Anhydrides of Arylfuran and Arylpyran Pseudoacids: Formation and Structures; C–O Bond Lengths Trends in Pseudo o-Formylbenzoic Acid Derivatives

Article abstract of DOI:10.1007/s10870-019-00798-1

Abstract: Three methods for producing anhydrides of arylfuran and arylpyran pseudoacids were explored. These included thermal dehydration, phosgene or thionly chloride activation and decomposition, and dicyclohexylcarbodiimide activation and coupling. Derivatives of the cyclic forms of o-formylbenzoic acid, o-acetylbenzoic acid, 2-carboxyphenylacetaldehyde and of 4,4-dimethyl-3,4-dihydro-3-hydroxy-[1H]-isobenzopyran-1-one were formed including dipseudoanhydides and normal-pseudo anhydrides. Crystal and molecular structures for meso and (R,R/S,S)-bis(1[3H]-isobenzofuranone-3-yl)ether, (R,R/S,S)-bis(3-methyl-1[3H]-isobenzofuranone-3yl)ether, meso (3,4-dihydro-[1H]-isobenzopyran-1-one-3-yl)ether, 3-benzoyloxy-1[3H]-isobenzofuranone, 3-benzoyloxy-3-methyl-1[3H]isobenzofuranone, 3-(4′-nitrobenzoyloxy)-4,4-dimethyl-3,4-dihydro-[1H]-isobenzopyran-1-one, and (1[3H]-isobenzofuranone-3-yl)(4,4,dimethyl-3,4-dihydro-[1H]-isobenzopyran-1-one-3-yl)ether are reported. Endocyclic pseudoacyl C–O bonds are always longer than the exocyclic pseudoacyl C–O bonds. It is possible to refine the previously established C–O bond length dependencies on the pK_a (of the conjugate acids) of the leaving groups for 3-substituted 1-[3H]-isobenzofuranones. Of six dipseudoanhydrides studied, conformations are found with exocyclic C–O(ether) linkages synclinal to the endocyclic C–O and away from the ring (exo conformation) in two meso structures, two of three RR/SS forms and in a chiral unsymmetrical form. An endo conformation is observed in one of the RR/SS forms. In three normal-pseudo anhydrides, both endo and exo conformations are observed. Graphic Abstract: Synthetic methods for formation of anhydrides of several arylfuran and arylpyran pseudoacids are described, and the pseudoacyl C–O bond length trends are determined for leaving groups spanning over 30 pK_a units.[Figure not available: see fulltext.]

Full text of DOI:10.1007/s10870-019-00798-1

Journal of Chemical Crystallography
https://doi.org/10.1007/s10870-019-00798-1
ORIGINAL PAPER
Anhydrides of Arylfuran and Arylpyran Pseudoacids: Formation
and Structures; C–O Bond Lengths Trends in Pseudo o‑Formylbenzoic
Acid Derivatives
Emily O’Loughlin1 · Edward J. Valente1
Received: 19 May 2019 / Accepted: 2 July 2019
© Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract
Three methods for producing anhydrides of arylfuran and arylpyran pseudoacids were explored. These included ther-
mal dehydration, phosgene or thionly chloride activation and decomposition, and dicyclohexylcarbodiimide activation
and coupling. Derivatives of the cyclic forms of o-formylbenzoic acid, o-acetylbenzoic acid, 2-carboxyphenylacetalde-
hyde and of 4,4-dimethyl-3,4-dihydro-3-hydroxy-[1H]-isobenzopyran-1-one were formed including dipseudoanhydides
and normal-pseudo anhydrides. Crystal and molecular structures for meso and (R,R/S,S)-bis(1[3H]-isobenzofuranone-3-yl)
ether, (R,R/S,S)-bis(3-methyl-1[3H]-isobenzofuranone-3yl)ether, meso (3,4-dihydro-[1H]-isobenzopyran-1-one-3-yl)ether,
3-benzoyloxy-1[3H]-isobenzofuranone, 3-benzoyloxy-3-methyl-1[3H]isobenzofuranone, 3-(4′-nitrobenzoyloxy)-4,4-dime-
thyl-3,4-dihydro-[1H]-isobenzopyran-1-one, and (1[3H]-isobenzofuranone-3-yl)(4,4,dimethyl-3,4-dihydro-[1H]-isobenzo-
pyran-1-one-3-yl)ether are reported. Endocyclic pseudoacyl C–O bonds are always longer than the exocyclic pseudoacyl
C–O bonds. It is possible to refne the previously established C–O bond length dependencies on the pKa (of the conjugate
acids) of the leaving groups for 3-substituted 1-[3H]-isobenzofuranones. Of six dipseudoanhydrides studied, conformations
are found with exocyclic C–O(ether) linkages synclinal to the endocyclic C–O and away from the ring (exo conformation)
in two meso structures, two of three RR/SS forms and in a chiral unsymmetrical form. An endo conformation is observed in
one of the RR/SS forms. In three normal-pseudo anhydrides, both endo and exo conformations are observed.
Graphic Abstract
Synthetic methods for formation of anhydrides of several arylfuran and arylpyran pseudoacids are described, and the pseu-
doacyl C–O bond length trends are determined for leaving groups spanning over 30 pKa units.
Keywords Pseudoacids · Anhydrides · Coupling reactions · C–O bonds · Bürgi-Dunitz angle
* Edward J. Valente
valentee@up.edu
Extended author information available on the last page of the article
Vol.:(0123456789)
1 3

Journal of Chemical Crystallography
O
O
Introduction
3, R = H
1, R = H
O
O
4, R = CH3
2, R = CH3
The derivative chemistry of cyclic oxocarboxylic acids
(pseudoacids) is regiochemically and stereochemically more
varied than that of (normal) carboxylic acids. Functions cor-
responding to carboxylic acid derivatives are possible for
the pseudoacyl group and include anhydrides which can be
symmetric or unsymmetric, and dipseudo or normal-pseudo
[1, 2]. This paper describes anhydrides formed by pseudoac-
ids in many of these variants. Cyclization of oxocarboxylic
acids introduces the lactol chiral center, so derivative pseu-
doacid anhydrides are necessarily composed of enantiom-
ers or diastereomers [3, 4]. Methods for the formation of
pseudoacyl anhydrides have received relatively little atten-
tion. In some systems, intramolecular dehydration may be
favored, as in possibly the frst and well known example of
levulinic acid and its dehydration to α-angelicalactone [5, 6].
For oxocarboxylic acids with relative thermal stability, as in
o-formylbenzoic acid (3-hydroxy-1(3H)-isobenzofuranone),
intermolecular dehydration to a mixture of symmetric dip-
seudoanhydrides has been accomplished thermally [2, 7].
A symmetric normal-pseudo anhydride was produced from
open o-benzoylbenzoic acid and cyclic o-benzoylbenzoyl
chloride promoted with a base [2, 8, 9]. This oxocarbox-
ylic acid system does not favor cyclic forms probably limit-
ing general application of this method [10]. In the present
study, several coupling methods are explored using sim-
ple benzofuran and benzopyran pseudoacids and benzoic
acids. The structures have been determined to examine the
O–Csp3–O–Csp3–O sequences at the centers of dipseudoan-
hydrides, and the O–Csp3–O sequences of normal-pseudo
anhydrides. Systematic studies of Csp3–O bond-containing
species are useful in light of the inherent variability in its
OH
OH
R
R
R
Scheme 1 Structures of 3-hydroxy-1(3H)isobenzfuranone (1),
3-hydroxy-3-methyl-1(3H)-iso benzofuranone (2), 3-hydroxy-3,4-di-
hydro-[1H]-isobenzopyran-1-one (3), and 3-hydroxy-3,4-dihydro-
4,4-dimethy-[1H]-isobenzopyran-1-one (4), Cooper’s pseudoacid [15]
In Scheme 1, the structures are given for the four pseu-
doacids for which pseudoanhydride chemistry is explored.
Compounds 1 and 4 are relatively resistant to elimina-
tion reactions, while 2 and 3 are susceptible to intramo-
lecular dehydration to form unsaturated lactones or cyclic
anhydrides.
Method A
Thermal dehydration. Pseudoacid 1 can be dehydrated
directly by heating to 257 °C to the racemic (R,R/S,S) dip-
seudoanhydride, 5 and the meso (R,S/S,R) dipseuodanhy-
dride, 6 [2]. Phase 5 forms colorless needles, mp 216 °C,
which occur in the monoclinic system, space group I 2/a.
Phase 6 forms colorless plates, mp 234 °C, also in the
monoclinic system, space group P n. Phase 6 has also been
obtained by thermal decomposition of the chloroformate of
3-hydroxy-1(3H)isobenzofuranone, which was formed from
the pseudoacid (1), triphosgene and pyridine [16]. On heat-
ing above 90 °C, the chloroformate undergoes an exothermic
reaction, as monitored by diferential scanning calorimetry.
(Cl3CO)2C=O
heat
pyridine
RR / SS
5
meso
6
1
bond metrics which in a recent extensive theoretical study
of C–O bond lengths concluded that the large range of C–O
lengths is explained by an approximately linear depend-
ency with its bond critical point density. It is often easier
to explain variations than predict them, with comparisons
among similar compounds being most useful [11]. For
selected pyranoid and furanoid systems, there have been
several studies of C–O bond length trends [2, 12–14].
Pseudoacid 2 is somewhat susceptible to intramolecu-
lar dehydration. Where 2 is heated with a pseudoacyl hal-
ide and a base, the unsaturated lactone 7 is recovered [16].
Pseudoacid 2 can be dehydrated thermally to form the dias-
tereomeric dipseudoanhydrides, from which the (R,R/S,S)
isomer (8) was isolated in low yield.
1 3

Journal of Chemical Crystallography
heat
K2CO3
heat
8
7
2
Method B
dcci
Through the pseudoacyl halide. Pseudoacid 3 is sensitive
to intramolecular thermal dehydration, and it reacts with
thionyl chloride in chloroform solvent to form chiefy the
meso-dipseudoanhydride (9) and isochromenone (10).
CH2Cl2
dmap
6
1
H
H
O
O
O
O
O
O
O
R
S
SOCl2
CHCl3
O
+
O
O H
10
9
3
Method C
To form unsymmetric normal-pseudo anhydrides, DCCI
coupling was generally efective. Pseudoacids 1 and 2 react
with the active ester formed from benzoic acid to form the
corresponding enantiomeric anhydrides.
Using dicyclohexylcarbodiimide (DCCI). Compound 1 is
a relatively unhindered pseudoacid, and it forms an “active
dcci
11, R = H
CH2Cl2
dmap
12, R = CH3
ester” with DCCI which can be displaced by a second pseu-
In a third example pseudoacid 4 reacts with the active
esters of (substituted) benzoic acids forming the normal-
pseudo anhydrides 13–18. These are mostly oils, but com-
pounds 15 and 17 crystallize.
doacid. The meso-dipseudoanhydride (6) was isolated from
the reaction.
R3
R4
-H
-H
-H
13
14
-F
-H
-Cl
15
16
17
dcci
-H
-OCH3
-NO2
-H
CH2Cl2
dmap
-H
4
18
-NO2
1 3

Journal of Chemical Crystallography
Lastly, an attempt to produce an unsymmetric dipseu-
doanhydride was pursued with the pseudoacids least likely
to undergo dehydration (1, 4). In this fourth example using
the coupling method, a mixture of non-polar products were
isolated from which (R,R/S,S)-5 crystallized frst, followed
by the mixed anhydride 19.
[18]. Additionally, an anhydride was obtained from reac-
tion of 1 with an equivalent of dicyclohexylcarbodiimide
(DCCI) in CH2Cl2 at 0 °C to which was added a small
amount of 4-dimethyl aminopyridine (DMAP, see prepara-
tion of 11–17). Anhydride has Rf about 0.75 (TLC: silica,
dcci
dmap
1
4
19
5
The crystal and molecular structures of the anhydrides
5–11, 12, 17 and 19 have been determined, and the metrics
of the pseudoacyl linking groups have been examined. These
are compared with the limited literature available.
CHCl3:EtOAc 10:1) and after isolation by chromatography,
the major product proves to be polymorphs of the (R,R/S,S)
form 5 (5a, prisms; 5b rod-like needles). 1H-NMR (CDCl3,
25 °C), δH: 7.85, d, 2H, aryl–H; 7.65, t, 2H, aryl–H; 7.60,
d, 2H, aryl–H; 7.45, d, 2H, aryl–H; 6.90, s, 2H, Ps–H; 13C-
NMR (CDCl3, 25 °C), δC: 168.14, C=O; 144.10, 137.87,
131.09, 126.65, 124.69, 123.92, Ar–C’s; 99.05, Ps-C. For
5a and 5b, IR: (cm−1): 1769 cm−1, (ν C=O).
Experimental
NMR on a Bruker 400 MHz instrument using tetramethyl-
silane as standard. DSC on a Shimadzu DSC-5. IR on a
Perkin-Elmer FTIR. Most reagents were purchased from TCI
America or Sigma Aldrich, and used as received. Pseudoac-
ids 1 and 2 were commercially available. Compounds 3 and
4 were prepared by literature methods [15, 16].
3‑Methano‑1[3H]‑isobenzofuranone, 7
This material was produced as one of the products of the
reaction of 113 mg (0.689 mmol) 3-methyl-3-hydroxy-
1[3H]-isobenzofuranone (2) with 116 mg (0.690 mmol)
3-chloro-3-hydroxy-1[3H]-isobenzofuranone and 200 mg
(1.4 mmol) potassium carbonate in 8 mL dimethylforma-
mide at 120 °C for 5 h. On cooling and removal of the insol-
uble materials and the solvent, a somewhat volatile colorless
solid was isolated, IR: 1780 cm−1 (ν C=O), 1662 cm−1 (ν
C=C). 1H-NMR (CDCl3, 25 °C) δH: 7.4–7.8, m, 4H, aryl–H;
4.50, s, 2H, =CH2.
Bis(1[3H]‑isobenzofuranone‑3‑yl)ethers, (R,R/S,S)‑5
and meso‑6
A solution of 255 mg (1.70 mmol) of 1 in 8 mL dichlo-
romethane was combined under N2(g) with 250 mg
(0.085 mmol) triphosgene. Then, 69 μL (0.085 mmol) pyri-
dine was added slowly over 30 min. The reaction mixture
warmed. After 1.5 h, water was added, and the organic layer
was removed and evaporated in vacuo. The semi-solid mate-
rial obtained was recrystallized from benzene. A colorless
solid was obtained, mp 78.5 °C (DSC peak), having IR
(cm−1): 1786, 1763, 1741 (ν C=Os). On heating the solid
to 155 °C (sand bath), gases were evolved and the orange
solid obtained was recrystallized from ethyl acetate pro-
ducing two distinct phases: colorless needles, meso form
6, IR (cm−1): 1771, (ν C=O), mp 218 °C (DSC peak), and
colorless plates, (R,R/S,S) form 5, IR (cm−1) 1778, (ν C=O);
mp 234 °C (DSC peak). Both phases were also obtained
by thermal dehydration of 1 by heating to 250 °C, cool-
ing and recrystallizing the solid residue from ethyl acetate
Bis(1[3H]‑isobenzopyranone‑3‑yl)ether, meso, 9
To a solution of 3-hydroxy-[3H]-isobenzopyran-1-one
[2-(2′oxoethyl)benzoic acid] in chloroform, one equivalent
of thionyl chloride was added at room temperature. After
standing 3 h, the solvent was slowly evaporated precipitating
a colorless solid. On recrystallization from ethyl acetate, the
anhydride forms colorless crystals (yield undetermined). IR:
1765 cm-1 (ν C=O); 1H-NMR (CDCl3, 25 °C) δH: 7.4–7.8,
m, 8H, aryl–H; 4.50, d, 4H, CH2; 5.55, t, 2H, Ps–H. From
the residue of the recrystalization, the [1H]-isochromen-
1-one (10) was also recovered; IR: 1730 cm−1, (ν C=O);
mp 47 °C.
1 3

Journal of Chemical Crystallography
equivalent of Cooper’s pseudoacid (4, 79 mg, 0.409 mmol)
was added all at once followed by a catalytic amount of
DMAP. The mixture was stirred for 6 h at 0 °C. Dicyclohex-
ylurea began to precipitate, and TLC (SiO2, CHCl3:EtOAc
10:1) showed two materials with Rfs>0.7. After warming
to room temperature, the DCU was removed by fltration,
and the solvent volume reduced in an air stream. The prod-
uct mixture was applied to a thick-layer chromatography
plate (SiO2), and eluted with CHCl3:EtOAc 10:1. The Rf
0.88 material (fastest running) was compound 13; Rf 0.77
was benzoic active ester. Compound 13 was a colorless
3‑Benzoyloxy‑1[3H]‑isobenzofuranone, 11
Benzoic acid (50 mg, 0.43 mmol) was dissolved in 8 mL
CH2Cl2, and one equivalent of DCCI (87 mg, 0.43 mmol)
was added at 0 °C, and stirred for an hour. Then, o-formylb-
enzoic acid (1) (65 mg, 0.43 mmol) was added and a cata-
lytic amount of DMAP, and the mixture was allowed to stand
overnight at 4 °C. TLC (silica, CHCl3:EtOAc 10:1) showed
fve components. The fastest running component (Rf 0.92)
was the anhydride 11. After fltering the dicyclohexylurea
from the reaction mixture, and evaporating the solvent, a
thick layer chromatogram was run on the chloroform solu-
ble residue of the reaction, and the band at highest Rf was
removed and extracted, producing a colorless solid from
ethyl acetate. 1H-NMR (CDCl3, 26 °C), δH: 8.09, Ar–H5, d,
1H; 7.78, Ar–H6, t, 1H; 7.61, Ar–H7, t, 1H; 7.99, Ar–H8, d,
1H; 6.897, Ps–H, s, 1H; 7.695, Ph-ortho, d, 2H; 7.46, Ph-
meta, t, 2H; 7.27, Ph-para, d, 1H. IR: 1777 cm−1, ν(C=O)
furanone; 1740 cm−1, ν (C=O) acyl.
1
oil. H-NMR: (CDCl3, 26 °C), δH: 8.149, Ar–H8, d, 1H;
7.697, Ar–H7, t, 1H; 7.555, t, Ar–H6, t, 1H; 7.456, Ar–H5,
d, 1H; 1.492, methyls, s, 6H; 6.666, Ps–H, s, 1H; 7.839,
Ph2′–H, d, 2H; 7.381, Ph3′–H, t, 2H; 7.445, Ph4′–H, t, 1H.
13C-NMR (CDCl3, 26 °C), δC: 123.096, C–(C=O); 145.564,
C–(CMe2); 124.336, C5; 134.745, C6; 127.526, C7; 130.4,
C8; 164.385, C(=O); 97.894, Ps-C; 37.546, quat-C; 27.353,
Me; 21.995, Me; 162.65, C(=O, phenyl); 130.4, Cipso;
129.865, C2′; 128.502, C3′; 133.777, C4′.
3‑Benzoyloxy‑3‑methyl‑1[3H]‑isobenzofuranone, 12
3‑(p‑Fluorobenzoyloxy)‑4,4‑dimethyl‑3,4‑dihy‑
dro‑[1H]‑isobenzopyran‑1‑one, 14
Benzoic acid (50 mg, 0.41 mmol) was dissolved in 8 mL
CH2Cl2, and one equivalent of DCCI (87 mg, 0.41 mmol)
was added at 0 °C, and stirred for an hour. Then, o-acetylb-
enzoic acid (2) (68 mg, 0.41 mmol) was added along with
a catalytic amount of DMAP, and the mixture allowed to
stand overnight at 4 °C. TLC (silica, CHCl3:ethyl acetate
10:1) showed fve components. The fastest running compo-
nent (Rf 0.9) was benzoic anhydride. Compound 12 had Rf
0.8. After fltering the dicyclohexylurea from the reaction
mixture, and evaporating the solvent, a thick layer chroma-
togram was run on the chloroform soluble residue of the
reaction, and the band at Rf 0.8 was removed and extracted,
producing a colorless crystalline solid from ethyl acetate.
1H-NMR (CDCl3, 26 °C), δH: 8.147, Ar–H5, d, 1H; 7.624,
Ar–H6, t, 1H; 7.482, Ar–H7, t, 1H; 7.950, Ar–H8, d, 1H;
2.121, Me, s, 3H; 8.118, Ph-ortho, d, 2H; 7.415, Ph-meta,
t, 2H; 7.624, Ph-para, d, 1H. 13C-NMR (CDCl3, 26 °C), δC:
170.36, 163.81, C(=O)’s; 147.90, 134.58,130.66, 128.86,
125.58, 122.02, aryl-C’s; 105.66, pseudoacyl-C; 25.25,
methyl-C. IR: 1770 cm−1, ν(C=O) furanone; 1730 cm−1, ν
(C=O) acyl.
The method used to make compound 13 was followed here.
The product with Rf 0.89 (SiO2, CHCl3:EtOAc; 10:1) was
compound 14, an oil. 1H-NMR (CDCl3, 26 °C), δH: 7.049,
Ar–H8, d, 1H; 7.049, Ar–H7, t, 1H; 7.696, t, Ar–H6, t, 1H;
8.141, Ar–H5, d, 1H; 1.482, methyls, singlets, 6H; 6.642,
Ps–H, s, 1H; 7.860, Ph2′–H, dd, 2H; 7.443, Ph3′–H, dd,
2H. 13C-NMR (CDCl3, 26 °C), δC: 123.019, C–(C=O);
145.479, C–(CMe2); 124.909, C5; 134.791, C6; 128.131,
C7; 130.415, C8; 163.417, C(=O); 97.972, Ps-C; 37.515,
quat-C; 27.361, Me; 21.932, Me; 162.549, C(=O, phenyl);
132.460, Cipso; 127.565, C2′; 115.654, C3′; 167.436, C4′.
3‑(p‑Chlorobenzoyloxy)‑4,4‑dimethyl‑3,4‑dihy‑
dro‑[1H]‑isobenzopyran‑1‑one, 15
The product with Rf 0.94 (SiO2, CHCl3:EtOAc; 10:1) was
compound 15, a solid. 1H-NMR (CDCl3, 26 °C), δH: 7.463,
Ar–H8, d, 1H; 7.455, Ar–H7, t, 1H; 7.690, t, Ar–H6, t, 1H;
8.159, Ar–H5, d, 1H; 1.483, methyl, s, 3H; 1.476, methyl,
s, 3H; 6.639, Ps–H, s, 1H; 7.357, Ph-ortho, dd, 2H; 7.776,
Ph-meta, dd, 2H. 13C-NMR (CDCl3, 26 °C), δC: 122.996,
C–(C=O); 145.433, C–(CMe2); 124.320, C5; 134.807,
C6; 127.116, C7; 130.439, C8; 163.587, C(=O); 105.400,
Ps-C; 37.515, quat-C; 27.369, Me; 21.940, Me; 162.495,
C(=O, phenyl); 127.588, Cipso; 131.205, C2′; 128.913, C3′;
140.36, C4′.
3‑Benzoyloxy‑4,4‑dimethyl‑3,4‑dihydro‑[1H]‑iso‑
benzopyran‑1‑one, 13
The general method was as follows: In a 50 mL round bot-
tom fask 50 mg (0.409 mmol) of benzoic acid was com-
bined with 1 equivalent (84 mg, 0.409 mmol) of DCCI
and enough dichloromethane at 0 °C (ice-bath) to dissolve
the substances. The mixture was stirred for 1 h, then 1
1 3

Journal of Chemical Crystallography
Table 1 Crystallographic information on dipseudoanhydride structures 5, 6, 8, 9, 19
Compound
5a
5b
6
8
9
19
Formula
FW
Temp. (K)
Crystal system
Space group
a (Å)
C16H10O5
282.25
297
Mono clinic
C 2/c
13.8519(8)
8.1410(4)
11.7772(6)
90
103.628(5)
90
1298.70(12)
4
C16H10O5
282.25
297
Ortho rhombic
P bca
6.0908(3)
15.4037(8)
27.6505(17)
90
90
90
2494.2(2)
8
C16H10O5
282.25
296
Mono clinic
P n
4.448(2)
6.496(3)
22.227(9)
90
91.32(5)
90
C18H14O5
310.30
296
Mono clinic
C 2/c
23.500(10)
8.393(3)
15.869(7)
90
103.05(3)
90
C18H14O5
310.30
295
Mono clinic
P 21/n
14.125(22)
7.300(10)
15.148(32)
90
97.24(15)
90
C19H16O5
324.33
110
Tetragonal
I −4
19.7930(3)
19,7930(3)
8.07666(16)
90
b (Å)
c (Å)
α (o)
β (o)
90
90
γ (o)
Volume (Å3)
Z
641.9(5)
2
3049(2)
8
1549(5)
4
3164.05(10)
4
F000
1168
1.445
1892, 1427
98, 0
0.0305
0.0681
1.089
+0.14, −0.11
584
1.453
1980, 1529
191, 0
0.0439
0.1208
1.062
292
1.460
1287, 914
191, 2
0.0479
0.1088
1.050
1296
1.352
3520, 2057
209, 0
0.0540
01256
648
1.330
3572, 846
209, 1
0.0671
0.1214
0.978
1360
1.362
2781, 2742
335, 39
0.0317
0.0829
1.074
dcalc (Mg/m3)
Unique ref., I>4σI
Parameters, restraints
R1 (I>4σI)
wR2(all)
GooF
1.053
+0.18, −0.17
Δρmax
,
min (e−/Å3)
+0.25, −0.16
+0.19, −0.23
+0.21, −0.21
+0.14, −0.19
Estimated standard deviations in parentheses
C(=O); 98.506, Ps-C; 37.499, quat-C; 27.501, Me; 21.940,
Me; 162.208, C(=O, phenyl); 134.977, Cipso; 130.981, C2′;
123.670, C3′; 159.916, C4′.
3‑(p‑Methoxybenzoyloxy)‑4,4‑dimethyl‑3,4‑dihy‑
dro‑[1H]‑isobenzopyran‑1‑one, 16
The product at Rf 0.84 (SiO2, CHCl3:EtOAc; 10:1) was
compound 16, an oil. 1H-NMR (CDCl3, 26 °C), δH: 7.486,
Ar–H8, d, 1H; 7.454, Ar–H7, t, 1H; 7.689, t, Ar–H6, t, 1H;
8.158, Ar–H5, d, 1H; 1.483, methyl, s, 3H; 1.481, methyl,
s, 3H; 6.644, Ps–H, s, 1H; 7.804, Ph2′–H, d, 2H; 6.860,
Ph3′–H, d, 2H; 3.834, OCH3, s. 13C-NMR (CDCl3, 26 °C),
δC: 123.189, C–(C=O); 145.681, C–(CMe2); 124.305, C5;
134.652, C6; 127.457, C7; 130.369, C8; 164.005, C(=O);
97.678, Ps-C; 37.569, quat-C; 27.299, Me; 21.963, Me;
162.781, C(=O, phenyl); 120.936, Cipso; 132.026, C2′;
113.795, C3′; 164.044, C4′; 55.437, OCH3.
3‑(m‑Nitrobenzoyloxy)‑4,4‑dimethyl‑3,4‑dihy‑
dro‑[1H]‑isobenzopyran‑1‑one, 18
The product with Rf 0.83 (SiO2, CHCl3:EtOAc; 10:1) was
compound 18, an oil. 1H-NMR (CDCl3, 26 °C), δH: 7.470,
Ar–H8, d, 1H; 7.489, Ar–H7, t, 1H; 7.624, t, Ar–H6, t, 1H;
8.403, Ar–H5, d, 1H; 1.517, methyls, s, 6H; 6.682, Ps–H,
s, 1H; 8.645, PhC2′, s; 8.165, PhC4′, d, 1H; 7.725, PhC5′,
t, 1H; 8.147, PhC6′, d, 1H. 13C-NMR (CDCl3, 26 °C),
δC: 122.794, C–(C=O); 145.177, C-(CMe2);124.785, C5;
135.016, C6; 127.759, C7; 129.912, C8; 162.526, C(=O);
98.498, Ps-C; 37.515, quat-C; 27.346, Me; 21.963, Me;
162.255, C(=O, phenyl); 130.501, PhCipso; 124.382, PhC2′;
148.267, PhC3′; 127.759, PhC4′; 128.138, PhC5′; 135.318,
PhC6′.
3‑(p‑Nitrobenzoyloxy)‑4,4‑dimethyl‑3,4‑dihy‑
dro‑[1H]‑isobenzopyran‑1‑one, 17
The product with Rf 0.83 (SiO2, CHCl3:EtOAc; 10:1) was
compound 17, a solid, recrystallized from ethyl acetate.
1H-NMR (CDCl3, 26 °C), δH: 7.718, Ar–H8, d, 1H; 7.473,
Ar–H7, t, 1H; 7.488, t, Ar–H6, t, 1H; 8.173, Ar–H5, d, 1H;
1.508, methyls, s, 6H; 6.670, Ps–H, s, 1H; 8.222, Ph-2′–H,
d, 2H; 8.015, Ph-3′–H, d, 2H. 13C-NMR (CDCl3, 26 °C),
δC: 122.818, C–(C=O); 145.185, C–(CMe2); 124.351,
C5;134.025, C6; 127.751, C7; 130.539, C8; 162.489,
(1[3H]‑Isobenzofuranone‑3‑yl)(4,4,dimethyl‑3,4‑di‑
hydro‑[1H]‑isobenzopyran‑1‑one‑3‑yl)ether, 19
To a solution of o-formylbenzoic acid (1, 75 mg, 0.50 mmol)
and 3-hydreoxy-4,4-dimethyl-3,4-dihydroisobenzopyran-
1-one (4, 96 mg, 0.50 mmol) in 5.0 mL CH2Cl2, 103 mg
1 3

Journal of Chemical Crystallography
Table 2 Crystallographic information on normal-pseudo anhydride
structures 11, 12, 17
Compound
11
12
17
Formula
FW
Temp. (K)
Crystal system
Space group
a (Å)
C15H10O4
254.24
297
C16H12O4
268.27
297
C18H15NO6
341.32
101
Monoclinic Orthorhombic Triclinic
P 21/c
P bca
7.6616(4)
10.8625(5)
31.0942(12)
90
90
90
P −1
13.7593(4)
7.6299(2)
11.8981(5)
90
92.215(3)
90
8.5727(6)
8.7135(6)
11.0926(6)
76.685(5)
75.424(5)
85.131(6)
780.0(9)
2
b (Å)
c (Å)
α (o)
β (o)
Fig. 2 Thermal ellipsoid plot (50% envelopes) of the molecular struc-
ture of 9 (meso) showing the approximate mirror
γ (o)
Volume (Å3)
Z
1248.15(7)
4
2587.8(2)
8
F000
528
1.353
1120
1.377
356
1.453
dcalc (Mg/m3)
Unique ref., I>4σI
4091
1988
5020
2597
1584
4374
Parameters, restraints
R1 (I>4σI)
wR2(all)
172, 0
0.0544
0.1186
1.012
182, 0
0.0329
0.0876
1.028
226, 0
0.0365
0.1036
1.030
GooF
Δρmax
,
+0.27
+0.11
+0.43
(e−/Å3)min
−0.14
−0.14
−0.23
Estimated standard deviations in parentheses
Fig. 3 Thermal ellipsoid plot (50% envelopes) of the molecular struc-
ture of 5a shown down the two-fold axis
Fig. 1 Thermal ellipsoid plot (50% envelopes) of the molecular struc-
ture of 6 (meso) showing the approximate mirror
Fig. 4 Thermal ellipsoid plot (50% envelopes) of the molecular struc-
ture of 5b shown down the approximate two-fold axis
(0.50 mmol) DCCI was added and stirred at 0 °C until
the reactants were in solution. Then, a catalytic amount
of DMAP was added. The mixture stood for 48 h at
−10 °C, then warmed to room temperature, and tlc [silica;
CHCl3:ethyl acetate (10:1)] showed bands at Rf 0.85 (major),
0.75 (major), 0.60 (minor). Dicyclohexylurea was fltered
and the dichloromethane solution was concentrated. The
oily mixture was separated by thick-layer chromatography
[silica, CHCl3:ethyl acetate (10:1)]. The Rf 0.85 band was
the isophthalide of 4; the Rf 0.6 band was the active ester of
1, each determined by nmr. The Rf 0.75 band by nmr showed
about 30% of the symmetric dipseudoanhydride 5 (RR/SS)
or 6 (meso), and 70% of a second anhydride with pseudoacyl
1 3

Journal of Chemical Crystallography
dipseudoanhydride 19. For 19: IR: 1778 cm−1 (νC=O fura-
1
none), 1733 cm−1 (νC=O, pyranone); H-NMR (CDCl3,
25 °C), δH: (6-ring) 8.1, d, 1H, ar–H nearest C=O; 7.7, t,
1H; 7.6, t, 1H; 7.4, d, 1H; 5.65, s, 1H, Ps–H; 1.41, s, 3H,
Me; 1.48, s, 3H, Me; (5-ring) 7.8, d, 1H, ar–H nearest C=O;
7.6, t, 1H; 7.4, t, 1H; 7.6, d, 1H; 6.8, s, 1H, Ps–H; 13C-NMR
(CDCl3, 25 °C), δC: 168.08; (5-ring)C=O; 163.26; (6-ring)
C=O; benzopyran: 123.73, C–(C=O); 145.93, C(CMe2),
124.69, C3; 131.38, C4; 127.40, C5; 130.23, C6; 104.85,
Ps-C; 37.1, quat-C; 27.0, 22.0 Me’s; benzofuran: 144.29,
134.86, 134.68, 126.57, 125.52, 123.07, ar–C’s; 98.4, ben-
zofuran Ps-C;
Crystallography
Specimens suitable for single-crystal difraction experiments
were mounted with epoxy atop a fne glass fber for room
temperature data collection, or adhered to a fne nylon loop
with fuorocarbon oil for low temperature data collection.
A Rigaku Gemini difractometer with a CCD camera was
used for 5a, 5b, 11, 12, 17 and 19, and a Nicolet-Bruker
P3 difractometer with a scintillation counter were used for
6, 8, and 9. Data for the difraction experiments is given
for the dipseudoanhydrides in Table 1 and for the normal-
pseudo anhydrides in Table 2. Structures were solved with
SHELXS-86 and refned by full-matrix least-squares meth-
ods with SHELXL-97 [17]. Non-H atoms were refned with
anisotropic librational factors; H-atoms were assigned posi-
tions riding on their non-H atoms with isotropic librational
factors of 120% or 150% (methyls) of the Ueq of the non-H
atoms. Absorption corrections were applied. Thermal ellip-
soid plots of each of the structures are given in Figs. 1, 2,
3, 4, 5, 6, 7, 8 and 9. Selected bonding metrics are given in
Table 3.
Fig. 5 Thermal ellipsoid plot (50% envelopes) of the molecular struc-
ture of 8 shown nearly down the approximate two-fold axis
Fig. 6 Thermal ellipsoid plot (50% envelopes) of the molecular struc-
ture of 11
Crystals of the (R,R/S,S) diastereomer 5 apparently
form three polymorphs, monoclinic 5a, orthorhombic 5b,
and a monoclinic structure previously reported [2]. For 5a,
twinned, non-merohedral, pseudo cell was approximately
hexagonal, a = b = 8.034 Å, c = 57.2 Å, γ = 119.1o, but
exactly orthorhombic, C-centered with a=13.8 Å, b=8.14
Å, c=57.27 Å. In the specimens examined, perfect twinning
on the a-axis of a C-centered monoclinic cell was found (see
Table 2) and the two twin components had almost exactly
the same domain size, with 2485 refections observed in
one component, and 2490 refections in the second, and 770
perfectly overlapped. Twin refnement was satisfactory and
the scale factor for the major component was 0.511(1).
Crystals of 6, the meso isomer, were typically afected
by non-crystallographic translational symmetry along the
n-glide. The specimen reported here was largely free of this
challenge. This structure has also been reported, and the two
determinations agree closely [18].
Fig. 7 Thermal ellipsoid plot (50% envelopes) of the molecular struc-
ture of 12
signals for both an arylfuran and an arylpyran group. On
fractional crystallization from ethyl acetate, the (R,R/S,S)
form (5a) crystallized frst, followed by the unsymmetric
1 3

Journal of Chemical Crystallography
Fig. 8 Thermal ellipsoid plot
(50% envelopes) of the molecu-
lar structure of 17
Crystals of 7 were obtained by sublimation, color-
less rods, monoclinic, space group C c, a = 7.916(7)
Å, b = 13.396(13) Å, c = 13.620(16) Å, β = 96.13(8),
V=1436(3) Å3, Z=8 (2 molecules/asymmetric unit), 293 K,
Mo Kα, C9H6O2, Mr =292.28 g/mol [19].
A second phase of 3-chloro-1[3H]-isobenzofuranone,
C8H5ClO2, was included in the analysis of bond metrics.
This phase was reported previously, monoclinic, space group
P 21/c, a = 12.938(7) Å, b = 8.027(4) Å, c = 7.184(4) Å,
β=94.87(4)o, V=743.4(7) Å3, Z=4 [19]. In this structure:
n C–O is 1.409(3)Å; angle On-C–Cl is 108.7(2)o. It was a
polymorph of another phase reported earlier, orthorhombic,
space group P bca, V=1475.2(12) Å3, Z=8 [2].
Crystals of the unsymmetric dipseudoanhydride, 19, form
a conglomerate, and the specimen studied was of the R,R’
diastereomer; Flack 0.07(14). The arylfuran moiety was
ordered but the arylpyran moiety was modeled with two
Fig. 9 Thermal ellipsoid plot (50% envelopes) of the molecular struc-
ture of the unsymmetric dipseudoanhydride 19
Table 3 Carbon-oxygen bond metrics in anhydrides [P=pseudoacyl; N=normal carboxyl; x=exocylic; n=endocyclic; estimated standard devi-
ations in parentheses]
Compound
5a
5b
6
8
9
19
11
12
17
Ps C=O
1.202(1)
1.369(1)
1.443(1)
1.404(1)
1.404(1)
1.443(1)
1.369(1)
1.202(1)
1.199(3)
1.366(3)
1.440(2)
1.404(2)
1.411(2)
1.436(3)
1.368(3)
1.199(3)
1.191(5)
1.371(6)
1.449(6)
1.397(5)
1.416(5)
1.437(6)
1.386(7)
1.190(6)
1.200(3)
1.370(3)
1.461(2)
1.407(2)
1.416(2)
1.461(2)
1.358(2)
1.197(2)
1.192(5)
1.346(6)
1.462(5)
1.438(4)
1.447(4)
1.455(5)
1.362(5)
1.196(5)
1.196(2)
1.374(2)
1.444(2)
1.407(2)
1.418(3)
1.435(5)
1.375(5)
1.208(3)
1.194(2)
1.364(2)
1.430(2)
1.417(2)
1.194(2)
1.371(2)
1.442(2)
1.434(2)
1.212(1)
1.355(1)
1.442(1)
1.415(1)
Ps=C–O
Ps n C–O
Ps x C–O
Ps’ x C–O
Ps’ n C–O
Ps’=C–O
Ps’ C=O
N O–C=
N C=O
1.374(2)
1.190(2)
1.359(2)
1.201(2)
1.358(1)
1.201(1)
τ OCOCa
−87.0(1)
−87.0(1)
(5)exo
−67.2(2)
−61.8(2)
(5)exo
−98.7(5)
+85.1(5)
(5)exo
−80.8(2)
−80.3(2)
(5)endo
−84.7(4)
+82.7(4)
(6)axial
exo
−99.8(3)
−92.3(4)
(5)exo
(6)axial
exo
−86.6(2)
+60.7(2)
+84.6(1)
Conform.
(5)exo
(5)endo
(6)equat.
Confg.
R,R/S,S
R,R/S,S
meso
R,R/S,S
meso
R,R’
Racemate
Racemate
Racemate
aTorsion angles for a common relative confguration; (5) refers to arylfuran and (6) to arylpyran rings. For 19, arylfuran entries precede
arylpyran entries; metrics for the major conformer
1 3

Journal of Chemical Crystallography
x
n
Scheme 2 Resonance structures
-
-
-
for normal-pseudo anhydrides
B
C
A
Scheme 3 Resonance structures
-
-
for dipseudoanhydrides
x
x' n'
n
B
-
A
-
D
C
contributors, major component 0.645(8), difering in con-
formation about the exo C5–O5–Oether–C6 torsion, −99.8(3)o
(major), −87.5(4)o (minor).
Discussion
Chemistry
A variety of methods for forming pseudoanhydrides has
been explored and found to be useful. Efective methods
beyond thermal dehydration have been demonstrated, each
involving (putatively) reactive intermediates. The displace-
ment of a pseudochloride by a nucleophilic oxygen seems
the more likely mechanism for formation of 9 and perhaps
the formation of a pseudoester of o-benzoylbenzoyl chloride
by sodium benzoate [2]. The new methods demonstrated
here involve the dicyclohexylcarbodiimide coupling reac-
tion. Formation of the active esters of normal carboxylic
acids is a well known frst step in acyl substitution, and it is
shown here that pseudoacids (1, 2, 4) are able to displace the
activating group and form the anhydrides. Pseudoacyl oxy-
gens are expected to be better nucleophiles than carboxylic
acid oxygens, so this is not unanticiptated. The reaction to
form the dipseudoanhydride 19, however, provides tentative
evidence of another mechanism. Relatively unhindered pseu-
doacids (those from aldehydo acids) may apparently form
pseudoacyl active esters, which can be displaced by a pseu-
doacid. Intermediate pseudoacyl active esters have not been
observed yet, so this mechanism will require more evidence.
Fig. 10 C–O Bond Lengths at the Pseudoacyl Carbons in Arylfuran
Pseudoacyl Derivatives of o-Acylbenzoic Acids, estimated standard
deviations (x 2); outliers with flled markers (see text)
contributions to the ground state from resonance contribu-
tors A and B (Scheme 2). A test for this hypothesis may
be found comparing pseudoacyl C–O lengths, where the
exocyclic C–O bonds (x) and the endocyclic C–O bonds
(n) should have similar lengths. In both structures, n C–O
is longer than x C–O for these normal-pseudo anhydrides
(n 1.441Å, x 1.416Å, diference 0.025Å, N = 3, Table 2).
This result implies that the endocyclic carboxylate is the
better leaving group, and that the endocyclic carboxyl (part
of the pseudoacid) is the stronger acid. For normal-pseudo
anhydrides, contributions to the ground state structure from
resonance forms like B (Scheme 2) are important.
Structures
Normal-pseudo anhydrides (11, 12, 17). In each of these
structures, the pseudoacyl carbon bears competing exocyclic
and endocyclic carboxylate groups. In the examples 11 and
12 (Fig. 6 and 7), the cyclic form is an arylfuran ring and
the carboxylates are (substituted) benzoates. With similar
basicities (about pKa ~ 5), we might expect roughly equal
It has been observed preciously that at pKa 2.4 for the
(conjugate acid of the) exocyclic group would show equal n
C–O and x C–O lengths in an arylfuran pseudoacyl system
[2]. The C–O data from the arylpyran system (17) is similar
to the furans, and this example is included in the set though
1 3

Journal of Chemical Crystallography
structures show this disparity (n 1.449Å, x 1.407Å; difer-
ence 0.042Å, N=14), and this diference is slightly larger
than in the normal-pseudo anhydrides (vide supra).
With the addition of the arylfuran pseudoacyl derivative
data from 5a, 5b, 6, 8, 11, 12, and 19 to the limited informa-
tion in the literature, the C–O bond length functions for the
arylfuran system can be reconstructed [2, 18–20]. Figure 10
shows the C–O bond length trends at the pseudoacyl car-
bon for cyclic o-acylbenzoic acid derivatives. The range of
pKa’s (conjugate acid of the implied leaving groups) is now
extended to include the pseudoacyl chlorides. A pKa of 8 is
used for the treatment of the pseudoacyl leaving group [2].
Trends are reasonably well established, with the n C–O func-
tion (in Å)=1.4287+0.0022322 pKa (N=20, R2 =0.83),
and x C–O (in Å) = 1.4408 − 0.0039882 pKa (N = 16,
R2 =0.75). In the previous determination, which excluded
the pseudoacyl chlorides, the n C–O slope was smaller and
the x C–O slope was larger [2]. The crossover length, the
distance at which endocyclic and exocyclic C–O’s are equal,
is 1.433 Å at a pKa of 1.94. Since this is about 3 pK units
more acidic than normal carboxylic acids, this represents
the efective increase in the endocyclic leaving group abil-
ity owing to ring formation. A model for this is captured in
resonance structures A, B (Scheme 3).
Fig. 11 On–C–Yx Bond Angles at the Pseudoacyl Carbons for Aryl-
furan Pseudoacyl Derivatives of o-Formylbenzoic Acid, estimated
standard deviations (×2); see text
the C–O bond length dependency on leaving group ability
has not been established for the arylpyrans yet. The efec-
tive enhanced acidity of the endocyclic (pseudo)carboxyl is
tentatively supported and estimated to be about 3 pK units
stronger relative to a nominal carboxylic acid.
Dipseudoanhydrides
Clues to the source of this efect may be found by exami-
nation of the arylfurans from o-formylbenzoic acid including
fve (5a, 5b, 6, 11, 19) reported here. Structures for these
span the range of leaving group pKa explored above. Fig-
ure 11 shows the On–C–X angles at the pseudoacyl carbon
(all exo conformers, see below and Table 2), for which a
trend is evident while the correlation is modest (R2 =0.71).
The longer n C–O’s show angles of departure (~112o) of
the endocyclic leaving group above the Bürgi-Dunitz angle
(107o) [21]. This suggests that the interaction of the endo-
cyclic nucleophile in ring formation may approach along
a non-optimal trajectory, for which a stronger endocyclic
Lewis-basicity or a weaker leaving group Lewis-basicity are
partial remedies. The changing polarization (partial ionic
character) of the C–O bonds follow diferent dependencies
(slopes of the two C–O functions difer by about a factor of
2) with the endocyclic function more restricted. Even with
Five of the six dipseudoanhydrides studied are symmetrical
(either meso or racemate of R,R/S,S isomers) (Figs. 1, 2, 3,
4, 5). Only in crystals of 5a (an RR/SS form) does the crystal
lattice use the molecular symmetry with the ether oxygen
lying on the crystallographic twofold axis in C 2/c, making
half-molecules the asymmetric unit. In the others (5b, 6, 8,
9) and in a sixth (19, an unsymmetrical anhydride between
pseudoacids 1 and 4) molecules occupy general positions.
The dipseudoanhydrides (5, 6, 8, 9, 19) studied comprise
both arylfuran and arylpyran examples. These structures
present competing pseudocarboxyl (C, D, Scheme 3) or car-
boxyl leaving groups (A, B, Scheme 3), a disparity between
n C–O and x C–O is still expected, since carboxylate is a
better leaving group than pseuodcarboxylate. If structures
like A, B are more important than C, D (Scheme 3), then n
C–O would be longer than x C–O. All dipseuodanhydride
Scheme 4 Drawing of arylfuran
and arylpyran conformations
looking down the pseudoacyl
C–Oether bond. Orientation of
the exocyclic Oether–Cpseudoacyl
group is shown with a darkened
bond
1 3

Journal of Chemical Crystallography
Scheme 5 Drawing of arylfuran conformations looking down the pseudoacyl C–Oether bond. Orientation of the endo- and exocyclic Oether
–
C
pseudoacyl group is shown with a darkened bond
Scheme 6 Drawing of arylfuran conformations looking down the pseudoacyl C–Oether bond. Orientation of the endo- and exocyclic Oether–Cacyl
group is shown with a darkened bond
better leaving groups (lower conjugate acid pKa), the endo-
cyclic angle of approach is still above 107o.
Conformations
This analysis focused on arylfurans, and Fig. 10 omits
the benzopyranoid structures. Similar length disparities
(n C–O > x C–O) are observed in the arylpyrans for the
dipseudo anhydride 9, normal, pseudo anhydride, 17, and
unsymmetric dipseudo anhydride 19 (Table 3). Also, in the
diastereomereic pairs of mucochloric psedoanhydrides, a
furanoid system, n C–Os are longer than x C–Os (n 1.430Å,
x 1.398Å, diference 0.032Å, N = 4) [7]. From Fig. 10, it
is clear that the n C–O lengths in the normal-pseudo anhy-
dride of o-benzoylbenzoic acid (pKa 3.54), its psueudo
methyl ester (pKa 15.9), dipseudoanhydride 8 (pKa 8), and
for pseudoacid o-acetylbenzoic acid (pKa 15.7) are modest
positive outliers [2, 20]. These are compounds with four
non-H atoms including aryl and alkyl substitutions on the
pseudoacyl carbon, and their C–O bonds are systematically
slightly lengthened by steric efects [22]. A narrowed analy-
sis of only the cyclic derivatives of o-formybenzoic acid,
which form the majority of the study group, does not alter
the slopes appreciably, with the crossover C–O distance
reduced to 1.428 Å at a pKa of 1.81. For this set, n C–O (in
Å)=1.4242+0.0022211 pKa (N=15, R2 =0.96), and for x
C–O (in Å)=1.4346 − 0.035136 pKa (N=11, R2 =0.63).
Of the fve symmetric dipseudoanhydrides structures studied
(5a, 5b, 6, 8, 9) two are meso and three are (R,R/S,S) forms.
The ring systems are fairly rigid groups. For both benzofuran
and benzopyran systems, linking (ether) oxygens are dis-
placed from the mean ring planes. Orientations of the rings
with respect to each other can be described by the O(ring)–
C(pseudo)–O(ether)–C(pseudo′) torsions which are typically
gauche and synclinal to the ring C–O and substituents are
either exo (oriented away from the rings) or endo (oriented
over the ring). Scheme 4 shows the conformations down the
C(pseudo)-O(ether) bonds for meso forms with exo confor-
mations. Torsion angles relevant to the conformations are
given in Table 2. Molecules in 6 and 9 occupy general posi-
tions, and the mirror symmetry of the meso forms are not
displayed in the crystal.
Dipseudoanhydrides with (R,R/S,S) confgurations show
both endo and exo conformations (Scheme 5). Compound
5a retains is molecular two-fold in the crystal while 5b and
8 occupy general positions and molecules show approximate
two-fold symmetry.
The arylpyran anhydride moiety of 9 has an axial
(α-anomer) conformation additionally (see Scheme 4). In
unsymmetric anhydride 19, the arylpyran part has an axial
conformation and the pseudoacyl attachment is exo. For the
1 3

Journal of Chemical Crystallography
8. Weinges K, Hepp M, Huber-Patz U, Irngartinger H (1987) Che-
mie der Ginkgolide, III. Bilobalid/iso-Bilobalid – Strukturbeweis
durch Röntgenbeugung. Liebigs Ann Chem 12:1079–1085
9. Lalancette RA, Vanderhof PA, Thompson MW (1990) 2-Benzo-
ylbenzoic acid: structures and hydrogen-bonding patterns of the
anhydrous and hydrated form. Acta Crystallogr A C46:1682–1686
10. Bhatt MV, Kamath KM, Ravindranathan M (1971) Aspects of
tautomerism. Part II. Reactions of the pseudo-acid chloride of
o-benzoylbenzoic acid with nucleophiles. J Chem Soc C. https://
doi.org/10.1039/J39710001772
arylfuran part of 19, its pseudoacyl substituent also has an
exo conformation. Arylfuran normal-pseudo anhydrides 11
and 12 are racemates, and these show both endo and exo
conformations (Scheme 6). As noted above, arylpyrans in 9
and 19 are in axial conformations while in 17, the pseudoa-
cyl nitrobenzoyloxy group is equatorial (β-anomer).
11. Demaison J, Csaszar AG (2012) Equilibrium CO bond lengths. J
Mol Struct 1023:7–14
Supplementary Materials Available
12. Briggs AJ, Glenn R, Jones PG, Kirby AJ, Ramaswamy P (1984)
Bond length and reactivity. Stereoelectronic efects on bonding in
acetals and glucosides. J Am Chem Soc 106:6200–6206
13. Jones PG, Kirby AJ (1984) Simple correlation between bond
length and reactivity. Combined use of crystallographic and
kinetic data to explore a reaction coordinate. J Am Chem Soc
106:6207–6212
Crystallographic information for (5a: 1913208; 5b: 1913205; 6:
1913211; 8: 1913212; 9: 1913207; 11: 1913209; 12: 1913206;
17: 1913210; 19: 1915554) have been deposited with the Cam-
bridge Crystallographic Data Center. Structural data can be
obtained 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).
14. Ruggiero G, Thaggard AL, Valente EJ, Eggleston DS (1990)
Structural variations in 3,4-dihydro-2H-pyran ketals: acyl and
aryl warfarin derivatives. Acta Crystallogr A B46:629–637
15. Cooper WJ, Smith TN, Barker AK, Webb JA, Valente EJ (2003)
Pseudoacids. III. Formation and structures of new cyclic oxocar-
boxylic acids. J Chem Crystallogr 33(5–6):375–382
16. Schöpf C, Kühn R (1950) Notiz über 2-Oxy-hydrindon-(1). Chem
Ber 83:390–394
Acknowledgements We thank Marilyn Brooks, Brian MacFarland,
Derek Thomas Letort for early synthetic explorations. EJV thanks the
National Science Foundation for support of crystallographic equipment
(MRI-0604188).
17. Sheldrick GM (2008) A short history of SHELX. Acta Crystallogr
A A64:112–122
18. Li W, Yin H, Wen L, Li K, Fan W (2009) 3,3′-Oxybi[isobenzo-
furan-1(3H)-one]. Acta Crystallogr E 65:o2577
References
19. Letort DT (2000) Synthetic methods towards pseudoacid deriva-
tives. Honors Essay, Mississippi College, Clinton
1. Mowry DT (1950) Mucochloric acid. I. Reactions of the pseudo
acid group. J Am Chem Soc 72:2535–2537
20. Valente EJ, Fuller JF, Ball JD (1998) Pseudoacids I: 4- and
5-oxoacids. Acta Crystallogr A B54:162–173
2. Valente EJ, Martin SB, Sullivan LD (1998) Pseudoacids. II.:
2-Acylbenzoic acid derivatives. Acta Crystallogr A B54:264–276
3. Valters RE, Flitsch W (1985) In: Katritzy AR (ed) Ring-chain
tautomerism. Plenum Press, New York
21. Bürgi H-B, Dunitz JD (1994) Structure correlations, vol 2. VCH
Publishers, Weinheim
22. Bürgi H-B, Dunitz JD, Lehn JM, Wipff G (1974) Stereo-
chemistry of reaction paths at carbonyl centers. Tetrahedron
30(12):1563–1572
4. Jones PR (1963) Ring-chain tautomerism. Chem Rev
63(5):461–487
5. Wolf L (1885) Zur Kenntniss der Terpene und der ätherischen
Oele. Annalen 229:258
Publisher’s Note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional afliations.
6. Bredt J (1886) Über Acetyllävulinsäure und die Constitution der
γ-Ketonsäuren. Annalen 236:225–240
7. Supinski M, Valente EJ (2016) Mucochloric pseudoanhydrides. J
Chem Crystallogr 46:263–268
Afliations
Emily O’Loughlin1 · Edward J. Valente1
1
Department of Chemistry, University of Portland, 5000
North Willamette Blvd, Portland, OR 97203, USA
1 3