N-tritylhydroxylamines: Preparations, structures, base strengths, and reactions with nitrous acid and perchloric acid

Article abstract of DOI:10.1039/b103569j

N-Trityl, N-(4-methoxytrityl), N-(4,4′-dimethoxytrityl), and N-(4,4′,4″-trimethoxytrityl) derivatives of hydroxylamine, O-methylhydroxylamine, and O-benzylhydroxylamine have been prepared and characterised. Additionally, N,O-ditrityl- and N,O-bis(4,4′-dimethoxytrityl)-hydroxylamines have been made, and the X-ray crystal structure of the former has been determined. The pK_a value of O-benzylhydroxylammonium in water (6.2) and of its N-trityl analogue in aqueous acetonitrile (7.5) have been measured. The N-tritylhydroxylamines all decompose under aqueous acidic conditions to give the corresponding trityl alcohols, and rate constants for uncatalysed and hydronium ion catalysed reactions of N-(4,4′-dimethoxytrityl)-O-methylhydroxylamine have been measured by stopped flow kinetics at 25 °C. This compound compares in reactivity with N-alkyl-N-(4,4′-dimethoxytrityl)amines rather than with 4,4′-dimethoxytritylamine. Attempted nitrosation of N-tritylhydroxylamine and its O-alkyl derivatives gave trityl alcohol, the intermediate N-nitroso compound being detectable but too unstable to isolate. From N-trityl-O-benzylhydroxylamine, attempted nitrosation led to the formation of triphenylmethane in addition to trityl alcohol, benzyl alcohol, and trityl benzyl ether. The mildly acidic conditions used for attempted nitrosation of methoxy-substituted N-tritylhydroxylamines led to deamination before addition of the nitrosating agent.

Full text of DOI:10.1039/b103569j

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N-Tritylhydroxylamines: preparations, structures, base strengths,
and reactions with nitrous acid and perchloric acid
Moisés Canle L.,a William Clegg,b Ibrahim Demirtas,c Mark R. J. Elsegood,b Johanna Haider,d
Howard Maskill*d and Peter C. Miattd
2
a Chemistry Department, University of La Coruña, 15071 La Coruña, Spain
b X-Ray Crystallography Unit, Chemistry Department, University of Newcastle upon Tyne,
Newcastle upon Tyne, UK NE1 7RU
c Present address, Department of Chemistry, University of Gaziosmanpasa, 60250 Tokat,
Turkey
d Chemistry Department, University of Newcastle, Newcastle upon Tyne, UK NE1 7RU
Received (in Cambridge, UK) 18th April 2001, Accepted 27th June 2001
First published as an Advance Article on the web 13th August 2001
N-Trityl, N-(4-methoxytrityl), N-(4,4Ј-dimethoxytrityl), and N-(4,4Ј,4Љ-trimethoxytrityl) derivatives of
hydroxylamine, O-methylhydroxylamine, and O-benzylhydroxylamine have been prepared and characterised.
Additionally, N,O-ditrityl- and N,O-bis(4,4Ј-dimethoxytrityl)-hydroxylamines have been made, and the X-ray crystal
structure of the former has been determined. The pKa value of O-benzylhydroxylammonium in water (6.2) and of
its N-trityl analogue in aqueous acetonitrile (7.5) have been measured. The N-tritylhydroxylamines all decompose
under aqueous acidic conditions to give the corresponding trityl alcohols, and rate constants for uncatalysed and
hydronium ion catalysed reactions of N-(4,4Ј-dimethoxytrityl)-O-methylhydroxylamine have been measured by
stopped flow kinetics at 25 ЊC. This compound compares in reactivity with N-alkyl-N-(4,4Ј-dimethoxytrityl)amines
rather than with 4,4Ј-dimethoxytritylamine. Attempted nitrosation of N-tritylhydroxylamine and its O-alkyl
derivatives gave trityl alcohol, the intermediate N-nitroso compound being detectable but too unstable to isolate.
From N-trityl-O-benzylhydroxylamine, attempted nitrosation led to the formation of triphenylmethane in addition
to trityl alcohol, benzyl alcohol, and trityl benzyl ether. The mildly acidic conditions used for attempted nitrosation
of methoxy-substituted N-tritylhydroxylamines led to deamination before addition of the nitrosating agent.
we proposed a step-wise mechanism involving an intermediate
Introduction
alkyloxodiazonium ion (RN2O)ϩ rather than a concerted frag-
Hydroxylamine derivatives are α-effect ambident nucleophiles;1
mentation of the protonated substrate. Thus, the reaction
involves the rate-limiting step with elementary rate constant k
in Scheme 1 rather than the path with rate constant kЈ. We
they occur in nature and some synthetic analogues have potent
biological activity.2,3 The relatively recent discovery that nitric
oxide has wide-ranging physiological effects,4 and that some
planned to nitrosate N-trityl-O-alkylhydroxylamines in order to
nitrosated hydroxylamines decompose under mild conditions
investigate whether providing the possibility of a substantially
with release of nitric oxide,5 has led to renewed interest in the
more stable carbenium ion intermediate caused the fragment-
chemistry of hydroxylamine and its derivatives.
We have already reported investigations of the acid-induced
ation to become concerted, i.e. follow the kЈ route in Scheme 1
and by-pass the formation of the intermediate oxodiazonium
ion. We also planned to investigate whether fragmentation,
step-wise or concerted, to give a much more stable carbenium
solvolysis of N-nitroso-N,O-dialkylhydroxylamines which liber-
ate nitrous oxide, Scheme 1.6,7 In these reactions, acid catalysis
ion intermediate affects the need for acid catalysis.
In a parallel investigation of the acid-induced deamination
reactions of N-tritylamines,8 we discovered remarkable rate
enhancements (ca. 106) caused by replacing R = H with
R = alkyl or aryl, Scheme 2.9 We also observed that N-trityl
Scheme
1
Acid-catalysed hydrolysis of N-nitroso-N,O-dialkyl-
hydroxylamines.
Scheme 2 Acid-catalysed deamination of substituted tritylamines.
is required at least in part because alkoxide RЈOϪ is not suf-
ficiently good a nucleofuge in the initial heterolysis. Principally
on the basis of an α-deuterium kinetic isotope effect of unity,7
substituents have an appreciable base-strengthening effect upon
arylamines ArNH2 (up to ca. 8 pK units); this was ascribed
to the steric prevention of resonance between the aryl ring
1742
J. Chem. Soc., Perkin Trans. 2, 2001, 1742–1747
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b103569j

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(including its substituents) and the amino group.10 As part of an
investigation into the cause of these dramatic effects upon rate
and equilibrium constants, we made tritylamines substituted
with hydroxy and alkoxy groups on nitrogen (R = OH and OR,
Scheme 2), i.e. N-trityl- and N-trityl-O-alkyl-hydroxylamines,
with a view to measuring rate constants for their deamination
and pKa values of their conjugate acids.
We now report the synthetic aspects, base strength measure-
ments, and an initial rate study of an investigation linking the
two projects mentioned above. By an X-ray crystal structure
determination, we are also able to correct an earlier literature
supposition regarding the structure of ditritylhydroxylamine.11
If it subsequently proves generally possible to alkylate substi-
tuted N-tritylhydroxylamines on oxygen and then remove the
substituted trityl group under mildly acidic conditions in high
yield (Scheme 3), the way will be open for the use of substituted
Fig. 1
Scheme 3 Trityl as a protecting group in the synthesis of O-
alkylhydroxylamines.
trityl as a protecting group in a general flexible synthesis of
O-alkylhydroxylamines, RONH2. This will be complementary
to the older method by O-alkylation of N-hydroxyphthalimide
then removal of the phthalic residue under strongly basic/
nucleophilic conditions,12 and appreciably easier and safer.
Results and discussion
Preparations of tritylhydroxylamines
Baeyer and Villiger13 described a reaction of triphenylmethanol
and hydroxylamine under acidic conditions, then Mothwurf11
reported a reaction of triphenylmethyl chloride and hydroxyl-
amine under basic conditions, but no single pure product was
isolated in either case. Subsequently, Guthmann and Stieglitz14
synthesised N-trityl-O-methylhydroxylamine, and Ayres and
Hauser15 reported the O-benzyl analogue. We have found that,
in general, introduction of a single trityl group onto the nitro-
gen of hydroxylamine and its O-methyl or O-benzyl derivatives
to give TrNHOH and TrNHOR (R = Me or CH2Ph) is straight-
forward using trityl chloride in pyridine as solvent. Yields are
good and crystalline products well characterised.
Fig. 2 Structures of hydroxylamines.
N-(4-Methoxytrityl)hydroxylamines (MMTrNHOR) were
also preparable from 4-methoxytrityl chloride, but were less
easy to isolate with MMTrNHOH appreciably less stable than
the O-methyl and O-benzyl analogues, and usually requiring
chromatographic purification on either silica or alumina.
N-(4,4Ј-Dimethoxytrityl)hydroxylamines, prepared from 4,4Ј-
dimethoxytrityl tetrafluoroborate, were less stable to even
mildly acidic conditions, but were preparable and could be
chromatographed. Prepared from 4,4Ј,4Љ-trimethoxytrityl
tetrafluoroborate, the N-(4,4Ј,4Љ-trimethoxytrityl)hydroxyl-
amines were even less stable and decomposed on attempted
chromatography on silica; they could be purified by alumina
chromatography with a basic eluent or by recrystallisation.
parable to C–N bond lengths reported in four structures of
N,O-dialkylhydroxylamines in the Cambridge crystallographic
data-base,16 but longer than the corresponding C–O bond
lengths. The angles C–N–O and N–O–C are 110.25(13)Њ and the
inversion centre enforces a C–N–O–C torsion angle of exactly
zero, whereas the previous four structures have torsion angles
ranging from 101.5 to 149.3Њ. There are no hydrogen-bond
interactions, the centre of the molecule being sterically shielded
by the bulky substituents. It is interesting that, in contrast,
the data-base contains 32 structures of N,N-dialkylhydroxyl-
amines, so the N,N-isomers represent a large majority of known
dialkylhydroxylamines. Presumably, the steric bulk of the first
N-trityl group prevents further N-alkylation even though the
nitrogen remains more basic than the oxygen. This property of
the trityl group can be exploited in its use as a protecting group
for nitrogen in the ambident hydroxylamine as over-alkylation
on nitrogen can be a problem with less bulky alkyl groups.3 We
also prepared the N,O-bis(4,4Ј-dimethoxytrityl)hydroxylamine
(DMTrNHODMTr) from hydroxylamine and 4,4Ј-dimethoxy-
trityl tetrafluoroborate; it was isolated as an oil and, although
the 1H-NMR spectrum confirmed its formation, it was too
unstable to allow complete purification and characterisation.
Compounds prepared are shown in Fig. 2 and Table 1.
Preparations of ditritylhydroxylamines
There is a single report by Mothwurf11 of ditritylhydroxyl-
amine which was presumed to be the N,N-ditrityl isomer
(Tr2NOH) on the basis of indirect evidence. However, our X-ray
crystallographic results (Fig. 1) on the product from hydroxyl-
amine and two equivalents of trityl chloride clearly show that
the compound is the N,O-ditrityl isomer (TrNHOTr). It is
disordered across a centre of symmetry such that the O and NH
are interchangeable; the N–trityl and O–trityl bond lengths
are thereby indistinguishable, with a value of 1.470(2) Å, com-
J. Chem. Soc., Perkin Trans. 2, 2001, 1742–1747
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Table 1 Summary of tritylhydroxylamines 1–4
Comp.
R1
R2
R3
R4
Mp/ЊC
1a11
1b14
1c15
1d11
2a27
2b
H
H
H
H
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
H
H
H
H
H
H
H
MeO
MeO
MeO
MeO
MeO
MeO
MeO
H
H
H
H
H
H
H
H
H
H
H
MeO
MeO
MeO
H
Me
CH2Ph
Trityl
H
Me
CH2Ph
H
Me
CH2Ph
Dimethoxytrityl
H
Me
CH2Ph
132–134
90–91
115–116
199–200
113–116
89–91
80–81
136–137
86–87
80–81
Oil
139–140
125–126
81–83
2c
3a
3b
Fig. 3 Decomposition of 3b in aqueous perchloric acid at 25 ЊC (the
bars indicate 5% error ranges on rate constants).
3c
3d
4a
Table 3 Kinetics of acid-induced deamination of N-(dimethoxytrityl)-
amino compounds, 25 ЊC, ionic strength (NaClO4) = 1 mol dmϪ3
4b
4c
Comp.
ko/sϪ1
kH/dm3 molϪ1 sϪ1
Co-solvent
Table 2 pKa values of hydroxylammonium and related ions in water,
25 ЊC
DMTrNHOMe (3b)a
0.20
1.3
2% CH3CN
2% CH3CN
1% CH3CN
b
DMTrNH2
3.1 × 10Ϫ5
4.2
1.6 × 10Ϫ5
179
Ion
pKa
DMTrNHBnb
a [DMTrNHOMe]0 ca. 2 × 10Ϫ5 mol dmϪ3
.
b Ref. 9.
ϩ
NH4
9.8a
ϩ
MeNH3
10.65b
10.8b
9.8b
ϩ
Me2NH2
Me3NHϩ
Reactions of N-tritylhydroxylamines
NH3OHϩ
6.06c
5.9d
MeNH2OHϩ
Me2NHOHϩ
NH3OMeϩ
In early qualitative tests, we established that all our N-trityl-
hydroxylamines were unstable to acidic conditions, and that
this instability increased with increasing methoxy substitu-
tion in the trityl group. When aqueous acetonitrile solutions of
N-trityl-O-methylhydroxylamines, with and without methoxy
substituents, were treated with aqueous perchloric acid at
room temperature, the colour characteristic of the trityl cation
was immediately observed and the corresponding alcohol was
readily detected by TLC.
5.2e
4.6e
MeNH2OMeϩ
Me2NHOMeϩ
NH3OCH2Phϩ
TrNH2OCH2Phϩ
4.75e
3.65e
6.2f
7.5g
a Ref. 30. b Ref. 18. c Ionic strength = 1.0 mol dmϪ3, ref. 31. d Ref. 32.
e Ref. 19. f Ionic strength (NaClO4) = 0.1 mol dmϪ3, 5% MeCN, present
work. g Ionic strength (NaClO4) = 0.1 mol dmϪ3, 38% MeCN, present
work.
Our normal method for measuring rates of reaction of
substituted N- and O-trityl compounds is to monitor the form-
ation of the substituted trityl cation by UV absorption spec-
troscopy.8,9,20 The concentration of the substituted trityl cation
in equilibrium with the alcohol (Scheme 2) is a function of
the acidity of the medium;20,21 so, the higher the acidity, the
higher the equilibrium concentration of the cation and hence
the easier it is to measure its rate of formation. However, the
deamination reactions are acid catalysed and, depending upon
the particular compound, too high an acidity may lead to the
reaction being immeasurably fast using conventional or even
stopped-flow techniques. In the case of tritylamines, 4,4Ј-
dimethoxytritylamine was the most convenient to investigate as
appreciable concentrations of the dimethoxytrityl carbenium
ion exist in equilibrium with the alcohol at low hydronium ion
concentrations in water. Consequently, in the present context,
we initiated our kinetics study with the N-(4,4Ј-dimethoxytrityl)
substituted compound 3b, this being more readily available
than 3a. In contrast to the reaction of 4,4Ј-dimethoxytrityl-
amine under similar conditions, this reaction proved too fast to
be measurable by conventional UV kinetics, and stopped-flow
methodology was required. The pseudo first-order rate con-
stant was measured at 25 ЊC at different low concentrations of
perchloric acid ([substrate] Ӷ [H3Oϩ]), and the results are
shown in Fig. 3 and Table 3. They clearly indicate catalysed and
uncatalysed reaction channels for compound 3b, as was
observed for tritylamines in general, but the rate constants
obtained are much greater than those for DMTrNH2 and
broadly comparable with those for DMTrNHR.8,9 The differ-
ences between DMTrNHR and DMTrNHOR, however, are
interpretableonthebasisofourreportedmechanismfordeamin-
ation of tritylammonium ions, Scheme 4.8,9 Replacement of an
alkyl on the nitrogen by an alkoxy yields an α-effect nucleofuge/
nucleophile,22 so there will be a higher proportion of internal
return for the hydroxylamine, i.e. k1/kϪ1 in Scheme 4 will be
Base strengths of hydroxylamines
A routine pH titration technique was used for determining the
pKaЈs of alkylhydroxylammonium ions.10,17 Acetonitrile was
used as cosolvent to overcome solubility difficulties in water
alone for O-benzylhydroxylamine and its N-trityl derivative (1c)
but our previous work indicates that this is unlikely to have an
appreciable effect.10 The initial acidic pH of the solution for
titration was chosen to minimise solvolytic deamination of the
N-trityl-O-benzylhydroxylammonium ion.8,9 As seen in Table 2,
introducing a hydroxy group weakens the base strength of
ammonia by almost 4 pKa units, but then there are only small
differences between the base strengths of hydroxylamine,
N-methylhydroxylamine, and N,N-dimethylhydroxylamine
which is unsurprising in view of the close similarity between the
base strengths of ammonia, methylamine, dimethylamine, and
trimethylamine.18 The effect of alkyl groups on the oxygen is
less clear cut; the O-benzyl compound is similar in base strength
to the parent hydroxylamine whereas an O-methyl substituent
in hydroxylamine, N-methylhydroxylamine, and N,N-dimethyl-
hydroxylamine appears to be base weakening.19 Although the
result for 1c is imprecise due to difficulties in measuring equi-
librium properties of a compound which is to some degree
unstable to the reaction conditions, N-tritylation modestly
increases the base strength of O-benzylhydroxylamine, i.e. the
N-trityl reduces the base weakening effect of the N-alkoxy
group. However, this effect is much smaller than the effect of
N-trityl upon the base strengths of substituted anilines.10 In the
latter, the N-trityl is able to negate completely the powerful
base-weakening effects through resonance of aryl groups
attached to nitrogen, but in hydroxylamines it has only a small
effect on the inductive base-weakening effect of an OR group.
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deep red precipitate was filtered at the pump and dried under
vacuum (1.3 g, 89%, mp 194–196 ЊC, lit.,26 193–196 ЊC).
4,4Ј,4Љ-Trimethoxytrityl tetrafluoroborate. Aqueous tetra-
fluoroboric acid (40%, 2.2 cm3, 13 mmol) was added drop-wise
over 1 h to an ice-cold solution of 4,4Ј,4Љ-trimethoxytrityl
alcohol (2.17 g, 6.2 mmol) in acetic anhydride (12 cm3).
Dilution of the red reaction mixture with ether (30 cm3) gave
plum coloured crystals which were filtered at the pump
and dried under vacuum (2.98 g, 74%, mp 176–178 ЊC, lit.,27
177–178 ЊC).
N-Tritylhydroxylamine (1a). A solution of trityl chloride (300
mg, 1.08 mmol) in pyridine (1 cm3) was added drop-wise over
5 min to a solution of hydroxylammonium chloride (90 mg,
1.3 mmol) in pyridine (1 cm3) and the solution was stirred at
room temperature for 11 h as pyridinium chloride crystallised.
Water (15 cm3) was added and the precipitated mixture of trityl
alcohol and N-tritylhydroxylamine was filtered at the pump
then separated by column chromatography (80 : 20, petrol–
ethyl acetate). The hydroxylamine was recrystallised from
9 : 1 petrol–ethyl acetate (215 mg, 72%, mp 132–134 ЊC, lit.,11
126–134 ЊC; δH: 4.60 (1H, br, NH), 7.17–7.40 (15H, m, arom)).
Scheme 4 Mechanism for deamination of N-tritylammonium ions
under acidic conditions.
smaller than for alkyl-substituted analogues, with correspond-
ingly smaller overall rate constants, k0 and kH.
N-Nitroso-N-tritylhydroxylamines
Following Mothwurf,11 Schlenk and Bergmann23 reported a
nitrosation reaction of the parent tritylhydroxylamine with
amyl nitrite and hydrochloric acid in ether now seen to have
been unsuccessful. In the present study, attempts to isolate N-
nitroso-N-trityl-O-methylhydroxylamine by the usual acidified
sodium nitrite method failed.6 The N-trityl-O-methylhydroxyl-
ammonium ion appeared adequately stable under mildly acidic
conditions in aqueous ethanol at 0 ЊC, and addition of ice-cold
aqueous sodium nitrite led to a yellow coloration, presumably
the N-nitroso compound. However, following the usual work-
N-Trityl-O-methylhydroxylamine (1b). A solution of trityl
chloride (300 mg, 1.08 mmol) in pyridine (1 cm3) was added
drop-wise over 5 min to a solution of methoxylammonium
chloride (108 mg, 1.3 mmol) in as little pyridine as possible
(ca. 1 cm3). The reaction was stirred for ca. 15 h as pyridinium
chloride crystallised, then water (15 cm3) was added and the
mixture was extracted with dichloromethane (3 × 3 cm3). The
combined organic phase was dried (Na2SO4), filtered, and the
solvent was evaporated under reduced pressure. The residual
hydroxylamine and trityl alcohol were separated by column
chromatography (80 : 20, petrol–ethyl acetate), and the
hydroxylamine was recrystallised from ethyl acetate–petrol (196
mg, 63%; mp 90–91 ЊC, lit.,14 91 ЊC; δH: 3.52 (3H, s, OCH3), 6.29
(1H, br, NH), 7.23–7.31 (15H, m, arom)).
1
up, the only products identified by TLC and H NMR were
trityl alcohol (presumably by decomposition of the transient
N-nitroso-product, Scheme 1) and unreacted starting material.
Attempted nitrosation using isoamyl (3-methylbutyl) nitrite
under non-aqueous conditions also failed,24 as did attempts to
nitrosate N-tritylhydroxylamine itself. Interestingly, triphenyl-
methane was identified amongst the products of attempted
nitrosation of the N-trityl-O-benzyl analogue. Presumably,
hydride transfer occurs between the closely proximate trityl
cation and benzyl alcohol generated in the decomposition of
the transient nitroso compound. As trityl is well known as
a hydride abstracting agent,25 this finding indicates that nitros-
ation did indeed occur but that, under the reaction conditions,
the product decomposes by the heterolytic mechanism.6,7
Methoxy-substituted N-trityl-O-alkylhydroxylamines under-
went immediate deamination upon dissolution in the acidic
medium (Scheme 2) before the nitrosating agent had been
added, and the only products detected were the methoxy
substituted trityl alcohols in equilibrium with the methoxy-
substituted trityl cations.
N-Trityl-O-benzylhydroxylamine (1c). Trityl chloride (330
mg, 1.18 mmol) and O-benzylhydroxylammonium chloride
(160 mg, 1.00 mmol) in pyridine (3 cm3) were stirred under
nitrogen for approximately 60 h. Water was added to the reac-
tion mixture which was then extracted with dichloromethane
(3 × 5 cm3). The combined organic extract was washed with
saturated copper() sulfate solution (2 × 8 cm3) then with water,
dried (MgSO4), filtered, and evaporated under reduced pressure
to yield an off-white solid which was then chromatographed
(dichloromethane, 1% triethylamine) to yield a white solid (240
mg, 0.66 mmol, 66%, mp 115–116 ЊC (sharp), lit.,15 118–119 ЊC;
δH: 4.72 (2H, s, CH2), 6.32 (1H, br, NH), 7.15–7.37 (20H, m,
arom); δC: 73.99, 75.99, 126.91, 127.66, 127.78, 128.21, 128.33,
129.18, 137.78, 144.50).
Experimental
N,O-Ditritylhydroxylamine (1d). A solution of hydroxyl-
ammonium chloride (26 mg, 0.37 mmol) in pyridine (2 cm3) was
added to a stirred solution of trityl chloride (210 mg, 0.8 mmol)
in pyridine (3 cm3), and the reaction was stirred for 3 h. After
the usual work-up, the dichloromethane phase was dried
(Na2SO4), filtered, and the solvent was evaporated under
reduced pressure. The crystalline residue was chromatographed
twice (first, 80 : 20 dichloromethane–petrol, second, 90 : 10
petrol–ether); white crystals were obtained and recrystallised
from ethyl acetate–petrol (65 mg, 34%, mp 199–200 ЊC (sharp),
lit.,11 184 ЊC; δH: 1.54 (1H, br, NH), 7.12–7.24 (30H, m, arom);
C: 88.16, H: 6.04, N: 2.70%; C38H31NO requires C: 88.17, H:
6.04, N: 2.71%)
Preparations
TLC was carried out with aluminium backed Kieselgel 60 F254
plates (Merck), 0.2 mm thickness, and column chromatography
with silica gel (BDH, 40–63 µm). Unless otherwise stated,
1H and 13C NMR spectra were recorded on a Bruker
WP-200 instrument (200 MHz for 1H) with tetramethylsilane as
standard and CDCl3 as solvent; coupling constants (J) are
given in Hz.
4,4Ј-Dimethoxytrityl tetrafluoroborate. Aqueous tetrafluoro-
boric acid (40%, 1.4 cm3, 8 mmol) was added drop-wise over
30 min to a solution of 4,4Ј-dimethoxytrityl alcohol (1.2 g,
3.8 mmol) in acetic anhydride (5 cm3) at such a rate that the
temperature did not exceed 25 ЊC. The red solution was stirred
for a further 2 h, then was diluted with ether (25 cm3); the
N-(4-Methoxytrityl)hydroxylamine (2a). A solution of 4-
methoxytrityl chloride (231 mg, 0.7 mmol) in pyridine (3 cm3)
J. Chem. Soc., Perkin Trans. 2, 2001, 1742–1747
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was added drop-wise to a solution of hydroxylammonium
chloride (57 mg, 0.8 mmol) in pyridine (1 cm3). The reaction
was stirred overnight at room temperature during which time
pyridinium chloride crystallised. After the usual work-up, two
columns (first, 80 : 20 petrol–ethyl acetate, then dichlorometh-
ane) were necessary to separate 4-methoxytrityl alcohol (mp
79–80 ЊC) from the product (white crystals, 127 mg, 52%, mp
113–116 ЊC, lit.,28 100–110 ЊC; δH: 3.77 (3H, s, OCH3), 6.81 (2H,
d, J 8.9, H-3,5), 7.12–7.33 (12 H, m, arom); δC: 55.42, 72.38,
112.97, 126.77, 127.80, 128.86, 130.25, 136.79, 143.54, 158.26;
C: 78.76, H: 6.72, N: 3.87%; C20H19NO2 requires C: 78.40, H:
6.58, N: 4.57%).
C: 75.99, H: 6.15, N: 3.88%; C22H23NO3 requires C: 75.84, H:
6.36, N: 4.01%).
N-(4,4Ј-Dimethoxytrityl)-O-benzylhydroxylamine (3c). The
reaction was as described for the unsubstituted trityl compound
but using 4,4Ј-dimethoxytrityl tetrafluoroborate (260 mg, 0.7
mmol) and O-benzylhydroxylammonium chloride (117 mg,
0.8 mmol) and gave white crystals (130 mg, 45%, mp (recryst.
petrol–ethyl acetate) 80–81 ЊC; δH: 3.78 (6H, s, OCH3), 4.70
(2H, s, CH2), 6.24 (1H, br, NH), 6.80 (4H, d, J 8.9, H-3,3Ј,5,5Ј),
7.17–7.30 (14H, m, arom); δC: 55.24, 73.10, 76.04, 113.01,
126.76, 127.61, 127.70, 128.23, 128.30, 129.04, 130.33, 136.95,
137.93, 144.99, 158.33; C: 79.13, H: 6.85, N: 3.20%; C28H27NO3
requires C: 78.85, H: 6.62, N: 3.28%).
N-(4-Methoxytrityl)-O-methylhydroxylamine (2b). Methoxyl-
ammonium chloride (96 mg, 0.8 mmol) and 4-methoxytrityl
chloride (231 mg, 0.75 mmol) were reacted as described above
for the unsubstituted trityl compound. The work-up produced
a yellow oil which was dissolved in a few drops of ethyl acetate
to which petrol was added until the solution became cloudy.
The product crystallised overnight and was recrystallised from
ethyl acetate–petrol to give a white solid (170 mg, 74%, mp 89–
91 ЊC; δH: 3.51 (3H, s, NOCH3), 3.78 (3H, s, OCH3), 6.26 (1H,
br, NH), 6.81 (2H, d, J 8.9, H-3,5), 7.20–7.30 (12H, m, arom);
δC: 55.35, 72.6, 112.99, 126.80, 127.76, 128.86, 130.18, 136.87,
143.8, 158.0; C: 78.92, H: 6.66, N: 4.35%; C21H21NO2 requires
C: 78.97, H: 6.63, N: 4.39%).
N,O-Bis(4,4Ј-dimethoxytrityl)hydroxylamine (3d). The pro-
cedure for the unsubstituted bis(trityl)hydroxylamine was used
but starting from dimethoxytrityl tetrafluoroborate; the initial
product (a colourless oil, δH: 3.77 (12H, s, OCH3), 5.45 (1H, s,
NH), 6.78–7.27 (26H, m, arom)) turned yellow overnight and
did not crystallise.
N-(4,4Ј,4Љ-Trimethoxytrityl)hydroxylamine (4a). The reaction
was as described for the monomethoxytritylhydroxylamine
using 4,4Ј,4Љ-trimethoxytrityl tetrafluoroborate (210 mg,
0.5 mmol) and hydroxylammonium chloride (40 mg, 0.6 mmol).
As the product decomposed on silica and alumina, it was
isolated by crystallisation from ether–petrol in the refrigerator
for 48 h as orange crystals (80 mg, 44%, mp 139–140 ЊC;
δH: 1.60 (1H, br, OH), 3.87 (9H, s, OCH3), 6.94 (6H, d, J 8.9,
H-3,3Ј,3Љ,5,5Ј,5Љ), 7.77 (6H, d, J 8.9, H-2,2Ј,2Љ,6,6Ј,6Љ); δC:
55.21, 72.52, 113.07, 130.04, 137.12, 158.29; C: 72.01, H: 7.23,
N: 3.65%; C22H23NO4 requires C: 71.72, H: 7.11, N: 3.80%).
N-(4-Methoxytrityl)-O-benzylhydroxylamine (2c). The reac-
tion was as for the unsubstituted trityl compound but starting
with 4-methoxytrityl chloride (271 mg, 0.8 mmol) and O-benzyl-
hydroxylammonium chloride (140 mg, 0.9 mmol). Following
the usual work-up, chromatography, and recrystallisation
(ether–petrol), white crystals were obtained (206 mg, 65%, mp
80–81 ЊC; δH: 3.77 (3H, s, OCH3), 4.64 (2H, s, CH2), 6.29 (1H,
br, NH), 6.80 (2H, d, J 8.9, H-3,5), 7.15–7.35 (17H, m, arom);
δC: 55.24, 73.10, 76.01, 113.02, 126.81, 127.61, 127.71, 128.20,
128.30, 129.12, 130.40, 136.95, 137.86, 144.76; C: 82.16, H:
6.08, N: 3.58%; C27H25NO2 requires C: 82.00, H: 6.37, N:
3.54%).
N-(4,4Ј,4Љ-Trimethoxytrityl)-O-methylhydroxylamine
(4b).
The reaction was as described for the dimethoxytrityl com-
pound but starting from trimethoxytrityl tetrafluoroborate (336
mg, 0.8 mmol) and methoxylammonium chloride (73 mg, 0.9
mmol). The crude product gave white crystals from petrol–ethyl
acetate in the refrigerator overnight which were recrystallised
from ethyl acetate–petrol (176 mg, 58%, mp 125–126 ЊC;
δH: 3.50 (3H, s, NOCH3), 3.78 (9H, s, OCH3), 6.80 (6H, d,
J 8.9, H-3,3Ј,3Љ), 7.17–7.21 (6H, m, H-2,2Ј,2Љ,6,6Ј,6Љ); δC:
55.23, 62.00, 72.59, 113.04, 130.11, 137.14, 158.30; C: 72.92,
H: 6.38, N: 3.80%; C23H25NO4 requires C: 72.80, H: 6.64, N:
3.69%).
N-(4,4Ј-Dimethoxytrityl)hydroxylamine (3a). 4,4Ј-Dimeth-
oxytrityl tetrafluoroborate (312 mg, 0.8 mmol) and hydroxyl-
ammonium chloride (60 mg, 0.9 mmol) were reacted as
described for the monomethoxy compound, but for just 3 h,
then the reaction was worked up in the usual way. The product
was chromatographed twice (first, 80 : 20 petrol–ethyl acetate;
second, dichloromethane) to give colourless crystals (107 mg,
40%, mp 136–137 ЊC; δH: 3.78 (6H, s, OCH3), 6.82 (4H, d, J 8.9,
H-3,3Ј,5,5Љ), 7.17 (4H, d, J 8.9, H-2,2Ј,6,6Ј), 7.25–7.26 (5H, m,
arom); δC: 55.26, 113.69, 126.18, 127.83, 129.84, 130.00,
130.39, 136.50, 158.04; C: 74.68, H: 6.93, N: 3.89%; C21H21NO3
requires C: 74.75, H: 6.87 N: 4.15%).
N-(4,4Ј,4Љ-Trimethoxytrityl)-O-benzylhydroxylamine
(4c).
The procedure described for N-tritylhydroxylamine was
followed using trimethoxytrityl tetrafluoroborate (336 mg,
0.8 mmol) and O-benzylhydroxylammonium chloride, and gave
white crystals (234 mg, 65%, mp 81–83 ЊC; δH: 3.78 (9H, s,
OCH3), 4.69 (2H, s, CH2), 6.22 (1H, br, NH), 6.79 (6H, d,
J 8.9, H-3,3Ј,3Љ,5,5Ј,5Љ), 7.19 (6H, d, J 8.9, H-2,2Ј,2Љ,6,6Ј,6Љ),
7.24–7.26 (5H, m, arom); δC: 55.25, 72.70, 113.01, 127.61,
128.30, 130.27, 137.20, 138.00, 158.31; C: 76.69, H: 6.65, N:
3.01%; C29H29NO4 requires C: 76.46, H: 6.42, N: 3.07%).
N-(4,4Ј-Dimethoxytrityl)-O-methylhydroxylamine (3b).
A
solution of dimethoxytrityl tetrafluoroborate (312 mg, 0.8
mmol) in pyridine (1.5 cm3) was added drop-wise to a solution
of methoxylammonium chloride (75.2 mg, 0.9 mmol) in
pyridine (1 cm3) and the resultant yellow solution was stirred
for 2 h, then quenched with water (20 cm3) and extracted with
dichloromethane (3 × 3 cm3). The combined organic phase was
washed with saturated aqueous copper() sulfate (2 × 5 cm3),
dried (Na2SO4), and filtered, then the solvent was evaporated
under reduced pressure. Column chromatography of the resi-
due (80 : 20, petrol–ethyl acetate) gave a pale yellow oil which
crystallised from ethyl acetate–petrol overnight in the refrig-
erator. The product was recrystallised at Ϫ78 ЊC from petrol–
ether (151 mg, 54%, mp 86–87 ЊC; δH: 3.50 (3H, s, NOCH3),
3.77 (6H, s, OCH3), 6.23 (1H, br, NH), 6.80 (4H, d, J 8.9, H-
3,3Ј,5,5Ј), 7.17–7.30 (9H, m, arom); δC: 55.23, 61.97, 73.03,
113.05, 126.77, 127.73, 128.89, 130.19, 136.87, 144.95, 158.34;
Attempted nitrosation of N-tritylhydroxylamines
The following is representative.
N-Trityl-O-benzylhydroxylamine (1c). The attempted nitros-
ation of 1c using either nitrous acid6 in aqueous ethanol or
isoamyl nitrite24 in dichloromethane–methanol failed to yield
the desired product. Approximately the same combination
of trityl alcohol, benzyl alcohol, trityl benzyl ether, and tri-
phenylmethane was shown to be formed from both reactions
by a combination of TLC, GLC, and NMR; there were minor
1746
J. Chem. Soc., Perkin Trans. 2, 2001, 1742–1747

View Article Online
2 Y. Isowa, T. Takashima, M. Ohmori, H. Kurita, M. Sato and
unidentified products, but starting material and trityl ethyl
ether from the reaction in aqueous ethanol were shown to be
absent.
K. Mori, Bull. Chem. Soc. Jpn., 1972, 45, 1461; E. Quiñoà and
P. Crews, Tetrahedron Lett., 1987, 28, 2467; M. Strasser, P. Cooper,
B. Dewald and T. Payne, Helv. Chim. Acta, 1988, 7, 1156; A. R.
Carroll and P. J. Scheuer, Tetrahedron, 1990, 46, 6637.
3 M. A. Staszak and C. W. Doecke, Tetrahedron Lett., 1994, 35,
6021.
X-Ray crystallography†
Crystal data for 1d: C38H31NO, M = 517.6, triclinic, space group
4 R. M. J. Palmer, A. G. Ferrige and S. Monacada, Nature, 1987, 327,
524.
¯
P1, a = 8.677(6), b = 9.042(6), c = 10.769(7) Å, α = 113.29(4),
β = 90.24(4), γ = 115.20(3)Њ, V = 686.9(8) Å3, Z = 1; R(F,
F 2 > 2σ) = 0.0370, Rw(F 2, all data) = 0.0947 for 185 parameters
and 2409 unique data. The molecule lies on an inversion centre,
and so is disordered with O and N atoms effectively super-
imposed. The half-occupancy H atom bonded to N was located
and refined subject to a bond length restraint; other H atoms
were constrained with a riding model.29
5 J. Saavedra and L. Keefer, Chem. Br., 2000, 30.
6 H. Maskill, I. D. Menneer and D. I. Smith, J. Chem. Soc., Chem.
Commun., 1995, 1855; J. I. Bhat, W. Clegg, M. R. J. Elsegood,
H. Maskill, I. D. Menneer and P. C. Miatt, J. Chem. Soc., Perkin
Trans. 2, 2000, 1435.
7 J. Haider, M. N. S. Hill, I. D. Menneer, H. Maskill and J. G. Smith,
Chem. Commun., 1997, 1571.
8 C. Bleasdale, B. T. Golding, W. H. Lee, H. Maskill, J. Riseborough
and E. Smits, J. Chem. Soc., Chem. Commun., 1994, 93; J. Crugeiras
and H. Maskill, J. Chem. Soc., Perkin Trans. 2, 1998, 1901.
9 M. C. Lopez, J. C. Martinez, I. Demirtas, H. Maskill and E. Stix,
Org. React. (N.Y.), 1997, 31, 71.
10 M. Canle L., W. Clegg, I. Demirtas, M. R. J. Elsegood and
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11 A. Mothwurf, Ber. Dtsch. Chem. Ges., 1904, 37, 3150.
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5, 511; G. H. L. Nefkens and G. I. Tesser, J. Am. Chem. Soc., 1961,
83, 1263.
13 A. Baeyer and V. Villiger, Ber. Dtsch. Chem. Ges., 1902, 35, 3013.
14 W. S. Guthmann and J. Stieglitz, J. Org. Chem., 1936, 1, 31.
15 E. B. Ayres and C. R. Hauser, J. Org. Chem., 1948, 13, 116.
16 F. H. Allen and O. Kennard, Chem. Des. Autom. News, 1993, 8, 31.
17 A. Albert and E. P. Serjeant, Ionization Constants of Acids and
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18 H. Maskill, The physical basis of organic chemistry, Oxford
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19 T. C. Bissot, R. W. Parry and D. H. Campbell, J. Am. Chem. Soc.,
1957, 79, 796.
pKa Determinations
A pH titration method was used for both compounds,17 and has
already been described.10 A combined glass electrode coupled
to a Metrohm 716 DMS Titrino automatic titrator was used to
record the pH during the titration of the conjugated acid of
the hydroxylamine against standard sodium hydroxide. The
reported pKa values were optimized by fitting the experimental
results to the appropriate sigmoidal equations derived from the
Henderson–Hasselbach equation using a non-linear optimiz-
ation algorithm.
Kinetics of deamination of N-(4,4Ј-dimethoxytrityl)-O-methyl-
hydroxylamine (3b)
The rates of decomposition of the title compound under acidic
conditions were investigated under the usual pseudo first-order
conditions at 25 ЊC using stopped flow equipment kindly made
available to us by Professor D. L. H. Williams at the University
of Durham. The observed pseudo first-order rate constants
were plotted against [HClO4] to give the second-order catalytic
constant from the gradient and the first-order rate constant for
the uncatalysed reaction from the intercept.
20 J. Crugeiras and H. Maskill, Can. J. Chem., 1999, 77, 530;
J. Crugeiras and H. Maskill, J. Chem. Soc., Perkin Trans. 2, 2000,
441.
21 W. H. Lee and H. Maskill, J. Chem. Soc., Perkin Trans. 2, 1994,
1463.
22 N. S. Isaacs, Physical organic chemistry, Longman, London,
1987.
Acknowledgements
23 W. Schlenk and E. Bergmann, Justus Liebigs Ann. Chem., 1928, 464,
1.
We thank EPSRC for a studentship (PCM) and equipment
(WC and MRJE), the EU Erasmus programme (JH), the
Turkish Government for a studentship (ID), Professor D. L. H.
Williams at the University of Durham for advice and access
to stopped flow kinetics instrumentation, and Dr S. Jones
(Newcastle) for helpful discussions.
24 P. S. J. Canning, K. McCrudden, H. Maskill and B. Sexton, J. Chem.
Soc., Perkin Trans. 1, 1999, 2735.
25 M. E. Jung, J. Org. Chem., 1976, 41, 1479; M. E. Jung and M. L.
Speltz, J. Am. Chem. Soc., 1976, 98, 7882; P. Barua, N. C. Barua and
R. P. Sharma, Tetrahedron Lett., 1983, 24, 5801.
26 C. Bleasdale, S. B. Ellwood and B. T. Golding, J. Chem. Soc., Perkin
Trans. 1, 1990, 803.
27 A. P. Henderson, J. Riseborough, C. Bleasdale, W. Clegg, M. R. J.
Elsegood and B. T. Golding, J. Chem. Soc., Perkin Trans. 1, 1997,
3407.
† CCDC reference number 163627. See http://www.rsc.org/suppdata/
p2/b1/b103569j/ for crystallographic files in .cif or other electronic
format.
28 M. S. Newman and P. M. Hay, J. Am. Chem. Soc., 1953, 75,
2322.
29 G. M. Sheldrick, SHELXTL manual, version 5.1, Bruker AXS Inc.,
Madison, WI, USA, 1997.
30 M. N. Hughes and G. Stedman, J. Chem. Soc., 1963, 2824.
31 P. Lumme, P. Lahermo and J. Tummavouri, Acta Chem. Scand.,
1965, 19, 2175.
32 M. N. Hughes, T. D. B. Morgan and G. Stedman, Chem. Commun.,
1966, 241.
References
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J. Chem. Soc., Perkin Trans. 2, 2001, 1742–1747
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