New method for the synthesis of 2-aza-1,3-butadienes

Article abstract of DOI:10.1080/00397910600946033

2-Aza-1,3-butadienes have been synthesized from carbonyl compounds and 1,1,1,3,3,3-hexamethyl-disilazane in the presence of cobalt-containing catalysts. The best yields (up to 95%) were achieved in the case of aldehydes branched in the α-position and 2-methylcyclohexanone. In the case of two α,β-unsaturated ketones, pyridine derivatives were found as the main products. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600946033

Synthetic Communicationsw, 36: 3693–3702, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600946033
New Method for the Synthesis of
2-Aza-1,3-Butadienes
Attila Sisak
Research Group for the Petrochemistry of the Hungarian Academy of
Sciences, Hungary
Abstract: 2-Aza-1,3-butadienes have been synthesized from carbonyl compounds and
1,1,1,3,3,3-hexamethyl-disilazane in the presence of cobalt-containing catalysts. The
best yields (up to 95%) were achieved in the case of aldehydes branched in the
a-position and 2-methylcyclohexanone. In the case of two a,b-unsaturated ketones,
pyridine derivatives were found as the main products.
Keywords: 2-Aza-1,3-butadienes, pyridine derivatives, carbonyl compounds,
1,1,1,3,3,3-hexamethyl-disilazane, cobalt catalysts
2-Aza-1,3-butadienes are important intermediates of various nitrogen-
containing heterocycles.[1–9] However, the synthetic routes leading to these
substances involve often several reaction steps[2,3] and/or the starting
materials are hardly accessible.[3,6,8]
We have found a simple, one-pot method to prepare a series of alkyl- and
aryl-substituted 2-azabutadienes (Chart 1). A carbonyl compound was heated
with a slight excess of 1,1,1,3,3,3-hexamethyl-disilazane (HMDSA) at 60–
1208C in toluene or without solvent under argon in the presence of an
anhydrous Co(II) salt. CoBr2, CoI2, and an ionic complex of the type
[CoB6][Co(CO)4]2 (B ¼ base) formed from [Co2(CO)8] under the reaction con-
ditions[10,11] proved the most efficient catalysts, but some other transition-metal
compounds were active as well. The products were analyzed by gas chromato-
graphy (GC) and the gas chromatography-mass spectrometry (GC-MS) method
Received in the U.K. December 11, 2005
Address correspondence to Attila Sisak, Research Group for the Petrochemistry of
´
the Hungarian Academy of Sciences, H-8201 Veszprem, P.O. Box 158, Hungary.
E-mail: sis014@almos.vein.hu
3693

3694
A. Sisak
Chart 1.
(Table 1). The isolated new azadienes were characterized also by IR, 1H NMR,
and 13C NMR spectra (Table 2). In the cases of R2 = R3, more isomeric
2-azadienes were formed. Suggested structures of the isolated and characterized
isomers of 1 compounds are compiled in Table 3.
Only aldehydes branched in the a-position (R1 ¼ H, R2 = H, R3 = H)
gave 1 in good yields; the linear ones led to nonvolatile (presumably
polymeric) products. In the case of ketones, by-products such as silyl
enol ethers were formed as well (Table 1). Sterically hindered ketones
(2-methyl-3-pentanone, campher, etc). could not be converted under the
reaction conditions. Interestingly, 4-phenyl-3-buten-2-one (R4 ¼ Ph) and
4-(2-furyl)-3-buten-2-one (R4 ¼ 2-furyl) gave pyridine derivatives (2) as
main products (Chart 2, Table 2). From conjugated dicarbonyl compounds
(2,4-pentanedione, ethyl 3-oxobutanoate), silyl enol ethers were formed; a
nonconjugated diketone, 2,5-hexanedione, however, provided the ring-
closure product 2,5-dimethyl-pyrrol (cf. Ref. [14]).
Corriu and coworkers [3] prepared 2-azadienes and pyridine derivatives
starting from N,N-bis(trimethylsilyl) enamines and carbonyl compounds in
the presence of catalytic amounts of bases such as F2. Under our reaction
conditions, N,N-bis(trimethylsilyl) enamines may be formed as intermediates
catalyzed by Co-complexes (Scheme 1). In the second step, the inter-
mediate reacts with a second molecule of aldehyde or ketone leading to 1
analogous to that proposed by Corriu and his coworkers. In the case of

Table 1. Products of the cobalt-catalyzed reaction of carbonyl compounds and HMDSAa
2-Aza-1,3-butadiene
(selectivity [w/w%]b/[ratio
of the isomers found]c)
Substrate (conversion)
Other productsc
e
e
2-Ethyl-butanal (100)
2-Methyl-pentanal (100)f,g
1a (95d/[1.0])
1b (93d/[0.38:0.62]
,1
Pentanal (100)
Nonvolatile products
Silyl enol ether (main product)
4-Methyl-2-pentanone (100)
2-Methyl-3-pentanone (,1)
Cyclohexanone (13)h
1c (27/[0.68:0.21:0.11])
—
—
e
1d (95/[1.0])
1d (32d/[1.0])
1e (82d/[0.07:0.62:0.11:0.20])
1f (16/[1.0])
,1
Cyclohexanone (96)f,g
Silyl enol ether, dehydrated aldol dimer, unknown main product (Mþ ¼ 274 m/z)
Silyl enol ether, silyl alkyl ether
2-Methyl-cyclohexanone (90)f
Cyclopentanone (100)f
Dehydrated aldol dimer, nonvolatile products
2,4-Pentanedione (100)
2,5-Hexanedione (81)f,g
4-Methyl-3-penten-2-one (32)f
Ethyl 3-oxo-butanoate (88)f
Acetophenone (35)
Diphenyl-acetaldehyde (98)f
4-Phenyl-3-buten-2-one (95)
4-(2-Furyl)-3-buten-2-one (85)f
Silyl enol ether (main product), nonvolatile products
2,5-Dimethylpyrrole (main product)
Silyl enol ether (main product)
,1
1g (17/[1.0])
,1
Ethyl 3-amino-2-butenoate, silyl enol ether (main product)
Silyl enol ether (main product), dehydrated aldol dimer, uncharacterized products
Silyl enol ether, uncharacterized products
1h (24/[0.32:0.68])
1i (75d/[1.0])
1j (8/[0.58:0.42])
,1
2a (main product), silyl enol ether, uncharacterized products
2b (main product), silyl enol ether, uncharacterized products
a[Carbonyl compound]:[HMDSA]¼1:1, 5 mol% [Co2(CO)8] catalyst, 1108C, CO atmosphere, toluene solvent, unless otherwise stated.
bBased on GC analysis unless otherwise stated.
cBased on GC-MS analysis.
dIsolated yield.
eNot determined.
f5 mol% anhydrous CoBr2 catalyst.
gNo solvent.
h7 mol% Bu4N[Co(CO)4] catalyst.

Table 2. Properties of the products 1 and 2
IR (CH2Cl2,
n(C55C),
13C NMR (CDCl3, d,
ppm)
Product
Bpa, Mp (8C)
MS (m/z)
cm21
)
1H NMR (CDCl3, d, ppm)
1a (R1 ¼ H,
90–9110
181 (Mþ), 152, 110 (base 1625
peak), 55, 41
0.88 (6 H, t, J ¼ 7.4 Hz), 1.02 (3 H, t, 11.46, 12.57, 13.04,
R2 ¼ R3 ¼ Et)
J ¼ 7.4 Hz), 1.04 (3 H, t,
22.59, 24.90, 26.62,
47.73, 135.88, 142.94,
166.10
J ¼ 7.4 Hz), 1.50 (4 H, quintet,
J ¼ 7.4 Hz), 2.1 (1 H, m), 2.20 (2 H,
q, J ¼ 7.4 Hz), 2.48 (2 H, q,
J ¼ 7.4 Hz), 6.37 (1 H, s), 7.37 (1H,
d, J ¼ 6.6 Hz)
0.8–1.0 (6 H, m), 1.04 (3 H, m), 1.1–
1.8 (6 H, m), 1.81 (3 H, s), 2.01 (2 H,
m), 2.36 (1 H, m), 6.35 (1 H, s,
broad), 7.37 (1 H, m)c
1b (R1 ¼ H,
91–9410 b
181 (Mþ), 110, 82, 55
(base peak), 41
1624
1618
R2 ¼ Me, R3 ¼ Pr)
1c (R1 ¼ Me,
65–743 d
181 (Mþ), 166 (base
peak), 138, 124, 41
0.86 (6 H, d, J ¼ 6.5), 0.90 (6 H, d,
J ¼ 6.6), 1.86 (1 H, m), 1.97 (2 H, d,
J ¼ 7.2), 2.08 (3 H, s), 2.10 (1 H,
octet, J ¼ 6.6), 2.26 (2 H, d,
R2 ¼ H, R3 ¼ iPr)
J ¼ 6.6), 5.99 (1 H, s, broad)e

1d (R1 þ R2 ¼
108–1115
93–963
177 (Mþ, base peak),
134, 81, 79, 41
1621
1.55–1.75 (6 H, m), 1.86 (4 H, m),
2.12 (4 H, m), 2.35 (4 H, m), 5.3 (1
H, t, J ¼ 3.8 Hz)
(CH2)5, R3 ¼ H)f
1e (R1 þ R2 ¼
205 (Mþ), 191, 162 (base 1630
peak), 148, 41
1.11 (3 H, d, J ¼ 7.3 Hz), 1.2–2.5 (17
H, m), 1.39 (3 H, s, broad)e
CH(CH2)4,
R2 ¼ Me)
1f (R1 þ R2 ¼
(CH2)4, R3 ¼ H)g
149 (Mþ), 148 (base
peak), 162), 120, 91,
41
177 (Mþ), 149, 81 (base 1626
peak), 79, 41
1g (R1 ¼ Me,
71–803 d
1.85 (9 H, s, broad), 2.15 (9, H, s,
broad), 6.03 (2 H, s, broad), 6.49 (1
H, s), 7.20 (1 H, s)
R2 ¼ H,
R3 ¼ CH ¼ CMe2)
1h (R1 ¼ Me,
R2 ¼ H, R3 ¼ Ph)g
221 (Mþ), 115, 91, 77
(base peak), 51
1641
1i (R1 ¼ H, R2 ¼ Ph, 176 (mp)
R3 ¼ Ph)
6.95 (1 H, d, J ¼ 11.7), 7.1–7.6 (20 H, 77.20, 119.85, 126.75,
m), 8.08 (1 H, s), 8.42 (1 H, d,
J ¼ 11.7)
127.13, 128.14,
128.38, 129.37,
129.69, 129.80,
136.94, 157.93,
162.12
1j (R1 ¼ Me, R2 ¼ H,
R3 ¼ trans-
273 (Mþ, base peak),
272, 196, 169, 91
CH ¼ CHPh)g
(continued)

Table 2. Continued
IR (CH2Cl2,
n(C55C),
13C NMR (CDCl3, d,
ppm)
Product
Bpa, Mp (8C)
MS (m/z)
cm21
)
1H NMR (CDCl3, d, ppm)
2a (R4 ¼ Ph)
120–1350.1 g 271 (Mþ), 270 (base
peak), 194, 127, 77
1632
2.38 (3 H, s), 6.73 (1 H, d, J ¼ 16.6), 27.43, 117.32, 120.05,
7.1–7.7 (13 H, m)
125.46, 127.04,
127.74, 128.07,
128.25, 128.66,
128.78, 130.46, 137.
21, 138.75, 149.33,
155.72, 158.68
2b (R4 ¼ 2-furyl)g
251 (Mþ), 223, 197 (base
peak), 83, 63
aPressure in mm Hg, 1 mm Hg ¼ 133.32 Pa.
bBp: 898.5 [12]
.
cMixture of two isomers.
dThe fraction was further purified by chromatography (see text).
eMajor Isomer.
fSee ref. [13].
gNot isolated.

2-Aza-1,3-butadienes
3699
Table 3. Suggested structures of the isolated and charac-
terized isomers of 1 compoundsa
2-Aza-1,3-
butadiene
Structure
1a
1b
1c
1d
1e
1g
1i
aCf. Tables 1 and 2.
bOnly isomer found.
some a,b-unsaturated carbonyl compounds, ring closure of 1 and subsequent
dehydrogenation takes place, presumably, resulting in 2 (cf. Ref. [3]).
EXPERIMENTAL
General
All manipulations involving air-sensitive compounds were carried out by the
usual Schlenk technique using deoxygenated, dry solvents and gases as well as

3700
A. Sisak
Chart 2.
reaction vessels with magnetic stirring. Gas chromatograms were recorded on
a Hewlett-Packard model 5830 A chromatograph (with FID), and GC-MS
analyses were performed on a Hewlett-Packard 5890 series II GC-MSD
equipment using SPB1 (Supelco) capillary columns (30 m). Infrared spectra
were recorded by using a 0.06 to 0.12-mm CaF2 cuvette on Specord M 80
1
(Carl Zeiss, Germany). H and NMR 13C NMR spectra were obtained on a
Varian Unity 300 spectrometer.
Synthesis of 1
In a typical procedure, 0.44 g (2.0 mmol) of CoBr2, 2.5 ml (20.0 mmol)
2-methylpentanal, and 4.6 ml (22.0 mmol) of HMDSA were heated
Scheme 1.

2-Aza-1,3-butadienes
3701
gradually to 1108C. Evolution of ammonia gas indicated the beginning of the
reaction. The mixture was stirred for 6 h at 1108C. GC and GC-MS analysis
showed the quantitative conversion of 2-methylpentanal and the formation
of two isomers of 1b (Tables 1 and 2). The mixture of the two isomers was
isolated by distillation in vacuo in 91% yield (cf. Ref. [10]).
Synthesis of 2a
The procedure was modified so that 0.34 g (1.0 mmol) of Co2(CO)8, 2.9 g
(20 mmol) of 4-phenyl-3-buten-2-one, and 4.6 ml (22.0 mmol) of HMDSA
were heated in toluene (10 ml) at 1208C under a CO atmosphere for 6 h.
The reaction mixture was filtered, the solvent removed in vacuo, and the
residue fractionated. On the basis of GC-MS analysis (see Table 2), the
second fraction (120–1358C) at 0.1 mmHg pressure; 1 mm Hg ¼ 133.32
Pa) contained mostly 2a. This fraction was purified by thin-layer chromatography
(TLC) using a silica-gel plate and a 9:1 CH2Cl2/Et2O mixture as eluant.
Compound 2a was isolated as a pale yellow oil in 43% yield.
ACKNOWLEDGMENT
´
The authors acknowledge helpful discussion with F. Ungvary, G. Szalontai,
and B. Szabo, technical assistance of E. Fekete and E. Klujber, and
financial support from the Hungarian Academy of Sciences (Grant No.
OTKA T031934).
REFERENCES
1. Boger, D. L.; Wienreb, S. M. In Hetero Diels-Alder Methodology in Organic
Synthesis; Academic Press: San Diego, CA, 1987; p. 239, and references therein.
´
2. Barluenga, J.; Aznar, F.; Fustero, S.; Tomas, M. New perspective of carbo- and
hetero-1,3-dienes on organic synthesis. Pure Appl. Chem. 1990, 62, 1957–1966,
and references therein.
3. Corriu, R. J. P.; Moreau, J. J. E.; Pataud-Sat, M. Silylamines in organic synthesis:
Reactivity of N,N-bis(silyl) enamines toward electrophiles: A route to substituted
2-aza-1,3-butadienes and pyridines. J. Org. Chem. 1990, 55, 2878–2884.
´
4. Barluenga, J.; Tomas, M. Synthesis of heterocycles from azadienes. Adv. Hetero-
cycl. Chem. 1993, 57, 1–80, and references therein.
5. Ghosez, L. In Stereocontrolled Organic Synthesis; Blackwell: Oxford, 1994;
p. 193, and references therein.
6. Gilchrist, T. L.; d’A Rocha Gonsalvas, A. M.; Pinho e Melo, T. M. V. D. The use of
2-azadienes in the Diels–Alder reaction. Pure Appl. Chem. 1996, 68, 859–862,
and references therein.
7. Tietze, L. F.; Kettschau, G. Hetero Diels–Alder reaction in organic chemistry.
Top. Curr. Chem. 1997, 189, 1–120, and references therein.

3702
A. Sisak
8. Palacious, F.; Alonso, C.; Rubiales, G. Aza-Wittig reaction of N-vinylic phospha-
zenes with carbonyl compounds: Azadiene-mediated synthesis of isoquinolines
and 5,6-dihydro-2H-1,3-oxazines. J. Org. Chem. 1977, 62, 1146–1154.
´
9. Palcios, F.; Herran, E.; Rubiales, G.; Ezpeleta, J. M. Cycloaddition reaction of
2-azadienes derived from b-amino acids with electron rich and electron
deficient alkenes and carbonyl compounds: Synthesis of pyridine and 1,3-
oxazine derivatives. J. Org. Chem. 2002, 67, 2131–2135.
10. Calderazzo, F.; Ercoli, R.; Natta, G. In Organic Synthesis vis Metal Carbonyls;
Wiley-Interscience: New York, 1968; Vol. 1, pp. 83–86.
´
11. Sisak, A.; Marko, L. Mechanistic studies on the reactions of dicobalt octacarbonyl
with hard Lewis bases. J. Organoment. Chem. 1987, 330, 201–206.
12. Carbide and Carbon Chem. Corp; US patent 2319848, 1939.
13. Hervey, R. G.; Pataki, J.; Cortez, C.; Diraddo, P.; Yang, C. X. A new general
synthesis of polycyclic aromatic compounds based on enamine chemistry.
J. Org. Chem. 1991, 56, 1210–1217.
14. Banik, B. K.; Banik, I.; Rentreria, M.; Dasgupta, S. K. A Straightforward highly
efficient Paal–Knorr synthesis of pyrroles. Tetrahedron Lett. 2005, 46,
2643–2645, and references therein.