Thermal decomposition of N-acyloxy-N-alkoxyamides a new HERON reaction

Article abstract of DOI:10.1071/CH10350

The HERON reaction has been observed in the thermal decompositions of N-acyloxy-N-alkoxyamides 1b, members of the class of anomeric amides. The N,N-bisoxo-substitution results in reduced amide resonance and this, combined with an n_O-σ*_NOAcyl anomeric destabilization of the N-OAcyl bond, results in their intramolecular rearrangement to anhydrides 42 and alkoxynitrenes 43 in competition with homolysis of the N-OAcyl bond to alkoxyamidyls 51. The primary HERON product alkoxynitrenes are scavenged by oxygen, giving a nitrate ester, in competition with a rearrangement to nitriles and dimerization to hyponitrites, leading, under the conditions, to alcohols and aldehydes. Persistent alkoxyamidyls most likely form a 1,3-diradical in a solvent-cage reaction, which cyclizes to 3,5-disubstituted-(5H)-1,4,2-dioxazoles 47. Substituent effects support this competition reaction. CSIRO 2010.

Full text of DOI:10.1071/CH10350

RESEARCH FRONT
Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2010, 63, 1717–1729
Thermal Decomposition of N-Acyloxy-N-alkoxyamides
]
a New HERON Reaction
A
A
A
Jennifer P. Johns, Arjan van Losenoord, Cle´ment Mary,
A
A
A
Pierre Garcia, Damian S. Pankhurst, Adam A. Rosser,
and Stephen A. Glover
A B
,
A
Department of Chemistry, School of Science and Technology,
University of New England, Armidale, NSW 2351, Australia.
Corresponding author. Email: sglover@une.edu.au
B
The HERON reaction has been observed in the thermal decompositions of N-acyloxy-N-alkoxyamides 1b, members of the
class of anomeric amides. The N,N-bisoxo-substitution results in reduced amide resonance and this, combined with an
nO–s*NOAcyl anomeric destabilization of the N–OAcyl bond, results in their intramolecular rearrangement to anhydrides 42
and alkoxynitrenes 43 in competition with homolysis of the N–OAcyl bond to alkoxyamidyls 51. The primary HERON
product alkoxynitrenes are scavenged by oxygen, giving a nitrate ester, in competition with a rearrangement to nitriles
and dimerization to hyponitrites, leading, under the conditions, to alcohols and aldehydes. Persistent alkoxyamidyls
most likely form a 1,3-diradical in a solvent-cage reaction, which cyclizes to 3,5-disubstituted-(5H)-1,4,2-dioxazoles 47.
Substituent effects support this competition reaction.
Manuscript received: 23 September 2010.
Manuscript accepted: 22 October 2010.
Anomeric amides 1 (Chart 1) are defined as amides that bear two
heteroatoms at the amide nitrogen.[1,2] In all of these structures,
the amide nitrogen responds to the collective electronegativity
of the substituents in rehybridizing from sp2 to sp3. This facil-
itates an electron density distribution that better satisfies the
electron demand of the nitrogen substituents, X and Y. The
configurational change results in smaller angles at nitrogen
and reduced p-character of the lone-pair orbital with attendant
disconnection from the amide carbonyl, as evidenced by
spectroscopic properties, radically reduced amide isomerization
barriers, reactivity patterns, and theoretical attributes. The
properties of various congeners of this class of amides have been
reviewed,[1,2] as have the structural, theoretical, spectroscopic
properties, the reactivity patterns and biological activities
of N-acyloxy-N-alkoxyamides 1b.[3] There is ample evidence
of pyramidality in N-alkoxy-N-chloroamides (1a, X ¼ Cl),
N-acyloxy-N-alkoxyamides 1b, N,N-dialkoxyamides 1c,
N-alkoxy-N-aminoamides 1d, and N,N-dihaloamides 1f.[1–7]
In effect, in all these amides, resonance is to a large degree
diminished (Fig. 2a) and the contribution of structure II (Fig. 1)
to the resonance hybrid I 2 II 2 III is reduced. The combined
electronegativity of the triad of heteroatoms (XNY) also desta-
bilizes resonance form III (Fig. 1), and the best representation of
an anomeric amide is I.
Anomeric amides have different properties to those dis-
played by primary amides and secondary N-alkyl- or tertiary
N,N-dialkylamides in two respects. On the one hand, bishetero-
atom substitution at nitrogen impacts strongly on the nitrogen
hybridization and the degree of amide resonance. On the
other hand, the lone-pair synergy, as a consequence of anom-
eric effects operating through the nitrogen, influences both
conformational preferences and the reactivity of various
congeners.[1–3]
Fig. 2b illustrates that in XNY systems, as with anomeric
carbon centres,[8–10] two anomeric interactions are possible and
these involve either an nY–s*NX or an nX–s*NY overlap where nX
and nY represent the p-type lone pairs on X and Y and s*NX and
s*NY represent the N–X and N–Y antibonding orbitals. In either
case, the result is a net stabilization of the lone pair of electrons.
Except where the nitrogen is symmetrically substituted, one of
these interactions will be stronger.
O
N
R
Y
X
1a–X ꢂ Cl, Br, I, Y ꢂ OR
1b–X ꢂ OAcyl, Y ꢂ OR
1c–X ꢂ Y ꢂ OR
1d–X ꢂ NR2, Y ꢂ OR
1e–X ꢂ SR, Y ꢂ OR
1f– X ꢂ Y ꢂ halogen
Oꢀ
C
Oꢀ
C
O
C
ꢁ
N
N
N
I
II
III
Fig. 1. Resonance in a conventional amide.
Chart 1.
Ó CSIRO 2010
10.1071/CH10350
0004-9425/10/121717

RESEARCH FRONT
1718
J. P. Johns et al.
(a)
(b)
R
O
O
Poor overlap
N
σN*–Y
Low barrier
O
R
N
O
X
sp3N
Y
Y
C
R
C
N
R
nY
N
Y
nX
Y
X
X
σ*
N–X
X
Fig. 2. (a) Loss of resonance and (b) anomeric interactions in bisheteroatom-substituted amides.
CH3
Nu
O
O
O
O
O
NH·Ph
3
O
CH3
N Ph
Ar
δꢁ
Y
Ar
AcO
ꢁ
ꢁ AcOH
δꢁ
Y
C
C
C
C
R
N
R
N
R
NꢂY
ꢁ
Xꢀ
R
N
N
N
OR
Y
RO
X
X
δꢀ
(c)
ꢀ
X
δ
4
(a)
(b)
2
Fig. 3. (a) Polarized structure; (b) anomerically induced elimination;
Ph
O
(c) SN2 reaction at nitrogen.
CH3
ꢀ ꢁ
NꢂN
N
N
CH3
Ar
ꢁ
H3C
N
N
OR
Ph
Ph
O
5
6
7
ꢀ
O
C
C
ꢁ
Y
R
ꢁ
N
N
N
Y
Scheme 1.
Y
R
X
X
N-Acyloxy-N-alkoxyamides 1b constitute a class of direct-
acting mutagens whose biological activity, structure, and reactiv-
ity have been widely studied.[3,18,20,21,27–36] With acid catalysis,
they undergo SN1 reactions at nitrogen,[28,29] and they have been
shown to react bimolecularly with a variety of nucleophiles such
as aromatic amines,[3,18,21,22,36] thiols,[3] azide,[19,37] and hydro-
xide.[32] ReactionwitharomaticaminessuchN-methylaniline3in
methanol generates intermediate N-alkoxy-N-(N0-methylanilino)
amides 4 that themselves are anomeric and undergo the
HERON reaction (Scheme 1).[2–4,19,22–26,37,38] In this, the first
HERON reaction, the loosely bound lone pair on nitrogen drives
migration of the alkoxyl group from nitrogen to the carbonyl
carbon. The N–C bond breaks in concert with the migration,
yielding esters 5 and the 1,1-diazene 6 in what is, in effect, an SN2
reaction at the acyl carbon. Under these conditions, the diazene 6
dimerizes to the tetrazene 7. The reaction has been modelled
theoretically and proceeds with moderate activation energies of
Fig. 4. The HERON reaction of an anomeric amide.
Where one of the anomeric interactions at nitrogen, say the
nY–s* , is significantly stronger, the ground-state structures
should facilitate overlap between a lone-pair orbital on hetero-
atom Y with a s* orbital (Fig. 2b), resulting in shorter than
normal N–Y bonds, longer than normal N–X bonds and sig-
nificant barriers to rotation about the N–Y bond.
NX
NX
In an XNY system, another consequence of a strong nY–s*
NX
anomeric interaction should be polarization, as shown in Fig. 3a.
Where Y is a good electron-pair donor and X a strongly electron-
affinic atom or group, elimination might be expected, yielding a
stabilized nitrenium ion (Fig. 3b). Work in the authors’ labora-
tories and elsewhere has established that nitrenium ions are
strongly stabilized by neighbouring heteroatoms including oxy-
gen.[11–17] Such a process would be promoted by polar solvents,
as well as acid or Lewis-acid complexation with X. Thus,
unimolecular decomposition would be expected to be more
significant in strongly anomeric amides.
In systems with moderate anomeric overlap, this together
with negative hyperconjugation and anchimeric-assisted weak-
ening of the N–X bond should promote SN2 reactions at nitrogen
leading to loss of Xꢀ (Fig. 3c). SN2 reactivity of several
anomeric amides has been reported.[1–3,18–22]
84–105kJ molꢀ1 [4,39]
.
We recently reported that N-acyloxy-N-alkoxyamides
undergo HERON reactions in the gas phase under electrospray
ionization mass spectrometry (ESI-MS) conditions.[23] The
sodiated molecular ion 8 was observed to undergo collision-
induced decomposition to sodiated alkoxyamidyl radical 9,
sodiated anhydride 10, and to a limited extent, sodiated ester
11 (Scheme 2). Concurrent undetectable products should be the
acyloxyl radical 12, the alkoxynitrene 13, and the acyloxy-
nitrene 14.
WhereXisapoorleavinggroup,anomericdestabilizationofthe
N–X bond can lead to a novel rearrangement. The HERON (from
Heteroatom rearrangements on nitrogen) reactionA of anomeric
amides was discovered in the mid-1990s and involves a concerted
migration of the X atom or group from the amide nitrogen to the
carbonylcarbonwithexpulsionofaY-stabilizednitrene(Fig.4).[23]
To date, numerous examples of HERON reactivity have been
observed in the reactions of both ONO and NNO anomeric
systems[1,4,21,22,24–26] and it has recently been reviewed.[23]
B3LYP/6–31G(d) calculations on the model N-formyloxy-
N-methoxyformamide 8 (R1 ¼ Me, R2 ¼ R3 ¼ H) predict that
HERON rearrangement of both methoxyl and formyloxyl
are possible but with high activation energy (EA). Migration
of methoxyl (162 kJ molꢀ1) is more favourable by some
18 kJ molꢀ1 [23]
.
In this paper, we report that N-acyloxy-N-alkoxyamides
themselves undergo HERON reactions in non-polar solvents,
at high temperature, in competition with homolytic processes.
AFirst presented to the 2nd Heron Island Conference on Reactive Intermediates and Unusual Molecules, Heron Island, Australia, 1994.

RESEARCH FRONT
A New HERON Reaction
1719
O
N
Naꢁ
Naꢁ
Naꢁ
Naꢁ
O
O
O
N
R3
O
O
R3
ꢁ
R3
R2
O
R3
ꢁ
OR1
R2
OR1
C
R1
O
O
9
C
10
11
O2CR2
N–OR1
N–O2CR2
8
12
13
14
Scheme 2.
O
O
Cl
ꢁ
CH3
N – O
HERON
Cl
Ph
O
17
16
O
Ph
O
N
O
CH3
Cl
O
O
Radical
reactions
Ph
15
N
O
18
Scheme 3.
O
O
O
O
O
O
CN
H
OH
O
Cl
Cl
Cl
19 (6.25%)
20 (22.7%)
21 (16.3%)
22 (0.6%)
23 (6.6%)
O
NO2
O
OH
O
CH3
O
CH3
OH
Cl
26 (0.5%)
Cl
Cl
24 (7.0%)
25 (2.0%)
27 (9.7%)
Fig. 5. Products from HERON decomposition of N-acetoxy-N-(4-chlorobenzyloxy)benzamide 15. Average mass percentages for each product, calculated
from eight decompositions under identical conditions, are displayed in parentheses.
Results and Discussion
HERON mode of decomposition react further, leading to a
complex range of stable secondary products (Fig. 5), which in
this case are all detectable by 1H NMR spectroscopy (Fig. 6) as
well as GC-MS. These were 4-chlorobenzaldehyde 19, benzoic
acid 20, 4-chlorobenzyl benzoate 21, benzoic anhydride 22,
4-chlorobenzonitrile 23, 4-chlorobenzyl acetate 24, 4-chloro-
benzyl nitrate 25, 4-chlorobenzyl alcohol 26, and acetic acid 27.
The dioxazole 18 was also evident from characteristic reso-
nances for the methine at d 6.3 ppm and the ortho proton doublet
of the 3-phenyl ring, which appears at d 7.75 ppm.[40]
In polar solvents at room temperature, N-acyloxy-N-alkoxy-
amides undergo both SN1 and SN2 reactions at nitrogen. How-
ever, thermolysis of N-acyloxy-N-alkoxyamides in non-polar
solvents at elevated temperatures results in a mixture of products
that we attribute to both an intramolecular HERON reaction and
homolytic decomposition.
N-Acetoxy-N-(4-chlorobenzyloxy)benzamide 15 is suscep-
tible to decomposition at temperatures approaching 908C in
toluene. Initial decomposition (Scheme 3) occurs through two
competing reaction pathways, the foremost of which is a
HERON reaction, producing acetic benzoic anhydride 16 and
4-chlorobenzyloxynitrene 17. The minor pathway appears to
involve a radical decomposition leading ultimately to formation
of 5-(4-chlorophenyl)-3-phenyl-(5H)-1,4,2-dioxazole 18.
Primary products acetic benzoic anhydride 16 and the
reactive intermediate 4-chlorobenzyloxynitrene 17 from the
Evidence for the HERON Reaction Pathway
4-Chlorobenzyloxynitrene Formation
Acetic benzoic anhydride was a minor product but critical
evidence for the operation of the HERON reaction was the
observation of characteristic products from alkoxynitrene 17.
Although alkoxynitrenes have received little attention in the

RESEARCH FRONT
1720
J. P. Johns et al.
[rel]
27
6
4
2
*
21
20,21
23
22,16,18
24
18
19
25
26
0
8
6
4
2
[ppm]
Fig. 6. 1H NMR spectrum of a fully decomposed sample of N-acetoxy-N-(4-chlorobenzyloxy)benzamide 15 in [D8]toluene.
Numbers correspond to products 18–27 and * denotes the internal standard, diphenylethane.
(i)
ꢁ
PhCH2ꢀONO2
PhCHꢂO
PhCH2ON
28
29
30
(ii)
PhCHꢂNOH
31
ꢀN2
(iii)
Ph
O
Ph OH
Ph ON NO Ph
PhON
32
33
34
Scheme 4.
literature to date, they are believed to be stabilized nitrenes that
exist as triplet ground states.[41] Toscano and coworkers recently
showed that benzyloxynitrene 28 is efficiently scavenged by
molecular oxygen, giving nitrate ester 29 and benzaldehyde 30
(Scheme 4i) in competition with rearrangement to benzald-
oxime 31 (Scheme 4ii).[42,43] Furthermore, they suggest that
phenoxynitrene 32 can dimerize to the hyponitrite 33 that
decomposes thermally to phenoxyl radicals, leading to phenol
34 (Scheme 4iii).
4-Chlorobenzonitrile 23 has been identified and confirmed
1
as a product of decomposition by H NMR spectroscopy, 13C
NMR spectroscopy, and GC-MS with the aid of a standard. All
four protons resonate together in the 1H NMR spectrum in [D8]
toluene at d 6.65, well apart from the other aromatic protons
(Fig. 6). In the 13C NMR spectrum in [D8]toluene, three
resonances at d 146, 120, and 114 were characteristic and clear
of other aromatic signals (see Accessory Publication).
As benzyloxynitrene is known to rearrange to benzaldox-
ime,[42,43] we propose that 4-chlorobenzyloxynitrene 35 rear-
ranges to 36 and then 4-chlorobenzaldoxime 37, either in a
concerted fashion through the singlet state, which must form
from the initial HERON reaction, or in a stepwise fashion as
proposed by Toscano, after relaxation to the more stable triplet
state. In the presence of anhydride, the oxime can dehydrate via
the ester 38 to 4-chlorobenzonitrile (Scheme 5).
4-Chlorobenzyl nitrate 25 was identified as a product of
1
the decomposition by H NMR spectroscopy and GC-MS by
comparison with a standard, which was synthesized from silver
nitrate and 4-chlorobenzyl bromide. In support of this, decom-
positions of two identical mixtures, one purged with nitrogen
and the second purged with oxygen, were performed and the
reaction mixtures were analyzed by GC-MS. Although it was a
minor component of the mixtures, the yield of nitrate was shown
to increase with increasing concentration of oxygen (Fig. 7). A
similar observation could be made in the 1H NMR spectrum of
the two reaction mixtures (see Accessory Publication).
4-Chlorobenzaldoxime 37 was synthesized and monitored
by 1H NMR spectroscopy under standard reaction conditions in
[D8]toluene, with and without acetic anhydride. Whereas no
reaction occurred in the absence of acetic anhydride, as expected

RESEARCH FRONT
A New HERON Reaction
1721
(a)
MCounts
*
19
12.5
10.0
7.5
23
25
5.0
2.5
(b)
MCounts
12.5
10.0
7.5
5.0
2.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0 Minutes
Fig. 7. Decrease in concentrations of 4-chlorobenzyl nitrate 25 and increase in 4-chlorobenzaldehyde 19 and 4-chlorobenzonitrile
23 as the concentration of oxygen decreases from (a) mixture purged with oxygen, to (b) purged with nitrogen, as monitored by
GC-MS. The internal standard, diphenylethane, is labelled with *.
O
OH
N
4-ClC6H4
36
4-ClC6H4
N
N
4-ClC6H4
O
37
S0
(RCO)2O
H
O
N
O
N
COR
4-ClC6H4 CN
4-ClC6H4
N
4-ClC6H4
O
4-ClC6H4CH2
38
23
T1
35
Scheme 5.
the reaction containing both 4-chlorobenzaldoxime and acetic
anhydride reacted smoothlytoform4-chlorobenzonitrile(Fig. 8).
The unstable intermediate that is generated is presumably the
acetate ester of the oxime (38, R ¼ Me).
of 4-chlorobenzaldehyde relative to 4-chlorobenzyl alcohol.
However, under the reaction conditions, alcohol would be
expected to be consumed by reaction with anhydride, providing
a source of both 4-chlorobenzyl benzoate 21 as well as 4-
chlorobenzyl acetate 24, significant products from the reaction
(see below).
Finally, careful analysis of the GC-MS traces of the
reaction mixtures with different degrees of oxygen satura-
tion indicates that the 4-chlorobenzonitrile 23, which was
present in the reaction purged with nitrogen (Fig. 7b),
was reduced in concentration where oxygen was present
(Fig. 7a). In addition, there was a significant reduction in
the amount of 4-chlorobenzaldehyde 19. These factors
confirm that rearrangement to oxime and dimerization to
hyponitrite are competitive pathways with nitrate ester
formation. The presence of some benzaldehyde where nitrile
is largely eliminated may suggest that it is also formed
from the nitrate ester, as suggested by Toscano and
coworkers.[42,43]
1
4-Chlorobenzaldehyde 19 was identified by both H NMR
spectroscopy and GC-MS as a prominent product in the
decomposition mixtures, along with small amounts of 4-chloro-
benzyl alcohol 26. Alkoxynitrene could also be expected to
dimerize to form a hyponitrite 39, which would be likely to
decompose to N2 and two 4-chlorobenzyloxyl radicals 40, the
source of both 4-chlorobenzyl alcohol and 4-chlorobenzalde-
hyde (Scheme 6).[44,45]
The corresponding hyponitrite was synthesized from
4-chlorobenzyl bromide and silver hyponitrite and decomposed
in [D8]toluene at 908C, giving both 4-chlorobenzyl alcohol 26
(major) and 4-chlorobenzaldehyde 19 (minor) (Fig. 9), confirm-
ing that 39 can be the source of both products. Interestingly,
in the thermal decomposition mixtures of N-acetoxy-N-
(4-chlorobenzyloxy)benzamide, there is always a large excess

RESEARCH FRONT
1722
J. P. Johns et al.
(a)
Anhydride Formation
*
37
The presence of low yields of acetic benzoic anhydride in the
decomposition mixture of N-acetoxy-N-(4-chlorobenzyloxy)
1
benzamide was confirmed using H NMR spectroscopy and
(b)
GC-MS, with the use of a standard. However, the HERON
reaction is expected to produce equal amounts of acetic benzoic
anhydride and 4-chlorobenzyloxynitrene. The anhydride 16 was
synthesized and ultimately found to redistribute to a mixture of
benzoic anhydride and acetic anhydride in line with known
behaviour of mixed anhydrides on heating.[46,47] Furthermore,
in the presence of 4-chlorobenzyl alcohol 26, both 4-chloro-
benzyl acetate 24 and to lesser extent 4-chlorobenzyl benzoate
21 were generated, as illustrated in Fig. 10. The relative yields
are in line with the pKAs of acetic and benzoic acids (pKA 4.8 and
4.2 respectively).
Whereas in the decomposition of 15 most anhydride appears
to be consumed, in other analogous reactions, anhydrides and
mixed anhydrides are detectable, even in significant quantities
(Scheme 7). For instance, along with dioxazole 47a, N-benzoy-
loxy-N-butoxybenzamide 41a afforded benzoic anhydride 22
and the single ester butyl benzoate 45a, which were readily
detectable by both NMR spectroscopy and GC-MS (Fig. 11).
N-Butoxy-N-heptanoyloxybenzamide 41b produced significant
quantities of the unsymmetrical benzoic heptanoic anhydride
42b, which, although not observed in the 1H NMR spectrum of
38
38
23
(c)
(d)
(e)
8
6
4
2
[ppm]
Fig. 8. Conversion of 4-chlorobenzaldoxime 37 to 4-chlorobenzonitrile 23
at 908C in [D8]toluene; (a) 4-chlorobenzaldoxime with added acetic
anhydride (*); (b) after 1 h; (c) after 6 h; (d) after 23 h; (e) reference
4-chlorobenzonitrile.
–N2
N
O
C6H4-Cl-4
Scheme 6.
39
4-ClC6H4
19
26
O
N
17
4-ClC6H4
O
39
40
(a)
26
(b)
19
8
6
4
2
[ppm]
Fig. 9. 1H NMR spectra in [D8]toluene of (a) 4-chlorobenzyl hyponitrite 39 with 4-chlorobenzyl alcohol 26 and (b) 4-
chlorobenzaldehyde 19 and 4-chlorobenzyl alcohol 26 after complete decomposition at 908C.

RESEARCH FRONT
A New HERON Reaction
1723
*
16
(a)
26
16
22
(b)
(c)
27
21 24
(d)
(e)
8
6
4
2
[ppm]
Fig. 10. 1H NMR spectra in [D8]toluene of the reaction between acetic benzoic anhydride 16 and 4-chlorobenzyl alcohol 26 to
form benzoic acid 20, acetic acid 27, 4-chlorobenzyl benzoate 21 and 4-chlorobenzyl acetate 24. Benzoic anhydride 22 and acetic
anhydride (ꢁ) can also be detected with internal standard diphenylethane (*); (a) 0 min; (b) 0.25 h; (c) 0.5 h; (d) 4.5 h; (e) 18 h.
R1
N
O
43
R1
O
H
O
O
O
O
O
O
R1
R3
R1
HERON
R3
44
O
O
R1
R1
R3
O
R2
R3
O
R2
O
N
N
O
R2
O
47
42
45
46
41
a R1 ꢂ Pr, R2 ꢂ R3 ꢂ Ph
b R1 ꢂ Pr, R2 ꢂ heptyl, R3 ꢂ Ph
c R1 ꢂ Ph, R2 ꢂ Me, R3 ꢂ 4-tBu-C6H4
d R1 ꢂ 4-Cl-C6H4, R2 ꢂ hexyl, R3 ꢂ Ph
Scheme 7.
the reaction mixture, was detectable by GC-MS together with
butyl benzoate and butyl heptanoate 46b. Anhydride formation
in all cases is clearly attributable to HERON reactions.
and benzyloxynitrene 43c respectively. Formation of the esters
by intermolecular reactions between the alcohols and both
mixed anhydrides should yield eight esters. The resultant reac-
tion mixture from the decomposition was analyzed by GC-MS
and shown to contain all eight esters, identified from their
individual mass spectra (Fig. 12). Four of these, 45c with 46c
and 21 with 46d were esters that were formed from the
individual starting materials, but these were accompanied by
all four crossover esters, 4-chlorobenzyl esters 24 and 48 and
benzyl esters 49 and 50. This route to ester formation was
therefore confirmed (Chart 2).
The formation of two esters in all reactions where unsymme-
trical anhydrides are generated as primary HERON products is
the consequence of an intermolecular reaction between alcohols
44, derived from the corresponding alkoxynitrenes 43, and
mixed anhydrides 42 (Scheme 7). To confirm this, a ‘crossover’
decomposition reaction was carried out with equimolar quan-
tities of N-acetoxy-N-benzyloxy-4-tert-butylbenzamide 41c and
N-(4-chlorobenzyloxy)-N-heptanoyloxybenzamide 41d in [D8]
toluene. Decomposition at similar rates should produce in the
reaction two mixed anhydrides, 42c and 42d, and two alcohols,
4-chlorobenzyl alcohol 26 and benzyl alcohol 44c, from dimer-
ization and decomposition of the 4-chlorobenzyloxynitrene 17
From the GC-MS trace in Fig. 12, it is clear that there is a
preponderance of two esters, namely benzyl 4-tert-butyl benzo-
ate 45c and 4-chlorobenzyl benzoate 21 and this was also
observed in the 1H NMR spectrum of the reaction mixture

RESEARCH FRONT
1724
J. P. Johns et al.
(a)
(b)
22
47a
22
20
45a
45a
47a
47a
20
8.5
8
7.5
7
6.5
6
5.5
5
4.5
4
3.5
5
6
7
8
9
10 Minutes
f1 [ppm]
Fig. 11. (a) 1H NMR spectrum in [D8]toluene and (b) GC-MS trace of fully decomposed N-benzoyloxy-N-butoxybenzamide 41a.
MCounts
20
15
21
49
45c
46c
10
5
46d
24
50
48
4
5
6
7
8
9
10
11
12
13 Minutes
Fig. 12. GC-MS chromatogram of the reaction mixture from a joint decomposition of N-acetoxy-N-benzyloxy-4-tert-butylbenzamide 41c
and N-(4-chlorobenzyloxy)-N-(heptanoyloxy)benzamide 41d in [D8]toluene showing all eight esters. Mass spectral data for each ester are
presented in Table 1.
O
O
O
4-tBuC6H4
O
C6H4Cl-4
Hexyl
O
Ph
Ph
O
Ph
48
49
50
Chart 2.
(see Accessory Publication). Furthermore, the reaction of
4-chlorobenzyl alcohol with anhydrides from acetic benzoic
anhydride afforded a significantly greater yield of 4-chloroben-
zyl acetate than 4-chlorobenzyl benzoate (Fig. 10). Although the
reaction of the nitrene-derived alcohol with mixed anhydride
must be a source of the non-crossover esters 45, it is clearly not
the only source.
Formation of (5H)-1,4,2-Dioxazoles
Dioxazoles are formed in low yields in parallel with other pro-
ducts in these reactions. They are characterized in the 1H NMR
spectra (CDCl3) by the low-field benzylic methine at ,d 6.9[40]
and the ortho protons on the 2-phenyl ring at d 7.5, as well as
by the methine carbon at d 107–110 in the 13C NMR spectrum.
Although 18, from decomposition of the parent 15 in [D8]

RESEARCH FRONT
A New HERON Reaction
1725
toluene, was not readily detectable by GC-MS under the con-
1
ditions, it was clearly observable by H NMR spectroscopy at
of butyl benzoate 45a, indicating that the processes are in
competition with one another. Alkoxyamidyls are long-lived
radicals owing to stabilization of the nitrogen-centred radical by
the neighbouring oxygen,[48–53] and their generation by a variety
of methods leads to dimerization to hydrazines.[44,49,52,54] Dif-
fusion of 51 from the solvent cage (Scheme 8i) would therefore
be expected to lead to hydrazines 54 and ultimately to the esters
45 through double HERON reactions that we, and others, have
shown to occur.[4,23,25,38,39] The preponderance of the esters 45
over 46 can therefore be attributed to this second route to ester
formation.
similar chemical shifts (d 6.32 and d 7.75, Fig. 6). While 18 has
been synthesized previously, limited NMR data were reported.
In the present study, it was isolated from a large-scale decom-
position of 15 in toluene and we report here its full character-
ization together with data for several other analogues.
Aspects of dioxazole formation have been published in pre-
liminary form elsewhere.[2,3] Experiments in these laboratories
support a free-radical reaction process outlined in Scheme 8,
which involves solvent-cage formation of a 1,3-diradical 55 by
benzylic hydrogen abstraction from alkoxyamidyl 51 (by either
acyloxyl radical 52 or its decarboxylation product radical 53)
(Scheme 8ii). In certain cases, low yields of adducts 56 have been
detected andthese must arise from a competitive reactionbetween
alkoxyamidyls 51 and alkyl radicals 53 (Scheme 8iii). For
instance, N-butoxy-N-heptanoyloxybenzamide 41b gave, in addi-
tion to 3-phenyl-5-propyl-(5H)-1,4,2-dioxazole 47b, half as
much N-butoxy-N-hexylbenzamide (56, R1 ¼ Pr, R2 ¼ n-hexyl,
R3 ¼ Ph) identified by comparison with a synthetic reference
sample.
Dioxazole formation involves homolysis of the N–OAc
bond in competition with the HERON pathway, leading to
anhydrides together with alkoxynitrenes, and experiments
with various N-acetoxy-N-(4-substituted-benzyloxy)benzamides
support this. With a 4-methoxyl substituent on the benzyloxyl
1
group in 59b, dioxazole 60b was not observable by H NMR
spectroscopy or by GC-MS, but along with 18 from 15, the
heterocycle 60a was a significant product with a 4-nitro substi-
tuent in 59a. As benzoate esters can be formed by two processes
(from alcohol derived from alkoxynitrene or from dimerization
of alkoxyamidyls), the extent of radical reactivity can only be
estimated at between 25–36% for 15 and 31–43% for 59a. Little
dioxazole was detected from the 4-methoxy substrate 59b.
It is clear that more dioxazole is generated with the electron-
withdrawing para nitro group (Chart 3).
Calculations on the structure of the model diradical 55
(R1 ¼ R3 ¼ H) predict the singlet state to be more stable
than the triplet state by 110 kJ molꢀ1 and to be strongly
dipolar in character, which would facilitate cyclization to the
dioxazole.[2,3]
In a detailed study of the decomposition of N-acetoxy-N-
butoxybenzamide 57 and N-acetoxy-N-(1,1-dideuteriobutoxy)
benzamide 58, a primary deuterium isotope effect of 3.5 has
been observed in the formation of 3-phenyl-5-propyl-(5H)-
1,4,2-dioxazole 47a, confirming that the ease of cleavage of
an oxymethylenic C–H bond is integral to dioxazole formation
(S. A. Glover, D. S. Pankhurst, unpubl. data). In the same
experiment, an inverse isotope effect was found for formation
These substituent effects are in accord with the properties of
the HERON reactions; the HERON transition state generates
positive charge at the alkoxyl oxygen adjacent to the benzylic
position, which would be stabilized and destabilized by
electron-donor and electron-withdrawing groups respectively
(Fig. 13). The para substituents would have a much smaller
effect on the homolysis of the N–OAcyl bond.
While a donor alkoxyl group would be expected to promote
the HERON reaction giving anhydride in competition with
homolysis, the opposite effect would be expected with an
electron-withdrawing group.
X
H
R3
R3
O
N
H
R3
R1
O
N
O
O
N
O
Δ
(i)
O
–N2
2
41
Toluene, 90°C
45
51
R1
R1
54
R2
O
(a)
(b)
Ph
R2
X
δꢁ
O
O
52
(ii)
X
O
O
R1
O
O
R1
δꢁ
O
53
Oꢀ
H
O
N
O
R3
O
N
Ph
N
R3
N
(iii)
δꢀ
δꢀ
55
O
O
OCH2R1
O
N
R2
47
R3
Fig. 13. Electronic effects in the HERON transition state: (a) stabilization
by para electron-donor groups and (b) destabilization by para electron-
withdrawing groups.
56
Scheme 8.
O
O
O
X
Ph
OBu
Ph
OCD2Pr
Ph
OCH2
Me
X
O
N
N
N
O
Ph
O
O
Me
Me
O
N O
O
O
57
58
59
60
a X ꢂ NO2
b X ꢂ OMe
a X ꢂ NO2
b X ꢂ OMe
Chart 3.

RESEARCH FRONT
1726
J. P. Johns et al.
Conclusion
Chromatotron with plates coated with 2.0 mm of silica gel 60
F254 (Merck).
Thermal decomposition reactions of N-acyloxy-N-alkoxy-
amides generate complex reaction mixtures by two competing
mechanisms: a HERON reaction leads to anhydrides and
alkoxynitrenes, whereas homolysis of the N–OAcyl bond
affords alkoxyamidyl radicals. The three primary products are
all reactive under the reaction conditions. The alkoxynitrenes
can be captured by oxygen, yielding nitrate esters in competition
with rearrangement to oximes or dimerization to unstable
hyponitrites. The latter are sources of alkoxyl radicals that dis-
proportionate to alcohols and aldehydes. The anhydride reacts
with both oximes and alcohols, giving stable nitriles and esters.
Alkoxyamidyls are sources of dioxazoles and hydrazines, which
are an alternative route to esters by HERON reactions.
Synthesis of N-Acyloxy-N-alkoxyamides
Synthesis of N-butoxy-N-benzoyloxybenzamide 41a,[33] N-
benzyloxy-N-chloro-4-tert-butylbenzamide,[36] N-chloro-N-(4-
chlorobenzyloxy)benzamide, N-butoxy-N-chlorobenzamide,
N-acetoxy-N-(4-chlorobenzyloxy)benzamide 15, N-acetoxy-N-
(4-nitrobenzyloxy)benzamide 59a, and N-acetoxy-N-(4-meth-
oxybenzyloxy)benzamide 59b have been described before, as
have precursors butyl benzohydroxamate and 4-chlorobenzyl
benzohydroxamate.[29,31] All mutagenic N-acyloxy-N-alkoxy-
amides from this and previous studies are characterized
spectroscopically.
Substituent effects control the competition between these
two processes in a predictable manner. An electron-donor
methoxyl group on the para position of a benzyloxy group
promotes the HERON reaction at the expense of homolysis,
the converse of the impact of an electron-withdrawing NO2
group.
Although synthetically of limited value for the generation
of alkoxynitrenes, we have demonstrated that the heterolytic
decomposition pathway of N-acyloxy-N-alkoxyamides, at ele-
vated temperature and without the influence of a polar solvent,
is another clear-cut example a HERON reaction of an anomeric
amide. Under these conditions, heterolysis of the N–OAcyl bond
giving alkoxynitrenium ions is disfavoured and, under the
N-Butoxy-N-heptanoyloxybenzamide 41b
N-Butoxy-N-chlorobenzamide (0.5 g, 2.24 mmol) and sodium
heptanoate (0.48 g, 3.13 mmol) were stirred in dry acetone
(15 mL), in the dark at room temperature, for 48 h. On
completion of acyloxylation, the mixture was filtered and
concentrated under vacuum. Purification by centrifugal chro-
matography using 5% ethyl acetate/hexane afforded pure N-
butoxy-N-heptanoyloxybenzamide (0.51 g, 1.59 mmol, 71%)
as a pale yellow oil. nmax (CHCl3)/cmꢀ1 1782s (C¼O), 1724s
(C¼O). dH 7.78 (d, 2H), 7.54 (t, 1H), 7.43 (t, 2H), 4.19 (t, 2H),
2.34 (t, 2H), 1.63 (quin, 4H), 1.38 (sextet, 2H), 1.26 (t, 8H), 0.91
(t, 6H). dC 174.2, 171.1, 132.5, 132.0, 129.0, 128.2, 75.5, 32.1,
31.3, 30.1, 28.5, 24.2, 22.4, 19.0, 13.9, 13.7.
influence of a moderate nO–s*
anomeric destabilization,
NOAcyl
the acyloxyl group migrates from nitrogen to the carbonyl
carbon, resulting in alkoxynitrene formation. The elevated
temperature required for this rearrangement also promotes a
competitive homolysis of the N–OAcyl bond.
The reaction is in accord with theoretical attributes of the
HERON reaction pathway for N-formyloxy-N-methoxyforma-
mide, which predicts acyloxyl migration to be more favourable
than alkoxyl migration. No evidence could be found for a
reverse HERON reaction that would lead to esters and acyloxy-
nitrenes, although the chemistry of such electron-deficient
species is unknown.
The most likely route to formation of dioxazoles, in some
cases in reasonable yields, most probably involves a 1,3-di-
radical generated from the alkoxyamidyls in a solvent cage. The
details of this reaction process will be the subject of a future
paper from these laboratories.
N-Acetoxy-N-benzyloxy-4-tert-butylbenzamide 41c
N-Benzyloxy-N-chloro-4-tert-butylbenzamide (0.5 g, 1.57 mmol)
was stirred in the dark with anhydrous sodium acetate (0.18 g,
2.20 mmol) in dry acetone for ,14 h. The mixture was filtered
and concentrated under vacuum. Purification via centrifugal
chromatography with 10% ethyl acetate/hexane and con-
centration under vacuum afforded N-acetoxy-N-benzyloxy-4-
tert-butylbenzamide (0.42 g, 1.23 mmol, 78%) as a yellow oil.
dH 7.70 (d, 2H, o-ArCO), 7.42 (d, 2H, o-ArCH2), 7.34 (m, 5H),
5.18 (s, 2H, ArCH2O), 2.05 (s, 3H, CH3CO), 1.33 (s, 9H,
(CH3)3). dC 174.01, 168.21, 156.71, 134.90, 129.18, 128.64,
125.32, 128.47, 77.46, 35.13, 31.07, 18.78.
N-(4-Chlorobenzyloxy)-N-heptanoyloxybenzamide 41d
N-Chloro-N-(4-chlorobenzyloxy)benzamide (0.5 g, 1.69 mmol)
was stirred in the dark with anhydrous sodium heptanoate
(0.36 g, 2.36 mmol) in dry acetone for ,16 h. The mixture was
filtered and concentrated under vacuum. Purification via cen-
trifugal chromatography with 10% ethyl acetate/hexane and
concentration under vacuum afforded N-(4-chlorobenzyloxy)-
N-heptanoyloxybenzamide (0.46 g, 1.15 mmol, 68%) as a yel-
low oil. dH 7.71 (d, 2H), 7.56 (t, 1H), 7.42 (t, 2H), 7.30 (d, 2H),
7.21 (d, 2H), 5.13 (s, 2H), 2.25 (t, 2H), 1.53 (quin, 2H), 1.21
(complex m, 6H), 0.86 (t, 3H). dC 174.32, 171.09, 134.61,
133.16, 132.66, 131.77, 130.47, 129.00, 128.66, 128.26, 32.03,
31.27, 28.53, 24.49, 22.38, 13.94.
Experimental
Materials and Methods
Infrared spectra were recorded on a Perkin–Elmer 1600 series
FT-IR spectrophotometer as chloroform solutions. Mass spectra
were recorded on a Varian 1200 L triple quadrupole mass
spectrometer coupled to a Varian CP-3800 gas chromatograph;
the column used was a FactorFour Capillary Column, VF-5 ms,
30 m ꢂ 0.25 mm, 0.25 mm. Samples were injected into the
column at 1008C, which was held for 2 min before increasing by
408C per minute to the maximum temperature of 2508C, which
was maintained until the end of each run. The injector was at
523 K and the sample was subjected to a capillary voltage of
70 eV. NMR spectra were recorded in CDCl3 or [D8]toluene
on a Bruker Avance 300P FT NMR spectrometer with a 5-mm
1H inverse/BB z gradient probe, operating at 300.13 MHz
(1H) or 75.46 MHz (13C). Centrifugal chromatographic separa-
tions were performed on a 7294T model Harrison Research
Reference Standards
4-Chlorobenzonitrile, 4-chlorobenzaldehyde, 4-chlorobenzyl
alcohol, benzoic anhydride, benzoic acid, and acetic acid are
commercially available. 4-Chlorobenzyl acetate and 4-chloro-
benzyl benzoate were also available from previous studies.

RESEARCH FRONT
A New HERON Reaction
1727
4-Chlorobenzyl Nitrate[55] 25
using a fine capillary tube for a period of 20 min. The NMR
tubes were sealed with a cap and paraffin film and suspended
in an oil bath at a 908C. The decompositions were monitored
using H NMR, and were continued until the decomposition
was complete. Reactions were analyzed directly by NMR and
GC-MS.
p-Chlorobenzyl bromide was stirred with silver nitrate (equal
molar quantities) in acetonitrile for 24 h at room temperature.
Silver bromide precipitate was filtered off and the remaining
solution was concentrated under vacuum, producing approxi-
mately an 80% yield of p-chlorobenzylnitrate. Distillation at
1108C, 10 mm Hg, afforded pure p-chlorobenzylnitrate (lit.[55]
728C, 2 mm Hg). dH 7.34 (q, 4H), 5.37 (s, 2H).
1
Isolation of Dioxazoles
General Method
4-Chlorobenzaldoxime[56] 37
Dioxazoles 18, 47a, and 60a were separated from large-scale
reaction mixtures using TLC prep plates, coated with 2.0 mm of
silica gel 60 F254 (Merck), and using 10% ethyl acetate/hexane
as solvent. Further purification was achieved using centrifugal
chromatography and 2.5% ethyl acetate/hexane as solvent.
5-(4-Chlorophenyl)-3-phenyl-(5H)-1,4,2-dioxazole 18 was
isolated as colourless crystals; mp 50–528C. nmax (CHCl3)/cmꢀ1
1624 (CN), 1081 and 1050 (CO). dH 7.85 (d, 2H), 7.54 (t, 3H),
7.46 (m, 4H), 6.89 (s, lH). dC 159.1, 136.6, 133.6, 131.8, 129.0,
128.8, 128.1, 127.0, 122.6, 107.8. m/z (EI) 259 (Mþꢁ), 140, 139,
119 (M – (4-chlorobenzaldehyde)), 105, 91. (Lit.[40] 259 [Mþꢁ],
140, 139, 119, 105.) Calc. for C14Hl0O2NCl: C 64.01, H 3.88,
N 5.33, Cl 13.49%. Found: C 64.41, H 3.97, N 5.33, Cl 13.74%.
5-(4-Nitrophenyl)-3-phenyl-(5H)-1,4,2-dioxazole 60a was
isolated as pale yellow crystals; mp 127–1308C (lit.[40]
1308C). nmax (CHCl3)/cmꢀ1 1624 (CN), 1087 and 1060 (CO).
dH 8.33 (d, 2H), 7.86 (d, 2H), 7.80 (d, 2H), 7.56 (t, 1H), 7.48 (t,
2H), 7.02 (s, 1H). dC 159.0, 149.2, 141.8, 132.1, 128.9, 127.6,
127.0, 124.0, 122.1, 106.6. m/z (EI) 270 (Mþꢁ), 150, 119 (M –
(4-NO2-benzaldehyde)).
p-Chlorobenzaldehyde (0.5 g) and hydroxylamine hydro-
chloride (0.5 g), in ethanol (5 mL) and pyridine (0.5 mL), were
refluxed until reaction was complete (monitored by TLC).
Excess ethanol was removed under vacuum. Water was added
(5 mL) and the mixture was cooled in an ice bath, with stirring,
until crystallization was complete. The crystals were isolated
by filtration and then recrystallized from a minimal amount of
hot ethanol. mp 106–1088C (lit.[56] 104–1068C). dH 8.11 (s, 1H),
7.51 (d, 2H), 7.36 (d, 2H).
1,2-Bis(4-chlorobenzyloxy)diazene[57,58] 39
Silver hyponitrite was synthesized according to literature pro-
tocol.[57] 4-Chlorobenzyl bromide (1 g) was stirred in a 2:1
benzene/hexane solution (8 mL) in an ice bath. Over a period
of 40 min, an excess of silver hyponitrite was added and the
mixture was then stirred for 1 h at room temperature (at which
time there were no further changes in the appearance of the
precipitate). The precipitate was filtered off and washed with a
small portion of the reaction solvent. The remaining solution
was concentrated under vacuum, and the resulting crystals were
recrystallized from methanol in an acetone/liquid nitrogen slush
bath. The white crystals were collected, dried under vacuum,
and stored at ꢀ208C. dH 7.31 (complex m, 8H), 5.20 (s, 4H).
dC 129.94, 128.82, 128.69, 128.26, 74.71.
3-Phenyl-5-propyl-(5H)-(1,4,2)-dioxazole 47a was isolated
as a yellow oil. dH 7.82 (d, 2H), 7.49 (t, 1H), 7.44 (t, 2H), 6.07 (t,
1H), 1.94 (q, 2H), 1.60 (sextet, 2H), 1.02 (t, 3H). dC 131.5, 129.5,
128.6, 126.8, 109.8, 35.4, 16.5, 13.8. m/z (EI) 191 (Mþꢁ), 148
(M – propyl), 120. m/z (ESI) 192 (M þ 1), 214 (M þ 23), 231
(M þ 40).
N-Butoxy-N-hexylbenzamide
Crossover Experiment with N-Acetoxy-N-benzyloxy-
4-tert-butylbenzamide 41c and N-(4-Chlorobenzyloxy)-
N-heptanoyloxybenzamide 41d
N-butoxybenzamide (0.50 g, 2.59 mmol) and 1-bromohexane
(0.36 g, 2.18 mmol) were dissolved in 10% aqueous methanol
solution (10 mL), followed by the addition of potassium
hydroxide (0.17 g, 3.04 mmol). The mixture was stirred for
24 h, followed by the removal of methanol under vacuum
and the addition of an extra 20 mL of distilled water. The
aqueous mixture was extracted with dichloromethane (DCM)
(3 ꢂ 20 mL), followed by washing of the organic layer with
dilute HCl solution (20 mL), distilled water (20 mL), and 10%
Na2CO3 solution. The organic layer was dried over anhydrous
MgSO4, filtered, and concentrated under vacuum to afford
the crude product. Purification by centrifugal chromatography,
using 5% ethyl acetate/hexane, afforded pure N-butoxy-N-
hexylbenzamide as a brown oil. dH 7.66 (d, 2H), 7.44 (t, 1H),
7.38 (t, 2H), 3.74 (t, 2H), 3.68 (t, 2H), 1.69 (m, 8H), 1.30 (m,
4H), 0.92 (t, 3H), 0.83 (t, 3H). dC 169.8, 130.0, 129.3, 128.3,
127.8, 73.8, 46.5, 31.5, 29.7, 27.2, 26.4, 22.6, 19.0, 14.0, 13.6.
m/z (EI) 277 (w), 176, 135, 105.
Equimolar quantities of N-acetoxy-N-benzyloxy-4-tert-butyl-
benzamide 41c and N-(4-chlorobenzyloxy)-N-heptanoyloxy-
benzamide 41d were decomposed together according to the
1
standard procedure and the product mixture analyzed by H
NMR spectroscopy and GC-MS. Esters were identified from
their characteristic molecular ions and fragmentation patterns,
which are presented in Table 1.
Accessory Publication
A publication is available from the Journal’s website that
illustrates:
1. The effect of oxygen on the production of 4-chlorobenzyl-
nitrate 25 from thermal decomposition of N-acetoxy-N-(4-
chlorobenzyloxy)benzamide 15 as observed by 1H NMR
spectroscopy in [D8]toluene (Fig. S1);
2. The presence of 4-chlorobenzonitrile 23 in the 13C NMR
spectrum, in [D8]toluene, of a reaction mixture from thermal
decomposition of N-acetoxy-N-(4-chlorobenzyloxy)benza-
mide 15 (Fig. S2);
General Decomposition Procedure
Thermal decompositions of N-acyloxy-N-alkoxyamides in [D8]
toluene (typically 1.75 ꢂ 10ꢀ1 M) were carried out in NMR
tubes, with a known amount of diphenylethane as internal
standard. Unless otherwise specified, the solutions were
degassed with nitrogen, which was bubbled through the solution
3. The preponderance of non-crossover esters 45c and 21
in the 1H NMR spectrum from thermal decomposition

RESEARCH FRONT
1728
J. P. Johns et al.
Table 1. Ester fragmentations from crossover experiment with N-(4-chlorobenzyloxy)-N-heptanoyloxybenzamide 41d and N-acetoxy-N-benzyloxy-
4-tert-butylbenzamide 41c in [D8]toluene at 908C
R0CO2R00
R0
R00
Mþꢁ
R00–OHþ
R0COþ
C7H6Xþ (X ¼ H, Cl)
C6Hþ5
M – CHþ3 ꢁ
M – tBuþꢁ
46c
24
CH3
PhCH2
150
184
212
246
268
302
220
254
108
142
–
43
43
91
125
91
77
77
77
77
77
–
–
–
–
–
–
CH3
4-ClPhCH2
PhCH2
50
Ph
105
105
161
161
113
113
–
21
Ph
4-ClPhCH2
PhCH2
–
125
91
253
287
–
45c
48
4-tBuPh
4-tBuPh
Hexyl
Hexyl
–
212
–
4-ClPhCH2
PhCH2
–
125
91
49
108
142
–
–
–
46d
4-ClPhCH2
125
–
–
–
of N-acetoxy-N-benzyloxy-4-tert-butylbenzamide 41c
and N-(4-chlorobenzyloxy)-N-heptanoyloxybenzamide 41d
(Fig. S3).
[23] S. A. Glover, A. Rauk, J. M. Buccigross, J. J. Campbell, G. P.
Hammond, G. Mo, L. E. Andrews, A.-M. E. Gillson, Can. J. Chem.
2005, 83, 1492. doi:10.1139/V05-150
[24] J. M. Buccigross, S. A. Glover, J. Chem. Soc., Perkin Trans. 2 1995,
595. doi:10.1039/P29950000595
[25] J. M. Buccigross, S. A. Glover, G. P. Hammond, Aust. J. Chem. 1995,
48, 353.
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[26] S. A. Glover, in Merck Index, Organic Name Reactions ONR-43 2006
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