Hydroxylamine and pseudoacyl systems: Pseudo-oximes

Article abstract of DOI:10.1007/s10870-012-0377-7

Unhindered furan pseudoacyl chlorides react with hydroxylamine and a carbonate base to form oxidized cyclic N-hydroxyiminoimides. Thus, 3-chloroisobenzofuran-1-one forms 3-hydroximinoisoindolin-1-one (4) C ₈H₆N₂O₂. Molecules are nearly planar and E-secondary amides hydrogen-bond with oximes through N(H)...N 2.920 A and O(H)...O 2.720 A contacts, and form infinite chains. Mucochloryl chloride (2,3,4-trichlorodihydrofuran-1-one) forms a similar hydroxyiminoimide (5E)-3,4-dichloro-5-hydroxyiminopyrrol-2-one (6), C ₄H₂Cl₂N₂O₂. However, opianic acid forms a mixture of mostly N-hydroxyphthalimide [6,7-dimethoxy-N- hydroxyisoindolin-1,3-dione (9)], C₁₀H₁₀N ₂O₂, with small amounts of open oxime carboxylate [potassium 2,3-dimethoxy-6-(N-hydroxymethanoyl)benzoate (8) C₁₀H ₁₀NO₅K], and 2,3-dimethoxyphthalimide (10), C ₁₀H₉NO₄. These results suggest an intermediate pseudo-oxime, and such a derivative has been made in quantitative yield in a dehydration resistant arylpyran pseudoacyl system. 3-Chloro-4,4- dimethylisobenzopyran-1-one reacts with two equivalents of hydroxylamine and a carbonate base to form 2-hydroxy-3-(hydroxyamino)-4,4-dimethyl-3H-isoquinolin-1- one (14), C₁₁H₁₃N₂O₃, a pseudo-oxime. Pairs of pseudo-oximes form four hydrogen-bonds in two complementary sets, with N(H)...O 3.008 A and O(H)...O 2.685 A. Molecules are also linked in chains by hydrogen-bonds with O(H)...O 2.696 A. These products have been characterized by spectroscopy and X-ray diffraction. Graphical Abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s10870-012-0377-7

J Chem Crystallogr (2013) 43:6–13
DOI 10.1007/s10870-012-0377-7
ORIGINAL PAPER
Hydroxylamine and Pseudoacyl Systems: Pseudo-oximes
•
Anna M. Daniels Megan A. Supinski
•
•
•
Daniel P. Kennedy William D. Robinson
Edward J. Valente
Received: 12 January 2012 / Accepted: 6 November 2012 / Published online: 18 November 2012
Ó Springer Science+Business Media New York 2012
Abstract Unhindered furan pseudoacyl chlorides react with
hydroxylamine and a carbonate base to form oxidized cyclic
N-hydroxyiminoimides. Thus, 3-chloroisobenzofuran-1-one
forms 3-hydroximinoisoindolin-1-one (4) C8H6N2O2. Mole-
cules are nearly planar and E-secondary amides hydrogen-
Keywords Pseudoacid Á Pseudoacyl Á Pseudo-oxime Á
Hydrogen-bonding Á X-ray crystallography
Introduction
˚
bond with oximes through N(H)ÁÁÁN 2.920 A and O(H)ÁÁÁO
˚
2.720 A contacts, and form infinite chains. Mucochloryl
Pseudoacids are cyclic oxocarboxylic acids, typically
formed by intramolecular interaction of an aldehyde/ketone
with a carboxylic acid function [1]. The open-cyclic
equilibrium favors the cyclic structures where the inter-
acting groups are brought closer together such as in cis-
alkenes and o-disubstituted aryl systems [2, 3]. Pseudoacids
form a range of modified acid derivatives which are analo-
gous to yet distinct from those of normal carboxylic acids,
such as pseudoacyl halides, pseudoesters, pseudoamides and
pseudoanhydrides [4]. But pseudoacids are also pseudo-
aldehydes/ketones. Reaction outcomes produce typical car-
bonyl derivatives in strained systems such as o-benzoylbenzoic
acid [5] or cyclic structures (substituted furanones, pyridaz-
ones) in other systems [6]. For the oxime, pseudoacid systems
have been reported to form open-chain oxime/carboxylates
with a strong base and hydroxylamine [7]. Levulinic acid is an
aliphatic c-oxocarboxylic acid with an open-cyclic equilibrium
that favors the open form over the furanoic pseudoacid. It
produces an open oxime/acid when treated with hydroxyl-
amine and a base [8]. There is a liability toward oxidation in
some furanoid pseudoacid systems such as opianic acid to
hemipinic acid [9]. Use of hydroxylamine to form cyclic imides
from cyclic anhydrides has recently been reported [10], which
suggests that the products of pseudoacids and hydroxylamines
also should be examined carefully. Nitrogen derivatives of
arylpyran pseudoacids have not been pursued to any great
degree, so an initial comparison between the furanoid and
pyranoid systems might prove interesting. Since oxime deriv-
atives give rise to modified spectral properties with somewhat
chloride (2,3,4-trichlorodihydrofuran-1-one) forms a similar
hydroxyiminoimide (5E)-3,4-dichloro-5-hydroxyiminopyrrol-
2-one (6), C4H2Cl2N2O2. However, opianic acid forms a
mixture of mostly N-hydroxyphthalimide [6,7-dimethoxy-
N-hydroxyisoindolin-1,3-dione (9)], C10H10N2O2, with small
amounts of open oxime carboxylate [potassium 2,3-dime-
thoxy-6-(N-hydroxymethanoyl)benzoate (8) C10H10NO5K],
and 2,3-dimethoxyphthalimide (10), C10H9NO4. These results
suggest an intermediate pseudo-oxime, and such a derivative
has been made in quantitative yield in a dehydration resistant
arylpyran pseudoacyl system. 3-Chloro-4,4-dimethyliso-
benzopyran-1-one reacts with two equivalents of hydroxylamine
and a carbonate base to form 2-hydroxy-3-(hydroxyamino)-4,
4-dimethyl-3H-isoquinolin-1-one (14), C11H13N2O3, a pseudo-
oxime. Pairs of pseudo-oximes form four hydrogen-bonds in two
˚
complementary sets, with N(H)ÁÁÁO 3.008 A and O(H)ÁÁÁO
˚
2.685 A. Molecules are also linked in chains by hydrogen-bonds
˚
with O(H)ÁÁÁO 2.696 A. These products have been characterized
by spectroscopy and X-ray diffraction.
A. M. Daniels Á M. A. Supinski Á E. J. Valente (&)
Department of Chemistry, University of Portland,
5000 North Willamette Blvd, Portland, OR 97203, USA
e-mail: valentee@up.edu
D. P. Kennedy Á W. D. Robinson
Department of Chemistry and Biochemistry,
Mississippi College, Clinton, MS 39058, USA
123

J Chem Crystallogr (2013) 43:6–13
7
equivocal interpretations, crystallographic means were also
employed to identify the phases produced. In this work, we
report the results of the reactions of hydroxylamine with several
pseuodacid systems in the presence of carbonate as the base and
in polar protic and aprotic solvents.
d 4.5, s, 1H, –OH; 13C-nmr, CD3OD; d 161.3, C=O, d
143.6, 133.0,=C–Cl’s; d 84.1 C=N–OH; IR (solid, cm-1):
3196, mNH/OH; 1709 (s), mC=O; 1688 (s), mC=N; m1651
(m), mC=C; 1589 (w); 1550 (w); 1386 (w); 1329 (w); 1290
(m); 1240 (m); 1100 (s); 1059 (m); 965 (s) c(alkene); 880
(m); 720 (s) mC–Cl.
Experimental
N-Hydroxy-5,6-dimethylphthalimide (10)
Reagents and solvents were obtained from Aldrich
Chemical Corp., VWR Scientific, and TCI Chemical Corp.
and used as received. 3-Chloroisobenzofuran-1-one (1) was
made from o-formylbenzoic acid by a literature method
[11]. Mucochloryl chloride (2,3,4-trichlorodihydrofuran-
1-one, 2) was made from mucochloric acid, and freshly
distilled before use (bp 55 °C, 0.5 Torr). The pseudoacid
3-hydroxy-4,4-dimethylisobenzopyran-1-one (3) was made
by a literature method [12].
Opianic acid is converted quantitatively to its pseudoacyl
chloride (7) by treating with excess thionyl chloride. The
colorless solid 7 is a moisture sensitive solid, analysis:
1H-nmr: CDCl3, 25 °C: d 7.3, 2H, dd; 4.11, s, 3H, OMe;
3.96, s, 3H, OMe; 13C-nmr: CDCl3, 25 °C: d164.9, C=O;
154.0, 148.1, ArC–OMe; 139.7, 119.7, 118.3, 116.2, ArC’s;
85.1, C–Cl; 62.4, 56.8, OCH3s. Opianyl chloride (7),
0.109 g (0.48 mmol) is combined with 0.33 g (4.8 mmol)
hydroxylamine hydrochloride and 0.66 g (4.8 mmol)
potassium carbonate in 3.0 mL dimethylformamide, and
stirred for 2 days at 25 °C, resulting in a pale yellow
solution. Water is added and the precipitated materials are
collected by filtration. The solid mixture obtained is frac-
tionally crystallized from ethanol into which water is dif-
fused producing very few colorless prisms of open oxime
salt potassium 5,6-dimethoxy-2-(N-hydroxyimino) metha-
noylbenzoate (8). This is followed by the major product, long
colorless needles, mp 95 °C of 10. A very small amount of
colorless prisms of 5,6-dimethoxyphthalimide (9) are also
obtained. Each was characterized by X-ray crystallography
(vide infra) though there was insufficient sample to obtain
3-Hydroximinoisoindolin-1-one (4)
To a solution of 0.050 g (0.30 mmol) 1 in 5.0 mL 95 %
ethanol was added 0.208 g (3.0 mmol) hydroxylamine
hydrochloride and 0.42 g (3.0 mmol) potassium carbonate.
The mixture was stirred for 2 days at 25 °C during which
the initially colorless mixture became yellow. Then, the
solvents were evaporated under an air stream, and the res-
idue suspended in 10 mL water, and filtered. The insoluble
organic component was dissolved in ethanol, and allowed to
slowly crystallize producing prisms, 0.049 g (19 %), mp
255.9–257.3 °C. Analysis: 1H-nmr, CD3OD, d 7.6–8.0,
multiplets, 4H, aryl-Hs; d 4.8, s, 1H, N–H; d 3.3, s, 1H,=N–
OH; 13C-nmr, CDCl3; 120.3, 122.9, 130.2, 132.7, aryl
C–Hs; 134.1, 145.5, aryl C; 168.0, C=O, 178 C=N–OH; IR
(solid, cm-1): 3424 (broad), mNH; 3215, mOH; 2953 (w),
mCH aryl; 1706 9 (s), mC=O; 1678 (m), mC=N. Reaction
conditions employing pyridine or triethylamine as base and
solvent blackened and no identifiable products could be
extracted.
1
spectral data for 8 and 9. Analysis for 10: H-nmr CD3OD,
26 °C: d7.78, d, 1H, aryl-H; d 7.40, d, 1H, aryl-H; d 4.8, s,
1H, OH; d 3.97, s, 3H, OMe; d 3.75, s, 3H, OMe; 13C-nmr:
CD3OD, 26 °C: d 169.7, C=O; d 162.9, C=O; d 156.3, 144.5,
132.8, 127.6, 120.9, 119.5, aryl C’s; d 60.3, 55.2, OMe’s; IR
(solid, cm-1): 3224 broad, mOH; 2947, 2843, mCH; 1699 (s),
mC=O; 1598, 1493 aryl mC=C; 1263 (s), mC–O.
3-Chloro-4,4-dimethylisobenzopyran-1-one (11)
(5E)-3,4-Dichloro-5-hydroxyiminopyrrol-2-one (6)
To 1.00 g (4.8 mmol) 3-hydroxy-4,4-dimethylisobenzo-
pyran-1-one (3) was added 1.5 mL (2.46 g, 20.7 mmol)
thionyl chloride, and the mixture was stirred and heated to
45 °C for 2 days. Excess thionyl chloride was removed
under reduced pressure, and the residue (1.01 g, 99 %)
eventually crystallized as large colorless prisms, mp
82–85 °C. Analysis: 1H-nmr (CD3OD): d 7.98, d, 1H;
d 7.51, t, 1H; d 7.33, d, 1H; 7.26, t, 1H; d .446, s, 1H,
pseudoacyl-H; d 1.32, s, 3H, methyl; 1.27, s, 3H, methyl;
13C-nmr: d 165.773, C=O; d 146.783, 134.624, 130.017,
127.056, 124.786, 123.313, aryl-C’s; d 102.165, pseudoacyl
C; d 38.356, quaternary C; d 26.465, 21.904, gem-dimethyl
Mucochloryl chloride (2), 0.376 g (2.0 mmol) was dis-
solved in 2.5 mL 95 % ethanol and 0.690 g (9.9 mmol)
hydroxylamine hydrochloride and 1.40 g (10.1 mmol)
potassium carbonate were added. The mixture was stirred
for 3.5 days at 25 °C, during which the initially colorless
mixture became yellow. The solvent was evaporated in an
air stream, and the residue treated with water and filtered;
the insoluble organic phase was recrystallized from ethanol
to produce colorless plates, 0.250 g (69 %) mp 155 °C.
Analysis: 1H-nmr CD3OD, 25 °C d 5.0, s, 1H, N–H;
123

8
J Chem Crystallogr (2013) 43:6–13
Table 1 Relevant
4
6
8
crystallographic information for
4, 6, 8, 9, 10 and 14 (esd’s in
parentheses)
Formula
C8 H6 N2 O2
162.15
C4 H2 Cl2 N2 O2
180.98
C10 H10 K N O5
263.29
Formula weight
F(000)
336
360
544
Size (mm)
0.59 9 0.24 9 0.05
Orthorhombic
P 21 21 21
101(2)
0.89 9 0.37 9 0.14
Triclinic
0.29 9 0.17 9 0.05
Monoclinic
P 21/c
Crystal system
Space group
Cell constants (temp., K)
P -1
298(2)
298(2)
˚
a (A)
3.7784(6)
9.0723(15)
20.514(2)
90.000
7.2634(7)
7.6485(11)
12.2085(11)
93.523(10))
98.001(8)
101.844(11)
654.5(1)
8.6002(5)
20.3845(14)
6.5027(4)
90.000
˚
b (A)
˚
c (A)
a (o)
b (o)
c (o)
90.000
92.933(6)
90.000
90.000
3
˚
Volume (A )
Z, density (Mg/m3)
703.21(18)
4, 1.532
1,138.50(12)
4, 1.536
4, 1.847
l (mm-1
)
0.114
0.921
0.475
Data, Rmerge
4128, 0.0282
2153, 1831
99.8, 30.57
0.051, 0.089
0.039
6612, 0.0452
4011, 2455
99.8, 30.50
0.180, 0.390
0.152
6815, 0.0499
3488, 1248
99.9, 30.50
0.174, 0.144
0.0619
Unique data, I [ 4rI
Completeness (%), max. h
R, wR (unique data)
R (I [ 4rI)
Parameters, restraints
110, 0
183, 0
157, 1
Goodness-of-fit
3
1.002
1.026
1.009
˚
Dq(final) (e/A )
0.37, -0.29
9
2.22, -1.05
10
0.30, -0.63
14
Formula
C10 H9 N O5
223.18
C10 H9 N O4
207.19
C11 H14 N2 O3
222.24
Formula weight
F(000)
464
432
472
Size (mm)
0.40 9 0.04 9 0.02
Orthorhombic
P 21 21 21
298(2)
0.40 0.35 0.10
Monoclinic
P 21/c
0.35 9 0.26 9 0.08
Monoclinic
P 21/c
Crystal system
Space group
Cell constants (temp., K)
298(2)
101(2)
˚
a (A)
3.9579(3)
15.5058(11)
15.8646(14)
90.000
14.9948(11)
8.4383(4)
7.2942(5)
95.638(6)
918.47(10)
4, 1.498
13.1638(3)
6.3069(2)
13.4581(3)
108.256(3)
1061.09(5)
4, 1.391
˚
b (A)
˚
c (A)
b (o)
3
˚
Volume (A )
Z, density (Mg/m3)
973.6(1)
4, 1.523
l (mm-1
)
0.124
0.118
0.102
Data, Rmerge
3950, 0.0399
2155, 887
90.5, 28.55
0.1286, 0.0385
0.0375
9324, 0.0191
2819, 1877
99.9, 30.57
0.0647, 0.0991
0.0437
9809, 0.0262
3251, 2352
99.7, 30.61
0.0625, 0.0877
0.0396
Unique data, I [ 4rI
Completeness (%), max. h
R, wR (unique data)
R (I [ 4rI)
Parameters, restraints
Goodness-of-fit
146, 0
136, 0
152, 0
0.837
1.004
1.005
3
˚
Dq(final) (e/A )
0.15, -0.14
0.63, -0.16
0.34, -0.28
123

J Chem Crystallogr (2013) 43:6–13
9
C’s; IR: (solid, cm-1): 3072 (w), aryl mCH; 2975 (w), mCH;
1722 (s), mC=O; 1604 (m) aryl mC=C; 1452 (m), 1373 (m),
d HCH; 1,265 (s), mC–O; 703 (s) mC–Cl.
pattern was considerably affected by intensity from other
domains; the results are poor, but included here for
completeness.
2-Hydroxy-3-(hydroxyamino)-4,4-dimethyl-3H-
isoquinolin-1-one (14)
Discussion
To 0.050 g 11 dissolved in 1.0 mL of 95 % ethanol was
added 0.164 g (2.36 mmol) hydroxylamine hydrochloride
and 0.489 g (3.54 mmol) potassium carbonate. The mix-
ture was stirred for 3 days at 60 °C. Then 0.088 g
(1.27 mmol) hydroxylamine was added, and the mixture
stirred for another day, giving a colorless or very slightly
yellow solution with some insoluble salts. The solvent was
evaporated under an air stream, and the residue dissolved
in ethanol and filtered from the salts. On slow evaporation,
large colorless hexagonal crystals of 14 separate, mp about
160 °C with gas evolution and decomposition. Compound
14 is insoluble in water, acetone, acetonitrile or chloro-
form, but soluble in methanol. Analysis: 1H-nmr (CD3OD):
d 7.882, 7.863, d, 1H, aryl peri-H; d 7.375, t, 1H; aryl-H;
d 7.29, m, 2H; aryl-Hs; d 4.754, s, 2H, OHs; d 4.206, s, 1H,
pseudoacyl-H; d 1.47, s, 3H, methyl; d 1.28, s, 3H, methyl;
13C-nmr: d 163.3, C=O; d 146.2, 132.0, 127.1, 126.5,
125.9, 123.4, aryl-C’s; d 85.9, pseudoacyl C; d 38.4, qua-
ternary C; d 31.3, 21.8, gem-dimethyl C’s. IR (solid,
cm-1): 3258 (m, broad), mNH; 3177 (m, broad), mOH; 3063
(w), aryl mCH; 2983 (m), mCH; 1698 (s); mC=O.
Pseudoacid systems chosen for study include three which
favor the cyclic furanoid forms (o-formylbenzoic acid,
mucochloric acid and opianic acid) and one dehydration
resistant cyclic arylpyran (3-hydroxy-4,4-dimethyliso-
benzopyran-1-one). Since the pseudoacid forms are some-
what unreactive, we elected to employ their pseudoacyl
chlorides instead so that less stringent reaction conditions
could be pursued. An excess of hydroxyamine hydrochlo-
ride was reacted with 3-chloroisobenzofuran-1-one (1),
mucochloryl chloride (2), opianyl chloride (3), and
3-chloro-4,4-dimethylisobenzopyran-1-one (4) and potas-
sium carbonate.
2
4
1
3
The choice of base is important in these reactions, since
use of pyridine or triethylamine usually leads to decom-
position. Cleaner reactions have resulted from use of
sodium carbonate or potassium carbonate. Compounds 1, 2
and 4 are only slowly hydrolyzed in polar solvents with
water present, so 95 % ethanol could be used in the reac-
tions. Opianyl chloride is more rapidly hydrolyzed, so
dimethylformamide was used as a replacement. Diffraction
methods were used to complement other spectroscopic
identifications, since oxime products were difficult to
identify from spectroscopy alone.
Crystallography
Single crystals of 4, 6, 8–10, 14 were chosen for crystal-
˚
lographic study with Mo Ka radiation (k = 0.71073 A).
Data were collected on an Oxford Gemini system. Relevant
details of the crystallographic experiments are given in
Table 1. The structures were solved with SHELXS-86 [13],
and refined with SHELXL-97 [14]. All non-H atoms were
found in initial E-maps, and were refined with attendant
anisotropic librational parameters. H-atoms on carbons
were assigned calculated locations; some H-atoms on
nitrogens and oxygens were located in the different fourier
maps, and their positions were refined with the usual for-
shortened N–H and O–H lengths. Computed metrics
involving Hs use uncorrected (foreshortened) N–H and
O–H locations. All Hs were assigned isotropic librational
parameters equal to 120 % of the Ueq of the attached
atoms. No corrections for extinction were found to be
necessary. For structure 6, crystals are invariably multiple
or twinned. After examination of a number of specimens,
the best that could be found had a major domain with at
least five other recognizable similar and disoriented com-
ponents. The structure has been solved but the diffraction
Reaction of 1 produced the hydroxyimino/amide 4
(Fig. 1), formation of which involves oxidation of the
pseudoacid and two equivalents of hydroxylamine. We
Fig. 1 Thermal ellipsoid plot (50 % enclosures) of 4 showing
intermolecular H-bonds
123

10
J Chem Crystallogr (2013) 43:6–13
speculate that the reaction proceeds through an interme-
diate hydroxyamino/hydroxyamide 5, which then under-
goes dehydration/oxidation.
molecules comprise the asymmetric unit of the triclinic
structure (P-1), a molecules are essentially planar and
arranged in sheets in which weak intermolecular ClÁÁÁCl
–O
O
O
+
O
NH OH
2
NH2OH
NHOH
H
NH2OH
NHOH
H
O
O
base
Cl
Cl
1
O
N
O H
O
O
O
Cl
Cl
N
H
N
O H
N
H
base
H
:B
N
N
O H
NHOH
O H
4
5
6
˚
Crystals of 4 are large well formed colorless prisms
from ethanol, mp 255.9–257.3 °C. Molecules are nearly
planar, with only the hydroxy group very slightly departing
from the plane described by the remaining eleven non-H
atoms of the molecule. In the crystal, molecules for inter-
molecular hydrogen-bonds with two neighbors using both
the hydroxyimino and cyclic imide functions. The resulting
C11(7) [15] chains link the planar molecules (using planes
described by the ring and carbonyl oxygen atoms), forming
pleats or corrugations with an interplanar angle of 21.7(1)o
and every other molecule parallel with their mean planes
interactions (at 3.44(2) and 3.46(2) A) alternate with
intermolecular hydrogen-bonding within the sheets. These
sheets closely match the [201] crystal planes (d201
=
˚
3.24 A), and F201 = 238, 66 % of the F000 = 359. This
feature provides an explanation for the multiple or twinned
occurrence of the crystals, with crystal domains parallel to
and disoriented relative to these dominant packing planes.
hydrogen-bonding links molecules within the sheets and in
chains. The hydroxyimine is linked in chains to the car-
˚
bonyl O with OÁÁÁO distances 2.78(2) and 2.79(2) A, and
angle at H 158o and 144o. The imine N is syn to the imide
NH coplanar suggesting that an intramolecular N–HÁÁÁO
hydrogen-bond is present; for this NÁÁÁO is 2.60(2) and
˚
displaced by 1.7 A perpendicular to the planes. Between
pairs of molecules, the three atom=N–O–H group donates
and accepts hydrogen-bonds from the four atom Z-imide
H–N–C=O group, forming a ring with R22(7) pattern.
Hydroxyl donates to carbonyl with OÁÁÁO distance
o
o
˚
2.61(2) A, and the angle at H is 93 and 92 . Within sheets,
imides form complementary hydrogen-bonds around
inversion centers, with NÁÁÁO distances of 2.88(1) and
o
o
o
˚
˚
2.720(2) A and angle at H 165 , and imide donates to
2.87(1) A, and angles at H 167 and 169 .
o
˚
imine with NÁÁÁN distance 2.920(2) A and angle at H 146 .
In contrast to the two systems just described, opianyl
chloride 7 forms several products on reaction with
hydroxylamine and a carbonate base in DMF. All of these
The imine N is syn to the imide NH coplanar suggesting
that an intramolecular N–HÁÁÁO hydrogen-bond is present;
o
˚
for this NÁÁÁO is 2.624(2) A, and the angle at H is 93 . A
weak intermolecular C–HÁÁÁO(carbonyl) hydrogen bond
˚
may also be present with CÁÁÁO 3.337(3) A, angle at H
o
139.5(4) . The hydroxyimino C=N is 1.278(2) A, the
˚
˚
amide Cacyl–N is 1.381(2) A, the other C–N is 1.397(2) A.
˚
˚
The carbonyl C=O is 1.224(2) A. These are generally in
agreement with typical values for these bonds [16]. Aryl
˚
ring C–C bonds are similar with a mean distance 1.392 A
˚
and a range of 0.004 A, with C4–C5 1.390(2) A, C4–C9
˚
˚
1.395(2) A, C5–C6 1.393(2) A, C6–C7 1.396(2) A, C7–C8
˚
˚
˚
1.390(2) A, C8–C9 1.388(2) A.
˚
A similar product is isolated from the reaction of mu-
cochloryl chloride (2) and hydroxylamine. This hydroxyi-
mino/amide (6, Fig. 2), also involves oxidation of the
pseudoacid and two equivalents of hydroxylamine. Two
Fig. 2 Thermal ellipsoid plot (30 % enclosures) of 6
123

J Chem Crystallogr (2013) 43:6–13
11
products are polar and quite soluble in ethanol though less
soluble in water. Careful fractional crystallization has
permitted separation, and solubility and crystal morphol-
ogy allow the phases to be distinguished. First, a minor
component which is least soluble in ethanol separates; it is
the potassium salt of the open oxime, or potassium 5,6-
dimethoxy-2-(N-hydroxyimino)methanoylbenzoate (8, Fig. 3).
It is followed by the major product N-hydroxyimide (9, Fig. 4),
and then another minor component, the imide of hemipinic acid
(10, Fig. 5). An hydroxyimino/amide product related to 4 or 6
was not found.
Bond lengths and angles for 8–10 are in normal ranges
[16].
In the three furanoic pseudoacyl systems just described,
all three show products with hydroxylamine and a car-
bonate base which have undergone oxidation. To examine
the results in an arylpyran system, we employed the
dehydration resistant system 3-hydroxy-4,4-dimethyliso-
benzopyran-1-one (3), beginning with its pseudoacyl
chloride (11). Arylfuran pseudoacyl halides react with
secondary amides to form tertiary pseudoamides [4].
Similarly, following the usual procedure with exactly two
equivalents of morpholine, 11 reacts to form a pseud-
omorpholinamide (12), an equal amount of an unexpected
open aldehyde/secondary morpholinamide (13) and an
equivalent of morpholinium chloride. The oily aldehyde/
amide 13, after chromatographic separation, was reacted
with excess hydroxylamine in an attempt to form a solid
derivative oxime.
O
O
N
O
O
O
O
O
O
O
–
K+
O
H
N
H
N
OH
O
O
8
10
9
OH
O
O
O
O
2
O
N
H
N
O
O
O
+
H
N
Cl
12
13
O
11
Salt 8 is centrosymmetric and monoclinic. Potassium
ions coordinate to six Os (at 2.73, 2.74, 2.84, 2.89, 2.94,
The product in this reaction was a colorless solid which
instead no longer retained the morpholine group. Single-
crystal X-ray diffraction revealed a centrosymmetric
monoclinic structure for 14 as a N-hydroxyamide/hydro-
xylamine in which clearly two equivalents of hydroxyl-
amine have reacted with the pseudoacyl system (Fig. 6).
This material is analogous to the putative intermediate 5 in
the o-formylbenzoic acid scheme. Compared to the
˚
˚
3.36 A), and one N atom (3.11 A). Each O, including the
methoxy Os coordinate K?. Hydroxyimino Os donate a
˚
hydrogen-bond to carboxylate O, with OÁÁÁO 2.63(1) A,
and angle at H 178o. N-Hydroxyimide 9 forms slender
orthorhombic needles from ethanol/water. Molecules are
hydrogen-bonded in C11(5) chains with hydroxyl donors
o
˚
and carbonyl acceptors, OÁÁÁO 2.66(1) A, angle at H 156 .
This carbonyl also has a close contact with a methoxy
˚
carbon, CÁÁÁO 3.08(1) A. The second carbonyl has an
intermolecular close contact with a aryl carbon, CÁÁÁO
˚
3.29(1) A.
The imide of hemipinic acid 10 is centrosymmetric and
monoclinic, and molecules form sheets through hydrogen-
bonding interactions, with the sheets parallel to and
approximately between the crystal [10-1] planes. In the
sheets, molecules form hydrogen-bonds in C11(4) chains
with imide N–H donors and one of the two carbonyl Os,
o
˚
with NÁÁÁO 3.03 A, angle at H 162 . This carbonyl O also
˚
accepts a weak (aryl)C–HÁÁÁO contact, with CÁÁÁO 3.39 A,
angle at H 168o. The other carbonyl O also accepts a weak
o
˚
(aryl)C–HÁÁÁO contact, with CÁÁÁO 3.32 A, angle at H 158 .
Fig. 3 Thermal ellipsoid plot of potassium salt 8 (30 % enclosures)
123

12
J Chem Crystallogr (2013) 43:6–13
Fig. 5 Thermal ellipsoid plot (30 % enclosures) of 10
Fig. 4 Thermal ellipsoid plot (30 % enclosures) of N-hydroxyimide
of opianic acid, 9
pseudoacid (C11H12O3) from which 14 is derived, its for-
mula C11H14N2O3 represents a gain of N2H2. Since typical
aldehydes/ketones gain NH on forming their oximes, we
describe 14 and putative intermediate 5 as pseudo-oximes.
The pseudoacyl carbon is not oxidized in these transfor-
mations, and it retains two bonds to N(OH) groups, in an
analogy to normal N-hydroxyimines (oximes). It proved
difficult to reproduce the yields of 14 by this synthetic
method, and use of tertiary amines gave very dark reaction
products from which 14 could not be retrieved. Since 11 is
soluble but does not react with aqueous ethanol, we reacted
11 with excess hydroxylamine hydrochloride in 95 %
ethanol and potassium carbonate or sodium carbonate at
60 °C. This produced pseudo-oxime 14 cleanly and
quantitatively.
Fig. 6 Thermal ellipsoid plot (50 % enclosures) of 14 showing
complementary intermolecular H-bonds
four intermolecular hydrogen-bonds, two complementary
o
˚
NÁÁÁO [3.008(1) A; angle at H 144 ] and two complemen-
o
˚
tary OÁÁÁO [2.685(1) A; angle at H 153 ]. Additionally,
O
O
O
O
OH
NH2OH (excess)
N
NH2OH (excess)
N
O
95% ethanol
OH
H
N
H
K2CO3
>90%
base
Cl
11
13
O
14
Crystals of 14 are well-formed hexagonal tablets which
grow large [001] and [00-1] faces, bounded by [100],
[-100] and [010], [0-10]. The dehydration that apparently
occurs readily in the (aryl)furan systems requires heating to
above 160 °C for 14. Both N-hydroxyamide and hydrox-
yamino groups engage in pairwise complementary inter-
molecular hydrogen-bonding. The five-atom hydroxyamide
O=C–N–O–H donates and accepts hydrogen-bonds from
the three atom hydroxyamino H–N–O group (Fig. 6),
forming rings with pattern R22(8). A longer path, R22(12),
can also be described between these groups. Thus, there are
molecules form infinite chains along b by intermolecular
O–HÁÁÁO hydrogen-bonds between hydroxyamino O donors
˚
and carbonyl O acceptors, with OÁÁÁO 2.696(1) A and with
angle at H 175o.
The molecular structure shows the pseudoacyl hydrox-
yamino group disposed axially. The endocyclic C–N(OH)
˚
distance is 1.462(2) A, and the exocyclic C–N(OH) dis-
˚
tance is 1.448(2) A. The exocyclic C–N is shorter by
˚
0.014 A, suggestive of the usual bond disparities found in
a-anomeric systems. The magnitude of the difference is
much smaller than that observed in pseudoacids, which
123

J Chem Crystallogr (2013) 43:6–13
13
References.
have the O–C–O anomeric sequence and a C–O bond
˚
length disparity of about 0.08 A. The orientation of the
¨
¨
1. Bredt J (1886) Ueber acetyllavulinsaure und die constitution der
¨
hydroxyamino group places the non-bonding electron pair
on N synclinal with the adjacent endocyclic C–N bond, a
conformation consistent with nN?r*C–N donation, and
associated with an operative exo-anomeric effect. A recent
review of oximes and hydroxylamines shows no references
to a similar pair of adjacent functions [17].
c-Ketonsauren. Annalen der chemie 236:225–240
2. Langlois DP, Wolff H (1948) Pseudo esters of levulinic acid.
J Am Chem Soc 70:2624–2626
3. Mowry DT (1950) Mucochloric acid. I. Reactions of the pseudo
acid group. J Am Chem Soc 72:2535–2537
4. Valente EJ, Martin SB, Sullivan LD (1998) Pseudoacids. II.
2-Acylbenzoic acid derivatives. Acta Crystallogr A B54:264–276
5. Bhatt MV, Ravindranathan M (1973) Aspects of tautomerism. Part
V. Solvent, substituent, and steric effects on the ring-chain tau-
tomerism of o-benzoylbenzamides. J Chem Soc Trans 2:1160–1166
6. Mowry DT (1953) Mucochloric Acid. II. Reactions of the alde-
hyde group. J Am Chem Soc 75:1909–1910
Conclusions
Furanoid pseudoacyl chlorides react with hydroxylamine to
form oxidized imide products which may form through
dehydration of an intermediate pseudo-oxime. A dehydra-
tion resistant arylpyran pseudoacyl chloride forms a sta-
ble pseudo-oxime (N-hydroxyamido/hydroxylamine) with
hydroxylamine and a carbonate base.
7. Samogyi L (1985) Isoindoline derivatives of opianic acid. Liebigs
Ann Chem 94:1679–1691
8. Dolfus W (1892) Ueber die configuration von c-ketoximsauren.
Chem Ber 25:1926–1936
9. Matthiessen A, Foster GC (1868) Researches on the constitution
of narcotine and of its products of decomposition. Annalen der
Chem (Supplem. 5): 332. Also cited in ‘‘Recent Advances in
Organic Chemistry’’, Stewart AW, Longmans, Green & Co.,
1908; Chapter X (section C.) pp 200–201
10. Benjamin E, Hijji Y (2008) The synthesis of unsubstituted cyclic
imides using hydroxylamine under microwave irradiation. Mol-
ecules 13:157–169
Supplementary Materials
Crystallographic information files have been deposited
with the Cambridge Crystallographic Data Centre for
crystal structures 4 (860347), 6 (860348), 8 (860349), 9
(860350), 10 (860351), 14 (860352). CCDC data can be
obtained free of charge from www.ccdc.cam.ac.uk/conts/
retrieving.html (or from the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK;
fax: ?44 1223 336033).
11. Newman MS, McCleary CD (1941) Normal and pseudoesters of
2-benzoylbenzoic acid types. J Am Chem Soc 63:1537–1541
12. Cooper WJ, Smith TN, Barker AK, Webb JA, Valente EJ (2003)
Pseudoacids. III. Formation and structures of new cyclic oxo-
carboxylic acids. J Chem Crystallogr 33:375–384
13. Sheldrick GM (1986) SHELX-86 Program for crystal structure
¨
¨
solution. University of Gottingen, Gottingen
14. Sheldrick GM (2008) A short history of SHELX. Acta Cryst
A64:112–122
15. Etter MC, MacDonald JC, Bernstein J (1990) Graph-set analysis
of hydrogen-bond patterns in organic crystals. Acta Cryst
B46:256–262
Acknowledgments EJV acknowledges the National Science Foun-
dation (MRI Grant No 0604188) for support of crystallographic
equipment.
16. Burgi H-B, Dunitz JD (1994) Structure Correlation, vol 2. VCH,
Weinheim
¨
17. Rappoport Z, Liebman JF (eds) (2009) The Chemistry of
hydroxylamines, oximes and hydroxamic acids Part 1. Wiley,
New York
Conflict of interest The authors declare that they have no com-
mercial conflicts of interest.
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