Synthesis and thermal decomposition of N,N-dialkoxyamides

Article abstract of DOI:10.1039/c1ob00008j

N,N-Dialkoxyamides 1c, a virtually unstudied member of the new class of anomeric amides, amides bearing two electronegative atoms at nitrogen, have been synthesised in useful yields directly from hydroxamic esters using phenyliodine(iii)bis(trifluoroacetate) (PIFA). Infrared carbonyl stretch frequencies and carbonyl ¹³C NMR properties have been reported, which support strong inhibition of amide resonance in these amides. Their thermal decomposition reactions in mesitylene at 155°C proceed by homolysis to form alkoxyamidyl and alkoxyl free radicals in preference to HERON rearrangements to esters. The reactions follow first-order kinetics and for a series of N,N-dimethoxy-4-substituted benzamides, activation energies of 125-135 kJ mol^-1 have been determined together with weakly negative entropies of activation.

Full text of DOI:10.1039/c1ob00008j

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PAPER
Synthesis and thermal decomposition of N,N-dialkoxyamides†‡
Katherine M. Digianantonio, Stephen A. Glover,* Jennifer P. Johns and Adam A. Rosser
Received 4th January 2011, Accepted 5th April 2011
DOI: 10.1039/c1ob00008j
N,N-Dialkoxyamides 1c, a virtually unstudied member of the new class of anomeric amides, amides
bearing two electronegative atoms at nitrogen, have been synthesised in useful yields directly from
hydroxamic esters using phenyliodine(III)bis(trifluoroacetate) (PIFA). Infrared carbonyl stretch
frequencies and carbonyl 13C NMR properties have been reported, which support strong inhibition of
amide resonance in these amides. Their thermal decomposition reactions in mesitylene at 155 ◦C
proceed by homolysis to form alkoxyamidyl and alkoxyl free radicals in preference to HERON
rearrangements to esters. The reactions follow first-order kinetics and for a series of
N,N-dimethoxy-4-substituted benzamides, activation energies of 125–135 kJ mol-1 have been
determined together with weakly negative entropies of activation.
Introduction
Anomeric amides are defined as amides that are substituted at
nitrogen with two electronegative atoms (1a–f).1 This configura-
tion at nitrogen radically alters the amide characteristics since the
Scheme 1
electronegative requirements of the heteroatoms are best satisfied
if the nitrogen assumes sp3 hybridisation in which the nitrogen
lone pair becomes localised in a hybrid orbital with reduced
p-character, resulting in significantly reduced amide resonance.
In addition, such amides usually exhibit ground-state anomeric
effects through the amide nitrogen, which influence their structure
and reactivity; with a good leaving group at nitrogen (1a and 1b)
they can undergo SN1 and SN2 reactions at the amide nitrogen,2–9
but with poor leaving groups (1d) and with 1b in non-polar
solvents they undergo the unusual HERON reaction in which
anomeric destabilisation results in migration of one substituent
from nitrogen to the carbonyl carbon with attendant formation of
a stabilised nitrene (Scheme 1).9–16
calculations predict a high degree of pyramidality at nitrogen
(Winkler–Dunitz c values17,18 vary from 58.5◦ for 1b to 31◦ for
˚
˚
1e), long C–N bonds in the range of 1.405 A for 1b to 1.38 A for
1e, but relatively small twist angles (Winkler–Dunitz t parameters
typically less than 10◦).§
These predictions are borne out
9,15,19–22
by structural data where this is available and by spectroscopic
data.1,9,15 While theoretical, spectroscopic and structural data
for ONCl, ONOAc, and ONN systems have been reported, the
properties of dialkoxyamides 1c are virtually unknown. Some
spectroscopic properties of only a limited number have been
reported to date1,15 though we have recently obtained crystallo-
graphic data for two members of this class, which demonstrates,
as predicted, a high degree of pyramidality at nitrogen and very
23
long N–C bonds.¶ Crystallographic data has been reported for
urea analogues, N,N-dimethoxyurea and N,N-dimethoxy-N¢-(4-
nitrophenyl)urea,24 which also possess highly pyramidal nitrogens
and long N–C bonds but, on account of the competing a-amino
group, are not representative of true anomeric amides.
N,N-Dialkoxyamides 1c can be synthesised by solvolysis of
N-alkoxy-N-chloroamides 1a in aqueous alcohol1,11 or by the
reaction of N,N-dialkoxyamines with acyl halides or isocyanates.25
In this paper we report a new synthesis of these rare amides
Spectroscopic, theoretical and structural evidence has been
presented for a range of such amides (1a–f). Notably, theoretical
Chemistry Department, School of Science and Technology, University of
New England, Armidale, New South Wales, 2351, Australia
† Dedicated to the late Athel Beckwith FRS, a good friend and an
outstanding chemist, who influenced in many positive ways the careers
and lives all those who were drawn to him and his chemistry.
§ A c value of 60◦ corresponds to a completely tetrahedral nitrogen and a
t value of 0◦ corresponds to alignment of the lone pair on nitrogen with
the carbonyl carbon 2pz orbital.
¶ N-Ethoxy-N-methoxy-4-nitrobenzamide (3a) and N-methoxy-N-(4-
‡ Electronic supplementary information (ESI) available. See DOI:
10.1039/c1ob00008j
nitrobenzyloxy)benzamide (3f) have c values of 58◦ and 56◦ and N–C
˚
˚
bond lengths of 1.45 A and 1.42 A respectively.
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as well as their thermal decomposition reactions, which unlike
other anomeric amides that undergo heterolytic HERON rear-
rangements, are radical in nature.
are sources of alkoxynitrenium ions 8.1,2,9,15 N,N-Dialkoxyamides
9 are generated by capture of the nitrenium ion by alcohol.
Reactions were carried out either in solvent as nucleophile or,
where higher alcohols were introduced, the hydroxamic ester was
dissolved in acetonitrile and treated with PIFA in the presence
of excess alcohol. Yields of N,N-dialkoxyamides 2, 3a–f and 4
produced by the PIFA method ranged between 40 and 96%.
N,N-Dialkoxybenzamides 2–4 are typical anomeric amides,
exhibiting radically reduced amide resonance. The carbonyl
stretch frequencies in the infrared (Table 1), while not as high
as those of the analogous N-acyloxy-N-alkoxyamides (typically
1718–1742 cm-1),1,9,15 were mostly between 20–30 cm-1 higher than
their parent hydroxamic esters. This is in accord with relative the-
oretical values for N,N-dimethoxyamides 10a and 10b and N,N-
dimethylamides 11a and 11b computed at the B3LYP/6-31G(d)
level;15,19,22 scaled carbonyl stretch frequencies for 10b and 11b
were computed to be 1740 and 1673 cm-1 respectively.22 The amide
nitrogens in 10a and 10b are also predicted to be highly pyramidal
Results and Discussion
A limited number of N,N-dialkoxyamides have been synthe-
sised by solvolysis of N-chlorohydroxamic esters in aqueous
alcohols but only one experimental method has been reported
in detail.11 Aqueous methanolysis of N-chloro-N-methoxy-4-
methylbenzamide afforded a 26% yield of N,N-dimethoxy-4-
methylbenzamide 2c. However, this method results in low yields
since the reaction produces hydrochloric acid, which reacts
with starting N-chloroamides producing hydroxamic esters and
chlorine (Scheme 2).
with average angles at nitrogen of 115◦ and 114◦ respectively and
15,19,22
˚
˚
both have long N–C(O) bonds, 1.4 A and 1.42 A respectively.
Recent X-ray data confirm these predictions.23 Consistent with
the spectroscopic data, N,N-dialkoxyamides have very low amide
isomerization barriers. Earlier NMR studies on N,N-dimethoxy-
4-methylbenzamide (2c) showed that the methoxyl resonances
were identical down to -90 ◦C. In addition the benzylic methylene
protons of N-benzyloxy-N-methoxybenzamide (3g) remained
isochronous down to the same temperature putting a limit of ca
32 kJmol-1 on any isomerization process.1
Scheme 2
Recently, hydroxamic esters themselves have been found to
be oxidised to N-alkoxynitrenium ions by hypervalent iodine
reagents,26–31 which have been used in a variety of cyclisations
onto aromatic rings and, very recently, onto alkenes.26 We recently
found that in the presence of alcohols, either as solvents or
as reagents in acetonitrile, phenyliodine(III)bis(trifluoroacetate)
(PIFA) reacts with a range of hydroxamic esters 5 giving
N,N-dialkoxyamides 9 in synthetically useful yields and with
short reaction times (Scheme 3). Presumably the intermediate
is the N-(trifluoroacetoxyiodobenzene) derivative 6 or the N-
trifluoroacetoxy compound 7, formed through ligand coupling.
Both 6 and 7 are themselves anomeric amides and in polar media
13C NMR carbonyl chemical shifts, reported here for the first
time, are very similar to those of N-acyloxy-N-alkoxyamides (very
close to 174 ppm and about 8 ppm higher than the precursor
hydroxamic esters).9,15 While in both anomeric amides the amide
resonance interaction is greatly reduced, the carbonyl shifts are not
ketonic and appear some 20 ppm upfield of aryl/alkyl ketones. The
origin of this upfield shift from that of ketones, parallels that of
esters, anhydrides and acid chlorides. The triad of electronegative
atoms adjacent to the carbonyl in pyramidal N,N-dialkoxyamides
and N-acyloxy-N-alkoxyamides destabilises the polar resonance
form of their carbonyls relative to ketones. These carbonyls
have greater double bond character resulting in higher electron
density at carbon, higher field carbonyl chemical shifts and
higher carbonyl vibrational frequencies. These observations are
Scheme 3
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Table 1 IR carbonyl stretch frequenciesa and 13C NMR chemical shiftsb for N,N-dialkoxyamides (R1ON(OR2)COR3) and their precursor hydroxamic
esters (R1ONHCOR3)
R1
R2
R3
Amide n/cm-1
Hydroxamic ester n/cm-1
13C NMR/ppm
Me
Me
Me
Me
Et
Bu
Bu
Bu
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
Ph
1711
1712
1710
1705
1708
1713
1702
1717
1702
1709
1704
1703
1710
1683
1687
1685
1687
174.3
173.2
174.3
173.8
173.8
173.8
173.1
171.8
174.0
174.3
171.6
174.0
174.1
4-ClC6H4
4-MeC6H4
4-MeOC6H4
4-NO2C6H4
4-ClC6H4
4-BrC6H4
4-NO2C6H4
Ph
1655c(Me)
1695 (Bu), 1687 (Me)
1696 (Bu)
1695 (Bu)
4-ClC6H4CH2
4-NO2C6H4CH2
Et
Bu
Bu
1687 (4-ClC6H4CH2)
1691(4-NO2C6H4CH2)
1692
Ph
4-NO2C6H4
Ph
Ph
Bu
Bn
1654
1654 (Bu), 1678 (Bn)
a Solution state in CHCl3 b CDCl3. c Nujol or neat.
Table 2 Percentage conversion of N,N-dimethoxybenzamides 2a–d to
hydroxamic esters 16, methyl benzoates 17 and N-(3,5-dimethylbenzyl)-
N-methoxybenzamides 18 in mesitylene at 155 ◦C
in line with those of Neovonen and coworkers, whose systematic
study of 13C NMR shift data for ester carbonyls showed that
electron density is actually greater at such carbons; reactivity
enhancement of ester carbonyls relative to ketones is actually due
to destabilisation of the ground states of the esters by the electron-
withdrawing substituents rather than positive polarisation at
carbon.32,33
Anomeric amides bearing poor leaving groups have been
found to undergo the HERON rearrangement. N-Alkoxy-N-
aminoamides 1d rearrange readily to alkyl esters and aminon-
itrenes in methanol, a process driven by a strong nN–s*NO
anomeric destabilisation of the N–O bond.9–15 N-Acyloxy-N-
alkoxyamides 1b, which undergo both acid-catalysed SN1 and
SN2 reactions at nitrogen in polar solvents, also undergo the
HERON rearrangement in toluene at 90 ◦C giving anhydrides and
alkoxynitrenes.9,14–16 While the alkoxyl oxygen is a weak anomeric
donor when compared to nitrogen in 1d, the driving force is
stabilisation of the developing negative charge on the migrating
carboxylate group in the transition state. However, in the case
of thermolysis of 1b, this reaction pathway is in competition
with radical N–OAc dissociation to acyloxyl and N-alkoxyamidyl
radicals.
Dialkoxyamide
(2)
Alkoxyamide
(16)/%
Methyl
benzoate(17)/%
Adduct
(18)/%
2a
2b
2c
2d
56
66
44
25
9
23
11
21
22
15
28
37
The reactions have a higher temperature requirement than
thermolysis of N-acyloxy-N-alkoxyamides (1b) and 2a–d decom-
posed smoothly within 1.5–2.0 h in mesitylene at 155◦ C. The
primary products in all cases were the corresponding hydroxamic
esters 16, methyl esters 17 and adducts N-(3,5-dimethylbenzyl)-N-
methoxybenzamides 18 (Scheme 5). The adducts (18) were isolated
chromatographically in a separate experiment and quantified
together with 16 and 17 either by HPLC, or by NMR using
diphenylethane as an internal standard after careful removal
of mesitylene under reduced pressure. Yields from the four
dialkoxyamides are presented in Table 2.
The significant amounts of mesitylene adduct 18 from these
reactions, as well as the formation of hydroxamic esters 16,
is consistent with a homolysis reaction giving N-alkoxyamidyl
and methoxyl radicals (Scheme 6). Methoxyl radicals 19 could
disproportionate to methanol and formaldehyde, which would be
undetectable under the conditions (Scheme 6, path i) or react
with solvent generating methanol and 3,5-dimethylbenzyl radicals,
which combine with alkoxyamidyl radicals 20 to generate 18
(Scheme 6, Path ii). However, on account of the high reactivity
of alkoxyl radicals, hydrogen abstraction from mesitylene is much
more likely than disproportionation. Solvent-cage transfer of a
hydrogen to alkoxyamidyls 20 producing hydroxamic esters 16
and formaldehyde is also possible (Scheme 6, path iii). Though
hydrogen abstraction from mesitylene by alkoxyamidyl radicals 20
leading to 16 cannot be precluded, it is considered less likely since
in alkoxyamidyls such as 20, the nitrogen-centred radical is capto-
dative stabilised by the neighbouring oxygen and the carbonyl.34–39
Relative to amidyl radicals, which are known to be electrophilic in
nature and good hydrogen abstractors,40–45 the high energy SOMO
in alkoxyamidyls makes them electronically similar to nucleophilic
Thermolysis studies have been carried out with a number of
N,N-dialkoxyamides (2a–d, 3e) and while these could in principle
undergo a HERON reaction to esters 12 and alkoxynitrenes 13
(Scheme 4, path i), the products point to the primary process being
homolysis of a nitrogen–oxygen bond to give an alkoxyamidyl
radical 14 and an alkoxyl radical 15 (Scheme 4, path ii).
Scheme 4
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Scheme 5
Scheme 6
aminyl radicals, which are poor abstractors of hydrogen from
carbon.35,46
alkoxy-N-aminoamides (1d) or N-acyloxy-N-alkoxyamides (1b)
since the anomeric effect is weaker in this case.
ꢀ
Two mechanisms are possible for the formation of the esters
17. Alkoxyamidyls generated under a variety of conditions are
well known to dimerise to hydrazines, which decompose to
esters.35,36,38,47,49,50 Therefore 20 can dimerise to give the symmetrical
hydrazines 21 and ultimately 17 (Scheme 6, path iv). We and others
have more recently shown this decomposition to involve a double
HERON rearrangement to two molecules of ester with liberation
of nitrogen, as 21 are NNO anomeric amides.1,9,11,12,14,15,21,51,52 That
N-alkoxyamidyl radicals are sufficiently unreactive with the sol-
vent and can therefore undergo dimerisation is evidenced by their
interception of the secondary mesityl radicals giving 18. A second
direct route to the esters could be HERON rearrangement of N,N-
dialkoxyamides themselves (Scheme 4, path i). This reaction would
be less favourable than the corresponding rearrangement of N-
Following a recent study on the thermal decomposition of N-
acyloxy-N-alkoxyamides 1b, which in toluene undergo a HERON
reaction giving anhydrides and alkoxynitrenes,16 a HERON re-
arrangement of N,N-dialkoxyamides would also be expected
to generate alkoxynitrenes. These relatively rare nitrenes, which
have a triplet ground state, have been shown to rearrange to
oximes, dimerise to hyponitrites and react with oxygen to give
nitrate esters.53–55 In the thermal decomposition of N-acyloxy-N-
alkoxyamides the identification of products derived from these
processes confirmed the operation of a HERON reaction.16
However, alkoxynitrenes identified in those studies contained
either benzylic or long-chain alkyl groups and the likely volatile
nature of products from similar reactions of methoxynitrene makes
detection of a HERON pathway to esters more difficult in this case.
The fate of 4-chlorobenzyloxynitrene 23 from the thermal
decomposition of N-acetoxy-N-(4-chlorobenzyloxy)benzamide
22 is known. The products 4-chlorobenzyl nitrate 24, 4-
chlorobenzonitrile 25 (formed under the conditions from 4-
chlorobenzaldoxime 26) and 4-chlorobenzaldehyde 27 were all
ꢀ Intramolecular additions of alkoxyamidyls to alkenes at 110 ◦C in
DMSO/dioxane has recently been reported,47 but under the same con-
ditions they do not undergo intramolecular allylic hydrogen abstraction or
addition to a benzene substituent on the alkoxyl side chain, in support of
our earlier findings on amidyl cyclisations in the biphenyl-2-carboxamide
system.35,48 This constitutes further evidence of their low electrophilicity.
1
detectable by MS and H NMR. Thermolysis of the N-methoxy
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Scheme 7
Fig. 1 GC-MS trace of the reaction mixture from thermal decomposition of N-(4-chlorobenzyloxy)-N-methoxybenzamide 3e at 155 ◦C in mesitylene.
Numbers correspond to structures in Scheme 7; * denotes minor, unidentified products.
analogue of 22, 3e, in mesitylene at 155 ◦C afforded a complex
reaction mixture (Scheme 7) that was analysed by GC-MS. The
chromatographic trace is shown in Fig. 1 together with assignment
of the major products. Mass spectral fragmentation patterns for
these are presented in Table 5.
Qualitatively the two possible esters from the decomposition,
methyl benzoate 17a at retention time (r.t.) 3.3 min. and 4-
chlorobenzyl benzoate 31 at r.t. 6.7 min. are relatively minor
products. The major products, present in similar amounts, are
4-chlorobenzaldeyde 27 and N-methoxybenzamide 16a at r.t.
3.5 and 4.4 respectively. This, together with the fact that N-(4-
chlorobenzyloxy)benzamide 32 is also a very minor product, in-
dicates that the major decomposition pathway is homolysis of the
Scheme 8
bond between nitrogen and the 4-chlorobenzyloxyl group giving
N-methoxybenzamidyl radical 35 and 4-chlorobenzyloxyl radical
36 (Scheme 8). It also supports hydrogen transfer from the 4-
chlorobenzyloxyl radical 36 to 35 giving the N-methoxybenzamide
(16a) and 4-chlorobenzaldehyde (27) (Scheme 8, path (i)). 4-
Chlorobenzyl alcohol 29, which would be produced by dispro-
portionation or hydrogen abstraction from mesitylene (Scheme 8,
pathways (ii) and (iii)) is clearly a minor component since
it is present in low yield (at the retention time of 4.1 min).
Lending further support to this is the fact that we recently
showed that 4-chlorobenzyloxyl radicals 36, generated indepen-
dently upon thermal decomposition of the hyponitrite, 1,2-
bis(4-chlorobenzyloxy)diazene (37) in toluene, gave mainly al-
cohol and only a limited quantity of 4-chlorobenzaldehyde
(Scheme 9),16 which must be generated by an alternative process
from 36.
Several minor solvent-derived oxidation products were detected
in the form of mesitaldehyde 33, 3,5-dimethylbenzyl alcohol 28a,
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Table 3 Arrhenius parameters and rate constants at 373 K for thermal
decomposition of N,N-dimethoxybenzamides (2a–d)
Amide ln A
EA/kJmol-1 DS‡/J K-1mol-1
106k373/dm3mol-1s-1
Scheme 9
2a
2b
2c
2d
27.68
125.3 1.7 -23.3 4.1
2.96
4.24
2.12
2.24
28.404 126.5 7.6 -17.1 18.6
29.632 132.5 1.5 -6.9 3.6
30.310 134.4 6.0 -1.2 14.6
3,5-dimethylbenzyl chloride 28b, and 1,2-di(3,5-dimethylphenyl)
ethane 34, presumably all derived from hydrogen abstraction
from solvent. While the source of alcohol and aldehyde is most
likely reaction with molecular oxygen, the origin of 28b and of
benzamide 30 is unknown. A number of minor components could
not be identified.
The absence of 4-chlorobenzyl nitrate 24, 4-chlorobenzonitrile
25 or 4-chlorobenzaldoxime 26, whose ions were not present
anywhere in the chromatogram, suggests that the HERON rear-
rangement of methoxyl that would lead to methyl benzoate (17a)
and 4-chlorobenzyloxynitrene (23) is not a significant pathway.
The reverse HERON reaction that would lead to 4-chlorobenzyl
benzoate and methoxynitrene cannot be excluded on this evidence
but formation of the esters by dimerisation of alkoxyamidyls and
double HERON decomposition suggests this as the most likely
route to esters 17a and 31, and the most likely route for formation
of 17 from 2.
Table 2 indicates a clear trend in the yields of hydroxamic
ester 16 and ester 17, which are related; low yields of methyl
ester correlate with high yields of hydroxamic ester and vice
versa. This is consistent with both products being formed from
methoxybenzamidyl radicals. The yields suggest that, relative to
hydrogen and chlorine, para-methyl and para-methoxyl groups
disfavour hydrogen transfer leading to a greater degree of dimeri-
sation. A similar electronic effect has recently been reported in
the competition between intramolecular 1,5-exo cyclisation and
dimerisation of alkoxyamidyl 39 generated by oxidation of the
hydroxamic ester 38 with o-iodoxybenzoic acid (IBX) (Scheme 10).
Whereas the acetamide 38a typically gave an 83% conversion to
isoxazolidine 40a and ester 41a (through the hydrazine) in the
ratio 70 : 30, the p-methoxybenzamide 38b afforded only a trace
of cyclic material, the major product being the ester 41b (40%).
A 4-methoxyphenacyl group would further raise the energy of the
Table 4 Rate constants for the thermal decomposition of N,N-
dialkoxyamides 2a–d in mesitylene
2a
2b
2c
2d
T/K105 k/s-1
T/K105 k/s-1
T/K 105 k/s-1 T/K 105 k/s-1
391 1.95 0.03 388 2.22 0.07 401 4.18 0.18 399 3.79 0.19
401 4.74 0.06 398 4.59 0.06 412.5 12.4 0.99 404 6.11 0.16
409 10.25 0.4 408 13.76 0.31 417 19.8 0.53 407 8.71 0.29
419 25.57 0.37 417 38.54 0.44 424 35.9 0.61 413 13.62 0.16
426 46.71 3.1 429 78.90 2.20 427 46.6 0.72 418 24.99 0.27
SOMO and disfavour hydrogen transfer in our reactions and the
5-exo-cyclisation of 39b.**
The thermal decomposition of 2a–d in mesitylene was moni-
tored by HPLC and shown to be a first order process. From rate
studies at different temperatures Arrhenius activation parameters
were obtained (Table 3).
Rates of decomposition at 373 K are similar, although formation
of methoxybenzamidyls from 2c and 2d would appear to have
looser transition states requiring higher activation energies than
those for decomposition of 2a and 2b.
Interestingly, considering that the major decomposition path-
way is a homolytic process the DS‡ are slightly negative. Thermal
decomposition of diacyl peroxides and dialkyl peroxides require a
similar EA to those found for N,N-dialkoxyamides but their DS‡
are appreciably more positive (typically around +40 JK-1mol-1).56
We attribute this in part to conjugation in alkoxyamidyl radicals.
ESR hyperfine coupling constants, AN , for alkoxyamidyls are
** B3LYP/6-31G(d) SOMO energies of benzamidyls 20a–d are computed
to be –6.78, –6.66, –6.58 and –6.2 eV respectively.
Scheme 10
Fig. 2 (a) Resonance-stabilisation in N-alkoxyamidyl radicals; (b) spin density in N-methoxyacetamidyl radical calculated at B3LYP/6-31G(d) level of
theory.
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Table 5 GC-MS Retention times and fragmentation patterns for products from decomposition of N-(4-chlorobenzyloxy)-N-methoxybenzamide (3e) in
mesitylene at 155 ◦
C
Product
Retention time/min Parent and fragment ions
Methyl benzoate 17a
3.3
3.5
3.7
3.9
4.0
136 (M+∑, 40%), 105 (100, M-(OCH3), 77 (32), 51 (20).
4-Chlorobenzaldehyde 27
3,5-Dimethylbenzaldehyde 33
3,5-Dimethylbenzyl chloride 28b
3,5-Dimethylbenzyl alcohol 28a
140 and 142 (M+∑, 100 and 38%), 139 (92, M-H), 111 (53, M-CHO), 75 (30, M-[CHO, HCl]).
134 (M+∑, 100%), 133 (75, M-H), 105 (48, M-CHO), 91 (17, M-[CHO, CH2]), 77 (16).
154 and 156 (M+∑, 30 and 10%), 119 (100, M-Cl), 91 (15, M-[Cl, 2 ¥ CH2]), 77 (8).
136 (M+∑, 100%), 121 (58, M-CH3), 107 (33, M-[CH3,CH2]), 105 (25, M-CH3O), 93 (54,
M-C3H7), 91 (60, M-[CH3O,CH2]), 77 (23).
4-Chlorobenzyl alcohol 29
N-Methoxybenzamide 16a.
4.1
4.4
142 and 144 (M+∑, 70 and 23%), 141(10, M-H), 125 (12, M-OH), 107 (100, M-Cl), 89 (15,
C7H6), 79 (86, C6H7), 77 (80, C6H5).
151 (M+∑, 100%), 105 (99, M-NHOMe), 91 (24, C7H6), 77 (98, C6H5), 51 (85).
Benzamide 30
4.5
6.7
121, (M+∑,100%), 105 (95, M-NH2), 77 (70, C6H5), 51 (30).
246 and 248(M+∑, 46 and 16%), 125 (95, M-PhCO2), 105 (100, M-OCH2C6H4Cl), 89 (30, M-
[PhCO2, HCl]), 77 (58, C6H5), 51.
4-Chlorobenzyl benzoate 31
1,2-Di(3,5-dimethylphenyl)ethane 34 7.4
N-(4-Chlorobenzyloxy)benzamide 32 8.2
238, (M+∑, 25%), 119 (12, M-C9H11), 105 (100, C8H9+), 91 (8), 77 (24).
261 and 263(M+∑, 9% and 3%), 125 and 127(100 and 33, M-PhCONO), 89 (8, M-[PhCONO,
HCl]).
1.04 mT35,37–39 as opposed to about 1.48 mT for amidyls,34,57,58
and alkoxyamidyls are not only resonance-stabilised by the
carbonyl, they are strongly delocalised onto the alkoxyl oxygen
(Fig. 2a), a main source of their stabilisation and the reduced
AN value. Fig. 2b shows the spin density distribution in N-
methoxyacetamidyl radical calculated at B3LYP/6-31G(d). The
resonance forms in Fig. 2a and spin density distribution in Fig. 2b
indicate that stabilisation of alkoxyamidyls involves pi overlap
between nitrogen, the carbonyl and alkoxyl oxygen p-orbitals,
which would be expected to result in some restricted rotation about
both the N–C and N–O bonds and impose additional constraints
in the transition state for homolysis.
chloroform. Mass spectra were recorded on a Varian 1200L
Quadrupole mass spectrometer coupled to a Varian CP-3800 gas
chromatograph; the column used was a FactorFour Capillary
Column, VF-5ms, 30m x 0.25mm, 0.25mm. Samples were injected
into the column ◦at 100 ◦C which was held for 2 min. before
increasing by 40 C per minute until the maximum temperature
◦
of 250 C, which was maintained until the end of each run. The
injector was 523 K and the sample was subjected to a capillary
voltage of 70 eV. TOF ESI accurate mass determinations were
obtained from the Mass Spectral Unit of the Australian National
University. Nuclear magnetic resonance spectra were recorded in
CDCl3 on a Bruker Avance 300P FT NMR spectrometer with a 5-
mm 1H inverse/BroadBand probe with a z-gradient, operating at
300.13 MHz (1H), 75.46 MHz (13C). Kinetic runs and yield analysis
were performed on a Millipore-Waters system HPLC using an
automatic gradient controller, Waters 501 and 510 pumps and a
U6K injector. A C18 reverse phase radial-pak column was eluted
with acetonitrile/water mixtures and the detector used was a 481
lambda-max LC spectrophotometer (set at 254 nm) linked to a
740 data module.
Conclusion
N,N-Dialkoxyamides can be synthesised directly from hydroxamic
esters using phenyliodine(III)bis(trifluoroacetate). Their IR and
1H NMR spectroscopic properties are similar to those of other
anomeric amides and are further evidence of diminished amide
resonance when two electronegative atoms are present on nitrogen.
Thermal decomposition of N,N-dialkoxyamides proceeds by
homolysis of a nitrogen—oxygen bond generating alkoxyl and
alkoxyamidyl free radicals. No evidence could be found for a
HERON rearrangement process; esters, which are a significant
product, are more than likely formed from dimerisation of
alkoxyamidyl radicals to hydrazines that are known to produce
esters by HERON rearrangements. The decompositions follow
unimolecular kinetics and EA’s are in a similar range to those of
other alkoxyl radical sources.
Apart from this study, the chemistry of N,N-dialkoxyamides
is virtually unexplored. The new synthetic procedure outlined
in this paper should make possible further investigation of this
unusual class of anomeric amides. We will shortly present the
first X-ray structures of two members of this class and studies of
their properties as free radical initiators as well as their solvolytic
behaviour at various pH’s are underway in our laboratories.
Synthesis of N-alkoxybenzamides
Hydroxamic esters N-methoxy-4-methylbenzamide,11 N-ethoxy-
4-nitrobenzamide,12 N-butoxybenzamide, N-butoxy-4-chloroben-
zamide, N-butoxy-4-bromobenzamide, N-butoxy-4-nitroben-
zamide,2 N-(4-chlorobenzyloxy)benzamide and N-(4-nitroben-
zyloxy)benzamide2 have been reported previously.
General synthesis of N-methoxybenzamides59
Potassium benzohydroxamates60 were stirred overnight with MeI
(1.8 equivalents) and Na2CO3 (1.2 equivalents) in 50% aqueous
methanol (240 cm3). The mixtures were refluxed for 2 h and
the methanol removed under reduced pressure. The resulting
aqueous mixture was acidified with dilute HCl and extracted
with dichloromethane, which was dried over anhydrous Na2CO3
and concentrated under reduced pressure. The crude product was
purified by crystallisation or chromatography.
Experimental
Materials and methods
Infrared spectra were recorded on a Perkin–Elmer1600 series
fourier-transform (FT)-IR spectrophotometer as solutions in
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N-Methoxybenzamide
and dried over anhydrous MgSO4. Centrifugal chromatography
in 10% ethyl acetate/hexane and concentration in vacuo gave the
title compound (0.157 g, 50%) as a yellow oil. nmax(CHCl3)/cm-1
1712; dH(300 MHz; CDCl3) 3.79 (6H, s, N(OCH3)2), 7.39 (2H, d,
m-Ar-H), 7.73 (2H, d, o-Ar-H); dC(75 MHz; CDCl3) 60.49 (2 ¥
q), 128.5 (2 ¥ d), 130.6 (2 ¥ d), 130.7 (s) 138.9 (s), 173.2 (s). m/z
(ESI) 216.0426 and 218.0395 ([M+ H+]. C9H11NO335Cl requires
216.0427 and C9H11NO337Cl requires 216.0398).
Potassium benzohydroxamate (8.06 g, 0.50 mmol) was reacted
with MeI (12.57 g, 0.09 mmol) and Na2CO3 (7.59 g, 0.058 mol).
Work-up afforded an oil which was purified by flash chromatogra-
phy. N-Methoxybenzamide (3.58 g, 47%) was a low-melting solid,
mp 60 ◦C (from benzene) (lit.,59 63.5–64.5 ◦C); nmax (CHCl3)/cm-1
1683 (C O)); dH(300 MHz; CDCl3) 3.81 (3 H, s, NH-OCH3),
7.38 (2 H, t, m-Ar-H), 7.48 (1 H, t, p-Ar-H), 7.75 (2 H, d, o-Ar-H);
dC(75 MHz; CDCl3) 64.24 (q, NHOCH3), 127.10 (2 ¥ d, m-Ar),
128.50 (2 ¥ d, o-Ar), 131.73 (s, i-Ar) 131.91 (d, p-Ar), 166.39 (s,
N,N-Dimethoxy-4-methylbenzamide 2c. N-Methoxy-4-me-
thylbenzamide (0.275 g, 1.67 mmol) was dissolved in methanol
(10 cm3). PIFA (1.08 g, 2.51 mmol) was added and the mixture
was stirred for 5 min. The solution was quenched with 10%
NaHCO3, extracted with dichloromethane, washed with brine,
and dried over anhydrous MgSO4. Centrifugal chromatography
in 10% ethyl acetate/hexane and concentration in vacuo gave the
title compound (0.17 g, 43%) as a yellow oil. nmax(CHCl3)/cm-1
1710; dH(300 MHz; CDCl3) 2.40 (3H, s, Ar-CH3), 3.80 (6H, s,
N(OCH3)2, 7.22 (2H, d, m-Ar-H), 7.70 (2H, d, o-Ar-H);
dC(75 MHz; CDCl3) 21.61 (q) 60.29 (2 ¥ q), 128.9 (2 ¥ d), 129.4
(2 ¥ d), 137.5 (s), 143.3 (s), 174.3 (s). m/z (ESI) 196.0970 ([M+
H+]. C10H14NO3 requires 196.0974).
C
O).
N-Methoxy-4-methoxybenzamide
Potassium p-methoxybenzohydroxamate (10.26 g, 0.05 mol) was
reacted with MeI (12.57 g, 0.09 mol) and Na2CO3 (7.59 g,
0.058 mol). The title compound was obtained as an al-
most pure solid (3.34 g, 37%). Recrystallisation gave pure
N-methoxy-4-methoxybenzamide, mp 101 ◦C(from ethyl ac-
etate/cyclohexane) (lit.,61 100–102.5 ◦C); nmax(CHCl3)/cm-1 1687
(C O); dH(300 MHz; CDCl3) 3.801 (3H, s, NH-OCH3), 3.804
(3H, s, Ar-OCH3) 6.84 (2H, d, m-Ar-H), 7.75 (2H, d, o-Ar-H);
dC(75 MHz; CDCl3) 55.24 (q, Ar-OCH3) 64.09 (q, NHOCH3),
113.64 (2 ¥ d, m-Ar), 123.89 (s, i-Ar), 128.97 (2 ¥ d, o-Ar), 162.40
(s, p-Ar), 166.09 (s, C O).
N,N-Dimethoxy-4-methoxybenzamide 2d. N-Methoxy-4-me-
thoxybenzamide (0.329 g, 1.82 mmol) was dissolved in methanol
(10 cm3). PIFA (1.17 g, 2.73 mmol) was added and the mixture
was stirred for 5 min. The solution was quenched with 10%
NaHCO3, extracted with dichloromethane, washed with brine,
and dried over anhydrous MgSO4. Centrifugal chromatography
in 10% ethyl acetate/hexane and concentration in vacuo gave
the title compound (0.184 g, 0.87 mmol, 48%) as a yellow
oil. nmax(CHCl3)/cm-1 1705; dH(300 MHz; CDCl3) 3.79 (6H, s,
N(OCH3)2), 3.85 (3H, s, Ar-OCH3), 6.91 (2H, d, m-Ar-H), 7.82
(2H, d, o-Ar-H); dC(75 MHz; CDCl3) 55.46 (q) 60.13 (2 ¥ q),
113.5 (2 ¥ d), 124.2 (s), 131.7 (2 ¥ d), 163.2 (s), 173.8 (s). m/z (ESI)
212.0923 ([M+H+]. C10H14NO4 requires 212.0239).
N-Methoxy-4-chlorobenzamide
Potassium p-chlorobenzohydroxamate (9.28 g, 0.05 mol) was re-
acted with MeI (12.57 g, 0.09 mol) and Na2CO3 (7.59 g, 0.058 mol).
The solid obtained after extraction into dichloromethane
was almost pure. Recrystallisation gave pure N-methoxy-4-
chlorobenzamide (4.28 g, 46%), mp 105 ◦C(from ethyl acetate-
cyclohexane) (lit.,61 106–108 ◦C); nmax(CHCl3)/cm-1 1687 (C O);
dH(300 MHz; CDCl3) 3.85 (3H, s, NH-OCH3), 7.36 (2H, d,
m-Ar-H), 7.67 (2H, d, o-Ar-H); dC(75 MHz; CDCl3) 64.22 (q,
NHOCH3), 128.55 (2 ¥ d, m-Ar), 128.80 (2 ¥ d, o-Ar), 129.95 (s,
i-Ar), 138.22 (s, p-Ar), 173.02 (s, C O).
N-Ethoxy-N-methoxy-4-nitrobenzamide 3a. N-Ethoxy-4-nit-
robenzamide (0.216 g, 1.00 mmol) was dissolved in methanol
(10 cm3). PIFA (0.64 g, 1.50 mmol) was added in one portion and
the mixture was stirred for 5 min. The solution was quenched with
10% NaHCO3 (aq), extracted with dichloromethane, washed with
brine, and dried over anhydrous MgSO4. Centrifugal chromatog-
raphy in 10% ethyl acetate/hexane and concentration in vacuo gave
the title compound (0.139 g, 58%) as a pale yellow solid, which
crystallised as prisms mp 45–47 ◦C (from ethyl acetate/hexane
by solvent displacement); nmax(CHCl3)/cm-1 1708.2; dH(300 MHz;
CDCl3) 1.25 (3H, t), 3.79 (3H, s), 4.12 (2H,q), 7.93 (2H, d), 8.27
(2H,d); dC(75 MHz; CDCl3) 13.52 (q), 60.57 (q), 69.95 (t), 123.30
(2 ¥ d), 130.06 (2 ¥ d), 138.36 (s), 149.83 (s), 173.83 (s); m/z (ESI)
263.0644 [M+Na+]. C10H12N2O5Na requires 263.0644)
Synthesis of N,N-dialkoxyamides
N,N-Dimethoxybenzamide
2a. N-Methoxybenzamide
(0.645 g, 4.27 mmol) was dissolved in methanol (10 cm3). PIFA
(2.754 g, 6.4 mmol) was added and the mixture was stirred
for 5 min. The solution was quenched with 10% NaHCO3,
extracted with dichloromethane, washed with brine, and dried
over anhydrous MgSO4. Centrifugal chromatography in 10%
ethyl acetate/hexane and concentration in vacuo gave the title
compound (0.504 g, 65%) as a yellow oil. nmax(CHCl3)/cm-1
1711; dH(300 MHz; CDCl3) 3.81 (6H, s, N(OCH3)2), 7.43 (2H, t,
m-Ar-H), 7.53 (1H, t, p-Ar-H), 7.79 (2H, d, o-Ar-H); dC(75 MHz;
CDCl3) 60.48 (2 ¥ q), 128.2 (2 ¥ d), 129.2 (2 ¥ d), 132.4 (s) 132.6
(d), 174.3 (s). m/z (ESI) 204.0637 ([M+ Na+]. C9H11NO3Na
requires 204.0637).
N-Butoxy-N-methoxy-4-chlorobenzamide 3b. N-Butoxy-4-
chlorobenzamide (0.192 g, 0.842 mmol) was dissolved in methanol
(10 cm3). PIFA (0.54 g, 1.26 mmol) was added in one portion and
the mixture was stirred for 5 min. The solution was quenched
with 10% NaHCO3 (aq), extracted with dichloromethane, washed
with brine, and dried over anhydrous MgSO4. Centrifugal
chromatography in 10% ethyl acetate/hexane and concentration
in vacuo gave the title compound (0.085 g, 44%) as a pale yellow
oil. nmax(CHCl3)/cm-1 1713.0; dH(300 MHz; CDCl3) 0.89 (3H, t),
N,N-Dimethoxy-4-chlorobenzamide 2b. N-Methoxy-4-chlo-
robenzamide (0.2695 g, 1.45 mmol) was dissolved in methanol
(10 cm3). PIFA (0.935 g, 2.18 mmol) was added and the mixture
was stirred for 5 min. The solution was quenched with 10%
NaHCO3, extracted with dichloromethane, washed with brine,
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1.37 (2H, sx), 1.61 (2H, qn), 3.77 (3H, s), 4.01 (2H,t), 7.40 (2H,
d), 7.76 (2H,d); dC(75 MHz; CDCl3) 13.67 (q), 19.08 (t), 30.16
(t), 60.12 (q), 73.33 (t), 128.39 (2 ¥ d), 130.67 (2 ¥ d), 130.94 (s),
138.36 (s), 173.83 (s); m/z (ESI) 258.0895 and 260.0869 ([M+H+].
C12H17NO635Cl requires 258.0897 and C12H17NO637Cl requires
260.0867).
58%) as a pale yellow oil. nmax(CHCl3)/cm-1 1709.4; dH(300 MHz;
CDCl3) 3.77 (3H, s), 5.11 (2H, s), 7.41–7.54 (5H, m), 7.78 (2H,d),
8.19 (2H,d); dC(75 MHz; CDCl3) 60.38 (q), 73.79 (t), 123.65 (2 ¥
d), 128.28 (2 ¥ d), 129.26 (4 ¥ d), 132.04 (s), 132.80 (d), 142.60
(s), 147.93 (s), 174.33 (s) one signal obscured; m/z (ESI) 303.0981
([M+H+]. C15H15N2O5 requires 303.0981).
N-Butoxy-N-methoxy-4-bromobenzamide
3c. N-Butoxy-
N,N-Diethoxy-4-nitrobenzamide 4a. N-Ethoxy-4-nitroben-
zamide (0.152 g, 0.722 mmol) was dissolved in 10 cm3 of
methanol. PIFA (0.53 g, 1.23 mmol) was added in one portion
and the mixture was stirred for 5 min. The solution was quenched
with saturated NaHCO3, extracted with dichloromethane which
was washed with brine, and dried over anhydrous MgSO4 and
concentrated to give an oil. Centrifugal chromatography in 10%
ethyl acetate/hexane afforded the title compound as a pale yellow
oil. Yield: 62%; nmax(CHCl3)/cm-1 1704.2 (C O); dH(300 MHz;
CDCl3) 1.24 (6H, t) 4.11 (4H, q) 7.94 (2H, d) 8.28 (2H, d);
dC(75 MHz; CDCl3) 13.49 (2 ¥ q), 69.63 (2 ¥ t), 123.19 (2 ¥
d), 130.01 (2 ¥ d), 138.55 (s), 149.67 (s), 171.58 (s); m/z (ESI)
277.0800 ([M+Na+]. C11H14N2O5Na requires 277.0800).
4-bromobenzamide (0.207 g, 0.761 mmol) was dissolved in
methanol (10 cm3). PIFA (0.491 g, 1.14 mmol) was added and the
mixture stirred for 5 min. The solution was quenched with 10%
NaHCO3, extracted with dichloromethane, washed with brine,
and dried over anhydrous MgSO4. Centrifugal chromatography
in 10% ethyl acetate/hexane and concentration in vacuo gave the
title compound as a yellow oil (0.113 g, 49%). nmax(CHCl3)/cm-1
1702.1;dH(300 MHz; CDCl3) 0.89 (3H, t), 1.34 (2H, sx), 1.61
(2H, qn), 3.77 (3H, s), 4.01 (2H, t), 7.57 (2H, d), 7.68 (2H,d);
dC(75 MHz; CDCl3) 13.69 (q), 19.10 (t), 30.17 (t), 60.17 (q), 73.39
(t), 127.22 (s), 130.79 (2 ¥ d), 131.29 (2 ¥ d), 131.40 (s), 173.11 (s),
one signal obscured; m/z (ESI) 324.0211 and 326.0191 ([M+Na+].
C12H16NO379BrNa requires 324.0211 and C12H16NO381BrNa
requires 326.0191).
N,N-Dibutoxybenzamide 4b. N-Butoxybenzamide (0.380 g,
1.97 mmol) was dissolved in 5.0 cm3 of 1-butanol. PIFA (1.27 g,
2.95 mmol) was added in one portion and the mixture was stirred
for 5 min. The solution was quenched with saturated NaHCO3,
extracted with dichloromethane, washed with brine, and dried
over anhydrous MgSO4. Removal of solvent afforded the title
compound as a pure yellow oil. Yield: 96%. nmax(CHCl3)/cm-1
1703.1 (C O); dH(300 MHz; CDCl3) 0.87 (3H, t) 1.35 (4H, sx)
1.56 (4H, p) 4.01 (4H, t) 7.40 (2H, t) 7.48 (1H, t) 7.77 (2H, d);
dC(75 MHz; CDCl3) 13.7 (2 ¥ q), 19.1 (2 ¥ t), 30.2 (2 ¥ t) 73.0
(2 ¥ t), 127.9 (2 ¥ d), 129.2(2 ¥ d), 132.1(d) 132.7 (s) 174.0 (s); m/z
(ESI) 288.1575 ([M+Na+]. C15H23NO3Na requires 288.1576).
N-Butoxy-N-methoxy-4-nitrobenzamide
3d. N-Butoxy-4-
nitrobenzamide (0.160 g, 0.670 mmol) was dissolved in 10 cm3 of
methanol. PIFA (0.430 g, 1.00 mmol) was added in one portion
and the mixture was stirred for 5 min. The solution was quenched
with saturated NaHCO3, extracted with dichloromethane,
washed with brine, and dried over anhydrous MgSO4. Centrifugal
chromatography in 10% ethyl acetate/hexane afforded the title
compound as a pale yellow oil. Yield: 30%; nmax(CHCl3)/cm-1
1716.7 (C O); dH(300 MHz; CDCl3) 0.86 (3H, t) 1.33 (2H, sx)
1.61 (2H, p) 3.80 (3H, s) 4.02 (2H, t) 7.93 (2H, d) 8.26 (2H, d);
dC(75 MHz; CDCl3) 13.64 (q) 19.05 (t), 30.09 (t), 60.60 (q), 73.90
(t), 123.25 (2 ¥ d), 123.50 (s),130.04 (2 ¥ d), 130.68 (s), 149.80
(s), 171.75 (s); m/z (ESI) 291.0956 ([M+Na+]. C12H16N2O5Na
requires 291.0957).
N-Benzyloxy-N-butoxybenzamide 4c. N-Butoxybenzamide
(0.107 g, 0.554 mmol) and benzyl alcohol (0.141 g, 1.30 mmol)
were dissolved in 5.0 cm3 of acetonitrile. PIFA (0.36 g, 0.837 mmol)
was added in one portion and the mixture was stirred for 5 min.
The solution was quenched with saturated NaHCO3, extracted
with dichloromethane, washed with brine, and dried over
anhydrous MgSO4. Purification by centrifugal chromatography
with 10% ethyl acetate/hexane afforded the title compound as a
yellow oil. Yield: 29%. nmax(CHCl3)/cm-1; dH(300 MHz; CDCl3)
0.88 (3H, t) 1.33 (2H, sx) 1.60 (2H, p) 4.02 (2H, t) 4.98 (2H,
s) 7.25–7.31 (5H, m) 7.42 (2H, t) 7.51 (1H, t) 7.77 (2H, d);
dC(75 MHz; CDCl3) 13.7 (q), 19.1 (t), 30.1 (t), 73.2 (t), 75.0 (t),
128.0 (2 ¥ d), 128.4 (2 ¥ d), 128.6 (d), 129.2 (4 ¥ d), 132.2 (d),
132.7 (s), 135.1 (s), 174.1 (s); m/z (ESI) 322.1419 ([M+Na+].
C18H21NO3Na requires 322.1419).
N-(4-Chlorobenzyloxy)-N-methoxybenzamide 3e. N-4-Chlo-
robenzyloxybenzamide (0.20 g, 0.76 mmol) was dissolved in
methanol (10 cm3). PIFA (0.493 g, 1.15 mmol) was added and the
mixture was stirred for 1 h. The solution was quenched with 10%
NaHCO3, extracted with dichloromethane, washed with brine,
and dried over anhydrous MgSO4. Centrifugal chromatography
in 10% ethyl acetate/hexane and concentration in vacuo gave the
title compound (0.123 g, 55%) as a yellow oil. nmax(CHCl3)/cm-1
1702.1; dH(300 MHz; CDCl3) 3.77 (3H, s), 4.96 (2H, s), 7.27 (4H,
q), 7.41 (2H, t), 7.52 (1H, t), 7.76 (2H, d); dC(75 MHz; CDCl3)
60.3 (q), 74.3 (t), 128.2 (2 ¥ d), 128.7 (s), 129.2 (2 ¥ d), 130.5 (2 ¥
d), 132.4 (s), 132.5 (d), 133.6, 134.6, 174.2 (s). m/z (ESI) 314.0560
and 316.0530 ([M + Na+]. C15H14NO335ClNa requires 314.0560
and C15H14NO337ClNa requires 316.0530).
Decomposition of N,N-dimethoxybenzamides 2a–d. N,N-
Dimethoxybenzamide (0.1 g) and diphenyl (0.02 g) (internal
standard) were placed in a 10 cm3 two-neck pear-shaped flask.
Mesitylene (5 cm3), pre-heated to the appropriate temperature,
was added and the flask submerged in a constant temperature
oil bath. The reaction was carried out under an atmosphere of
N2. The mixture was allowed to heat to constant temperature and
aliquot’s were taken at regular intervals. The consumption of N,N-
dimethoxybenzamide was monitored by hplc using the peak ratio
of dimethoxybenzamide to diphenyl. Rate constants at different
temperatures are presented in Table 4.
N-Methoxy-N-(4-nitrobenzyloxy)benzamide 3f. N-(4-Nitro-
benzyloxy)benzamide (0.114 g, 0.419 mmol) was dissolved in
methanol (10 cm3). PIFA (0.270 g, 0.629 mmol) was added
in one portion and the mixture was stirred for 5 min. The
solution was quenched with 10% NaHCO3 (aq), extracted with
dichloromethane, washed with brine, and dried over anhydrous
MgSO4. Centrifugal chromatography in 10% ethyl acetate/hexane
and concentration in vacuo gave the title compound (0.073 g,
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Product analysis
3 A. M. Bonin, S. A. Glover and G. P. Hammond, J. Chem. Soc., Perkin
Trans. 2, 1994, 1173–1180.
4 S. A. Glover, G. P. Hammond and A. M. Bonin, J. Org. Chem., 1998,
63, 9684–9689.
5 J. J. Campbell and S. A. Glover, J. Chem. Res. (S), 1999, 474–475.
6 S. A. Glover, Arkivoc, 2001, 143–160 Part xii, Issue in Honour of
O. S. Tee, ms. OT-308C.
7 S. A. Glover and G. Mo, J. Chem. Soc., Perkin Trans. 2, 2002, 1728–
1739.
8 K. L. Cavanagh, S. A. Glover, H. L. Price and R. R. Schumacher,
Aust. J. Chem., 2009, 62, 700–710.
9 S. A. Glover, in Adv. Phys. Org. Chem., ed. J. Richard, Elsevier, London,
2008, vol. 42, pp. 35–123.
The products of decomposition of N,N-dimethoxybenzamide
2a, N,N-dimethoxy-4-chlorobenzamide and N,N-dimethoxy-4-
methoxybenzamide 2d were separated by centrifugal chromatog-
raphy with the aim of characterising adducts 18a, 18b and 18d.
The formation of 18c from N,N-dimethoxy-4-methylbenzamide
2c has been described previously.11
N-(3,5-Dimethylbenzyl)-N-methoxybenzamide 18a; nmax(CH-
Cl3)/cm-1 1646 cm -1 (C O); dH(300 MHz; CDCl3) 2.32 (6H, s,
ArCH3), 3.48 (3H, s, OCH3), 4.85 2H, s, CH2), 6.94 (1H, s, p¢-
Ar), 7.00 (2H, s, o¢-Ar), 7.69 (2H, d o-Ar) 7.39, 7.41 (3H, m, p-Ar);
dC(75 MHz; CDCl3) 21.26 (q, Ar-CH3), 50.00 (t, CH2), 61.87 (q,
NOCH3), 125.95 (2 ¥ d, o¢-Ar), 129.39 (d, p¢-Ar) 136.09 (s, i¢-Ar),
138.16 (s, m¢-Ar), 127.99 and 128.16 (2 ¥ d, o,m-Ar), 130.57 (d,
p-Ar), 134.15 (s, i-Ar), 169.64 (s, C O).
10 J. M. Buccigross and S. A. Glover, J. Chem. Soc., Perkin Trans. 2, 1995,
595–603.
11 J. M. Buccigross, S. A. Glover and G. P. Hammond, Aust. J. Chem.,
1995, 48, 353–361.
12 S. A. Glover, G. Mo and A. Rauk, Tetrahedron, 1999, 55, 3413–
3426.
13 G. Mo, Ph.D., University of New England, 1999.
14 S. A. Glover, A. Rauk, J. M. Buccigross, J. J. Campbell, G. P. Hammond,
G. Mo, L. E. Andrews and A.-M. E. Gillson, Can. J. Chem., 2005, 83,
1492–1509.
N-(3,5-Dimethylbenzyl)-N-methoxy-4-chlorobenzamide 18b;
n
max(CHCl3)/cm-1 1639.4 cm -1 (C O); dH(300 MHz; CDCl3)
2.31 (6H, s, ArCH3), 3.45 (3H, s, OCH3), 4.84 (2H, s, CH2), 6.94
(1H, s, p¢-Ar), 6.98 (2H, s, o¢-Ar), 7.37 (2H, d, m-Ar), 7.68 (2H,
d, o-Ar); dC(75 MHz; CDCl3) 21.31 (q, Ar-CH3), 49.94 (t, CH2),
62.01(q, NOCH3), 126.06 (2 ¥ d, o¢-Ar), 128.30 (d, o-Ar), 129.54
(d, p¢-Ar), 129.95 (d, m-Ar), 132.02 (s, i-Ar), 135.95 (s, i¢-Ar),
136.82 (s, p-Ar), 138.29 (s, m¢-Ar), 168.38 (s, C O); m/z (ESI)
326.0925 ([M+Na+]. C17H18NO223Na35Cl requires 326.0924) .
N -(3,5-Dimethylbenzyl)- N -methoxy-4-methoxybenzamide
18d; nmax(CHCl3)/cm-1 1634 (C O); dH(300 MHz; CDCl3) 2.31
(6H, s, Ar-CH3), 3.49 (3H, s, NOCH3), 3.83 (3H, s, Ar-OCH3),
4.85 (2H, s, CH2), 6.89 (2H, d, m-Ar), 6.93 (1H, s, p¢-Ar), 7.00
(2H, s, o¢-Ar), 7.77 (2H, d, o-Ar); dC(75 MHz; CDCl3) 21.21 (q, Ar-
CH3), 50.195 (t, CH2), 55.22 (q, Ar-OCH3), 61.67 (q, N-OCH3),
113.21 (d, m-Ar), 125.89 (2 ¥ d, o¢-Ar), 129.28 (d, p¢-Ar), 130.56 (d,
o-Ar), 136.26 (s, m¢-Ar), 138.07 (s, i¢-Ar), 161.51 (s, p-Ar), 168.96
(s, C O), one overlapping signal (s, i-Ar).
15 S. A. Glover, in The Chemistry of Hydroxylamines, Oximes and
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N,N-Dimethoxybenzamide (0.025 g) was decomposed in mesity-
lene at 155 ◦C under the same conditions as those used for
the kinetic analysis. Decompositions were complete between
1.5 to 2 h. External standards for each of the corresponding
N-methoxybenzamide (16), methyl benzoate (17) and N-(3,5-
dimethylbenzyl)-N-methoxybenzamide (18) to be analysed were
prepared. The reaction mixture was made up to 10 cm3 in a
volumetric flask and analysed by hplc.
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N-(4-Chlorobenzyloxy)-N-methoxybenzamide
(0.025
g,
◦
0.086 mmol) was decomposed in mesitylene at 155 C under the
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