Nucleophilic aromatic substitution of hydrogen in the reaction of tert- alkylamines with nitrosobenzenes - Synthesis and NMR study of N-(tert-alkyl)- ortho-nitrosoanilines

Article abstract of DOI:10.1002/(SICI)1099-0690(199901)1999:1<29::AID-EJOC29>3.0.CO;2-M

The reaction of primary amines bearing tertiary alkyl groups (e.g. R- NH₂; R = tBu, 1-adamantyl) with nitrosobenzenes has been found to proceed by oxidative nucleophilic aromatic substitution of hydrogen, thereby affording N-(tert-alkyl)ortho- and -para-nitrosoanilines. The replacement of hydrogen proceeds more rapidly than the replacement of ortho- or para-nitro or -bromo substituents. With p-nitronitrosobenzene, both ortho-hydrogen atoms are substituted to afford N,N'-di(tert-alkyl)-4-nitro-2-nitroso-1,3- phenylenediamines 8a,b. The addition of oxidizing agents (e.g. MnO₂) increases the yield of products. ¹H-, ¹³C-, ¹⁴N- and ¹⁵N-NMR studies have confirmed the structures of the compounds under investigation. In ortho- nitrosoanilines, the rotamer with the nitroso group syn to the amino group is favored.

Full text of DOI:10.1002/(SICI)1099-0690(199901)1999:1<29::AID-EJOC29>3.0.CO;2-M

FULL PAPER
Nucleophilic Aromatic Substitution of Hydrogen in the Reaction of
tert-Alkylamines with Nitrosobenzenes – Synthesis and NMR Study of
N-(tert-Alkyl)-ortho-nitrosoanilines
Dmitriy L. Lipilin,[a] Aleksandr M. Churakov,*[a] Sema L. Ioffe,[a]
Yuri A. Strelenko,[a] and Vladimir A. Tartakovsky[a]
Keywords: Nitrosobenzenes / ortho-Nitrosoanilines / 2-Nitroso-1,3-phenylenediamines / Nucleophilic aromatic
substitution / Oxidative nucleophilic substitution of hydrogen
The reaction of primary amines bearing tertiary alkyl groups
(e.g. R–NH2; R = tBu, 1-adamantyl) with nitrosobenzenes has
been found to proceed by oxidative nucleophilic aromatic
substitution of hydrogen, thereby affording N-(tert-alkyl)-
ortho- and -para-nitrosoanilines. The replacement of
hydrogen proceeds more rapidly than the replacement of
ortho- or para-nitro or -bromo substituents. With p-
nitronitrosobenzene, both ortho-hydrogen atoms are
substituted to afford N,NЈ-di(tert-alkyl)-4-nitro-2-nitroso-1,3-
phenylenediamines 8a,b. The addition of oxidizing agents
(e.g. MnO2) increases the yield of products. 1H-, 13C-, 14N-
and 15N-NMR studies have confirmed the structures of the
compounds under investigation. In ortho-nitrosoanilines, the
rotamer with the nitroso group syn to the amino group is
favored.
the nitroso group to afford N-(tert-butyl)-o-nitrosoaniline
(2a) and N-(tert-butyl)-p-nitrosoaniline (3a) in a combined
yield of ca. 30%.[3] Azoxybenzene (4a) was also generated
in this reaction in ca. 60% yield (Scheme 1, Table 1).
Introduction
As a rule, amines attack nitrosobenzenes at the N atom
of the nitroso group[1a]. Thus, reaction of primary amines
RϪNH2 (R ϭ Me, Et, CH2Ph) with nitrosobenzene in
CHCl3 as solvent yields alkylphenyldiazenes. tert-Butyl-
amine does not react under such conditions.[2] In some
cases, amines can displace nucleofugal groups (e.g. OH,
OR, NH2, NHR) in nitrosobenzenes at the position para to
the nitroso group (SNAr reactions). Transamination of
para-nitrosoanilines provides an example of such a reac-
tion.[1b] We have not been able to find any references to
reactions of nitrosobenzenes with amines, or with other nu-
cleophiles, which might proceed by nucleophilic aromatic
substitution of hydrogen (SNArH reactions).
We wish to report that the reaction of nitrosobenzenes
with primary amines bearing a tertiary alkyl group (i.e.
RϪNH2; R ϭ tBu, 1-adamantyl) in aprotic dipolar solvents
proceeds through nucleophilic aromatic substitution of hy-
drogen to afford N-(tert-alkyl)-ortho- and -para-nitroso-
anilines. The aim of the work described herein was to in-
vestigate this novel reaction.
Scheme 1
Compound 2a was obtained as a low-melting brown
solid, and was found to be rather stable at room tempera-
ture. Its structure will be discussed below. In contrast, the
yellow para-substituted compound 3a proved to be unstable
in the absence of a solvent, although in solution (CH2Cl2,
benzene) it could be stored for several days with practically
no decomposition. The stability of 3a was enhanced by the
Results and Discussion
The reaction of nitrosobenzene (1a) with tert-butylamine
was found to proceed in an unusual manner, compared with
the corresponding reactions with other primary amines, e.g.
MeNH2 or EtNH2. The nitroso group remained intact and
the amine replaced hydrogen at a position ortho or para to
1
presence of a small amount of hydrochloric acid. The H-
and 13C-NMR spectra of 3a resemble those of N-methyl-p-
nitrosoaniline.[4] The structure of 3a was further confirmed
by its oxidation to the stable nitro derivative 5. It is note-
worthy that attempts to synthesize 3a by the FisherϪHepp
reaction were unsuccessful.[5a,5b]
[a]
N. D. Zelinsky Institute of Organic Chemistry, Russian Aca-
demy of Sciences,
Leninsky prosp. 47, 117913 Moscow, Russian Federation
Fax: (internat.) ϩ 7-095/135-5328
E-mail: churakov@cacr.ioc.ac.ru
Eur. J. Org. Chem. 1999, 29Ϫ35
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1434Ϫ193X/99/0101Ϫ0029 $ 17.50ϩ.50/0
29

D. L. Lipilin, A. M. Churakov, S. L. Ioffe, Y. A. Strelenko, V. A. Tartakovsky
FULL PAPER
The reaction also proceeded successfully when tBuNH2
was used as solvent. In this case, ortho-substituted 2a was
produced almost exclusively, whereas in CH3CN or DMSO
the predominant product was the para-substituted isomer
3a (see Table 1).
The reaction of substituted nitrosobenzenes was also in-
vestigated. o-Nitronitrosobenzene (1b, Scheme 1) was found
to react much faster than nitrosobenzene. In CH3CN, this
reaction reached completion within 2 h at room tempera-
ture. The ortho-substituted isomer 2b was the principal
product. The product of nitro-group displacement, i.e. 2a,
was not observed.
The introduction of a nitro group on the aromatic ring
has contrasting influences on the stabilities of ortho- and
para-nitrosoanilines. Whereas the ortho compound 2b be-
comes more stable and can be stored at room temperature
for a long time, the stability of the para product 3b de-
creases. It could be separated from the other isomer by
chromatography, but partly decomposed to give a tar on
concentrating the solution. Its structure was confirmed so-
lely on the basis of mass-spectrometric data.
Scheme 2
The reaction of tert-butylamine with nitrosobenzene can
be considered as an oxidative nucleophilic substitution of
hydrogen,[6] involving nucleophilic attack of tBuNH2 at the
ortho position of nitrosobenzene to give first the σH adduct
6a and then the oxime 6b. This oxime is subsequently
oxidized by a second molecule of nitrosobenzene to yield
2a and phenylhydroxylamine. The latter, in turn, couples
with nitrosobenzene to afford azoxybenzene (4a). One can
envisage the para-substituted compound 3a being formed in
a similar way.
The azoxy compound 4b formed in this reaction was
found to be 2-hydroxy-2Ј-nitroazoxybenzene. This com-
pound was shown by Bamberger et al.[8] to be the normal
product of condensation of o-nitrophenylhydroxylamine
with o-nitronitrosobenzene. Interpretation of NMR data
(see Experimental Section) showed the hydroxy group in 4b
to be located on the ring, and connected with the N-oxide
nitrogen atom of the azoxy group.
The important aspect of the reaction under investigation
is the regioselectivity of the nucleophilic attack at the ortho
versus the para position relative to the nitroso group. The
directing effect of the NO2 group at the ortho position is
usually accounted for in terms of intramolecular hydrogen
Scheme 3
We suggest that the transformation of oxime 6b into the bonding in the zwitterionic σ adduct.[6c] The same expla-
nitroso compound 2a could proceed in two stages, the first nation could be invoked to account for the predominant
being the tautomerization of oxime 6b to give intermediate formation of the ortho-substituted compound 2b from ni-
hydroxylamine 6c, and the second being the oxidation of 6c tronitrosobenzene 1b. However, in the case of nitrosoben-
to nitroso compound 2a. If this is the case, the rearomatiz- zene 1a, the para-substituted isomer 3a was predominant
ation step should be the result of proton transfer in the when the reaction was carried out in the same solvent.
6b Ǟ 6c tautomerization, in contrast to well-known SNArH Thus, it is apparent that the problem of regiospecificity in
reactions in the nitroaromatic series, where the rearomati- the nitrosobenzene series is rather complicated and a
zation step is the result of an oxidation process.[6a,6b]
The reason why tBuNH2 does not attack the nitrogen quired.
thorough investigation of the reaction mechanism is re-
atom of the nitroso group to give azo compounds is not
p-Nitronitrosobenzene (1c) underwent coupling with
quite clear. It is noteworthy that the Mg salt of tert-bu- tBuNH2 to afford the ortho-substituted compound 2c. The
tylamine reacts readily with the nitroso group of ni- product of para substitution, i.e. 3a, which might have re-
trosobenzene to afford an azo compound.[7]
sulted from a nucleophilic displacement of nitro group, was
The rate of the reaction of tBuNH2 with nitrosobenzene not detected.
depends strongly on the solvent used. The reaction proceeds
When 2,4-dibromonitrosobenzene (1d) was treated with
much faster in DMSO than in CH3CN. In non-polar sol- tBuNH2, substitution of hydrogen took place, but not the
vents (benzene) and in hydroxy solvents (EtOH) it does not displacement of a bromine atom. The latter reaction did,
take place at all. It should be noted that the reaction only however, occur with 2,4,6-tribromonitrosobenzene (7),
reaches completion when excess tBuNH2 is used. In our albeit much more slowly (Scheme 5). It is noteworthy that
experiments we used a threefold excess of tBuNH2. In this the NϭO group also remained intact in this reaction. Both
connection, it seems plausible that stages of the reaction reactions yielded the same ortho-substituted compound 2d.
mechanism 1a Ǟ 6a Ǟ 6b (Scheme 3) are reversible and
In conclusion, it can be stated that substitution of the
that the transformation 6b Ǟ 6c is a base-catalyzed process. ring hydrogen atom (SNArH reaction) is preferred to the
30
Eur. J. Org. Chem. 1999, 29Ϫ35

Reaction of tert-Alkylamines with Nitrosobenzenes
Table 1. Reaction of nitroso compounds 1aϪd and 2c with tert-butylamine (CH3CN as solvent, unless stated otherwise)
FULL PAPER
No.
Substrate
Temp. [°C]
Time [h]
Oxidant
Products (yield,%)
1
1a
1a
1a
1b
1b
1b
1c
1c
1c
1c
1c
1c
1d
2c
2c
20
20
20
20
20
20
40
20
20
40
20
60
45
40
20
144
50
29
4
0.5
1.7
1.2
2.5
1.4
0.5
72
5
Ϫ
Ϫ
Ϫ
Ϫ
2a (6)
3a (17)
4a (39)
4a (62)
4a (50)
4b (60)
4b (19)
4b (14)
4c (34)
4c (< 5)
4c (< 5)
4c (< 5)
Ϫ
2[a]
3[b]
4
2a (10)
2a (27)
2b (26)
2b (55)
2b (13)
2c (27)
2c (70)
2c (92)
2c (74)
8a (10)
8a (81)
2d (29)
8a (23)
8a (55)
3a (22)
3a (< 1)
3b (6)[c]
5
MnO2
DMAAD
Ϫ
MnO2
DMAAD
NBS
Ϫ
MnO2
Ϫ
Ϫ
3b (11)[c]
6
3b (5)[c]
7
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
8
9
10
11
12
13
14
15
Ϫ
4d (36)
Ϫ
1
1.3
23
DMAAD
Ϫ
[a] DMSO as solvent. Ϫ [b] The reaction was carried out without solvent. Ϫ [c] A tentative yield of 3b as it decomposed on concentrating
the solution.
2c became almost quantitative when the bis(N,N-dimeth-
ylamide) of azodicarboxylic acid (DMAAD) was used
(Table 1). It was used in analogy to diethyl azodicarb-
oxylate, which is known to oxidize hydroxylamines to ni-
troso compounds, but could not be used here as it reacts
with tBuNH2. The use of MnO2 or N-bromosuccinimide
resulted in good yields of 2c. The bromination of tBuNH2
with NBS is very fast, hence the actual oxidant of the inter-
mediate hydroxylamine is likely to be N-bromo-tert-bu-
tylamine.
o-(tert-Butylamino)-substituted nitrosobenzene 2c, bear-
ing the strongly electron-withdrawing nitro group in the
para position, underwent further displacement of hydrogen
with excess tBuNH2 to afford the diamine 8a (Scheme 6).
It was obtained in 10% yield directly from p-nitronitrosob-
enzene (1c), and in 81% yield using MnO2 (Table 1).
Scheme 4
Scheme 5
substitution of nucleofugal groups, e.g. NO2 and Br (SNAr
reaction), in the nitrosobenzene series. This observation is
consistent with MakoszaЈs generalization,[6d] that inter-
mediate σH adducts are formed more rapidly than σX ad-
ducts. It should be noted that nucleophilic substitution in
nitronitrosobenzenes 1b,c takes place ortho to the nitroso
Scheme 6
We extended this reaction to another primary amine of
and not ortho to the nitro group. This regiospecificity can similar structure, namely 1-adamantylamine. In DMSO as
be attributed to the high stability of intermediate oximes of solvent, the reaction of 1c proceeded in the expected man-
the type 6b (see Scheme 3).
ner, to give ortho-substituted compound 2e in 29% yield. As
To increase the yield of N-(tert-butyl)nitrosoanilines, the already mentioned, a high base concentration in the reac-
reaction of nitrosobenzenes with tBuNH2 was carried out tion medium is necessary for the reaction to proceed
in the presence of an oxidant. The results are summarized rapidly. As the solubility of 1-adamantylamine is limited,
in Table 1. The yield of 2b increased to a maximum (55%) pyridine was added to accelerate the reaction (see Table 2).
when MnO2 was employed, while that of azoxy compound
The disubstituted compound 8b was successfully ob-
4b decreased to 19% under these conditions. The yield of tained from 2e when MnO2 was used as an oxidant. This
Eur. J. Org. Chem. 1999, 29Ϫ35
31

D. L. Lipilin, A. M. Churakov, S. L. Ioffe, Y. A. Strelenko, V. A. Tartakovsky
FULL PAPER
Table 2. Reaction of nitroso compounds 1c and 2e with 1-adaman-
tylamine (DMSO as solvent)
Table 3. 13C-NMR chemical shifts[a] (δ values, calculated δ in
parentheses) of 2aϪe and 8aϪb in CDCl3 at 297 K (*dynamic
broadening is observed)
No. Substrate Temp. [°C] Time [h] Oxidant Products (yield,%)
2a[b,c]
2b
2c[d] 2d
2e[e]
8a[f]
8b[g]
1
2
1c
1c
40
40
40
60
60
5.5
2.5
2
Ϫ
MnO2
Ϫ
MnO2
MnO2
2e (29) 4c (54)
2e (65) 4c (15)
2e (26) 4c (55)
C-1 135.1 (128.0) 134.5 133.2* 136.0 134.3* 137.4 137.5
C-2 156.7 (158.7) 146.3 154.8 151.0 155.2 146.2 146.1
C-3 141.4 (141.8) 157.4 144.3* 138.8 141.8* 153.1 152.7
C-4 115.7 (114.1) 108.8 109.1 123.4 109.0 91.2 91.6
C-5 137.2 (133.3) 136.7 150.3 132.7 150.7 155.4 155.0
C-6 116.2 (110.6) 120.8 113.5 119.3 114.2 94.4 94.9
3[a] 1c
4[a] 1c
5
8
8b (59)
8b (38)
Ϫ
2e
15
Ϫ
[a] The reaction was carried out in the presence of a 10-mol excess
of pyridine.
Me
29.1
28.4 29.2 29.5
29.49,
29.53
52.0,
52.3
CMe3 51.3
52.4 52.0 52.0
compound could also be obtained in 59% yield starting
from 1c. Addition of pyridine also accelerated this reaction [a] Assignments were made using the following procedures: 2D CH
COSY (for 2a), proton-coupled spectroscopy (for 2d and 8a), selec-
(see Table 2).
tive proton decoupling (for 2aϪe), NOESY (for 2a,b and 8a), selec-
tive polarization transfer (for 2bϪd and 8a), APT (for 8a,b) . Ϫ
[b] The spectra were obtained at 243 K (the signals of C-1 and C-3
are broadened at 297 K). Ϫ [c] The calculations were based on the
NMR Study of ortho-Nitrosoanilines
chemical shifts of N,N-dimethyl-para-nitrosoaniline 9[11] (CDCl3,
at 213 K): δ ϭ 110.63 (C-2 and C-6), 109.74 (C-3), 142.06 (C-5),
The structures of the compounds under investigation
155.20 (C-1), 162.59 (C-4). Ϫ [d] The spectra were obtained at 243
[e]
were confirmed by NMR spectrometry. All resonances in K. Ϫ For the adamantyl group of 2e: δ ϭ 29.35, 35.99, 42.11,
53.14. Ϫ [f] At 333 K, signals due to C-1 and C-3 were not observed
the 1H- and 13C-NMR spectra were unambiguously as-
[g]
owing to broadening. Ϫ
For the adamantyl group of 8b: δ ϭ
signed with the help of special procedures, including
NOESY and CH COSY (see notes to Table 3). Some of the
nitrosoanilines were also studied by 14N- and 15N-NMR
spectroscopy. The 14N-NMR spectrum of 2a showed a
broad signal due to the nitroso group at δ ϭ 397, and an
amino group signal at δ ϭ Ϫ284, both of which are typical
for these groups.[9] The 14N signal of the nitroso group in
2b was unobservably broad, but was clearly detected in the
15N-NMR spectrum at δ ϭ 375.3. The 15N signal of the
NHϪtBu group was readily detected by polarization trans-
fer from the NϪH proton to the 15N nucleus. The values of
29.40, 29.57, 36.25, 36.12, 42.15, 42.17, 53.11, 53.26.
Scheme 6
the coupling constants 1J(1H,15N) in 2aϪd decreased in the place, while at low temperatures all signals are sharp indi-
range 90Ϫ95 Hz, which is typical for amines.[9] This dem- cating the presence of only one rotamer in the solution. In
onstrates that these compounds are indeed the nitroso com- 2b,d, as well as in 8a,b, all the signals are well-resolved even
pounds, and not the quinone oxime isomers.
at room temperature.
The 13C-NMR data of nitrosoanilines listed in Table 3
The 13C-chemical shifts of ortho-nitrosoanilines were esti-
merit some comments. It has previously been reported that mated using additivity rules.[12] The shifts of 9 were taken
in nitrosobenzenes bearing an ortho substituent (e.g. as a basis for the calculations. As an illustration, the calcu-
[4b]
CH3
or NO2[10]), the rotamer having the NϭO group lated data for 2a are given in Table 3. Although this method
anti to the substituent is favored because of steric effects. In is not particularly precise, we can unambiguously state that
our case, two rotamers A and B can a priori be envisaged, in all the ortho-nitrosoanilines investigated, the NϭO group
in which the NϭO group is arranged syn to the amino is syn to the amino group, as in rotamer A. This rotamer is
group as in A, or anti as in B. These rotamers would give presumably favored because of intramolecular hydrogen
rise to discrete sets of 13C-NMR signals, where the shifts of bonding.
carbon atoms C-1 and C-3 ortho to the NϭO group would
The unusually low-field signal in the range δ ϭ 11Ϫ12 in
1
differ most markedly because of the large anisotropy of this the H-NMR spectra of 2aϪe can be assigned to the NH
function. For example, N,N-dimethyl-p-nitrosoaniline (9), in proton chelated by the NϭO group. The disubstituted com-
which rotation of the NϭO group is completely restricted pounds 8a,b showed two signals due to NH protons at δ ϭ
at low temperatures on the NMR timescale, exhibits a 12.8 and at δ ϭ 7.7. The former signal can be assigned to
chemical-shift difference of ca. 30 ppm between C-3 and the chelated NH proton. Selective polarization transfer
C-5.[11]
from these protons allowed the assignment of the C-4 and
1
The H- and 13C-NMR spectra of ortho-nitrosoanilines C-6 signals in 8a,b. The dynamic broadening at elevated
lacking a substituent at the 3-position (2a,c,e) are tempera- temperatures was taken into consideration in assigning the
ture-dependent (see notes to Table 3). At room temperature, C-1 and C-3 signals.
the C-1 and C-3 signals, as well as the 3-H signal are broad-
In conclusion, it should be noted that the synthesis of N-
ened, indicating that rotation of the NϭO group takes substituted ortho-nitrosoanilines is rather problematic.[1b,13]
32
Eur. J. Org. Chem. 1999, 29Ϫ35

Reaction of tert-Alkylamines with Nitrosobenzenes
FULL PAPER
products were separated as described above to give 2a (150 mg), 3a
(5 mg) and 4a (140 mg).
Only a few examples of this class of compounds are
known.[14] The described reactions could offer a new access
to compounds of this type.
Reaction of o-Nitronitrosobenzene (1b) with tert-Butylamine:
tBuNH2 (0.2 mL, 2.75 mmol) was added to a stirred solution of
1b (0.49 mg, 3.25 mmol) in acetonitrile (2 mL). After the reaction
was complete (see Table 1), the solvent was removed in vacuo, and
the residue was passed through a short column of silica gel, eluting
with benzene. The eluate was concentrated to dryness and the solid
residue was extracted with hexane. The residue after extraction was
identified as 4b (280 mg). The solvent was removed from the hexane
solution and the residue was chromatographed (silica gel, eluent
benzene) to yield 2b (187 mg) and 3b (43 mg).
Experimental Section
General: Melting points are uncorrected. o-Nitronitrosobenzene,[8]
p-nitronitrosobenzene,[15] 2,4-dibromonitrosobenzene,[16] 2,4,6-tri-
bromonitrosobenzene,[17]
mercury(II)
trifluoroacetate,[18]
MnO2,[19] and bis(N,N-dimethylamide) of azodicarboxylic acid
(DMAAD)[20] were prepared according to published procedures.
All other reagents were purchased from commercial sources. Ϫ
NMR spectra were recorded with a Bruker AM 300 instrument at
298 K unless otherwise stated; chemical shifts are δ values down-
field from internal TMS (1H, 13C) or external CH3NO2 (14N, 15N).
Ϫ Mass-spectral data were obtained at 70 eV by electron impact.
N-tert-Butyl-3-nitro-2-nitrosoaniline (2b): Black crystals, m.p.
108Ϫ112°C (hexane). Ϫ IR (KBr): ν˜ ϭ 1370 cmϪ1, 1550 (NO2). Ϫ
UV (CH3OH): λmax (lg ε) ϭ 215 nm (4.55), 228 (4.77), 300 (4.15),
1
465 (4.24). Ϫ H NMR (CDCl3): δ ϭ 1.49 (s, 9 H, tBu), 6.98 (d, 1
H, J ϭ 7.2 Hz, 6-H), 7.30 (d, 1 H, J ϭ 9.2 Hz, 4-H), 7.45 (dd, 1
H, J ϭ 9.2, 7.2 Hz, 5-H), 11.9 (s, 1 H, NH). Ϫ 14N NMR (CDCl3):
δ ϭ Ϫ276 (∆ν1/2 ϭ 900 Hz, NH), Ϫ9 (∆ν1/2 ϭ 200 Hz, NO2). Ϫ
15N NMR (CDCl3): δ ϭ Ϫ277.4 (NH), Ϫ9.2 (NO2), 375.3 (NO).
Reaction of Nitrosobenzene (1a) with tert-Butylamine
(A) In Acetonitrile: tBuNH2 (0.2 mL, 9.75 mmol) was added to a
stirred solution of 1a (0.35 g, 3.25 mmol) in CH3CN (2 mL). After
the reaction was complete (Table 1), the solvent was removed in
vacuo, the residue was dissolved in diethyl ether (20 mL), and the
resulting solution was extracted with 50 mL of 5% aqueous hydro-
chloric acid. The ethereal extract was dried (MgSO4) and the sol-
vent was removed in vacuo. The residue was crystallized to give
azoxybenzene (4a) (125 mg), m.p. 35Ϫ37°C (benzene), identical
with an authentic sample. The aqueous acidic solution was partly
neutralized with 5.6 g of Na2CO3 and then extracted with diethyl
ether. The solvent was removed in vacuo from the organic phase
and the residual oil was chromatographed (silica gel, eluent ben-
zene/diethyl ether, 5:1) to yield 2a (75 mg) and 3a (5 mg). The
remaining aqueous acidic solution was then completely neutralized
with Na2CO3 and extracted with further diethyl ether to give, after
chromatographic separation, additional portions of 2a (10 mg) and
3a (30 mg).
Ϫ
15N NMR, INEPT (CDCl3): δ ϭ Ϫ277 (J ϭ 91.4 Hz, NH). Ϫ
MS (70 eV); m/z: 223 [Mϩ]. Ϫ C10H13N3O3 (223.2): calcd. C 53.81,
H 5.87, N 18.82; found C 54.04, H 5.44, N 18.92.
N-tert-Butyl-3-nitro-4-nitrosoaniline (3b): The eluate from the afore-
mentioned chromatographic separation was concentrated to a small
volume at 0°C, CCl4 was added, and the resulting solution was
analyzed by mass spectrometry. Ϫ MS (70 eV); m/z: 223 [Mϩ].
1-(2-Hydroxyphenyl)-2-(2Ј-nitrophenyl)diazene 1-Oxide (4b): Bright-
yellow crystals, m.p. 46.5Ϫ48.5°C (benzene) (ref.[8] m.p. 48Ϫ49°C).
1
Ϫ IR (KBr): ν˜ ϭ 1360 cmϪ1, 1520 (NO2). Ϫ H NMR (CDCl3):
δ ϭ 6.93 (dd, 1 H, J ϭ 8.5, 7.2 Hz, 5-H), 7.08 (d, 1 H, J ϭ 8.4 Hz,
3-H), 7.44 (dd, 1 H, J ϭ 8.4, 7.2 Hz, 4-H), 7.46 (dd, 1 H, J ϭ 7.3,
8.2 Hz, 4Ј-H), 7.60 (d, 1 H, J ϭ 8.0 Hz, 6Ј-H), 7.66 (dd, 1 H, J ϭ
7.3, 8.0 Hz, 5Ј-H), 8.05 (d, 1 H, J ϭ 8.2 Hz, 3Ј-H), 8.12 (d, 1 H,
J ϭ 8.5 Hz, 6-H), 11.22 (s, 1 H, OH). Ϫ 13C NMR (CDCl3): δ ϭ
119.5 (C-3), 119.7 (C-5), 123.9 (C-6), 124.99 (C-3Ј), 125.02 (C-6Ј),
128.8 (C-4Ј), 131.6 (C-1), 134.0 (C-5Ј), 135.0 (C-4), 136.1 (C-1Ј),
143.0 (C-2Ј), 153.5 (C-2); the assignment was made with the aid of
13C{14N, 1H} NMR spectra, CH and HH COSY, and the APT
procedure. Ϫ 14N NMR (CDCl3): δ ϭ Ϫ47 [∆ν1/2 ϭ 280 Hz,
N(O)ϭ], Ϫ12 (∆ν1/2 ϭ 220 Hz, NO2). Ϫ MS (70 eV); m/z: 259 (100)
[Mϩ], 258 (90), 243 (30). Ϫ C12H9N3O4 (259.1): calcd. C 55.60, H
3.50, N 16.21; found C 55.39, H 3.87, N 16.15.
N-tert-Butyl-2-nitrosobenzene (2a): Brown crystals, m.p. 39Ϫ41°C
(pentane). Ϫ UV (CH3OH): λmax (lg ε) ϭ 228 nm (4.35), 302 (3.99),
472 (3.79). Ϫ 1H NMR (CDCl3, 243 K): δ ϭ 1.46 (s, 9 H, tBu),
6.88 (dd, J ϭ 7.5, 7.3 Hz, 1 H, 4-H), 7.05 (d, 1 H, J ϭ 8.9 Hz, 6-
H), 7.34 (ddd, J ϭ 8.9, 7.5, 1.7 Hz, 1 H, 5-H), 8.59 (d, J ϭ 7.3 Hz,
1 H, 3-H), 12.05 (s, 1 H, NH); at 298 K the signal of 3-H is broad-
ened. Ϫ 14N NMR (CDCl3, 323 K): δ ϭ Ϫ284 (∆ν1/2 ϭ 750 Hz,
NH), 397 (∆ν1/2 ϭ 2000 Hz, NϭO). Ϫ 15N NMR, INEPT (CDCl3):
δ ϭ Ϫ282.5 (J ϭ 94.7 Hz, NH). Ϫ MS (70 eV); m/z: 178 [Mϩ]. Ϫ
C10H14N2O (178.2): calcd. C 67.38, H 7.92, N 15.72; found C
67.77, H 7.39, N 15.81.
Reaction of p-Nitronitrosobenzene (1c) with tert-Butylamine: The
coupling of tBuNH2 with 1c was carried out according to the above
procedure to afford 2c (see Table 1) and bis(4-nitrophenyl)diazene
N-oxide 4c, m.p. 199Ϫ200°C (ref.[8] m.p. 200°C), identical to an
authentic sample.
N-tert-Butyl-4-nitrosoaniline (3a): Deep-yellow oil. Ϫ 1H NMR
([D6]DMSO, 403 K): δ ϭ 1.40 (s, 9 H), 6.77 (d, 2 H, J ϭ 8.2 Hz),
7.59 (d, 2 H, J ϭ 8.2 Hz); at 298 K all the signals are broadened.
N-tert-Butyl-5-nitro-2-nitrosoaniline (2c): Red crystals, m.p.
69Ϫ72°C. Ϫ IR (KBr): ν˜ ϭ 1340 cmϪ1, 1540 (NO2). Ϫ UV
(CH3OH): λmax (lg ε) ϭ 222 nm (4.23), 247 (4.24), 300 (4.07), 495
(3.84). Ϫ 1H NMR (CDCl3): δ ϭ 1.54 (s, 9 H, tBu), 7.61 (dd, 1 H,
J ϭ 9.1, 2.1 Hz, 4-H), 7.96 (d, 1 H, J ϭ 2.1 Hz, 6-H), 8.86 (d, 1
H, J ϭ 9.1 Hz, 3-H), 11. 0 (s, 1 H). Ϫ 14N NMR (CDCl3): δ ϭ
Ϫ285 (∆ν1/2 ϭ 600 Hz, NH), Ϫ14 (∆ν1/2 ϭ 160 Hz, NO2). Ϫ 15N
NMR, INEPT (CDCl3): δ ϭ Ϫ282.6 (J ϭ 91.1 Hz, NH). Ϫ MS
(70 eV); m/z 223 [Mϩ]. Ϫ C10H13N3O3 (223.2): calcd. C 53.81, H
5.87, N 18.82; found C 53.56, H 6.29, N 18.74.
Ϫ
13C NMR ([D6]DMSO, 403 K): δ ϭ 28.4, 50.8, 112.0 (broadened
at 298 K), 124.2 (not detected at 298 K due to broadening), 154.1,
162.6. Ϫ MS (70 eV); m/z: 178 [Mϩ].
(B) In DMSO: tBuNH2 (0.2 mL, 9.75 mmol) was added to a stirred
solution of nitrosobenzene (1a) (0.35 g, 3.25 mmol) in DMSO (1
mL). After the reaction was complete (see Table 1), the reaction
mixture was poured into water (10 mL) and extracted with diethyl
ether. The products were separated as described above to give 2a
(58 mg), 3a (128 mg) and 4a (200 mg).
(C) Without Solvent: Nitrosobenzene (1a, 0.3 g, 3.25 mmol) was Reaction of 2,4-Dibromonitrosobenzene (1d) with tert-Butylamine:
added to stirred tBuNH2 (5 mL). After the reaction was complete Excess tBuNH2 was added to a solution of 1d (0.5 g, 1.8 mmol) in
(see Table 1), the excess tBuNH2 was removed in vacuo and the
CH3CN (4 mL). The mixture was heated under reflux until the
Eur. J. Org. Chem. 1999, 29Ϫ35
33

D. L. Lipilin, A. M. Churakov, S. L. Ioffe, Y. A. Strelenko, V. A. Tartakovsky
reaction was complete (see Table 1). The solvent was then com- filtered off, the filtrate was concentrated in vacuo, and the residue
FULL PAPER
pletely evaporated in vacuo and the residue was chromatographed
was chromatographed on silica gel (see Table 1).
(silica gel, eluent benzene) to yield 2d (184 mg) and 4d (175 mg).
N-tert-Butyl-4-nitroaniline (5): A 0.5  solution of mCPBA in
CH2Cl2 (1 mL) was added dropwise to a stirred solution of 3a (89
mg, 0.5 mmol) in CH2Cl2 (2 mL). After 2 min, the reaction mixture
was carefully shaken with concentrated Na2CO3 solution until the
evolution of CO2 subsided. The organic layer was then separated
and dried (MgSO4). The solvent was evaporated to leave 5 as a
yellow solid (93 mg, 95%), m.p. 70Ϫ72°C (hexane, ref.[21] m.p.
3,5-Dibromo-N-tert-butyl-2-nitrosoaniline (2d): Brown crystals, m.p.
123Ϫ125°C. Ϫ UV (CH3OH): λmax (lg ε) ϭ 216 nm (4.31), 237
1
(4.32), 330 (4.11), 460 (3.84). Ϫ H NMR (CDCl3): δ ϭ 1.47 (s, 9
H, tBu), 7.22 (d, 1 H, J ϭ 1.7 Hz, 6-H), 7.31 (d, 1 H, J ϭ 1.7 Hz,
4-H), 12.23 (s, 1 H, NH). Ϫ 15N NMR, INEPT (CDCl3): δ ϭ
Ϫ281.8 (J ϭ 90.0 Hz, NH). Ϫ MS (70 eV); m/z: 338, 336, 334
(1:2:1) [Mϩ]. Ϫ C10H12N2OBr2 (336.0): calcd. C 35.74, H 3.60, N
8.34, Br 47.56; found C 35.64, H 3.89, N 8.30, Br 47.72.
1
71.1Ϫ71.6°C). Ϫ H NMR (CDCl3): δ ϭ 1.42 (s, 9 H), 6.62 (d, 2
H), 8.02 (d, 2 H).
N,NЈ-Di-tert-butyl-4-nitro-2-nitroso-1,3-phenylenediamine (8a): The
reaction of 2c with tBuNH2 in CH3CN was carried out as described
for the reaction of 1b. After the reaction was complete (see Table
1), the solvent was removed in vacuo, and the residue was passed
through a short column of silica gel, eluting with benzene. Diamine
8a was obtained as deep-blue crystals, m.p. 141Ϫ144°C (hexane).
Ϫ IR (KBr): ν˜ ϭ 1320 cmϪ1, 1540 (NO2). Ϫ UV (CH3OH):
λmax (lg ε) ϭ 214 nm (4.59), 244 (4.52), 275 (3.79), 410 (3.81), 600
(3.86). Ϫ UV (pentane): λmax ϭ 276 nm, 400, 560. Ϫ 1H NMR
(CDCl3): δ ϭ 1.46 [s, 9 H, tBu (C-1)], 1.52 [s, 9 H, tBu (C-3)], 6.75
(s, 2 H, Ar), 7.77 [s, 1 H, NH (C-3)], 12.79 [s, NH (C-1)]. Ϫ 14N
Bis(2,4-dibromophenyl)diazene N-Oxide (4d): Colorless crystals,
m.p. 149Ϫ150°C (benzene). Ϫ 1H NMR ([D6]DMSO): δ ϭ 7.79
(dd, 1 H, J ϭ 8.7, 2.1 Hz), 7.89 (AB system, 2 H), 7.93 (d, 1 H,
J ϭ 8.7 Hz), 8.11 (d, 1 H, J ϭ 2.1 Hz), 8.21 (d, 1 H, J ϭ 1.7 Hz).
Ϫ
13C NMR ([D6]DMSO): δ ϭ 115.3, 119.6, 122.0, 124.30, 124.6,
126.6, 131.2, 132.0, 135.3, 135.9, 140.7, 147.5. Ϫ 14N NMR
([D6]DMSO): δ ϭ Ϫ51 [J ϭ 270 Hz, N(O)ϭ]. Ϫ MS (70 eV); m/z:
518, 516, 514, 512, 510 (1:4:6:4:1) [Mϩ]. Ϫ C12H6Br4N2O (513.8):
calcd. C 28.05, H 1.18, Br 62.21, N 5.45; found C 28.16, H 1.22,
Br 62.45, N 5.47.
2d from 7: tert-Butylamine (7.5 mL, 65 mmol) was added to a
stirred solution of 2,4,6-tribromonitrosobenzene 7 (1.72 g, 5 mmol)
in CH3CN (65 mL). After 16 h at room temperature, the reaction
mixture was heated for an additional 10 min at 70°C. After cooling,
the solvent was removed in vacuo, the residue was washed with
15% aqueous hydrochloric acid, and chromatographed (silica gel,
eluent benzene) to yield 1.45 g (85%) of 2d, identical to the sample
obtained above.
NMR (CDCl3): δ ϭ Ϫ285 (∆ν1/2 ϭ 950 Hz, NH), Ϫ12 (∆ν1/2
ϭ
200 Hz, NO2). Ϫ MS (70 eV); m/z: 294 [Mϩ]. Ϫ C14H22N4O3
(294.6): calcd. C 57.13, H 7.53, N 19.03; found C 57.32, H 7.22,
N 19.10.
N,NЈ-Bis(1-adamantyl)-4-nitro-2-nitroso-1,3-phenylenediamine (8b):
1-Adamantylamine (60 mg, 0.4 mmol) and pyridine (0.2 mL, 2.68
mmol) were added to a stirred solution of 1c (20 mg, 0.134 mmol)
in DMSO (7 mL) in the presence of MnO2 (40 mg, 0.268 mmol).
After the reaction was complete (see Table 2), the DMSO solution
was poured into water (50 mL) and the resulting mixture was ex-
tracted with diethyl ether. The combined ethereal extracts were
dried (MgSO4) and the solvent was removed in vacuo. The residue
was chromatographed (silica gel, eluent benzene) to yield 8b (35
mg, 59%) as deep-blue crystals, m.p. 215Ϫ217°C (decomp.). Ϫ IR
(KBr): ν˜ ϭ 1330 cmϪ1, 1540 (NO2). Ϫ 1H NMR (CDCl3): δ ϭ
1.75 (s, 6 H), 1.77 (s, 6 H), 2.09 (s, 6 H), 2.15 (s, 6 H), 2.20 (br. s,
6 H), 6.82 (s, 2 H), 7.67 (s, 1 H, NH), 12.75 (s, 1 H, NH). Ϫ 14N
NMR (CDCl3): δ ϭ Ϫ17.30 (∆ν1/2 ϭ 200 Hz). Ϫ MS (70 eV); m/z:
450 [Mϩ]. Ϫ C26H34N4O3 (450.3): calcd. C 69.31, H 7.61, N 12.43;
found C 69.46, H 7.51, N 12.36.
Reaction of para-Nitronitrosobenzene (1c) with 1-Adamantylamine
in DMSO: 1-Adamantylamine (210 mg, 1.4 mmol) was added to a
stirred solution of 1c (90 mg, 0.6 mmol) in DMSO (30 mL). After
the reaction was complete (see Table 2), the DMSO solution was
poured into water (200 mL) and the resulting mixture was extracted
with diethyl ether. The combined ethereal extracts were dried
(MgSO4) and the solvent was removed in vacuo. The residue was
chromatographed (silica gel, eluent benzene) to yield 2e (52 mg)
and 4c (46 mg).
N-(1-Adamantyl)-5-nitro-2-nitrosoaniline (2e): Bright-red crystals,
m.p. 173Ϫ175°C (decomp.). Ϫ IR (KBr): ν˜ ϭ 1350 cmϪ1, 1550
1
(NO2). Ϫ H NMR (CDCI3): δ ϭ 1.79 (s, 6 H), 2.11 (s, 6 H), 2.23
(s, 3 H), 7.58 (dd, 1 H, J ϭ 9.4, 2.0 Hz, 4-H), 8.06 (d, 1 H, J ϭ
2.0 Hz, 6-H), 8.82 (d, 1 H, J ϭ 9.4 Hz, 3-H), 10.90 (s, 1 H, NH).
8b from 2e: 1-Adamantylamine (100 mg, 0.5 mmol) and MnO2 (30
mg, 0.34 mmol) were added to a stirred solution of 2e (50 mg, 0.17
mmol) in DMSO (17 mL). After the reaction was complete (see
Table 2), work-up was carried out as described above to give 8b
(29 mg).
Ϫ
14N NMR (CDCl3): δ ϭ Ϫ14 (∆ν1/2 ϭ 220 Hz, NO2). Ϫ MS (70
eV); m/z: 301 [Mϩ]. Ϫ C16H19N3O3 (301.3): calcd. C 63.77, H 6.36,
N 13.94; found C 63.56, H 6.67, N 13.87.
Reaction of 1c in the Presence of MnO2: This reaction of 1c with
1-adamantylamine was carried out as described above, but in the
presence of MnO2 (100 mg, 1.2 mmol, prepared from KMnO4 and
MnSO4 in H2SO4 and dried at 120°C,[19] see Table 2).
Acknowledgments
D. L., a student of Higher Chemical College, thanks the Inter-
national Soros Science Education Program (Grant s97-1626) for
financial support.
Reaction of 1c in the Presence of MnO2 and Pyridine: This reaction
of 1c with 1-adamantylamine was carried out as described above,
but in the presence of pyridine (0.45 mL, 4.65 mmol, see Table 2).
Reaction of 1a؊c and 2c with tert-Butylamine in the Presence of
an Oxidant
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34
Eur. J. Org. Chem. 1999, 29Ϫ35

Reaction of tert-Alkylamines with Nitrosobenzenes
FULL PAPER
[3]
[10]
[11]
The maximum calculated yield based on nitrosobenzene is
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33.3% for 2a or 3a and 66.7% for 4a.
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[4b]
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[O98251]
Eur. J. Org. Chem. 1999, 29Ϫ35
35