with EtOAc (1Â100 ml and 4Â50 ml). The combined
organic layers are washed with 2 N NaOH (2Â50 ml) und brine (2Â 50 ml), dried, and evaporated.
CC (Et2O/PE 7/3; for application onto the silica, the residue is taken up in CH2Cl2) affords 8 as a
colourless oil.
Yield: 4.24 g (94%); IR (®lm): ꢂ ˆ 1680 (C=O) cmꢁ1
;
1H NMR (CDCl3): ꢃ ˆ 3.30 (s, 4H,
SCH2CH2S), 3.72 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 4.20 (s, 2H, CH2), 6.70±7.00 (m, 4H, arom),
7.57±8.00 (m, 4H, arom) ppm; C19H20O3S2 (360.5); calcd.: C 63.30, H 5.59; found: C 63.15, H 5.61.

Oximes and Oxime Ethers of Monothioketalized 1,3-Diketones
945
2-(2-(4-Methoxyphenyl)-1,3-dithian-2-yl)-1-(4-methoxyphenyl)ethanone (9)
Preparation according to the procedure given for 8 with 2.1 g (19 mmol) of 1,3-propanedithiol,
puri®cation as described for 8. The combined fractions are concentrated until crystallization starts,
left at 4ꢀC, and sucked off; colourless crystals, yield: 1.68 g (36%). Evaporation of the mother liquor
gives 1.17 g (25%) as a pure oil which, however, could not be crystallized.
M.p.: 90ꢀC; IR (KBr): ꢂ ˆ 1663 (C=O) cmꢁ1
;
1H NMR (CDCl3): ꢃ ˆ 1.77±2.10 (m, 2H,
SCH2CH2CH2S), 2.53±2.83 (m, 4H, SCH2CH2CH2S), 3.58 (s, 2H, CH2), 3.77 (s, 3H, OCH3), 3.83
(s, 3H, OCH3), 6.70±6.93 (m, 4H, arom), 7.67±7.97 (m, 4H, arom) ppm; C20H22O3S2 (374.5); calcd.:
C 64.14, H 5.92; found: C 64.13, H 5.92.
(E)-2-(2-(4-Methoxyphenyl)-1,3-dioxolan-2-yl)-1-(4-methoxyphenyl)ethanone oxime (E)-(3)
At room temperature, 5.73 g (17.45 mmol) of 2 and 2.42 g (34.9 mmol) of hydroxylammonium
chloride are stirred in 30 ml of pyridine for 14 h. The mixture is poured into 500 ml of ice-cold 2 N
HCl and immediately extracted with 250 ml of EtOAc; the extract is instantly washed with satd.
NaHCO3 solution (200 ml) and brine (2Â50 ml), dried, and evaporated. The yellow residue (4.72 g
(E/Z) mixture) is stirred with 20 ml of Et2O for 1 h, sucked off, and recrystallized twice from 14 and
12 ml of benzene, resp., to afford (E)-3 as colourless crystals.
Yield: 2.93 g (49%); m.p.: 146±148ꢀC; IR (KBr): ꢂ ˆ 3300±3000 (OH), 1607 (C=N and
C=C) cmꢁ1
;
1H NMR (CDCl3): ꢃ ˆ 3.48 (s, 2H, CH2), 3.63±3.91 (m, 10H, OCH2CH2O and 2
OCH3), 6.71±6.97 (m, 4H, arom), 7.31±7.73 (m, 4H, arom), 8.26 (s, br, 1H, OH, exch.) ppm;
C19H21NO5 (343.4); calcd.: C 66.46, H 6.16, N 4.08; found: C 66.10, H 5.94, N 4.21.
(E)- and (Z)-2-(2-(4-Methoxyphenyl)-1,3-dioxolan-2-yl)-1-(4-methoxyphenyl)ethanone
O-methyloxime ((E)-4 and (Z)-4)
At room temperature, 3.28 g (10 mmol) of 2 and 1.0 g (12 mmol) of O-methylhydroxylammonium
chloride are stirred in 15 ml of pyridine for 16 h. The mixture is poured into 250 ml of ice-cold dil.
HCl (from 150 ml 2 N HCl and 100 g ice) and immediately extracted with Et2O (250 ml); the Et2O
layer is instantly washed with satd. NaHCO3 solution (200 ml) and brine (2Â70 ml), dried, and
concentrated. The diastereomers are separated by CC (Et2O/PE 1/1). In addition to 0.95 g (26%) of
(E/Z) mixture, there are obtained:
(E)-4: Pale yellow oil which solidi®es upon storage; yield: 1.47 g (41%); recrystallization from 14 ml
of 2-propanol (tends to separate as an oil, addition of seed crystals recommended) affords colourless
crystals.
Yield: 1.06 g (29%); m.p.: 61±62ꢀC; IR (KBr): ꢂ ˆ 1609 (C=N and C=C) cmꢁ1
;
1H NMR
(CDCl3): ꢃ ˆ 3.40 (s, 2H, CH2), 3.57±3.87 (m, 13H, OCH2CH2O and 3 OCH3), 6.68±6.93 (m, 4H,
arom), 7.23±7.43 (m, 2H, arom), 7.50±7.70 (m, 2H, arom) ppm; C20H23NO5 (357.4); calcd.: C 67.21,
H 6.49, N 3.92; found: C 66.89, H 6.65, N 4.06.
(Z)-4: Colourless crystals; yield: 0.24 g (7%); recrystallization from 0.8 ml of MeOH provides
colourless crystals.
Yield: 0.22 g (6%); m.p.: 93±94ꢀC; IR (KBr): ꢂ ˆ 1613 (C=N and C=C) cmꢁ1; 1H NMR (CDCl3):
ꢃ ˆ 3.17 (s, 2H, CH2), 3.60±3.87 (m, 13H, OCH2CH2O and 3 OCH3), 6.70±6.97 (m, 4H, arom),
7.23±747 (m, 4H, arom) ppm; C20H23NO5 (357.4); calcd.: C 67.21, H 6.49, N 3.92; found: C 67.02,
H 6.40, N 3.89.
(E/Z)-2-(2-(4-Methoxyphenyl)-1,3-dithiolan-2-yl)-1-(4-methoxyphenyl)ethanone oxime ((E/Z)-10)
1.80 g (5 mmol) of 8 and 1.39 g (20 mmol) of hydroxylammonium chloride are stirred in 5 ml of
pyridine at 80 ꢀC for 5 h. Pyridine is removed in vacuo; the residue is mixed with 20 ml of 2 N HCl

946
A. Kaiser and W. Wiegrebe
and extracted with EtOAc (3Â50 ml). The combined org. layers are washed with satd. NaHCO3
solution (2Â 30 ml) and brine (2Â 30 ml), dried, and evaporated to give a solid. Recrystallization
from EtOH affords (E/Z)-10 as colourless crystals.
Yield: 1.51 g (80%); melting range: 129±136ꢀC; IR (KBr): ꢂ ˆ 3234 (OH), 1605 (C=N and
1
C=C) cmꢁ1; H NMR (CDCl3): ꢃ ˆ 2.87±3.37 (m, 4H, 2 CH2), 3.57±3.90 (m, 8H, CH2 and 2
OCH3), 6.53±6.83 (m, 4H, arom), 7.03±7.57 (m, 4H, arom), 8.40 (s, br, 1H, OH, exch.) ppm;
C19H21NO3S2 (375.5); calcd.: C 60.77, H 5.64, N 3.73; found: C 60.55, H 5.79, N 3.72.
(E/Z)-2-(4-Methoxyphenyl)-1-,3-dithiolan-2-yl)-1-(4-methoxyphenyl)ethanone O-methyloxime
((E/Z)-11)
The procedure described for (E/Z)-10 is used with 0.84 g (10 mmol) of O-methylhydroxyl-
ammonium chloride instead of hydroxylammonium chloride. CC (Et2O/PE 1/1; for application onto
the silica, the residue is taken up in CH2Cl2) provides (E/Z)-11 as a colourless oil.
Yield: 1.65 g (85%); IR (®lm): ꢂ ˆ 1609 (C=N and C=C) cmꢁ1; 1H NMR (CDCl3): ꢃ ˆ 2.90±3.33
(m, 4H, 2 CH2), 3.58±3.83 (m, 11H, CH2 and 3 OCH3), 6.58±7.63 (m, 8H, arom) ppm; C20H23NO3S2
(389.5); calcd.: C 61.67, H 5.95, N 3.60; found: C 61.63, H 6.00, N 3.63.
(E/Z)-2-(2-(4-Methoxyphenyl)-1-,3-dithian-2-yl)-1-(4-methoxyphenyl)ethanone oxime ((E/Z)-12)
The procedure described for (E/Z)-10 is used with 1.87 g (5 mmol) of 9 instead of 8.
Recrystallization from CHCl3 gives (E/Z)-12 as colourless crystals.
Yield: 1.44 g (74%); melting range: 130±135ꢀC; IR (KBr): ꢂ ˆ 3228 (OH), 1605 (C=N and
C=C) cmꢁ1
;
1H NMR (CDCl3): ꢃ ˆ 1.67±2.00 (m, 2H, SCH2CH2CH2S), 2.47±2.73 (m, 4H,
SCH2CH2CH2S), 3.23 and 3.50 (2s, 2H, CH2 (Z) and (E) isomer), 3.75 (s, 6H, 2 OCH3),
6.53±6.80 (m, 4H, arom), 7.07±7.28 (m, 2H, arom), 7.50±7.75 (m, 2H, arom), 8.17 (s, br; 1H,
OH, exch.) ppm; C20H23NO3S2 (389.5); calcd.: C 61.67, H 5.95, N 3.60; found: C 61.29; H 5.80,
N 3.46.
(E/Z)-2-(2-(4-Methoxyphenyl)-1,3-dithian-2-yl)-1-(4-methoxyphenyl)ethanone O-methyloxime
((E/Z)-13)
Prepared according to the protocol given for (E/Z)-11 with 1.87 g (5 mmol) of 9 instead of 8:
colourless oil.
Yield: 1.82 g (90%); IR (®lm): ꢂ ˆ 1607 (C=N and C=C) cmꢁ1; 1H NMR (CDCl3): ꢃ ˆ 1.67±2.00
(m, 2H, SCH2CH2CH2S), 2.40±2.70 (m, 4H, SCH2CH2CH2S), 3.23 and 3.43 (2s, 2H, CH2 (Z) and
(E) isomer), 3.63 and 3.83 (2s, 3H, NOCH3 (E) isomer, NOCH3 (Z) isomer together with 6H of 2
C±OCH3), 6.57±6.82 (m, 4H, arom), 7.02±7.37 (m, 2H, arom), 7.48±7.77 (m, 2H, arom) ppm;
C21H25NO3S2 (403.6); calcd.: C 62.50, H 6.24, N 3.47; found: C 62.39, H 6.13, N 3.77.
Reaction of C-2-lithiated 2-(4-methoxyphenyl)-1,3-dithiane (14) with (E/Z)-2-chloro-1-
(4-methoxyphenyl)ethanone oxime ((E/Z)-15)
Under N2, 3.5 ml of a 1.6 M solution of n-BuLi in hexane are added to a solution of 1.13 g (5 mmol)
of 14 in 25 ml of dry THF at ꢁ78ꢀC. After stirring for 1 h at ꢁ78ꢀC, a solution of 0.40 g (2 mmol) of
(E/Z)-15 in 5 ml of dry THF is added. After 20 min of stirring at ꢁ78ꢀC, 5 ml of half-satd. NH4Cl
solution are added, the organic phase is separated, and the aqueous layer is extracted with EtOAc
(15 ml). The combined organic phases are washed with brine (2Â5 ml), dried, and evaporated to give
a pale yellow solid; yield 1.20 g, mixture of 14 and (E)-12 (1H NMR).

Oximes and Oxime Ethers of Monothioketalized 1,3-Diketones
947
(E/Z)-2-Chloro-1-(4-methoxyphenyl)ethanone O-(trimethylsilyl)oxime ((E/Z)-16)
At 0ꢀC, a solution of 2.63 g (26 mmol) of Et3N in 15 ml of dry benzene and a solution of 2.83 g
(26 mmol) of chlorotrimethylsilane in 15 ml of dry benzene are added simultaneously dropwise to a
solution of 5.0 g (25 mmol) of (E/Z)-15 in 65 ml of dry benzene under N2. After addition, stirring is
continued for 2 h at 0ꢀC, for 1 h at re¯ux, and for 20 min at 0ꢀC. The mixture is sucked off, the ®lter
cake is washed with dry benzene (2Â20 ml), and the combined ®ltrates are evaporated. Kugelrohr
distillation (7Â10ꢁ5 torr, oven temp. 140ꢀC) affords (E/Z)-16 as a colourless oil.
1
Yield: 3.85 g (57%); IR (®lm): ꢂ ˆ 1611 (C=N and C=C) cmꢁ1; H NMR (CDCl3): ꢃ ˆ 0.30 (s,
9H, Si(CH3)3), 3.83 (s, 3H, OCH3), 4.50 and 4.62 (2s, 2H, CH2 (E) and (Z) isomer), 6.98, 7.73 (AA0
BB0, JAB ˆ 9 Hz, 4H, arom) ppm; C12H18ClNO2Si (271.8); calcd.: C 53.02, H 6.67, N 5.15; found: C
53.16, H 6.62, N 5.30.
(Z)-2-Bromo-1-(4-methoxyphenyl)ethanone O-(trimethylsilyl)oxime ((Z)-17)
At 0ꢀC, 2.73 g (27 mmol) of Et3N and 4.13 (27 mmol) of bromotrimethylsilane, each dissolved in
10 ml of dry benzene, are added simultaneously dropwise to a solution of 3.66 g (15 mmol) of (Z)-2-
bromo-1-(4-methoxyphenyl)ethanone oxime [30] in 50 ml of dry benzene under N2. The resulting
mixture is stirred for 1 h at 0ꢀC and for 2 h at 50ꢀC. After further 20 min at 0ꢀC, the mixture is sucked
off, and the ®lter cake is washed with dry benzene (2 Â 20 ml). The combined ®ltrates are evaporated
and dried at the oil pump. 50 ml of PE are added, the gummy residue is kneaded with a glass rod, and
the PE is decanted. This procedure is repeated twice with 25 ml of PE each. Evaporation of the
combined PE solutions and Kugelrohr distillation (7Â10ꢁ5 torr, oven temp. 150ꢀC) gives (Z)-17 as a
pale yellow oil.
1
Yield: 3.30 g (69%); IR (®lm): ꢂ ˆ 1622 (C=N and C=C) cmꢁ1; H NMR (CDCl3): ꢃ ˆ 0.30 (s,
9H, Si(CH3)3), 3.80 (s, 3H, OCH3), 4.40 (s, 2H, CH2), 6.93, 7.73 (AA0BB0, JAB ˆ 9 Hz, 4H,
arom) ppm; C12H18BrNO2Si (316.3); C 45.57, H 5.74, N 4.43; found: C 45.40, H 5.56, N 4.41.
(E)-2-(2-(4-Methoxyphenyl)-1,3-dithian-2-yl)-1-(4-methoxyphenyl)ethanone oxime ((E)-12)
To a solution of lithiated 14 (5 mmol), prepared as described for the reaction of (E/Z)-15, a solution
of 1.36 g (5 mmol) of (E/Z)-16 in 5 ml of dry THF is added at ꢁ78ꢀC. After 30 min of stirring at
ꢁ78 ꢀC, the cooling bath is removed; stirring is continued for 20 min. 10 ml of AcOH and 5 ml of
H2O are added, and stirring is continued overnight. The mixture is alkalized by addition of 15 g solid
anhydrous Na2CO3 in small quantities and extracted with EtOAc (3Â50 ml). The combined EtOAc
layers are washed with satd. NaHCO3 solution (30 ml) and brine (2Â30 ml), dried, and evaporated.
Recrystallization from 15 ml of CHCl3 provides (E/Z)-12 as colourless crystals; yield: 1.56 g (80%).
Three further recrystallizations from CHCl3 afford isomerically pure (E)-12 as colourless crystals.
1
Yield: 0.96 g (49%); m.p.: 156ꢀC; IR (KBr): ꢂ ˆ 3228 (OH), 1605 (C=N and C=C) cmꢁ1; H
NMR (CDCl3): ꢃ ˆ 1.67±2.00 (m, 2H, SCH2CH2CH2S), 2.47±2.73 (m, 4H, SCH2CH2CH2S), 3.50 (s,
2H, CH2), 3.75 (s, 3H, OCH3), 3.78 (s, 3H, OCH3), 6.60±6.85 (m, 4H, arom), 7.13±7.33 (m, 2H,
arom), 7.60±7.80 (m, 2H, arom), 7.90 (s, 1H, OH, exch.) ppm; C20H23NO3S2 (389.5); calcd.: C
61.67, H 5.95, N 3.60; found: C 61.87; H 6.00, N 3.56.
Reaction of lithiated 14 with (Z)-17 / Desilylation with AcOH/H2O affording (E/Z)-12
Instead of (E/Z)-16, a solution of 1.60 g (5 mmol) of (Z)-17 in 5 ml of dry THF is added to a solution
of lithiated 14 (5 mmol). The crude product is boiled with 5 ml of CHCl3 and sucked off while hot.
The ®ltrate is left at 4ꢀC for crystallization, and the crystals are ®ltered off. This procedure is
repeated with 8 ml of CHCl3 to give (E/Z)-12 as colourless crystals. Yield: 1.03 g (53%).

948
A. Kaiser and W. Wiegrebe
The ®lter cake of the above CHCl3 extractions consists of dioxime 21a: colourless crystals, yield:
0.23 g; for analytical data, see Ref. [26].
Reaction of lithiated 14 with (E/Z)-16 / Desilylation with TBAF affording (E/Z)-12
Instead of (AcOH/H2O [17], a solution of 4.73 g (15 mmol) TBAF Á 3H2O [18] in 20 ml of THF is
added. After 45 min, 10 ml of satd. NH4Cl solution are added; the org. layer is separated, and the
aqueous layer is extracted with EtOAc (2Â20 ml). The combined org. phases are washed with brine
(2Â10 ml), dried, and evaporated. After drying at the oil pump, the oily residue is dissolved in 7 ml
of MeOH and left for 1 h for crystallization. Recrystallization from 10 ml of CHCl3 affords (E/Z)-12
as colourless crystals. Yield: 1.26 g (65%), data: see above.
Reaction of lithiated 14 with (Z)-17 / Desilylation with TBAF affording (E)-12
The procedures described above are used, affording stereochemically pure (E)-12; yield: 1.0 g
(51%).
(E)-2-(2-(4-Methoxyphenyl)-1,3-dithian-2-yl)-1-(4-methoxyphenyl)ethanone O-methyloxime
((E)-13)
At ꢁ78ꢀC, a solution of 1.07 g (5 mmol) of (Z)-18 in 5 ml of dry THF is added to a solution of
lithiated 14 (5 mmol) prepared as described above. After 2 h of stirring at ꢁ78ꢀC, the reaction is
terminated by addition of 6 ml of half-satd. NH4Cl solution; the org. layer is separated, and the
aqueous layer is extracted with Et2O (2 Â 20 ml). The combined org. phases are washed with brine
(2 Â 8 ml), dried, and evaporated to give a yellow oil which crystallizes upon drying at the oil
pump. Recrystallization from 30 ml of MeOH (tends to separate as an oil, addition of seed
crystals recommended; crystallization ®rst at room temp., then at 4ꢀC) affords (E)-13 as colourless
crystals.
1
Yield: 1.61 g (80%); m.p.: 92ꢀC; IR (KBr): ꢂ ˆ 1607 (C=N and C=C) cmꢁ1; H NMR (CDCl3):
ꢃ ˆ 1.67±2.00 (m, 2H, SCH2CH2CH2S), 2.40±2.70 (m, 4H, SCH2CH2CH2S), 3.43 (s, 2H, CH2), 3.63
(s, 3H, NOCH3), 3.77 (s, 6H, 2 OCH3), 6.63±6.83 (m, 4H, arom), 7.20±7.40 (m, 2H, arom), 7.63±
7.80 (m, 2H, arom) ppm; C21H25NO3S2 (403.6); calcd.: C 62.50, H 6.24, N 3.47; found: C 62.68, H
6.17, N 3.66.
Starting from (E/Z)-18, the crude product is puri®ed by CC (Et2O/PE 2/8) affording (E/Z)-12 as a
colourless oil; yield: 1.72 g (85%).
2,20-Bis(4-methoxyphenyl)-2,20-bi-1,3-dithianyl (20) and (E,E)-1,4-bis(4-methoxyphenyl)-
1,4-butandione bis(O-methyloxime) (21)
At ꢁ78ꢀC, a solution of 1.53 g (5 mmol) of (Z)-19 in 5 ml of dry THF is added to a solution of
lithiated 14 (5 mmol). After 1 h of stirring at ꢁ78ꢀC, the cooling bath is removed, and stirring is
continued for 30 min. 5 ml of half-satd. NH4Cl solution are added; the org. phase is separated, and
the aqueous phase is extracted with EtOAc (2Â15 ml). The combined org. layers are washed with
brine (2Â10 ml), dried, and evaporated to give a yellow solid (2.2 g) containing 20 and 21.
20: The residue is boiled with 13 ml of EtOH and sucked off while hot. The ®lter cake is
recrystallized from 11 ml of nitromethane to provide 20 as colourless crystals.
1
Yield: 0.43 g; m.p.: 197±198 ꢀC; IR (KBr): ꢂ ˆ 1601, 1503 (C=C) cmꢁ1; H NMR (CDCl3):
ꢃ ˆ 1.60±2.00 (m, 4H, 2 SCH2CH2CH2S), 2.28±2.77 (m, 8H, 2 SCH2CH2CH2S), 3.80 (s, 6H, 2
OCH3), 6.67, 738 (AA0BB0, JAB ˆ 9 Hz, 8H, arom) ppm; C22H26O2S4 (450.7); calcd.: C 58.63, H
5.82; found: C 58.33, H 5.84.

Oximes and Oxime Ethers of Monothioketalized 1,3-Diketones
949
21: Bisoxime ether 21 crystallizes from the ®ltrate; colourless crystals, yield: 0.45 g; for
analytical data, see Ref. [2].
(E)-2-(2-(4-Methoxyphenyl)-1,3-dithian-2-yl)-1-(4-methoxyphenyl)ethanone O-methyloxime ((E)-13)
from lithiated 1-(4-methoxyphenyl)ethanone O-methyloxime (23) and 2-(4-methoxyphenyl)-1,3-
dithienium tetra¯uoroborate (24)
At ꢁ78ꢀC, 7.0 ml of a 1.6 M solution of n-BuLi in hexane are added within 3 min to a solution of
1.79 g (10 mmol) of 23 in 20 ml of dry THF. After stirring for 40 min at ꢁ78ꢀC, 3.0 g (10.2 mmol) of
24 [7], suspended in 10 ml of dry THF, are added. After 45 min of stirring at ꢁ78ꢀC, the cooling bath
is removed and stirring is continued for 30 min. The reaction is terminated by addition of 4 ml of
H2O; the org. phase is separated, and the aqueous phase is extracted with EtOAc (50 ml). The
combined org. phases are washed with brine (2Â10 ml), dried, and evaporated. CC (Et2O/PE 1/1)
affords a yellow oil which is dissolved in 5 ml of Et2O. Then, 10 ml of PE and seed crystals are
added. At 4ꢀC, crystals of (E)-13 separate and are ®ltered off. Yield: 1.63 g (40%). For analytical
data, see above.
Hydrolysis of (E)-4 and (Z)-4 to (E)-3-methoxyimino-1,3-bis(4-methoxyphenyl)-1-propanone (25)
At room temp., a mixture of 0.18 g (0.5 mmol) of (E)- or (Z)-4, 2.5 ml of EtOH, 0.3 ml of H2O, and 7
drops of CF3COOH is stirred for 9 h, diluted with 15 ml of EtOAc, dried (K2CO3), and evaporated to
afford 0.13 g (83%) of 25 as colourless crystals. For analytical data, see Ref. [26].
2-(2-(4-Methoxyphenyl)-1,3-dioxolan-2-yl)-1-(4-methoxyphenyl)ethanamine (26)
6.3 g (17.6 mmol) of (E/Z)-4 and 53 ml (53 mmol) of a 1 M solution of BH3 Á THF in THF are heated
under re¯ux for 60 h. After cooling to 0 ꢀC, the excess of BH3 Á THF is carefully destroyed by
dropwise addition of 5 ml of H2O and 50 ml of 3 N NaOH. The mixture is re¯uxed for 15 min; THF is
evaporated, and the residue is extracted with EtOAc (3Â 50 ml). The combined EtOAc phases are
washed with brine (2Â 30 ml), dried, and evaporated. Puri®cation by CC (CH2Cl2/MeOH 9/1) yields
26 as a colourless oil.
1
Yield: 2.05 g (35%); IR (®lm): ꢂ ˆ 3386 (NH) cmꢁ1; H NMR (CDCl3): ꢃ ˆ 2.07±2.33 (m, 2H,
CH2), 2.80 (s, 2H, NH2, exch.), 3.50±4.23 (m, 11H, OCH2CH2O, 2 OCH3 and CH), 6.67±7.50 (m,
8H, arom) ppm; C19H23NO4 (329.4); calcd.: C 69.28, H 7.04, N 4.25; found: C 68.21, H 7.06, N 4.39
(better values for the carbon content could not be obtained).
2-(2-(4-Methoxyphenyl)-1,3-dithiolan-2-yl)-1-(4-methoxyphenyl)ethanamine (27)
5.84 g (15 mmol) of (E/Z)-11 and 60 ml (60 mmol) of a 1 M solution of BH3 Á THF in THF are heated
under re¯ux for 60 h. After cooling to 0ꢀC, the excess of BH3 Á THF is carefully destroyed by
dropwise addition of 7 ml of H2O und 6 ml of conc. HCl. The mixture is re¯uxed for 5 min, cooled,
alkalized by addition of 20 ml of H2O and 10 g of KOH in small amounts, and again re¯uxed for
10 min. After cooling, the THF phase is separated, and the aqueous phase is extracted with 50 ml of
THF. The combined THF phases are washed with brine (2Â15 ml), dried, and evaporated. CC
(CH2Cl2/MeOH 9/1) affords 27 as a colourless oil.
1
Yield: 4.69 g (86%); IR (®lm): ꢂ ˆ 3370 (NH) cmꢁ1; H NMR (CDCl3): ꢃ ˆ 1.50 (s, 2H, NH2,
exch.), 2.62±2.77 (m, 2H, CH2), 3.30±3.47 (m, 4H, SCH2CH2S), 3.67±3.87 (m, 1H, CH), 3.73
(s, 3H, OCH3), 3.78 (s, 3H, OCH3), 6.67±6.90 (m, 4H, arom), 7.00±7.23 (m, 2H, arom), 7.52±7.73
(m, 2H, arom) ppm; C19H23NO2S2 (361.5): calcd.: C 63.12, H 6.41, N 3.88; found: C 62.80, H 6.29,
N 3.96.

950
A. Kaiser and W. Wiegrebe
2-(2-(4-Methoxyphenyl)-1,3-dithian-2-yl)-1-(4-methoxyphenyl)ethanamine (28)
Starting from 6.05 g (15 mmol) of (E/Z)-13, the procedure given above for 27 affords 28 as a
colourless oil.
1
Yield: 4.80 g (85%); IR (®lm): ꢂ ˆ 3367 (NH) cmꢁ1; H NMR (CDCl3): ꢃ ˆ 1.47 (s, 2H, NH2,
exch.), 1.73±2.08 (m, 2H, SCH2CH2CH2S), 2.37 (d, J ˆ 6 Hz, 2H, CH2), 2.58±2.83 (m, 4H,
SCH2CH2CH2S), 3.77 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 4.05 (t, J ˆ 6 Hz, 1H, CH), 6.73±7.27 (m,
6H, arom), 7.77±7.97 (m, 2H, arom) ppm; C20H25NO2S2 (375.6); calcd.: C 63.96, H 6.72, N 3.73;
found: C 64.05, H 6.69, N. 3.77.
N-(2-(2-(4-Methoxyphenyl)-1,3-dioxolan-2-yl)-1-(4-methoxyphenyl)ethyl)acetamide (29)
At room temp., 0.81 g (2.46 mmol) of 26 dissolved in 30 ml of dry CH2Cl2 are stirred with 0.34 g
(4.3 mmol) of pyridine and 0.44 g (4.3 mmol) of Ac2O for 4 h. The mixture is diluted with 20 ml of
CH2Cl2, cooled to 0ꢀC, and quickly washed with ice-cold 2 N HCl (20 ml). The CH2Cl2 layer is
immediately separated and instantly washed with satd. NaHCO3 solution (20 ml) and brine (20 ml),
dried, and evaporated. CC (Et2O/CH2Cl2 7/3) affords 29 as a colourless oil.
Yield: 0.62 g (68%); IR (®lm): ꢂ ˆ 3292 (NH), 1650 (C=O) cmꢁ1; 1H NMR (CDCl3): ꢃ ˆ 1.90 (s,
3H, COCH3), 2.15±2.43 (m, 2H, CH2), 3.48±4.03 (m, 10H, OCH2CH2O and 2 OCH3), 4.77±5.07 (m,
1H, CH), 6.47±7.47 (m, 8H, arom, and 1H, NH, exch.) ppm; C21H25NO5 (371.4); calcd.: C 67.91, H
6.78, N 3.77; found: C 67.25, H 6.72, N 3.96.
N-(2-(2-(4-Methoxyphenyl)-1,3-dithiolan-2-yl)-1-(4-methoxyphenyl)ethyl)acetamide (30)
At room temp., 8.02 g (22.2 mmol) of 27 in 200 ml of dry CH2Cl2 are treated with 2.6 g (33 mmol) of
pyridine and 3.37 g (33 mmol) of Ac2O. After stirring for 4 h, the mixture is diluted with 100 ml of
CH2Cl2, washed with 2 N HCl (70 ml), satd. NaHCO3 solution (70 ml), and brine (70 ml), dried, and
evaporated. After drying at the oil pump, for foamy residue (9.05 g) is dissolved in 20 ml of Et2O and
left ®rst at room temp., then at 4ꢀC, then at ꢁ18ꢀC for crystallization to give slightly yellow crystals.
Yield: 8.17 g (91%); m.p.: 118ꢀC; IR (KBr): ꢂ ˆ 3261 (NH), 1644 (C=O) cmꢁ1
;
1H NMR
(CDCl3): ꢃ ˆ 1.77 (s, 3H, COCH3), 2.70±2.90 (m, 2H, CH2), 3.07±3.40 (m, 4H, SCH2CH2S), 3.75 (s,
3H, OCH3), 3.80 (s, 3H, OCH3), 4.63±4.95 (m, 1H, CH), 5.87 (d, J ˆ 10 Hz, 1H, NH, exch.), 6.70±
7.17 (m, 6H, arom), 7.50±7.73 (m; 2H, arom) ppm; C21H25NO3S2 (403.6); calcd.: C 62.50, H 6.24, N
3.47; found: C 62.39, H 6.27, N 3.62.
N-(2-(2-(4-Methoxyphenyl)-1,3-dithian-2-yl)-1-(4-methoxyphenyl)acetamide (31)
The procedure described for 30 is used starting from 8.34 g (22.2 mmol) of 28. CC (CH2Cl2/Et2O
7/3; for application onto the silica, the residue is taken up in CH2Cl2) affords 31 as a colourless foam.
Yield: 8.71 g (94%); IR (®lm): ꢂ ˆ 3280 (NH), 1650 (C=O) cmꢁ1; 1H NMR (CDCl3): ꢃ ˆ 1.72 (s,
3H, COCH3), 1.80±2.07 (m, 2H, SCH2CH2CH2S), 2.37±2.83 (m, 6H, CH2 and SCH2CH2CH2S),
3.73 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 4.83±5.17 (m, 1H, CH), 5.58 (d, J ˆ 9 Hz, 1H, NH, exch.),
6.67±7.15 (m, 6H, arom), 7.73±7.93 (m, 2H, arom) ppm; C22H27NO3S2 (417.6); calcd.: C 63.28, H
6.52, N 3.35; C 62.71, H 6.36, N 3.50.
N-(1,3-Bis(4-methoxyphenyl)-3-oxo-1-propyl)acetamide (32)
2.2 ml of H2O and 40 drops of CF3COOH are added to a solution of 0.74 g (2 mmol) of 29 in 6 ml of
slightly warmed EtOH. After 4 h at room temp. and 5 h at 4ꢀC, the crystals are sucked off, washed
successively with satd. NaHCO3 solution (2Â5 ml) and water (2Â6 ml), dried, and recrystallized
from 0.6 ml of EtOH to afford 32 as colourless crystals.

Oximes and Oxime Ethers of Monothioketalized 1,3-Diketones
951
Yield: 0.46 g (70%); m.p.: 128ꢀC; IR (KBr): ꢂ ˆ 3272 (NH), 1679 (C=O), 1636 (NC=O) cmꢁ1
;
1H NMR (CDCl3): ꢃ ˆ 1.97 (s, 3H, COCH3), 3.13±3.87 (m, 2H, CH2), 3.73 (s, 3H, OCH3), 3.87 (s,
3H, OCH3), 5.33±5.60 (m, 1H, CH), 6.70±7.00 (m, 4H, arom and 1H, NH, exch.), 7.13±7.33 (m, 2H,
arom), 7.80±8.00 (m, 2H, arom) ppm; C19H21NO4 (327.4); calcd.: C 69.71, H 6.47, N 4.28; found: C
69.44, H 6.54, N 4.30.
32 from 30 or 31
A solution of 11.3 g (40 mmol) of chloramine T (N-chlorotoluenesulfonamide sodium salt) in 35 ml
of MeOH and 9 ml of H2O is added to a solution of 10 mmol of 30 or 31 in 17 ml of MeOH. After
stirring at room temp. for 10 min the mixture is poured into 500 ml of H2O, alkalized by addition of
50 ml of 3 N NaOH, and extracted with EtOAc (3Â100 ml). The combined EtOAc phases are washed
with 3 N NaOH (3Â100 ml) and brine (2Â100 ml), dried, and evaporated.
After drying at the oil pump, recrystallization from 5 ml of EtOH affords 32 as colourless
crystals. Yield: 2.91 g (89%).
N-(3-Hydroxyimino-1,3-bis(4-methoxyphenyl)-1-propyl)acetamide (33)
3.27 g (10 mmol) of 32 and 1.74 g (25 mmol) of hydroxylammonium chloride in 8 ml of pyridine are
stirred for 3 h at 70ꢀC. Pyridine is removed in vacuo; the residue is thoroughly mixed with 30 ml of
2 N HCl and 20 ml of EtOAc and left for crystallization. The crystals formed are ®ltered off, washed
successively with 2 N HCl (10 ml), satd. NaHCO3 solution (2Â10 ml), and H2O (2Â10 ml), and dried
to give a ®rst crop (2.49 g) of crude 33.
After dilution of the ®ltrate with 20 ml of EtOAc, the org. phase is separated, washed with satd.
NaHCO3 solution (10 ml) and brine (2Â10 ml), dried, and evaporated to give a brown oil (0.58 g)
which crystallizes upon drying at the oil pump. The two crops are combined and recrystallized from
9 ml of nitromethane to afford 33 as colourless crystals.
Yield: 2.74 g (80%); m.p.: 172ꢀC; IR (KBr): ꢂ ˆ 3311 (br, OH and NH), 1648 (C=O) cmꢁ1
;
1H NMR (DMSO-d6): ꢃ ˆ 1.73 (s, 3H, COCH3), 2.93±3.23 (m, 2H, CH2), 3.73 (s, 3H, OCH3), 3.78
(s, 3H, OCH3), 4.97±5.33 (m, 1H, CH), 6.73±7.60 (m, 8H, arom), 8.26 (d, J ˆ 9 Hz, 1H, NH, exch.),
11.12 (s, 1H, OH, exch.) ppm; C19H22N2O4 (342.4); calcd.: C 66.65, H 6.48, N 8.18; C 66.43, H
6.58, N 8.15.
N-(3-Methoxyimino-1,3-bis(4-methoxyphenyl)-1-propyl)acetamide (34)
2.29 g (7 mmol) of 32 and 1.17 g (14 mmol) of O-methylhydroxylammonium chloride in 5 ml of
pyridine are stirred for 7 h at 70ꢀC. Pyridine is removed in vacuo; the residue is mixed with 25 ml of
2 N HCl and extracted with EtOAc (3Â40 ml). The combined org. layers are washed with satd.
NaHCO3 solution (30 ml) and brine (2Â30 ml), dried, and evaporated. After drying at the oil pump,
recrystallization from 4 ml of EtOH gives 32 as colourless crystals.
Yield: 1.54 g (69%); m.p.: 132ꢀC; IR (KBr): ꢂ ˆ 3305 (NH), 1652 (C=O) cmꢁ1
;
1H NMR
(CDCl3): ꢃ ˆ 1.87 (s, 3H, COCH3), 2.80±3.10 (m, 1H, HCH), 3.27±3.57 (m, 1H, HCH), 3.75 (s, 3H,
OCH3), 3.80 (s, 3H, OCH3), 3.93 (s, 3H, NOCH3), 4.83±5.23 (m, 1H, CH), 6.40 (d, J ˆ 7 Hz, 1H,
NH, exch.), 6.73±6.97 (m, 4H, arom), 7.12±7.33 (m, 2H, arom), 7.45±7.67 (m, 2H, arom) ppm;
C20H24N2O4 (356.4); calcd.: C 67.40, H 6.79, N 7.86; found: C 67.22, H 6.95, N 7.95.
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Received March 3, 1998. Accepted March 26, 1998