Synthesis and reactions of the first allenyl azo compounds

Article abstract of DOI:10.1246/cl.2003.360

Several propargylhydrazines were prepared and then oxidized by manganese dioxide to generate short-lived 1,1-diazenes, which produced novel allenyl azo compounds (8) through [2,3] sigmatropic rearrangement. Isomerization of 8 or nucleophilic addition to the title compounds lead to hydrazones as well as pyrazole derivatives.

Full text of DOI:10.1246/cl.2003.360

360
Chemistry Letters Vol.32, No.4 (2003)
Synthesis and Reactions of the First Allenyl Azo Compounds
Klaus Banert,ꢀ Manfred Hagedorn, and Jana Schlott
Chemnitz University of Technology, Institute of Chemistry, Strasse der Nationen 62, D-09111 Chemnitz, Germany
(Received November 29, 2002;CL-021021)
Several propargylhydrazines were prepared and then oxi-
On oxidation with activated manganese dioxide, the propar-
gylhydrazines 5 were converted into new allenes 8 and unwanted
pyrazoles 9 (Scheme 2). If yellow mercury(II) oxide was used to
transform 5 to 8 via 6, yields were lower. While the stability of
8c,h,i allowed the isolation in good yields and purity (Table 1),
the instability of allenyl azo compounds with R2 = H, especially
in the case of 8a and 8b, gave rise to significantly lower yields.
Nevertheless, 8c, 8d, and 8f were isolated with good purity by
preparative gas chromatography. Oxidation of 5g furnished only
8g and 9g, and thus, rearrangement of 6g to produce allyl
propargyl diazene (4,5-diazaocta-1,4-dien-7-yne) was not
dized by manganese dioxide to generate short-lived 1,1-diazenes,
which produced novel allenyl azo compounds (8) through [2,3]
sigmatropic rearrangement. Isomerization of 8 or nucleophilic
addition to the title compounds lead to hydrazones as well as
pyrazole derivatives.
The chemistry of azoalkenes has been investigated exten-
sively over the last decades owing to the interesting addition and
cycloaddition reactions of these extremely reactive conjugated
heterodienes.1 Whereas numerous synthetic methods are known
for the preparation of olefinic azo compounds,1a,b in which the
double bond is conjugated with the azo group, up to now no report
on allenyl azo compounds has been published. However, the
known2 [2,3] sigmatropic rearrangement of short-lived allylic
1,1-diazenes to allyl azo compounds can be modified not only to
produce azoalkenes3 but also in order to generate allenyl azo
compounds for the first time.
R2
R2
R2
R2
NR3
R3
MnO2
N
N
0 °C
R1
R1
NH2
5
6
Starting with secondary amines 1a–c, we prepared the
propargylhydrazines 5a–c by nitrosation followed by reduction
(Scheme 1). The hydrazines 5c–i were synthesized by alkylation
of 43 using propargyl chlorides (for 5c,e,f,h,i) or bromides (for
5d,g). Treatment of 3 (R1 = H, R2 = Me, X = Cl) with 4 (R3 =
Me) under mild conditions was claimed to lead mainly to the
isomeric product 1-(1,1-dimethyl-2-propynyl)-2-methylhydra-
zine and smaller amounts of a pyrazoline (7c) and a unsaturated
hydrazone.4 We found that the reaction of the same starting
materials in the presence of copper powder gave 5c5 in 69% yield.
The structure of 5c was proved by the independent synthesis via
2c.
∆
R2
R1
N
R1
R2
R1
N
R2
C
R2
R2
N
R2
+
N
N
R3
7
N
R3
R3
8
9
Scheme 2. Synthesis of allenyl azo compounds 8 via [2,3]
sigmatropic rearrangement of short-lived 1,1-diazenes 6, for the
key of R1, R2, and R3 see Table 1.
R2
R2
R2
NR3
NO
R2
NHR3
Table 1. Oxidationa of propargylhydrazines 5 to produce allenyl
azo compounds 8 and pyrazoles 9
a
R1
R2 R3
Yieldb of Yieldb of
R1
R1
5
8/%
9/%
1a–c
2a–c
a
b
c
d
e
f
g
h
i
H
Me
H
Me
CH2N3
H
H
H
H
H
H
Ph
Ph
53–77
51
92
34–44
24
b
Me Me
R2
R2
H
H
H
H
Me
Me
15–26
24
16–21
10
R2
R2
X
c
NR3
NH2
R3 NHNH2
+
Me
CH2CH=CH2
59–65
47
R1
R1
5a–i
3
4
Me (CH2)3CH=CH2 88
Me CH2CH2OH 95
Scheme 1. Synthesis of propargylhydrazines 5, forthe keyof R1,
R2, and R3 see Table 1;reagents and conditions: a) AcOH, H 2O,
NaNO2, 0 ꢁC, 92% 2a, 94% 2b, 81% 2c;b) LiAlH 4, Et2O, 36 ꢁC,
42% 5a, 37% 5b, 25% 5c;c) 0–20 ꢁC, 5–24 h, Et2O or without
solvent;copper powder and H 2O or EtOH in the case of 5c,h,i;
69% 5c, 75% 5d, 70% 5e, 61% 5f, 45% 5g, 50% 5h, 54% 5i.
aThe oxidations are performed using an excess of activated
manganese dioxide in CH2Cl2 or chloroform at 0 ꢁC and a
reaction time of 35–45 min.
bYields based on H NMR standard for 8a,b,d–g and 9d–g,
yields referred to isolated 8c,h,i.
1
Copyright ꢀ 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.4 (2003)
361
observed.
also prefer 1,4-addition of Grignard reagents to generate
hydrazones. However, in this case, the nucleophile did not attack
the nitrogen but the b-carbon atom.1a,8
All allenyl azo compounds 8 were unequivocally spectro-
scopically characterized.6 In the case of 8d–f, distinctive long-
range coupling with 7J ¼ 1:5{1:7 Hz was observed in the 1H
NMR spectra. The E configuration of 8 was established by
comparison of the physical and spectroscopic data with those of
other azo compounds3 and particularly by the very small low-field
shifts of the 1H NMR signals of 8 in the presence of Eu(fod)3. On
photolysis, 8 yielded at best only traces of the stereoisomer with a
Z-configurated azo group. Instead, the expected hydrocarbons,
e.g. pent-2-yne and 3-methylbuta-1,2-diene from 8d or but-2-yne
and buta-1,2-diene from 8f, were generated. Azo compounds 8d
and 8f tend to cyclize to furnish 9d and 9f in quantitative first-
order reactions when heated in a solution in benzene or chloro-
form to 30 ꢁC. Interestingly, the analogous reactions of 8c,h,i,
which imply the migration of a methyl group to afford 9c,h,i,
required prolonged reflux of a very dilute solution of the azo
compounds in benzene (yield 86–90%).7
On heating or distillation at higher temperature, the hydra-
zines 5c,f,i were partially isomerized to dihydropyrazoles 7.
However, these heterocycles are not intermediates in the
transformation 5 ! 9 as shown in control experiments starting
with 7 and activated MnO2.
In concentrated solution, or especially in the presence of a
base like NEt3, prototropic rearrangement to give hydrazones, for
instance 8d ! 10d, was the main reaction of allenyl azo
compounds (Scheme 3). On treatment with an excess of
nucleophiles such as alcohols, phenols, or ethyl acetoacetate, 8c
led to ring closure products 11, even at room temperature. On the
other hand, the reaction of 8c with isopropylmagnesium bromide
provided the hydrazone 12 on 1,4-addition. Simple azoalkenes
This work is Part 13 of the series ‘Rearrangement reactions’.
The research was supported by the Deutsche Forschungsgemein-
schaft and the Fonds der Chemischen Industrie.
Dedicated to Prof. Peter Welzel on the occassion of this 65th
birthday.
References and Notes
1
Reviews: a) O. A. Attanasi and L. Caglioti, Org. Prep.
Proced. Int., 18, 299 (1986). b) J. G. Schantl, Methoden Org.
Chem. (Houben-Weyl), E15, 909 (1993). c) O. A. Attanasi, P.
Filippone, and F. Serra-Zanetti, Prog. Heterocycl. Chem., 7, 1
(1995). d) J. G. Schantl, Farmaco, 50, 379 (1995). e) O. A.
Attanasi and P. Filippone, Top. Heterocycl. Syst.: Synth.
React. Prop., 1, 157 (1996). f) J. G. Schantl, Molecules, 1, 212
(1996).
2
3
4
5
J. E. Baldwin, J. E. Brown, and G. Hofle, J. Am. Chem. Soc.,
93, 788 (1971).
K. Banert and M. Hagedorn, Tetrahedron Lett., 33, 7331
(1992).
B. V. Ioffe, V. S. Stopskii, and Z. I. Sergeeva, J. Org. Chem.
USSR (Engl. Transl.), 3, 1131 (1967).
Compound 5c: Colorless solid, mp 60–62 ꢁC. 1H NMR
(CDCl3): d 1.33 (s, CMe2), 2.29 (s, CꢂCH), 2.42 (s, NMe),
2.99 (br. s, NH2). 13C NMR (CDCl3): d 28.0 (q, CMe2), 43.0
(q, NMe), 58.3 (s, CMe2), 72.6 (d, J ¼ 248 Hz, CꢂCH), 83.5
(d, J ¼ 48 Hz, CꢂCH). 15N NMR (C6D6): d À301:1 (NMe),
À296:4 (NH2). The external standard CH3NO2 (d ¼ 0) was
used.
¨
C
Et3N
6
Selected data for allenyl azo compounds. Compound 8c:
1
5
MeOH
88%
N
N
Yellow liquid. H NMR (CDCl3): d 1.87 (d, J ¼ 2:4 Hz,
N
CMe2), 3.78 (s, NMe), 6.79 (sept, 5J ¼ 2:4 Hz, C=CH). 13
C
NHMe
NMR (CDCl3): d 20.4 (q, CMe2), 56.3 (q, NMe), 104.1 (s,
CMe2), 115.7 (d, CH=C=C), 207.2 (CH=C=C). IR
(CDCl3): 2978, 2958, 2916, 1954 cmÀ1. GC MS (EI) m=z
(%): 110 (Mþ, 13), 109 (10), 67 (26), 43 (78), 41 (100).
8d
10d
Nu
Nu = OMe 78%
1
Compound 8d: Yellow liquid. H NMR (CDCl3): d 1.81 (t,
NuH
20 °C
Nu = OPh 77%
5J ¼ 2:9 Hz, CMe), 3.83 (t, 7J ¼ 1:7 Hz, NMe), 5.35 (qq,
5J ¼ 2:9 Hz, 7J ¼ 1:7 Hz, CH2). 13C NMR (CDCl3): d 12.8
(q, CMe), 56.6 (q, NMe), 80.5 (t, CH2), 123.7 (s, CMe), 215.3
(s, C=C=C). IR (CDCl3): 2966, 2914, 1976, 1946 cmÀ1. GC
MS (EI) m=z (%): 96 (Mþ, 23), 95 (19), 81 (5), 53 (26), 43
(100). Compound 8f: Yellow liquid. 1H NMR (CDCl3): d 3.87
N
Ac
Nu = CH
CO2Et
N
69%
11
C
N
7
4
7
N
(t, J ¼ 1:7 Hz, NMe), 5.51 (dq, J ¼ 6:0 Hz, J ¼ 1:7 Hz,
CH2), 7.02 (t, J ¼ 6:0 Hz, CH=C). 13C NMR (CDCl3): d
4
8c
56.6 (q, NMe), 82.7 (t, CH2), 117.7 (d, CH=C=C), 214.7 (s,
C=C=C). IR (CDCl3): 1935 cmÀ1. UV (pentane): ꢀmax
378 nm (" ꢃ 50), 230 nm (" ꢃ 10000). GC MS (EI) m=z (%):
82 (Mþ, 4), 43 (100), 39 (33).
1) Me2CHMgBr/THF
N
N
2) H3O
79%
7
8
For example, refluxing of a 0.003 molar solution of 8c in
benzene for 12 h gave 9c with 90% yield.
S. Bozzini, S. Gratton, A. Lisini, G. Pellizer, and A. Risaliti,
Tetrahedron, 38, 1459 (1982).
12
Scheme 3. Reactions of allenyl azo compounds.