Pyrido[1,2-a]pyrimidinones and Thiazolo[3,2-a]pyrimidinones: Precursors for pyridyl-and thiazolyliminopropadienones, R-N=C=C=C=O

Article abstract of DOI:10.1071/CH11414

2-Pyridyliminopropadienone 6 is formed together with 2-aminopyridine on flash vacuum thermolysis (FVT) of 2-pyridylamino-pyridopyrimidinone 16a and observed by Ar matrix IR spectroscopy, but the two products recombine on warming to room temperature to regenerate the starting material. FVT of the picolinylamino-pyridopyrimidinones 16b and 16c generated mixtures of pyridyliminopropadienone 6 and picolinyliminopropadienones 19b and 19c, respectively. These reactions can be understood in terms of fragmentation of the open-chain bis(2-pyridylamino)methyleneketene intermediates 20 or the thermal interconversion of pyridopyrimidinones 16 and mesoionic pyridopyrimidinium olates 21. 2-Thiazoyliminopropadienone 28 was obtained in an analogous manner by FVT of the 2-(methylthio)thiazolopyrimidinone 24. However, the corresponding dihydro derivative 31 yielded cyanoketene 36 as the major product.

Full text of DOI:10.1071/CH11414

CSIRO PUBLISHING
Aust. J. Chem. 2012, 65, 105–112
Full Paper
http://dx.doi.org/10.1071/CH11414
Pyrido[1,2-a]pyrimidinones and Thiazolo[3,2-a]
pyrimidinones: Precursors for Pyridyl- and
Thiazolyliminopropadienones, R N5C5C5C5O
]
A B
,
A C
,
Heidi Gade Andersen
and Curt Wentrup
A
School of Chemistry and Molecular Biosciences, The University of Queensland,
Brisbane Qld 4072, Australia.
B
Current address: Cheminova A/S, 7620 Lemvig, Denmark.
C
Corresponding author. Email: wentrup@uq.edu.au
2-Pyridyliminopropadienone 6 is formed together with 2-aminopyridine on flash vacuum thermolysis (FVT) of
2-pyridylamino-pyridopyrimidinone 16a and observed by Ar matrix IR spectroscopy, but the two products recombine
on warming to room temperature to regenerate the starting material. FVT of the picolinylamino-pyridopyrimidinones 16b
and 16c generated mixtures of pyridyliminopropadienone 6 and picolinyliminopropadienones 19b and 19c, respectively.
These reactions can be understood in terms of fragmentation of the open-chain bis(2-pyridylamino)methyleneketene
intermediates 20 or the thermal interconversion of pyridopyrimidinones 16 and mesoionic pyridopyrimidinium olates 21.
2-Thiazoyliminopropadienone 28 was obtained in an analogous manner by FVT of the 2-(methylthio)thiazolopyrimidinone
24. However, the corresponding dihydro derivative 31 yielded cyanoketene 36 as the major product.
Manuscript received: 25 October 2011.
Manuscript accepted: 3 December 2011.
Introduction
Results and Discussion
Iminopropadienones, R–N¼C¼C¼C¼O 3, are usually
prepared by flash vacuum thermolysis (FVT)[1] and sometimes
microwave heating[2] of Meldrum’s acid derivatives 1 or iso-
xazolopyrimidinones 2 (Eqn 1). However, pyridopyrimidinones
4 and the mesoionic pyridopyrimidinium olate valence isomers
Pyridyliminopropadienones
2-(2-Pyridylamino)-4H-pyrido[1,2-a]pyrimidin-4-ones 16 were
obtained in yields of 34–83 % by heating mixtures of the
2-chloro derivative 14 with the appropriate amine 15
(Scheme 4). Flash vacuum thermolysis (FVT), of the pyrimidin-
4-one 16a was investigated by IR spectroscopy of the products
isolated in Ar matrices at 7 K. The known bands[3,6] due to
2-pyridyliminopropadienone 6, started appearing at an FVT
temperature of 7008C. In particular, the IR spectrum is domi-
nated by a very strong band at 2249–2250 cmꢀ1. The generation
of iminopropadienone 6 was essentially complete at 9808C
(Scheme 5). The spectrum is shown in Fig. S1 and the observed
and calculated wavenumbers are listed in Table S1 in the
Accessory Publication.
The formation of 2-pyridyliminopropadienone 6 was
verified by isolating the product of FVT on a cold finger cooled
in liquid nitrogen followed by injection of a solution of
dimethylamine in dichloromethane onto the cold finger and
warming to room temperature. This yielded the malonic
amidoamidine derivative[3] 17 in 18 % yield together with
unchanged starting material 16a (Scheme 5). However, in an
analogous experiment without the addition of dimethylamine,
only the starting material 16a was isolated. This implies that the
initially formed iminopropadienone 6 reacts with the eliminated
2-aminopyridine 15a forming the mesoionic pyridopyrimidi-
nium olate 18; the latter tautomerises to the starting material
16a9 on warming up to room temperature. Note however that
the pyridine rings in 16a and 16a9 have been interchanged
O
R
O
O
–HCN
O
O
ϪMe2CO
ϪCO2
NH
N
N
R
C
ð1Þ
ϪHNCO
O
R
N
1
3
2
7 have also been employed in a few cases.[3,4] The reaction
mechanisms are illustrated in Schemes 1 and 2, where it will be
noted that the two reactions are quite different. In the first, it is
the pyridine ring of the pyridopyrimidinone 4 that becomes the
pyridyl moiety in the product iminopropadienone 6 after ring
opening to a ketene 5. In the second reaction, the pyridine ring
is split off as an aminopyridine 9, and C2-C4 of the pyrimidine
ring become the cumulene chain in the iminopropadienone
RNC3O 10.[3–5]
Moreover, the mesoionic and non-mesoionic pyridopyrimi-
dinones can interconvert thermally (e.g. 11 and 13) via the
ketene valence isomers 12 (Scheme 3).[6] Consequently, the
product mixture arising from interconvertible pyridopyrimidi-
nium olates and pyridopyrimidinones can be quite complicated.
Here we report on the generation of iminopropadienones from
pyrido- and thiazolopyrimidinones.
Journal compilation Ó CSIRO 2012
www.publish.csiro.au/journals/ajc

106
H. G. Andersen and C. Wentrup
(Scheme 6). It was shown in separate warm-up experiments with
IR monitoring that 2-pyridyliminopropadienone 6 started react-
ing at ,ꢀ1008C, and the reaction was essentially complete at
ꢀ408C.
(Scheme 7). However, we have shown elsewhere that non-
mesoionic and mesoionic pyridopyrimidinones interconvert on
FVT (Scheme 3)[3,5]; therefore, an alternative isomerization
16b - 21 - 22 is also possible (Scheme 8). In either case,
the observed products 15a, 15b, 6 and 19b will form.
The thermolysis of 16c was completely analogous, again
forming two amines 15a and 15c, and two iminopropadienones
6 and 19c (Schemes 7 and 8). The IR spectrum is shown in
Fig. S3 and the relevant observed and calculated absorptions are
listed in Table S3 (Accessory Publication).
The reaction was probed further by FVT of the 2-amino-4-
picolinyl derivative 16b (Scheme 7). The matrix IR spectrum of
the thermolysate revealed that four product were formed,
namely the two amines 15a and 15b, and the two iminopropa-
dienones 6 and 19b (Scheme 7). The IR spectra of 6 and 19b are
very similar, but the peaks due to 19b could be identified by
comparison with the matrix-isolation spectra of 6, 15a and 15b
as well as the calculated spectra (Fig. S2 and Table S2,
Accessory Publication).
Thiazolyliminopropadienone
Thiazolyliminopropadienone 28 was generated from the
thiazolo[3,2-a]pyrimidinone 24, itself obtained by decarboxyl-
ation of the acid 23 on FVT at 6008C (Scheme 9). There
is precedence for the use of methylthio and methoxy groups as
leaving groups in the thermal syntheses of iminopropadienones
from Meldrum’s acid precursors.[3,7]
Compounds 6 and 19 can be formed via tautomerisation in
the ring-opened ketene 20, itself formed according to Scheme 1
N
O
X
N
H
X
N
X
C
FVT
FVT of 24 with matrix isolation of the product in argon
at 7 K resulted in two products, interpreted as the desired
N
N
C
C
O
N
H
O
5b
4
5a
H2N
R4
R5
N
O
Cl
X = Cl, SMe, NMe2
ϩ
N
N
O
C
N
H
C
N
C C C O
15
14
ϪHX
N
X
N
6
5c
H
N
R4
R5
Scheme 1.
N
N
N
a: R4 ϭ Me, R5 ϭ H
b: R4 ϭ H, R5 ϭ Me
RЈ
R
N
RЈ
R
N
O
N
ϩ
N
16
Ϫ
N
N
Scheme 4.
H
H
C
O
O
7
8
O
NMe2
N
N
C
N
C C C O
H
Me2NH
FVT
RЈ
R
16a
N
C
C
C
O
N
–PyNH2
N
ϩ
6
NH
Me2NH
9a
9b
RЈ
N
NH
10
N
O
N
N
N
17
Scheme 2.
Scheme 5.
Me
Me
Me
N
N
R
N
N
R
N
O
N
Δ
R
N
N
N
N
N
N
H
FVT
C
O
O
11
12
13
Scheme 3.

RNCCCO
107
H
N
iminopropadienone 28 (2250 and 2245 cmꢀ1
)
and the
N
C
C C O
N
N
H2N
ketenimine 29 (2050 cmꢀ1) (Fig. 1). Methanethiol[8] was also
observed in the spectrum.
ϩ
N
N
N
N
Ring opening of 24 to the ketene 25 can lead to two processes,
(i) a 1,5-H shift to the conformers 26 and 27 followed by
elimination of MeSH to give the iminopropadienone 28, and
(ii) the familiar 1,3-shift of the MeS group,[8] which isomerises
the ketene 25 to the ketenimine 29 (Scheme 9). Such ketene–
ketenimine interconversions have been demonstrated to be
rapid, even at room temperature,[9] and the ketenimines are
usually thermodynamically more stable than the ketenes.[9,10]
Moreover, the same ketenimine 29 can form by addition of
MeSH to the iminopropadienone 28.[1,2] It has been shown
elsewhere that ketenimines similar to 29 do not eliminate MeSH
to form iminopropadienones or do so only to a very minor
extent.[3,11] Therefore, the two end products are 28 and 29,
which persist until very high FVT temperatures (9908C; Fig. 1).
There was good agreement between the experimental and
DFT-calculated IR spectra of 28 and 29 (Table S4). Calculations
of the relative energies indicated a very small difference
(1.2 kJ molꢀ1) between the s-E and s-Z conformers of 28 (the
s-E conformer is shown in Scheme 9). Therefore, the splitting of
the iminopropadienone band (2250 and 2245 cmꢀ1) is likely to
be due to the presence of both conformers in the matrix.
Analogous experiments were carried out with the 2,3-
dihydrothiazole derivative 31, obtained by FVT of the carbox-
ylic acid 30, itself prepared by a method analogous to that
reported[12] for 23 (Scheme 10). Compound 31was stable up to
,8008C on FVT, when new products appeared in the Ar matrix
IR spectrum (Fig. 2). The principal products are interpreted as
the iminopropadienone 35 (2244 cmꢀ1), the ketenimine 33
(2044 cmꢀ1; see below) and cyanoketene 36 (2164 (s) and
2239 (w) cmꢀ1). The latter was identified by comparison with
a previously prepared sample.[13] Bands due to MeSH[8] were
also present.
O
16a
6
15a
H
N
H
N
N
N
N
N
N
H
O
O
16a؅
18
Scheme 6.
H
N
H
N
N
O
R4
R5
N
R4
R5
N
N
NH
C
N
C
O
16b, c
20
R4
R5
N
C
C
C
O
O C C C N
N
+
N
6
19
ϩ
HN
R4
NH
NH
HN
R5
H2N
R4
R5
NH2
N
N
15b, c
15a
Iminopropadienones always exhibit extremely strong
absorptions due to the cumulenic stretching vibrations in
the 2200–2300 cmꢀ1 range. Consequently, the signal at
2244 cmꢀ1 in Fig. 2 corresponds to only a minor amount of
the iminopropadienone, and cyanoketene 36 is a major product.
The normal outcome is that the amount of iminopropadienone
increases with the temperature, but here the amount of
b: R4 ϭ Me, R5 ϭ H
c: R4 ϭ H, R5 ϭ Me
Scheme 7.
H
H
N
H
N
R4
R4
FVT
N
N
O
N
O
SMe
S
N
N
N
N
R5
N
R5
H
COOH
O
16b, c
21
23
FVT ϪCO2
H
N
N
R4
R5
N
S
SMe
HN
R4
R5
N
N
SMe
S
S
C
O
Ϫ
FVT
~1,3-SMe
CH
N
O
CH
N
N
HN
N
N
O
CH
C
C
C
SMe
O
22
24
29
25
NH
~1,5-H
MeSH
S
O
C
N
C C C O
Ϫ
NH
N
C C C O
N
N
SMe
N
S
S
R4
R5
6
O
C
C
C
N
SMe
N
–MeSH
NH
C
C
O
NH
N
b: R4 ϭ Me, R5 ϭ H
c: R4 ϭ H, R5 ϭ Me
19
26
27
28
Scheme 8.
Scheme 9.

108
H. G. Andersen and C. Wentrup
2.0
1.8
I
K
1.6
1.4
1.2
K
1.0
0.8
0.6
S
K
0.4
I
0.2
0.0
4000
3000
2000
1500
1000
400
Fig. 1. FTIR spectrum of (2-thiazolyl)iminopropadienone 28 and ketenimine 29 in Ar at 7 K, generated by FVT of 24 at 9908C.
I ¼ iminopropadienone 28, K ¼ ketenimine 29, S ¼ starting material 24 (1704, 1536, 1464 cmꢀ1).
S
now generate cyanoketene 26 by elimination of the stabilized
S,N-heterocyclic carbene thiazol-2-ylidene 40,[16] the formation
of which is analogous to the reported formation from thiazole-2-
carboxylic acid[17] (Scheme 12). However, carbene 40 is not
stable under FVT conditions,[17] and it was not observed directly.
Only minor bands were formed that can be ascribed to its
rearrangement to thiazole 41.[18] Instead, we observed promi-
nent absorptions due to isothiocyanic acid (HNCS)[19] (3509
and 1982 cmꢀ1) and acetylene[20] (3304, 3288, 1328 and
737 cmꢀ1) (Scheme 12). Fragmentation of the molecular ion
of carbene 40 to HNCS has also been observed in the collisional-
activation mass spectrum of m/z 85 derived from 2-
acetylthiazole.[21] The absence of significant bands ascribable
to ethylene in our spectra confirms that the fragmentation
happens after the hydrogen shifts generating the thiazole ring
(Scheme 12).
O
O
N
O
SMe
NH2
MeS
MeS
O
O
S
N
FVT
ϪCO2
N
ϪMeSH
ϪMe2CO
COOH
30
N
SMe
N
N
SMe
~1,3-SMe
S
S
S
C
FVT
CH
N
N
N
CH
C
O
SMe
O
O
S
31
32
33
~1,5-H
H
C
N
C C C O
N
SMe
ϪMeSH
N
C
S
N
NH
C
C
O
O
Thus, in summary, the FVT of the dihydrothiazolopyrimidi-
none 31 affords the iminopropadienone 35, which however
rearranges in a series of H-shifts to finally fragment to cyano-
ketene and thiazol-2-ylidene 40, the latter fragmenting to HNCS
and acetylene.
34
35
36
Scheme 10.
Conclusion and Outlook
iminopropadienone decreases at high temperature, and that
of cyanoketene increases.[3,7] Therefore, it is reasonable to
suggest that cyanoketene is formed at the expense of imino-
propadienone 35.
The formation of cyanoketene 36 was surprising. Isopropyl-
and tert-butyliminopropadienones undergo a retro-ene type
alkene elimination to form cyanoketene (Scheme 11).[13]
A different but related process for the formation of 36 from 35
is proposed in Scheme 12. Here, two consecutive 1,5-H shifts
generate the new ketenes 37 and 38. There is good prece-
dence[14] for a pseudopericyclic[15] 1,3-H shift from N to C of
the type transforming aminomethyleneketene 38 to imidoylk-
2-Pyridyliminopropadienone 6 is formed together with 2-
aminopyridine on FVT of 2-pyridylamino-pyridopyrimidinone
16a, but the two products recombine on warm-up to regenerate
the starting material.
FVT of the picolinylpyridopyrimidinones 16b and 16c
generated mixtures of pyridyliminopropadienone 6 and picoli-
nyliminopropadienones 19b and 19c, respectively, due to
processes that make the two pyridine rings equivalent.
2-Thiazoyliminopropadienone 28 was obtained in an analo-
gous manner by FVT of the 2-methylthiothiazolopyrimidinone
24. However, the corresponding dihydro derivative 31 gave only
a small yield of an iminopropadienone; instead, cyanoketene
36, isothiocyanic acid and acetylene were formed as major
products, and this is interpreted in terms of fragmentation of
the keteneimine 39 to cyanoketene and thiazol-2-ylidene 40.
etene 39. Thus, the several ketenes 37 39, together with the
]
ketenimine 33, each of which can exist in at least two
conformeric forms, may be responsible for the peaks in the
2000–2100 cmꢀ1 region seen in Fig. 2. The conformer 39 can

RNCCCO
109
800ЊC
850ЊC
900ЊC
1000ЊC
C
C
K
I
S
C
K
S
I
S
I
K
I
C
K
S
2280
1970
2280
1970 2280
1970
2280
1970
Fig. 2. Partial FTIR spectra (Ar, 7K) of the products of FVT of 31. I ¼ iminopropadienone 35 (2244 cmꢀ1), K ¼ ketenes and ketenimines (see text),
C ¼ cyanoketene 36 (2164, 2239 cmꢀ1), S ¼ HNCS (1982 cmꢀ1 (also 3509 cmꢀ1)).
H
C
H
C
R
thermolysis tube in a oven directly attached to the vacuum
system. After evacuating the system, the cryostat was turned on
and the pressure brought to 10ꢀ5 hPa while the spectroscopic
window reached a temperature of 7 K. Argon was passed over
the sample while it was sublimed through the thermolysis
tube maintained at various temperatures. The products were
co-deposited with Ar at 7 K for FTIR spectroscopy.
>300ЊC
N
C
ϪRC(CH3)CH2
N
C
C O
H3C
O
36
Scheme 11.
O
C
C
O
C
C
Preparative Flash Vacuum Thermolysis
N
C
C
C
O
~1,5-H
S
S
S
The starting materials were sublimed and subjected to
preparative FVT[24] at 8608C and 10ꢀ4 hPa. The products were
collected on a liquid nitrogen-cooled cold finger. Upon com-
pletion of the thermolysis, the system was isolated from the
pump and brought to atmospheric pressure with nitrogen gas.
The liquid nitrogen was removed from the cold finger, which
was rinsed with dichloromethane.
N
~1,5-H
N
N
N
H
N
H
H
35
37
38
~1,3-H
O
C
S
N
S
S
S
N
CH
N
N
HN
40
N
H
O
2-(2-Pyridylamino)-4H-pyrido[1,2-a]pyrimidin-4-one 16a
41
C
H
C
H
NC
This compound was prepared according to a literature proce-
dure.[25] A mixture of 2-chloro-4H-pyrido[1,2-a]pyrimidin-4-
one[26] 14 (0.005 mol, 0.90 g) and 2-aminopyridine 15a
(0.050 mol, 4.7 g) was melted and heated at 2008C under nitro-
gen for 4 h. After cooling, the residue was chromatographed on
silica gel. Elution with ethyl acetate afforded unreacted
2-aminopyridine, and further elution with ethyl acetate/acetone
(1:1) gave 16a as a yellow oil, which crystallized in ethyl
acetate: yield 0.68 g (57 %); mp 208–2108C (lit.[25] 209–
209.58C). nmax (Argon, 28 K)/cmꢀ1 3429w), 1719m, 1646w,
1592m, 1587s, 1578m, 1540s, 1517s, 1497m, 1481s, 1462m,
1444v., 1417m, 1376w, 1321m, 1232m, 1187w, 1151w, 774w.
dH (400.1 MHz, DMSO-d6) 9.96 (s, 1H, NH), 8.84 (dd, 3J6,7 7.0,
H-N=C=S
H-C C-H
C
O
H
39
36
Scheme 12.
The further use of arylimine derivatives of chloro-
pyridopyrimidinones and chlorothiazolopyrimidinones for
generation of the little-known class of bisiminopropadienes
Ar-N¼C¼C¼C¼N-Ar by FVT is under investigation. Pyrido-
pyrimidinones are of interest in their own right as potential
inhibitors of DNA-dependent protein kinase,[22] and an evalua-
tion of new derivatives is of interest.
5
4
5
J6,9 0.8, 1H, H-6), 8.30 (ddd, 3J6 ,5 5.0, J6 ,4 1.9, J6 ,3 0.8, 1H,
0
0
0
0
0
0
3
3
4
H-60), 7.85 (ddd, J4 ,3 9.0, J4 ,5 6.8, J4 ,6 1.8, 1H, H-4 ), 7.70
0
0
0
0
0
0
0
Experimental
(ddd, 3J8,9 8.4, 3J8,7 7.0, 4J8,6 1.8, 1H, H-8), 7.56 (d, 3J9,8 8.4, 1H,
H-9), 7.44 (ddd, 3J3 ,4 9.0, 4J3 ,5 1.0, 5J3 ,6 0.5, 1H, H-30) 7.15
(ddd, 3J7,8 6.9, 3J7,6 6.9, 4J7,9 1.3, 1H, H-7), 6.98 (s, 1H, H-3),
Matrix Isolation Procedure
0
0
0
0
0
0
The general procedure has been reported.[23,24] The starting
materials (,10-mg portions) were placed in
3
3
4
6.96 (ddd, J5 ,4 7.2, J5 ,6 5.0, J5 ,3 1.0, 1H, H-50).
0 0 0 0 0 0
a
quartz

110
H. G. Andersen and C. Wentrup
dC (100.6 MHz, DMSO-d6) 157.5 (C-2), 157.5 (C-4), 153.7
(C-20), 150.3 (C-9a), 147.3 (C-60), 137.7, 137.6 (C-8, C-40),
127.1 (C-6), 123.9 (C-30), 117.2 (C-50), 114.0 (C-7), 113.2 (C-9),
85.5 (C-3). m/z 238.
together with those of 6. (2-Pyridyl)iminopropadienone 6: nmax
(Argon, 7 K)/cmꢀ1 2250v., 2128m, 1611m, 1587m, 1567w,
1459w, 1433m, 1293w, 1261w, 1220w, 776w.
In a separate experiment, the pyridopyrimidinone 16a
(,50 mg portion) was sublimed in a stream of Ar through the
FVT tube at 9008C/10ꢀ5 hPa, and the products were deposited
on the window at 50 K (i.e. Ar was not condensing). The cryostat
was turned off, and IR spectra were recorded for every 10 K
temperature increase until room temperature. Observation of the
peak at 2239 cmꢀ1 (corresponding to 2249 cmꢀ1 in the matrix)
showed that reaction of 6 commenced at ,ꢀ1008C, and the
reaction was essentially complete at ꢀ408C.
2-(2-(4-Picolinyl)-amino)-4H-pyrido[1,2-a]pyrimidin-
4-one 16b
A mixture of 2-chloro-4H-pyrido[1,2-a]pyrimidin-4-one 14
(0.008 mol, 1.53 g) and 2-amino-4-picoline 15b (0.08 mol,
9.07 g) was melted and heated in a sealed Schlenk vessel under
vacuum at 2008C for 4 h. After cooling, the residue was chro-
matographed on silica gel with ethyl acetate as eluent. After
crystallisation in ethyl acetate white crystals were obtained:
yield 0.70 g (33 %); mp 2098C. nmax (Argon, 23 K)/cmꢀ1 3732m,
3705w, 1711s, 1658w, 1613w, 1600m, 1593m, 1585s, 1540s,
1521s, 1506w, 1483m, 1465w, 1452w, 1444m, 1425w, 1416m,
1343w, 1319w, 1295w, 1231m, 1185w, 1147w, 803w, 774w. dH
Thermolysis of 2-(2-(4-picolinyl)-amino)-4H-
pyrido[1,2-a]pyrimidin-4-one 16b
2-(2-(4-Picolinyl)-amino)-4H-pyrido[1,2-a]pyrimidin-4-one 16b
was subjected to FVT at 860 and 9808C with a sublimation
temperature of 1108C. At 8608C, there were still traces of 16b
(1711 cmꢀ1) in the IR spectrum of the thermolysate. The ther-
molysis was essentially complete at 9008C. Bands belonging to
2-aminopyridine (1484 and 1445 cmꢀ1), 2-amino-4-picoline
(1424 and 1307 cmꢀ1), (2-pyridyl)iminopropadienone 6 (2249,
1433, 777 cmꢀ1; see above) and (2-(4-picolinyl))iminopropa-
dienone 19 (2249 and 1397, 1189 cmꢀ1) were observed. 19: nmax
(Argon, 7 K)/cmꢀ1 2249v., 2149m, 1617m, 1593m, 1562w,
1477w, 1451w, 1397w, 1381w, 1261w, 1189w, 1130w, 823w.
(400.1 MHz, DMSO-d6) 9.90 (s, 1H, NH), 8.73 (d, 3J6,7 7.2, 1H,
H-6), 8.29 (ddd, 3J6 ,5 5.0, 4J6 ,4 1.9, 5J6 ,3 0.8, 1H, H-6 ), 7.70
(ddd, 3J8,9 8.3, 3J8,7 7.0, 4J8,6 1.8, 1H, H-8), 7.62 (d, 3J9,8 8.4, 1H,
H-9), 7.25 (s, H, H-30) 7.02 (dd, 3J7,8 7.2, 4J7,9 1.9, 1H, H-7), 6.96
0
0
0
0
0
0
0
(ddd, 3J5 ,4 7.1, J5 ,6 5.0, J5 ,3 1.1, 1H, H-5 ) 6.85 (s, 1H, H-3),
2.42 (s, 3H, CH3-40). dC (100.6 MHz, DMSO-d6) 157.8 (C-2),
157.4 (C-4), 153.7 (C-20), 150.3 (C-9a), 149.3 (C-40), 147.3
(C-60), 137.7 (C-8), 126.4 (C-6), 121.9 (C-30), 117.1 (C-50),
116.5 (C-7), 113.2 (C-9), 84.8 (C-3) 20.7 (CH3-40). m/z 252.
Anal. Calc. for C14H12N4O: C 66.66, H 4.79, N 21.21. Found:
C 66.45, H 4.82, N 21.26 %.
3
4
0
0
0
0
0
0
0
Thermolysis of 2-(2-(5-methylpyridyl)amino)-4H-
pyrido[1,2-a]pyrimidin-4-one 16c
2-(2-(5-Picolinyl)-amino)-4H-pyrido[1,2-a]pyrimidin-
4-one 16c
Compound 16c was subjected to FVT at 8608C with a sublimation
temperature of 1108C. Bands belonging to 2-aminopyridine
(1484 and 1445 cmꢀ1), 2-amino-5-picoline (1500, 1394 cmꢀ1),
(2-pyridyl)iminopropadienon 6 (2249, 1433, 777 cmꢀ1; see
above) and (2-(5-picolinyl))iminopropadienone 23 (2249 and
1470, 1376 cmꢀ1) were observed. 23: nmax (Argon, 7 K)/cmꢀ1
2249v., 2128m, 1611m, 1591m, 1540w, 1470m, 1375w, 1260w,
1228w, 833w.
A mixture of 2-chloro-4H-pyrido[1,2-a]pyrimidin-4-one 14
(0.008 mol, 1.50 g) and 2-amino-5-picoline 15c (0.08 mol,
9.05 g) was melted and heated in a sealed Schlenk vessel under
vacuum at 2008C for 4 h. After cooling, the residue was
chromatographed on silica gel, eluting with ethyl acetate.
Crystallisation in ethyl acetate afforded yellow crystals: yield
0.77 g (37 %); mp 2168C. nmax (Argon, 23 K)/cmꢀ1 3732w,
3431w, 1716m, 1707s, 1647w, 1591s, 1540s, 1518s, 1494v.,
1466s, 1441m, 1422w, 1388m, 1374m, 1319m, 1302w, 1283w,
1231m, 1186w, 1135w, 1028w, 836w, 772w. dH (400.1 MHz,
DMSO-d6) 9.86 (s, 1H, NH), 8.82 (d, 3J6,7 6.5, 1H, H-6), 8.12
(s, 1H, H-60), 7.83 (ddd, 3J8,9 8.6, 3J8,7 7.2, 4J8,6 1.2, 1H, H-8),
Reference Spectra
2-Aminopyridine 15a
Sublimation temperature: 208C. nmax (Argon, 23 K)/cmꢀ1
3535m, 3429m, 3074w, 3031w, 1611v., 1608v., 1586w, 1575m,
1497w, 1484s, 1445s, 1317m, 1273w, 1149w, 987w, 846w,
803w, 785w, 772w, 765w, 735w, 519w, 419w, 403m.
7.52 (d, 3J9,8 8.4, 1H, H-9), 7.49 (d, 3J4 ,3 8.4, 1H, H-40), 7.40
0
0
(d, 3J3 ,4 8.9, 1H, H-30), 7.13 (dd, J7,8 6.9, 3J7,6 6.9, 1H, H-7),
6.91 (s, 1H, H-3), 2.21 (s, 3H, CH3-50). dC (100.6 MHz, DMSO-
d6) 157.6 (C-2), 157.4 (C-4), 151.6 (C-20), 150.4 (C-9a), 146.9
(C-60), 138.4 (C-40), 137.6 (C-8), 127.1 (C-6), 126.0 (C-50),
123.9 (C-30), 113.9 (C-7), 113.0 (C-9), 85.1 (C-3) 17.2 (CH3-50).
m/z 252. Anal. Calc. for C14H12N4O: C 66.66, H 4.79, N 21.21.
Found: C 66.83, H 4.87, N 22.05 %.
3
0
0
2-Amino-4-picoline 15b
Sublimation temperature: 508C. nmax (Argon, 23 K)/cmꢀ1
3535m, 3429m, 3026w, 1624v., 1617v., 1594s, 1570m, 1491m,
1463s, 1425s, 1379w, 1307m, 1265w, 1178w, 1010w, 942w,
848w, 806m, 492w, 448w, 432w.
2-Amino-5-picoline 15c
Thermolysis of 2-(2-pyridylamino)-4H-pyrido[1,2-a]
pyrimidin-4-one 16a
Sublimation temperature: 458C. nmax (Argon, 23 K)/cmꢀ1
3732w, 3694w, 3526w, 3424w, 3022w, 2956w, 2935w, 1622s,
1594w, 1577w, 1501v., 1462w, 1394s, 1310w, 1264w, 1140w,
1020w, 818w.
2-(2-Pyridylamino)-4H-pyrido[1,2-a]pyrimidin-4-one 16a was
sublimed at 105–1158C and subjected to FVT over the tem-
perature range 700–9808C. At 7008C, starting material
(1719 cmꢀ1) and a small amount of (2-pyridyl)iminopropadie-
none 6 (2250, 1433, 776 cmꢀ1 [3]
were observed. In the range
)
3-(Dimethylamino)-3-(2-pyridylimino)-N,N-
dimethylpropanamide 17
from 800–9008C, a mixture of 16a and 6 was obtained. At
9808C, the formation of 6 was essentially complete. Bands
belonging to 2-aminopyridine (1484 and 1445 cmꢀ1) appeared
2-(2-Pyridylamino)-4H-pyrido[1,2-a]pyrimidin-4-one 16a
(0.43 mmol, 103 mg) was sublimed at 130–1408C and

RNCCCO
111
thermolysed at 8608C in the preparative FVT apparatus. The
cold finger was rinsed with a solution of dimethylamine in
dichloromethane. After warm-up to room temperature, the
solvent was evaporated, and the oily residue was subjected to
column chromatography. Elution with chloroform/acetone (1:1)
afforded unreacted 16a. Elution with chloroform/methanol
(10:1) gave 17 as a yellow-orange oil: yield (18 mg) 18 %. dH
(400.1 MHz, CDCl3) 8.23 (ddd, 3J6,5 5.0, 4J6,4 2.0, 5J6,3 0.8, 1H,
H-6) 7.50 (m, 1H, H-4), 6.78 (m, 2H, H-3, H-5), 3.55 (s, 2H,
CH2-30), 3.07 (s, 6H, N(CH3)2-20), 2.88 (s, 3H, N(CH3)-40), 2.76
(s, 3H, N(CH3)-40). The compound was identical to a previously
prepared sample.[3]
26.3 (C-2), 13.4 (SCH3). m/z 200. Anal. Calc. for C7H8N2OS2
C 41.98, H 4.03, N 13.99. Found: C 41.72, H 3.97, N 13 %.
Thermolysis of 7-methylthio-5H-thiazolo[3,2-a]
pyrimidine-5-one 24
Compound 25 was subjected to FVT over the temperature
range 800–10008C. The sublimation temperature was 60–708C.
At 8008C, only the precursor 24 (1709, 1536 and 1464 cmꢀ1
)
was observed. In the range from 850–10008C, a mixture of 24
(1709 cmꢀ1), a keteneimine (assigned as 29) (2050 cmꢀ1), and
signals ascribed to s-Z- and s-E-(2-thiazolyl)iminopropadienone
28 (2250 and 2245 cmꢀ1) were observed. 29: nmax (Argon 7 K)/
cmꢀ1 2050v., 1706s, 1486w, 1426w, 1413w, 1363w, 1281w,
1212w, 1152w, 1105m, 1060w, 1049w, 970w, 859w, 737m,
721m, 714w, 694w, 603w. s-Z-28: nmax (Argon 7 K)/cmꢀ1
2250v., 2164w, 1641w, 1486w, 1413w, 1276w, 1212w,
1105w, 1060w, 818w, 694w, 603w. s-E-28: nmax (Argon 7 K)/
cmꢀ1 2245v., 2127w, 1621m, 1480w, 1396w, 1276w, 1223w,
1118w, 1060w, 818w, 694w, 666w. Bands due to methanethiol
were observed at 963w, 1331w, 1434w, 2550vw, 2941w and
3007w cmꢀ1 in agreement with literature data.[8]
7-Methylthio-5H-thiazolo[3,2-a]pyrimidin-5-one 24
7-Methylthio-5-oxo-5H-thiazolo[3,2-a]pyrimidin-6-carboxylic
acid[12] 23 (0,41 mmol, 100 mg) was sublimed at 175–2008C and
subjected to preparative FVT at 6008C and 10ꢀ4 hPa. The cold
thermolysate was dissolved in dichloromethane. After warming
to room temperature, the solvent was evaporated giving 25 as
pale yellow crystals: yield 65 mg (79 %); mp 1388C. nmax
(Argon, 23 K)/cmꢀ1 2941w, 1704v., 1688m, 1600w, 1565w,
1536m, 1526m, 1486w, 1470m, 1464m, 1434w, 1363w, 1315w,
1181w, 1100m, 1082w, 970w, 890w, 819w, 777w, 697w. dH
Thermolysis of 2,3-dihydro-7-methylthio-5H-thiazolo
[3,2-a]pyrimidine-5-one 31
3
(400.1 MHz, DMSO-d6) 7.94 (d, J3,2 4.9, 1H, H-3), 7.45
3
(d, J2,3 4.7, 1H, H-2), 6.04 (s, 1H, H-6) 2.46 (s, 3H, SCH3).
Compound 31 was subjected to FVT over the temperature
range 700–10008C. The sublimation temperature was 65–758C.
At 7008C, starting material 31 (1692 and 1560 cmꢀ1) was the
only compound observed in the IR-spectra. From 800–9008C,
a mixture of 31, cyanoketene 36 (2164, 2239 cmꢀ1),[13] and
signals tentatively assigned to (4,5-dihydro-2-thiazolyl)imino-
dC (100.6 MHz, DMSO-d6) 167.5, 162.4 (quat. C-5, C-7)
155.9 C-8a, 121.7 (C-3), 112.4 (C-2), 97.6 (C-6), 13.3 (SCH3).
m/z 198. Anal. Calc. for C7H6N2OS2 C 42.41, H 3.05, N 14.13.
Found: C 42.42, H 3.08, N 13.81 %.
propadienone 35 (2244 cmꢀ1) and keteneimine 33 (2044 cmꢀ1
)
2,3-Dihydro-7-methylthio-5-oxo-5H-thiazolo[3,2-a]
pyrimidin-6-carboxylic acid 30
were observed. Cyanoketene (2164v., 2239m cmꢀ1) was the
major product observed at 10008C. Bands due to
methanethiol[8] were observed at 962, 1327, 1436, 1447, 2550
This compound was prepared by adaptation of the procedure
reported for 23,[12] but with substitution of 2-aminothiazoline
(0.016 mol, 1.6 g) for 2-aminothiazole: yield 3.2 g (81 %); mp
2788C. nmax (Argon, 23 K)/cmꢀ1 3702w, 1745m, 1734m,
1712m, 1622m, 1600m, 1542v., 1475v., 1468v., 1432m,
1387w, 1337w, 1314w, 1273w, 1242w, 1194w, 1125w,
1042w, 1001w, 955w, 866w, 803w, 689w. dH (400.1 MHz,
and 3007 cmꢀ1, bands due to HNCS[19] at 1982 and 3509 cmꢀ1
,
and bands due to acetylene[20] at 737, 1328, 3288 and
3304 cmꢀ1. Very weak bands assignable to thiazole[18] were
recorded at 799, 864, 881, 1041, 1239, 1322, 1383, 1484 and
3095 cmꢀ1
.
3
3
DMSO-d6) 4.44 (t, J3,2 7.9, 2H, H-3), 3.63 (t, J2,3 7.9, 2H,
H-2), 2.38 (s, 3H, SCH3). dC (100.6 MHz, DMSO-d6) 176.2
(COOH) 167.8, 164.9, 162.1 (quat. C-5, C-7, C-8a), 102.9 (C-6),
49.3 (C-3), 27.1 (C-2), 14.4 (SCH3). m/z 244 (41 %), 229 (8 %),
228 (11 %), 227 (15 %), 226 (100 %), 200 (9 %), 172 (16 %), 170
(16 %), 154 (8 %), 142 (10 %), 87 (9 %), 86 (12 %), 60 (22 %), 59
(13 %), 45 (14 %). Anal. Calc. for C8H8N2O3S2 C 39.33, H 3.30,
N 11.47. Found: C 39.40, H 3.28, N 11.40 %.
Accessory Publication
Ar matrix IR spectra and observed and calculated wavenumbers
of iminopropadienones 6, 19b, 19c, and 28 and full-scale IR
spectra of the products of FVT of 24 and 31 are available from
the Journal’s website.
Acknowledgements
This work was supported by the Australian Research Council, the Centre for
Computational Molecular Science at The University of Queensland, and the
QCIF, APAC and NCMAS national computing facilities.
2,3-Dihydro-7-methylthio-5H-thiazolo[3,2-a]
pyrimidin-5-one 31
2,3-Dihydro-7-methylthio-5-oxo-5H-thiazolo[3,2-a]pyrimidin-
6-carboxylic acid 30 (0.42 mmol, 103 mg) was sublimed at 150–
2008C and subjected to preparative FVT at 6008C and 10ꢀ4 hPa.
The procedure used for the workup of 25 was followed, yielding
31 as white crystals: yield 72 mg (85 %); mp 136–1388C. nmax
(Argon, 23 K)/cmꢀ1 2941w, 1692v., 1674m, 1600w, 1570m,
1560s, 1506w, 1498m, 1486m, 1474w, 1437w, 1386m, 1349w,
1315w, 1295w, 1229w, 1180w, 1152w, 1074m, 1022w, 970w,
885w, 836w, 823w. dH (400.1 MHz, DMSO-d6) 5.87 (s, 1H,
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