Cyanomethylamines and azidomethylamines: new general methods of the synthesis and transformations

Article abstract of DOI:10.1016/j.mencom.2009.09.018

Simple and efficient methods have been developed to obtain cyanomethylamines and azidomethylamines using reactions of methoxymethylamines with TMSCN and TMSN₃, respectively. In the case of dimethylformamide dimethylacetal, only one MeO group wa

Full text of DOI:10.1016/j.mencom.2009.09.018

Mendeleev
Communications
Mendeleev Commun., 2009, 19, 281–283
Cyanomethylamines and azidomethylamines: new general
methods of the synthesis and transformations†
Orudzh G. Nabiev, Zargalam O. Nabizade and Remir G. Kostyanovsky*
N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 495 651 2191; e-mail: kost@chph.ras.ru
DOI: 10.1016/j.mencom.2009.09.018
Simple and efficient methods have been developed to obtain cyanomethylamines and azidomethylamines using reactions of
methoxymethylamines with TMSCN and TMSN3, respectively. In the case of dimethylformamide dimethylacetal, only one MeO
group was substituted with CN, and an unexpected direction of the subsequent azidation was found. Adducts of azidomethylamines
with DMAD were studied, and the base-catalyzed isomerization of symmetric triazoles into non-symmetric ones was revealed.
Long-time investigations in the chemistry of cyanomethyl-
amines1(b),2 and azidomethylamines3 provided a number of
useful reagents, synthons and valuable materials (including
energetics).
The idea of this work is to use commercial reagents TMSCN
and TMSN3 both of which have strong nucleophile groups,
CN and N3, in order to synthesize cyanomethylamines 2 and
azidomethylamines 3, respectively, by aminomethylation with
alkoxymethylamines 1 (Scheme 1).
undergoes spontaneous fragmentation like unstable methoxyazide.
Thus, despite expectations, azidation of 5 results in the substi-
tution of CN group rather than MeO group, accompanied with
spontaneous fragmentation into MeN3 and DMF (Scheme 3).
Methylazide was isolated and characterized by 1H NMR spec-
trum (CDCl3) d: 3.00 (s) [cf. ref. 3(e)] and its transformation
into triazole 6 (Scheme 4).
‡
NMR spectra were measured on a Bruker WM-400 spectrometer
(400.13 MHz for 1H and 100.61 MHz for 13C), mass spectra, on a Bruker
spectrospin CMS-47 spectrometer with electrospray ionization, IR spectra,
on Perkin–Elmer RX-1000 and UV spectra, on a Specord UV/VIS spectro-
photometer.
TMSCN
TMSN3
R2NCH2CN
R2NCH2OR
R2NCH2N3
– TMSOR
– TMSOR
2
1
3
1
1a: yield 33%, bp 63 °C. H NMR (400 MHz, CDCl3) d: 2.4 (s, 6H,
Scheme 1
Me2N), 3.35 (s, 3H, MeO), 3.97 (s, 2H, NCH2O).
20
1b: yield 89%, bp 88–90 °C (1 Torr), [a]D +42.46 (c 3.02, MeOH).
Possibilities of such an approach are confirmed by the
earlier reported data on the cyanation of methoxymethylamines
with TMSCN/Et2O·BF3,1(b) syntheses of cyanomethylamines2(a)
and azidomethylamines3(a) by reactions of iminium salts with
Na and Ag cyanides and azides, as well as cyanosilylation of
aldehydes and ketones under the action of TMSCN.4 We have
accomplished the azidosilylation of bromal [in Et2O, 24 h, at
3
1H NMR (CDCl3) d: 1.4 (d, 3H, MeCH, J 6.7 Hz), 2.4 (s, 3H, MeN),
3.24 (s, 3H, MeO), 3.86 (q, 1H, HC, 3J 6.7 Hz), 4.1 (2H, OCH2N,
AB-spectrum, Δn 94.4 Hz, 2J –9.2 Hz), 7.32 (m, 5H, Ph).
1c: yield 34.5%, bp 34–36 °C (15 Torr). 1H NMR (CDCl3) d: 1.77 (tt,
4H, CCH2CH2C), 2.76 (t, 4H, CH2NCH2), 3.31 (s, 3H, MeO), 4.14 (s,
2H, NCH2O). MS, m/z: 503.1605 [M + Na]+; calc. for M+: 480.172.
1d: yield 65.5%, bp 66–67 °C (36 Torr). 1H NMR (CDCl3) d: 1.68, 1.76,
2.75 [10H, (CH2)5N], 3.30 (s, 3H, MeO), 4.12 (s, 2H, NCH2O).
1e: yield 43%, bp 96–98 °C (6 Torr). 1H NMR (CDCl3) d: 2.73 [s, 8H,
N(CH2CH2)2N], 3.3 (s, 6H, 2MeO), 4.0 (s, 4H, 2OCH2N).
1
20 °C, H NMR (CDCl3) d: 0.33 (s, 9H, Me3Si), 8.54 (s, 1H,
HC)] (Scheme 2).
1f: yield 53%, bp 81 °C (1 Torr). 1H NMR (CDCl3) d: 3.27 (s, 6H,
2MeO), 4.0 (s, 2H, CH2Ph), 4.24 (s, 4H, 2CH2O), 7.3 (m, 5H, Ph).
1g: yield 66%, bp 122–124 °C (1 Torr). 1H NMR (CDCl3) d: 1.6, 1.67,
1.78, 1.79, 2.04 (15H, Ad), 3.18 (s, 6H, MeO), 4.36 (s, 4H, NCH2O).
N3
OSiMe3
CBr3CH=O + Me3SiN3
Scheme 2
CBr3CH
1
1h: yield 54%, bp 105–107 °C (4 Torr). H NMR (CDCl3) d: 1.25 (t,
The smooth azidation of Me3N with a combination of PhIO/
3H, CMe), 3.34 (s, 3H, MeO), 3.51 (q, 2H, CH2C), 4.73 (s, 2H, NCH2O),
6.88 (m, 5H, Ph).
3(f)
TMSN3 can be explained by its oxidation to Me2NCH2OH
followed by aminomethylation of TMSN3.
1i: yield 53%, bp 86–88 °C (4 Torr). 1H NMR (CDCl3) d: 2.41 (s, 6H,
NMe2), 4.08 (s, 2H, OCH2N), 4.53 (s, 2H, OCH2O), 4.53 (s, 2H,
PhCH2), 7.34 (m, 5H, Ph).
Starting alkoxymethylamines 1‡ were prepared from the
corresponding amines and polyoxymethylene in MeOH according
to the known methods5 and used for the syntheses of cyano-
methylamines 2 and azidomethylamines 3 (Table 1).§,¶
§
General procedure. To a stirred Et2O solution of methoxymethylamine
equimolar quantity of TMSCN (CAUTION: Toxic!) was added and the
solution was left for 10–12 h at 20 °C. After evaporation of the solvent
the solid product (2e) was separated or liquid (2a,b) was distilled in a
vacuum.
+
·
Cyanomethylamines were characterized by NMR, MS (ions M
and M – CN+ are observed), and IR spectra (2020–2040 cm–1).§
Azidomethylamines were characterized by NMR, MS (ions
1
2a: bp 66–68 °C (80 Torr). H NMR (CDCl3) d: 2.35 (s, 6H, Me2N),
+
+
·
M
and M – N3 are observed), UV (245–250 nm) and IR spectra
3.49 (s, 2H, NCH2CN).
[2100–2110 cm–1, cf. ref. 3(g)].¶
2b: bp 105–107 °C (1 Torr), [a]D20 +132 (c 1.4, MeOH). 1H NMR
(CDCl3) d: 1.39 (d, 3H, MeCH, 3J 6.7 Hz), 2.4 (s, 3H, MeN), 3.46 (2H,
CH2CN, AB-spectrum, Δn 56 Hz, 2J –17.2 Hz), 3.49 (q, 1H, HC, 3J
6.7 Hz), 7.32 (m, 5H, Ph).
It was found that in the course of cyanation and azidation of
dimethylformamide dimethylacetal 4, only one MeO group is
substituted. Upon subsequent azidation, stable cyanation product 5
1
2e: mp 58–60 °C. H NMR (CDCl3) d: 2.66 [s, 8H, N(CH2CH2)2N],
†
3.54 (s, 2H, NCH2CN).
Geminal systems. Part 58. Previous communication, see ref. 1(a).
– 281 –
© 2009 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2009, 19, 281–283
Table 1 Synthesis of cyanomethylamines 2 and azidomethylamines 3 by reaction of methoxymethylamines 1 with TMSCN and TMSN3, respectively.
Products
R1R2NCH2OMe
R1R2NCH2CN (yield, %)
R1R2NCH2N3 (yield, %)
1a R1 = R2 = Me
2aa (94)
(R)-(+)-2b (94)
—
—
2e (94)
—
—
—
3ab (95)
(R)-(+)-3b (95)
3c (92)
3d (93)
(R)-(+)-1b R1 = Me, R2 = CHMePh
1c R1 + R2 = (CH2)4
1d R1 + R2 = (CH2)5
1e R1 + R2 = (CH2)2NCH2(OMe)(CH2)2
1f R1 = CH2OMe, R2 = CH2Ph
1g R1 = CH2OMe, R2 = Ad
1h R1 = Et, R2 = Ph
3e (91.5)
3f R1 = CH2N3, R2 = CH2Ph (90)
3g R1 = CH2N3, R2 = Ad (89)
3h (95)
aCompound 2a was also obtained by reaction of Me2NCH2OCH2OCH2Ph (1i) with TMSCN. bCompound 3a was also obtained by reaction of 1i with TMSN3.
DMAD
OMe
OMe
2 TMSCN
2 TMSN3
NCH2N3
NCH2Tz
Me2NCH
Et2O
– TMSOMe
3c
7
4
CN
N3
Me2NCH
Me2NCH
2 DMAD
Et2O
N3CH2N
NCH2N3
TzCH2N
NCH2Tz
OMe
OMe
5
3e
8
N3
TMSN3
Me2N CH
Me
MeONa
MeOH
– TMSCN
Tz'CH2N
NCH2Tz'
O
9
Me2NC=O + MeN3
2 DMAD
Et2O
PhCH2N(CH2N3)2
PhCH2N(CH2Tz)2
Scheme 3
3f
10
Synthetic perspectives of azidomethylamines were demon-
strated by reactions of [3 + 2] cycloaddition of 3c,e,f to dimethyl
acetylenedicarboxylate (DMAD), and the base-catalyzed rear-
rangement of symmetric triazole 8 into non-symmetric triazole 9
was found (Scheme 5).††
MeO2C
MeO2C
N
N
Tz =
N
Tz' =
N
N
N
MeO2C
MeO2C
Scheme 5
Data on the structures of 3e and 10 in crystals and 3a,c and 5
in gas phase will be published elsewhere.
This work was supported by the Russian Academy of
Sciences and the Russian Foundation for Basic Research (grant
no. 09-03-00537-a).
MeO2C
MeO2C
N
N
O
O
MeN3
+
N
References
Et2O
MeO
OMe
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Mendeleev Commun., 2007, 17, 178; (b) T. Chiba, I. Saitoh, M. Okimoto,
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DMAD
Me
6
Scheme 4
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¶
3a: bp 110 °C. 1H NMR (CDCl3) d: 2.41 (s, 6H, Me2N), 4.31 (s, 2H,
NCH2N3). 13C{1H} NMR (100.61 MHz, CDCl3) d: 41.31 (Me2N), 76.90
(NCH2N3).
3b: bp 110–112 °C (1 Torr), [a]D20 +27 (c 1.18, MeOH). 1H NMR
(CDCl3) d: 1.38 (d, 3H, MeCH, 3J 6.7 Hz), 2.42 (s, 3H, MeN), 3.75 (q,
3
1H, HC, J 6.7 Hz), 4.37 (dd, 2H, NCH2N3, AB-spectrum, Δn 88.2 Hz,
†† 5: yield 96%, bp 90–92 °C (80 Torr). 1H NMR (CDCl3) d: 2.35 (s, 6H,
Me2N), 3.38 (s, 3H, MeO), 4.56 (s, 1H, HCO). 13C{1H} NMR (CDCl3)
d: 38.86 (Me2N), 55.62 (MeO), 86.89 (CH), 113.92 (CN).
6: 1H NMR (CDCl3) d: 3.97 (s, 3H, MeO), 4.00 (s, 3H, MeO), 4.26 (s,
3H, MeN).
7: yield 93%, mp 69–70 °C. 1H NMR (CDCl3) d: 1.7, 1.73 (tt, 4H,
CCH2CH2C), 2.79, 2.82 (t, 4H, CH2NCH2), 3.97 (s, 6H, 2MeO), 5.51
(s, 2HNCH2N).
2J –8.6 Hz), 7.32 (m, 5H, Ph).
3c: bp 53–55 °C (10 Torr). 1H NMR (CDCl3) d: 1.79, 1.82 [tt, 4H,
C(CH2)2C], 2.78, 2.81 (t, 4H, CH2NCH2), 4.48 (s, 2H, NCH2N3),
13C{1H} NMR (CDCl3) d: 23.9 [C(CH2)2C], 49.07 (CH2NCH2), 71.44
(NCH2N3).
3d: bp 73–74 °C (10 Torr). 1H NMR (CDCl3) d: 1.71, 1.79, 2.79
[10H, (CH2)5N], 4.49 (s, 2H, NCH2N3).
3e: mp 109–110 °C. 1H NMR (CDCl3) d: 2.74 [s, 8H, N(CH2CH2)2N],
4.32 (s, 4H, 2NCH2N3). 13C{1H} NMR (CDCl3) d: 48.76 [s, N(CH2CH2)2N],
75.17 (s, NCH2N3). ICR (electrospray ionization) MS, m/z: 197.1266
[M + H]+; calc. for M+: 196.119.
8: yield 87%, mp 180–181 °C. 1H NMR (CDCl3) d: 2.71 [s, 8H,
N(CH2CH2)2N], 3.98 (s, 12H, 4MeO), 5.30 (s, 4H, 2NCH2N). 13C{1H} NMR
(CDCl3) d: 48.86 [N(CH2CH2)2N], 52.49 (4MeO), 72.68 (2NCH2N),
139.74 (C=N), 160.21 (C=O).
9: 1H NMR (CDCl3) d: 3.31 [s, 8H, N(CH2CH2)2N], 3.96 (s, 6H,
2MeO), 3.97 (s, 6H, 2MeO), 4.44 (s, 4H, 2NCH2N).
10: yield 61%, mp 127–128 °C. 1H NMR (CDCl3) d: 3.96 (s, 12H,
4MeO), 4.26 (s, 2H, PhCH2N), 5.62 (s, 4H, 2NCH2N), 7.1 (m, 5H,
Ph), 13C{1H} NMR (CDCl3) d: 52.28 (4MeO), 54.39 (PhCH2N), 72.44
(2NCH2N), 127.66, 128.28, 128.54, 135.25 (Ph), 139.54 (C=N), 159.71
(C=O).
3f: bp 102–103 °C (1 Torr). 1H NMR (CDCl3) d: 3.97 (s, 2H, PhCH2N),
4.36 (s, 4H, 2NCH2N3), 7.35 (m, 5H, Ph). 13C{1H} NMR (CDCl3) d:
53.35 (s, CH2Ph), 70.05 (s, NCH2N3), 127.51, 128.58, 135.98 (Ph).
1
3g: mp 68–69 °C. H NMR (CDCl3) d: 1.64, 1.68, 1.78, 2.13 (15H,
Ad), 4.55 (s, 4H, NCH2N3).
3h: bp 115–117 °C (2 Torr). H NMR (CDCl3) d: 1.27 (t, 3H, MeC),
1
3.53 (q, 2H, CH2C), 4.88 (s, 2H, NCH2N3), 7.26 (m, 5H, Ph).
– 282 –

Mendeleev Commun., 2009, 19, 281–283
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Received: 30th March 2009; Com. 09/3310
– 283 –