Synthesis and characterization of α,β-unsaturated hydroximoyl chlorides and hydroximates

Article abstract of DOI:10.1071/CH06188

New α,β-unsaturated hydroximoyl chlorides (PhC(Cl)≤CHC(Cl) ≤NOCH₃) and hydroximates (PhC(OCH₃)≤CHC(OCH ₃)≤NOCH₃) were prepared. The ZZ-isomer of PhC(Cl)≤CHC(Cl)≤NOCH₃ was prepared in four steps from e

Full text of DOI:10.1071/CH06188

Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2006, 59, 439–444
Synthesis and Characterization of α,β-Unsaturated Hydroximoyl
Chlorides and Hydroximates
James E. Johnson,A,D Ling Lu,A Houquan Dai,A Diana C. Canseco,A Krista M. Small,A
Debra D. Dolliver,B and Frank R. FronczekC
A Department of Chemistry and Physics, Texas Woman’s University, Denton, TX 76204, USA.
B Department of Chemistry and Physics, Southeastern Louisiana University, Hammond, LA 70402, USA.
C Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA.
D Corresponding author. Email: jjohnson@mail.twu.edu
New α,β-unsaturated hydroximoyl chlorides (PhC(Cl)=CHC(Cl)=NOCH3) and hydroximates (PhC(OCH3)=
CHC(OCH3)=NOCH3) were prepared. The ZZ-isomer of PhC(Cl)=CHC(Cl)=NOCH3 was prepared in four steps
from ethyl benzoylacetate. Ultraviolet irradiation of the ZZ-isomer gives a mixture of all four possible isomers.
Sodium methoxide was reacted with these isomers to determine the configuration about the carbon–carbon double
bond for each. The Z-isomers reacted with sodium methoxide to give the corresponding alkyne by elimination
whereas the E-isomers gave the substitution product. The configuration about the carbon–nitrogen double bond was
determined from the 1H NMR chemical shift of the NOCH3 group.
Manuscript received: 1 June 2006.
Final version: 20 July 2006.
OCH3
Introduction
X
X
C
N
C
N
The imine functional group (>C=N–) is an important
part of many therapeutic agents. For example, many third-
generation cephalosporins (cefpodoxime, ceftriaxone, and
ceftazidine)[1] contain an O-alkyloxime (N-alkoxyimine)
functional group.These compounds are among the most com-
monly prescribed antibiotics. The antibiotic gemifloxacin
(Factive),[2] developed by GlaxoSmithKline to help com-
bat the problem of bacterial resistance to antibiotics, also
contains an O-methyloxime group. Oximidines, which may
act as selective antitumor drugs, contain an O-alkyloxime
moiety (>C=NOCH3).[3] Therefore the need for a funda-
mental understanding of the mechanisms of the reactions of
compounds containing this functional group is apparent.
It is well known that compounds containing a carbon–
nitrogen double bond undergo photochemical and acid-
catalyzed Z/E-isomerization.[4–14] Athough much less com-
mon, base-catalyzed isomerization of imines have also been
reported.[15–17] We have been particularly interested in
mechanisms of acid- and base-catalyzed isomerization of
imines. Although the mechanisms of these isomerizations
have received some attention[6–17] they are still not com-
pletely understood. The high resistance of O-alkyloximes
and their derivatives to thermal Z/E-isomerization makes
these compounds ideally suited for studies on the acid- and
base-catalyzed Z/E-isomerization mechanism.
Ph
Ph
OCH3
1Z
1E
a: X = Cl
b: X = OCH3
c: X = OCH2CH3
Fig. 1.
OCH3
X
X
C
N
C
H
N
H
H
OCH3
C
C
C
C
H
Ph
Ph
2E
2Z
a: X = Cl
b: X = OCH3
Fig. 2.
catalysis when the isomerization is carried out in H36Cl/diox-
ane solution. Measurement of the rate of incorporation of
radioactive chloride during the isomerization of 1Ea to 1Za
demonstrated that the isomerization must take place by nucle-
ophilic attack on carbon to give a tetrahedral intermediate
(nucleophilic catalysis).
In1981wereported[13a] experimentalevidencethatunam-
biguously demonstrated that O-methylbenzohydroximoyl
chlorides (1Ea and 1Za, Fig. 1) isomerize by nucleophilic
More recently we have reported[14] on the kinetics
and mechanism of acid-catalyzed Z/E-isomerization of
O-methylbenzohydroximoyl chloride (1Za and 1Ea), methyl
© CSIRO 2006
10.1071/CH06188
0004-9425/06/070439

440
J. E. Johnson et al.
Cl
HO
EtO
C
O
C
O
CH3
O
H
(1) PCl5
(2) H2O
C
O
O
CH3
Cl
Cl
Ph
O
SOCl2
N
C
C
C
C
CH3
O
C
CH2
Ph
H
Ph
H
H
C
C
5
3
4
CH3ONH3Cl
NEt3
PCl
5
O
Fig. 3.
OCH3
Cl
C
N
H
CH3ONH3Cl
NEt3
Cl
Cl
C
O
C
C
O-methylbenzohydroximate (1Zb and 1Eb), ethyl
O-methylbenzohydroximate (1Zc and 1Ec), O-methylcinna-
mohydroximoyl chloride (2Ea and 2Za, Fig. 2), and methyl
O-methylcinnamohydroximate (2Eb and 2Zb). The kinet-
ics of Z/E-isomerization were studied in glacial acetic acid
and in dioxane solutions containing hydrochloric, trifluo-
romethanesulfonic, or tetrafluoroboric acid. This study
showed that the O-methylbenzohydroximoyl chlorides
only isomerize by nucleophilic attack by chloride ion
on the protonated imine (nucleophilic catalysis). Methyl
O-methylbenzohydroximate (1Zb and 1Eb) is capable of
isomerizing by either nucleophilic catalysis or by rotation
about the carbon–nitrogen double bond of the N-protonated
intermediate (an iminium ion; protonation–rotation mecha-
nism). Methyl O-methylcinnamohydroximate (2Zb and 2Eb)
isomerized only by the protonation–rotation mechanism.
Theoretical calculations supported the notion that increased
conjugation of protonated imines increases the rate of
iminium ion rotation.
The purpose of this work was to synthesize and char-
acterize new α,β-unsaturated hydroximoyl chlorides and
hydroximates whose conjugate acids are expected to have
lower rotational barriers than any compounds we have stud-
ied previously. We are especially interested in synthesizing
compounds that contain a methoxy group in the β-position
of cinnamohydroximoyl chlorides and hydroximates since
iminium ions from these compounds should have low barri-
ers to rotation (shown for a β-methoxycinnamohydroximate,
Fig. 3).
C
C
Ph
H
Ph
H
5
6
PCl5
Cl
C
OCH3
C
N
Cl
C
Ph
H
7ZZ
Scheme 1.
Cl
OCH3
Cl
C
H
N
h ν
C
C
Ph
7ZZ
Cl
C
Cl
Cl
OCH3
Ph
Cl
Ph
Cl
C
N
C
N
C
H
N
ϩ
C
C
ϩ
C
OCH3
C
C
OCH3
H
Cl
H
Ph
7ZE
7EE
7EZ
Scheme 2.
Cl
OCH3
OCH3
Cl
C
N
NaOCH3
CH3OH
Ph
C
C
C
C
C
Ph
H
N
OCH3
7ZZ
Cl
8Z
Results and Discussion
OCH3
NaOCH3
Methyl (Z)-β-chlorocinnamohydroxamate (6), O-methyl-β-
chlorocinnamohydroximoyl chloride (7ZZ, 7ZE, 7EE, and
7EZ), methyl O-methyl-β-phenylpropynohydroximate (8E
and 8Z), and methyl O-methyl-β-methoxycinnamohydroxi-
mate (9ZE and 9EE) were synthesized according to
Schemes 1–3. Methyl (Z)-β-chlorocinnamohydroxamate (6)
was prepared by two different methods (Scheme 1). In
the first method, ethyl benzoylacetate (3) was reacted with
phosphorus pentachloride followed by hydrolysis.[18] The
β-chlorocinnamic acid (4) produced in this reaction was a
mixture of Z- and E-isomers. As described previously,[18] the
Z-isomer selectively formed a precipitate of the barium salt
when a mixture of the E- and Z-isomers was dissolved in
aqueous ammonia followed by the addition of barium chlo-
ride.ThebariumsaltoftheZ-isomerwasfilteredandacidified
with hydrochloric acid to give (Z)-β-chlorocinnamic acid (4).
Cl
C
N
Ph
C
C
C
OCH3
OCH3
C
C
CH3OH
N
Ph
H
CH3O
7EZ
8E
Cl
C
CH3O
OCH3
Ph
Ph
NaOCH3
CH3OH
C
N
C
N
C
C
C
CH3O
H
Cl
H
7ZE
9ZE
CH3O
Cl
NaOCH3
CH3OH
Ph
Cl
Ph
C
H
N
C
H
N
C
C
C
C
OCH3
OCH3
CH3O
7EE
9EE
Scheme 3.

α,β-Unsaturated Hydroximoyl Chlorides and Hydroximates
441
formed in the smallest amount in the photoisomerization of
7ZZ.Also, it partially overlapped with 7ZZ when the mixture
was separated by column chromatography.
The four isomers of 7 were reacted with sodium methox-
ide (1:2 mol ratio of 7 to methoxide ion, Scheme 3).
Two of the isomers (7ZZ and 7EZ) underwent elimina-
tion of HCl to give the corresponding methyl O-methyl-
β-phenylpropynohydroximate (8Z and 8E). The other two
isomers (7ZE and 7EE) underwent substitution to give
methyl β-methoxy-O-methylcinnamohydroximate (9ZE and
9EE). Small sample sizes made isolation of the hydroxi-
mates 9ZE, 9EE, and 8E impractical, so these compounds
were identified only from their mass spectra obtained during
GC-MS analysis of the crude reaction products.
In our earlier work[19–24] it was found that the NMR
spectra of hydroximoyl halides,[19,22,23] hydroximates[25]
thiohydroximates,[24] hydroximoyl cyanides,[20] and amidox-
imes[21] were sufficiently different to make the assignment of
the configuration as long as both isomers were available. In
the halogen derivatives, the most stable isomers have always
been found to have the Z-configuration,[19,22,23] while with
hydroximates[15,25] the E-isomers predominate in DMSO
solution and an equilibium mixture of equal proportions of
Z- and E-isomers is produced in glacial acetic acid.[14] The
N-methoxyabsorptioninthe1HNMRspectrumofaZ-isomer
is further downfield than the absorption in the corresponding
E-isomer.
The four isomers of 7 were identified using the follow-
ing methods. The configuration about the carbon–carbon
double bond was determined from results of the reaction of
each isomer with sodium methoxide in methanol (Scheme 3).
The Z-isomers underwent an anti-elimination to give methyl
O-methyl-β-phenylpropynohydroximate. Because it is well
known that anti-elimination in vinyl halides is much faster
than syn-elimination,[26,27] it is reasonable to assume that
it is the Z-isomers (about the carbon–carbon double bond,
7ZZ and 7EZ) that underwent elimination to give 8Z and 8E
(identified only by their MS spectra). The structure of 7ZZ is
also consistent with the X-ray structural analysis of 6, which
shows that the carbon–carbon double bond in this compound
has the Z-configuration. Thus the reaction of 6 with PCl5
gives the expected hydroximoyl chloride (7ZZ) with reten-
tion of configuration at the carbon–carbon double bond. The
configuration about the carbon–nitrogen double bond was
determined by 1H NMR spectroscopy. In the closely related
Z- and E-isomers of O-methylcinnamohydroximoyl chloride
(2Za and 2Ea), and in all of the other hydroximoyl chlorides
that we have synthesized, the chemical shift of NOCH3 group
is further downfield in the Z-isomer. Table 1 gives a list of
the isomers with the order of retention time on a GC column
(J & W DB-5MS), retention on a column chromatography
column (silica gel), and the proton chemical shift of the
NOCH3 group.
Fig. 4. The three independent molecules of 6, with 50% ellipsoids.
Mean bond distances are C1–Cl1 1.739, C1–C2 1.335, C2–C3 1.479,
C3–O1 1.233, N1–C3 1.347, and N1–O2 1.390 Å.
Reaction of (Z)-β-chlorocinnamic acid with thionyl chloride
gave (Z)-β-chlorocinnamoyl chloride (5, not isolated) that
was reacted with methoxylamine hydrochloride and triethy-
lamine to give methyl (Z)-β-chlorocinnamohydroxamate (6).
Since 5 is likely to be formed as an intermediate in this
method, an alternate method of synthesizing 6 was devel-
oped (Scheme 1). In this procedure ethyl benzoylacetate was
reacted with phosphorus pentachloride followed by addition
of methoxylamine hydrochloride and triethylamine. In this
method column chromatography was necessary to prepare
pure 6.
The configuration of 6 was established by a single crystal
X-ray structure determination. Three independent molecules
are present in the asymmetric unit, as shown in Fig. 4.
There is good agreement in bond distances among the three
molecules, and mean values are given in the Fig. 4 cap-
tion. There is some variability, however, in the conformations
of the three. The C1–C2–C3–O1 torsion angle varies from
−2.4(2) to −14.7(2)◦, Cl1–C1–C4–C5 from −21.73(16)
to −36.63(17)◦, and C3–N1–O2–C10 from 88.58(15) to
96.79(14)◦. All N–H groups are involved in intermolecu-
lar hydrogen bonds, with carbonyl O1 atoms as acceptors.
The N1· · ·O1 distances range 2.7904(15)–2.8798(14) Å, and
N1–H–O1 angles range 161.3(16)–168.9(16)◦.
(Z,Z)-O-Methyl-β-chlorocinnamohydroximoyl chloride
(7ZZ) was synthesized (Scheme 1) by the reaction of 6 with
phosphorus pentachloride. All of the isomers (7ZE, 7EZ,
and 7EE) of (Z,Z)-O-methyl-β-chlorocinnamohydroximoyl
chloride (7ZZ) were prepared (Scheme 2) by prolonged
ultraviolet irradiation of a hexane solution of 7ZZ. GC-MS
analysis of the crude mixture indicated that the mixture con-
tained only three isomers. It was subsequently determined
that 7EZ and 7EE have identical retention times on the GC
column that we were using (J & W DB-5MS). The 1H NMR
spectrum of the crude product clearly showed that the pho-
tostationary mixture contained all four isomers 7ZZ, 7EZ,
7ZE, and 7EE in a 1.8:2.1:2.3:1.0 ratio. The isomers were
separated by column chromatography.Among those four iso-
mers, the 7EE isomer was the most difficult to isolate. It was
Conclusions
The structures of all four isomers of β-chlorocinnamohydrox-
imoyl chloride have been deduced. It is clear that improved

442
J. E. Johnson et al.
Table 1. 1H NMR chemical shifts, relative retention times, and reactivity of the stereoisomers of 7
Configuration
Retention order in gas
chromatography
(J & W DB-5MS)
Elution order in column
chromatography
(silica gel)
Reaction with excess
sodium methoxide
1H NMR
chemical shift
of NOCH3
EZ
EE
ZZ
ZE
1
1
3
2
1
2
3
4
Elimination to form alkyne
Substitution
Elimination to form alkyne
Substitution
3.89
3.84
4.07
3.97
yieldsforthesynthesisβ-methoxy-O-methylcinnamohydrox-
imates will require replacing the α-hydrogen with an alkyl or
aryl substituent in order to prevent the elimination reaction
observed in this work.
and the solid was collected. The precipitate was suspended in water and
acidified with hydrochloric acid (30 mL). The solid residue was puri-
fied by recrystallization from carbon tetrachloride. Pure 4 (15.8 g, 88%)
was obtained as a white microcrystalline solid. mp 146–147◦C (lit.[18]
145–146◦C). δH 6.61 (s, 1H), 7.43–7.46 (m, 3H), 7.70–7.13 (m, 2H). δC
115.4 (C), 127.4 (CH), 128.7 (CH), 131.1 (CH), 137.0 (C), 149.1(C),
168.8 (C).
Experimental
General Procedures
Methyl (Z)-β-Chlorocinnamohydroxamate 6 (Procedure 1)
Melting points were determined in a Mel-Temp capillary melting
point apparatus and are uncorrected. Infrared spectra of solids were
determined from Nujol mulls. Proton and carbon NMR spectra were
determined on a Varian Mercury 300 MHz spectrometer. Unless oth-
erwise noted, all NMR spectra were recorded in CDCl3 using TMS as
an internal standard. Low resolution mass spectra were determined on
Varian Saturn 3 ion-trap GC/MS spectrometer. Midwest Microlab (Indi-
anapolis, IN) performed the elemental analysis of the new compounds.
Photoisomerization was carried out using a Rayonet Photochemical
Reactor Model RPR-100 equipped with five lamps (254 nm) and a
merry-go-round rack. Separation of mixture of isomers was accom-
plished by column chromatography using silica gel (MN-Kieselgel 60,
70–130 mesh) that had been dried at 95◦C for ∼1 h before packing the
column. The progress of the chromatography was followed by thin-layer
chromatography.
Compound 4 (3.65 g, 0.02 mol) was mixed with thionyl chloride
(8.1 g, 0.06 mol) and chloroform (15 mL) and stirred for half an hour at
ambient temperature. The solution was then refluxed for approximately
3 h.The solvent and the excess thionyl chloride were evaporated at room
temperature at aspirator pressure. The residue was suspended in chlo-
roform (10 mL). This mixture was added to a stirred ice-cold solution
of methoxylamine hydrochloride (2.03 g, 0.024 mol) and triethylamine
(5.22 g, 0.06 mol) over a period of ∼30 min. The solution was then
refluxed for 4 h. The reaction mixture was cooled to room temperature,
washed with water, 0.2 N hydrochloric acid, saturated sodium bicarbon-
ate, and water. The organic layer was dried over anhydrous magnesium
sulfate overnight. The magnesium sulfate was removed by filtration and
the solvent was removed by rotary evaporation to give the crude prod-
uct. The crude product was purified by fractional crystallization from
chloroform and ether solution. Pure 6 (3.85 g, 96%) was obtained as
a white microcrystalline solid. mp 96–97◦C. (Found: C 56.56, H 4.67,
N 6.54, Cl 17.10. C10H10O2NCl requires C 56.74, H 4.73, N 6.62, Cl
16.78). δH 3.78 (s, 3H), 6.72 (s, 1H), 7.22–7.40 (m, 3H), 7.55–7.65 (m,
2H), 10.98 (s, 1H). δC 64.0 (CH3), 116.0 (CH), 126.9 (CH), 128.3 (CH),
130.2 (CH), 136.9 (C), 142.6 (C), 162.2 (C).
Crystal Structure Determination
The structure of 6 was determined, using data collected at T 110 K
with MoKα radiation (λ 0.71073 Å) on a Nonius Kappa CCD diffrac-
tometer. Crystal data: C10H10ClNO2, M 211.64, triclinic, space group
¯
P1, a 10.8798(15), b 11.3640(10), c 13.0891(14) Å, α 104.466(6),
β 101.454(5), γ 95.672(7)◦, V 1516.9(3) Å3, Z 6, Dx 1.390 g cm−3
,
Methyl (Z)-β-Chlorocinnamohydroxamate 6 (Procedure 2)
µ
3.50 cm−1
,
colourless crystal with dimensions 0.33 × 0.25 ×
Ethyl benzoylacetate (9.6 g, 0.05 mol) was added dropwise to a
cold suspension of phosphorus pentachloride (31.3 g, 0.15 mol) in dry
benzene (35 mL) with strong stirring for 1 h. After the addition had
been completed, the reaction mixture was stirred at ambient tempera-
ture for another 30 min, and then it was allowed to reflux for 30 min.
After the reaction, the mixture was allowed to cool gradually to ambi-
ent temperature, and a precipitate was observable. The solvent was
removed in vacuo quickly. The residue was suspended in chloroform
(10 mL) and added dropwise to a stirred ice-cold solution of methoxy-
lamine hydrochloride (2.51 g) and triethylamine (5.05 g) over a period
of ∼30 min. The solution was then refluxed for 4 h. The reaction mix-
ture was allowed to cool gradually to ambient temperature, and then
washed sequentially with water, 0.2 N hydrochloric acid (2 × 15 mL),
saturated sodium bicarbonate (2 × 15 mL), and water (2 × 15 mL). The
organic layer was dried over anhydrous magnesium sulfate overnight
and filtered, and the filtrate was concentrated in vacuo to give a 3.50 g
of crude product.The crude product was purified via column chromatog-
raphy on 70 g silica gel by elution with 10% ethyl acetate and hexane.
Pure 6 (4.5 g, 39%) was obtained as a colorless microcrystalline solid.
mp 96–97◦C.
0.23 mm, transmission coefficients 0.893–0.924, 38244 measured data
with θ < 30.5◦, 9143 unique data used in refinement, R 0.038 for 7229
observed data, 392 refined parameters. The X-ray crystallographic data
are available from the Cambridge Crystallographic Data Centre as
deposition no. 297168.
Synthetic Experimental Procedures
(Z)-β-Chlorocinnamic Acid 4
Ethyl benzoylacetate (3, 19.2 g, 0.1 mol) was added dropwise over
a period of one hour with strong stirring to a solution of phosphorus
pentachloride (50.30 g, 0.3 mol) in dry benzene (50 mL).[18] After the
addition had been completed, the reaction mixture was kept at ambient
temperature for 30 min and then it was refluxed for 30 min. After the
reaction, the mixture was allowed to cool gradually to ambient tempera-
ture. Ice water (20 g) was added slowly.The benzene layer was separated
and the aqueous layer was extracted with benzene (3 × 20 mL). The
combined benzene solution was extracted with water (2 × 10 mL) and
a saturated solution of sodium carbonate (3 × 20 mL) respectively. The
sodium carbonate solution was collected and acidified with hydrochlo-
ric acid (10 mL) until the pH was less than 7. The crude product was
obtainedasayellowsolid.Thecrudeproductthatcontains cis-andtrans-
isomers was dissolved in 30% ammonium hydroxide solution (30 mL),
which was followed by an addition of a saturated barium chloride solu-
tion (30 mL).The white precipitate that was formed was filtered in vacuo
(Z,Z)-β-Chlorocinnamohydroximoyl Chloride 7ZZ
Compound 6 (2.02 g, 0.01 mol) was mixed with phosphorus pen-
tachloride (6.26 g, 0.03 mol) with strirring in an ice bath.[19] The mixture
was then stirred for 22 h at room temperature. Hexane (20 mL) was

α,β-Unsaturated Hydroximoyl Chlorides and Hydroximates
443
added to the reaction mixture, and it was poured into an ice-water
mixture. The organic layer was separated and washed with a saturated
sodium bicarbonate solution and water respectively. The organic layer
was dried with anhydrous magnesium sulfate for 3 h. The mixture was
filtered and the solvent was evaporated. The crude product was purified
by column chromatography (silica gel, with 0.5% chloroform/hexane
until the product started to elute; the solvent was then changed to pure
hexane) to give a colorless liquid. (Found: C 52.27, H 4.00, N 6.07, Cl
30.80. C10H9ONCl2 requires C 52.20, H 3.94, N 6.09, Cl 30.82). δH
4.07 (s, 3H), 6.56 (s, 1H), 7.32–7.43 (m, 3H), 7.55–7.68 (m, 2H). δC
63.1 (CH3), 118.5 (CH), 126.8 (CH), 128.4 (CH), 129.9 (CH), 132.7
(C), 137.2 (C), 138.8 (C). νmax/cm−1 (neat) 1620. m/z 233 (4), 232 (14),
231 (16), 230 (53), 229 (22), 228 (69), 198 (84), 179 (21), 165 (57), 164
(32), 163 (53), 162 (100), 128 (85).
Methyl (E)-O-Methyl-β-phenylpropynohydroximate 8E
7EZ (0.46 g) was reacted with sodium methoxide (from 0.092 g of
sodium) in a similar manner to give a crude product with a different
retention time than 8Z and a mass spectrum identical to 8Z.
Methyl (Z,E)-β-Methoxy-O-methylcinnamohydroximate 9ZE
7ZE (0.46 g) was reacted with sodium methoxide (from 0.092 g of
sodium) in a similar manner to give a crude product. m/z 221 (8), 220
(36), 189 (100), 175 (9), 158 (9), 146 (9), 143 (12), 129 (49), 115 (36),
102 (18), 89 (17), 77 (19).
Methyl (E,E)-β-Methoxy-O-methylcinnamohydroximate 9EE
7EE (0.23 g) was reacted with sodium methoxide (from 0.069 g of
sodium) in a similar manner to give a crude product with a GC retention
time that was different than 9ZE and a mass spectrum identical to 9ZE.
(E,Z)-O-Methyl-β-chlorocinnamohydroximoyl Chloride 7EZ,
(E,E)-O-Methyl-β-chlorocinnamohydroximoyl Chloride 7EE, and
(Z,E)-O-Methyl-β-chlorocinnamohydroximoyl Chloride 7ZE
Acknowledgements
The Robert A. Welch Foundation (Grant Number M-020),
the Minority Biomedical Research Support Program of the
National Institutes of Health (NIH-MBRS Grant GM0825),
and the Texas Woman’s University Research Enhancement
Program supported this work. The South-Eastern Louisiana
Faculty Development Grant Program is also acknowledged.
The purchase of the diffractometer was made possible by
grant no. LEQSF (1999–2000)-ENH-TR-13, administrated
by the Louisiana Board of Regents.
A solution of (Z,Z)-O-methyl-β-chlorocinnamohydroximoyl chlo-
ride (7ZZ, 2.01 g) in hexane (44 mL) was placed in 4 quartz tubes. The
test tubes were irradiated in a Rayonet photochemical reactor (254 nm)
for 6 h. After irradiation, the hexane solution was immediately extracted
with saturated solution of sodium carbonate (2 × 15 mL). The hexane
extracts were dried over anhydrous magnesium sulfate and filtered.
The filtrate was concentrated in vacuo. The residue was analyzed by
1H NMR, and it was found to contain 7ZZ, 7EZ, 7ZE, and 7EE in a
1.8:2.1:2.3:1.0 ratio. The mixture was separated via column chromatog-
raphy on silica gel by eluting with chloroform in hexane.The percentage
of chloroform was increased from 1.1% to 1.8% to 2.0% to 3.3% during
the chromatography. The isomers eluted from the column in the order
7EZ, 7EE, 7ZZ, and 7ZE.
References
7EZ (0.03 g, 1.5%) was obtained as a colorless liquid. (Found: C
52.49, H 4.09, N 6.06, Cl 30.83. C10H9ONCl2 requires C 52.20, H 3.94,
N 6.09, Cl 30.82). δH 3.89 (s, 3H), 6.77 (s, 1H), 7.30–7.47 (m, 5H). δC
63.0 (CH3), 121.2 (CH), 128.0 (CH), 129.0 (CH), 129.7 (CH), 132.8
(C), 136.5 (C), 141.9 (C). m/z identical to 7ZZ.
7EE (0.005 g, 0.3%) was obtained as a colorless liquid. (Found: C
52.41, H 4.02, N 6.00, Cl 30.95. C10H9ONCl2 requires C 52.20, H 3.94,
N 6.09, Cl 30.82). δH 3.84 (s, 3H), 6.50 (1H), 7.32–7.45 (m, 5H). δC
63.5 (CH3), 121.6 (CH), 128.5 (CH), 129.5 (CH), 130.2 (CH), 133.2
(C), 137.0 (C), 142.3 (CH). m/z identical to 7ZZ.
7ZE(0.04 g, 2%)wasobtainedasacolorlessliquid. (Found: C52.53,
H 4.12, N 5.80, Cl 30.83. C10H9ONCl2 requires C 52.20, H 3.94, N 6.09,
Cl 30.61). δH 3.97 (s, 3H), 6.88 (1H), 7.35–7.48 (m, 3H), 7.60–7.74 (m,
2H). δC 63.1 (CH3), 114.9 (CH), 126.9 (CH), 128.4 (CH), 130.2 (CH),
136.6 (CH), 140.6 (C), 143.1 (CH). m/z identical to 7ZZ.
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Methyl (Z)-O-Methyl-β-phenylpropynohydroximate 8Z
Sodium metal (0.91 g, 0.040 mol) was reacted with methanol
(15 mL). The mixture was cooled to room temperature and (Z,Z)-
β-chlorocinnamohydroximoyl chloride 7ZZ (4.59 g, 0.0200 mol) in
methanol (6 mL) was added to the mixture. The solution was stirred
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(30 mL) and benzene (30 mL) were added to the residue. The water was
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sulfate. The magnesium sulfate was removed by filtration and washed
with benzene. The benzene was removed by rotary evaporation to give
crude product (3.02 g). The product was purified by vacuum distillation
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N 7.40). δH 3.99 (s, 3H), 3.92 (s, 3H), 7.30–7.45 (m, 3H), 7.50–7.60 (m,
2H). δC 58.8 (CH3), 64.1 (CH3), 77.8 (C), 99.8 (C), 121.7 (C), 129.7
(CH), 131.1 (CH), 133.2 (CH), 144.3 (C). νmax/cm−1 (neat) 2210, 2920.
m/z 189 (100), 174 (3), 158 (2), 143 (5), 129 (36), 115 (18), 102 (10),
89 (7).
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