Pyrido[1,2-a]pyrimidinones and Thiazolo[3,2-a]pyrimidinones: Precursors for Pyridyl- andThiazolyliminopropadienones, R]N5C5C5C5O

Heidi Gade AndersenA,B and Curt WentrupA,C

ASchool of Chemistry and Molecular Biosciences, The University of Queensland,

Brisbane Qld 4072, Australia.BCurrent address: Cheminova A/S, 7620 Lemvig, Denmark.CCorresponding author. Email: wentrup@uq.edu.au

2-Pyridyliminopropadienone 6 is formed together with 2-aminopyridine on flash vacuum thermolysis (FVT) of2-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 16band 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)methyleneketeneintermediates 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)thiazolopyrimidinone24. However, the corresponding dihydro derivative 31 yielded cyanoketene 36 as the major product.

Manuscript received: 25 October 2011.

Manuscript accepted: 3 December 2011.

Introduction

Iminopropadienones, R–N¼C¼C¼C¼O 3, are usually

prepared by flash vacuum thermolysis (FVT)[1] and sometimesmicrowave heating[2] of Meldrum’s acid derivatives 1 or iso-xazolopyrimidinones 2 (Eqn 1). However, pyridopyrimidinones

4 and the mesoionic pyridopyrimidinium olate valence isomers

O

OC

O

O1

N

3

RR

�Me2CO

N

NHN

O

OR

2

–HCN

�HNCO�CO2ð1Þ

7 have also been employed in a few cases.[3,4] The reactionmechanisms are illustrated in Schemes 1 and 2, where it will benoted that the two reactions are quite different. In the first, it is

the pyridine ring of the pyridopyrimidinone 4 that becomes thepyridyl moiety in the product iminopropadienone 6 after ringopening to a ketene 5. In the second reaction, the pyridine ringis split off as an aminopyridine 9, and C2-C4 of the pyrimidine

ring become the cumulene chain in the iminopropadienoneRNC3O 10.[3–5]

Moreover, the mesoionic and non-mesoionic pyridopyrimi-

dinones can interconvert thermally (e.g. 11 and 13) via theketene valence isomers 12 (Scheme 3).[6] Consequently, theproduct mixture arising from interconvertible pyridopyrimidi-

nium olates and pyridopyrimidinones can be quite complicated.Here we report on the generation of iminopropadienones frompyrido- and thiazolopyrimidinones.

Results and Discussion

Pyridyliminopropadienones

2-(2-Pyridylamino)-4H-pyrido[1,2-a]pyrimidin-4-ones 16were

obtained in yields of 34–83% by heating mixtures of the2-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 7K. The known bands[3,6] due to2-pyridyliminopropadienone 6, started appearing at an FVTtemperature of 7008C. In particular, the IR spectrum is domi-

nated by a very strong band at 2249–2250 cm�1. The generationof 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 theAccessory Publication.

The formation of 2-pyridyliminopropadienone 6 wasverified by isolating the product of FVT on a cold finger cooled

in liquid nitrogen followed by injection of a solution ofdimethylamine in dichloromethane onto the cold finger andwarming to room temperature. This yielded the malonic

amidoamidine derivative[3] 17 in 18% yield together withunchanged starting material 16a (Scheme 5). However, in ananalogous experiment without the addition of dimethylamine,

only the starting material 16awas isolated. This implies that theinitially formed iminopropadienone 6 reacts with the eliminated2-aminopyridine 15a forming the mesoionic pyridopyrimidi-

nium olate 18; the latter tautomerises to the starting material16a9 on warming up to room temperature. Note however thatthe pyridine rings in 16a and 16a9 have been interchanged

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Aust. J. Chem. 2012, 65, 105–112

http://dx.doi.org/10.1071/CH11414

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(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.

The reaction was probed further by FVT of the 2-amino-4-picolinyl derivative 16b (Scheme 7). The matrix IR spectrum ofthe 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 arevery similar, but the peaks due to 19b could be identified bycomparison with the matrix-isolation spectra of 6, 15a and 15b

as well as the calculated spectra (Fig. S2 and Table S2,Accessory Publication).

Compounds 6 and 19 can be formed via tautomerisation in

the ring-opened ketene 20, itself formed according to Scheme 1

(Scheme 7). However, we have shown elsewhere that non-

mesoionic and mesoionic pyridopyrimidinones interconvert onFVT (Scheme 3)[3,5]; therefore, an alternative isomerization16b- 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 iminopropadienones6 and 19c (Schemes 7 and 8). The IR spectrum is shown in

Fig. S3 and the relevant observed and calculated absorptions arelisted in Table S3 (Accessory Publication).

Thiazolyliminopropadienone

Thiazolyliminopropadienone 28 was generated from thethiazolo[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 asleaving groups in the thermal syntheses of iminopropadienonesfrom Meldrum’s acid precursors.[3,7]

FVT of 24 with matrix isolation of the product in argonat 7K resulted in two products, interpreted as the desired

N

N X

O

N

N C C C O

N

N XFVT

�HX

X = Cl, SMe, NMe2

COH

4 5a

N

N X

C

C

O

H

5b

6

N

N C

HX

CO

5c

Scheme 1.

N

NH

N

N

NH

R�

8

CO

N

N

RR�

H

9b

9a

N

C

C

C

O

R� R

�

N

N�

�

N

O

R�

7

H

R

10

Scheme 2.

N

NN

N

O

Me

N

N

11 12

N

N N

O

N

Me

H CO

N

N

Me

RRR

13

FVT

Δ

Scheme 3.

N

N N

N

O

H

16

R4

R5

N

N Cl

O14

N

H2N

R5

R4

�

15

a: R4 � Me, R5 � Hb: R4 � H, R5 � Me

Scheme 4.

N N

ONN

17

N C

O

NMe2

HMe2NHN

Me2NH

N

N C C C O

6

16aFVT

–PyNH2

Scheme 5.

106 H. G. Andersen and C. Wentrup

iminopropadienone 28 (2250 and 2245 cm�1) and the

ketenimine 29 (2050 cm�1) (Fig. 1). Methanethiol[8] was alsoobserved in the spectrum.

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 byelimination of MeSH to give the iminopropadienone 28, and(ii) the familiar 1,3-shift of the MeS group,[8] which isomerisesthe ketene 25 to the ketenimine 29 (Scheme 9). Such ketene–

ketenimine interconversions have been demonstrated to berapid, even at room temperature,[9] and the ketenimines areusually thermodynamically more stable than the ketenes.[9,10]

Moreover, the same ketenimine 29 can form by addition ofMeSH to the iminopropadienone 28.[1,2] It has been shownelsewhere that ketenimines similar to 29 do not eliminateMeSH

to form iminopropadienones or do so only to a very minorextent.[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). Calculationsof the relative energies indicated a very small difference(1.2 kJmol�1) between the s-E and s-Z conformers of 28 (the

s-E conformer is shown in Scheme 9). Therefore, the splitting ofthe iminopropadienone band (2250 and 2245 cm�1) is likely tobe 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 matrixIR spectrum (Fig. 2). The principal products are interpreted asthe iminopropadienone 35 (2244 cm�1), the ketenimine 33

(2044 cm�1; see below) and cyanoketene 36 (2164 (s) and2239 (w) cm�1). The latter was identified by comparison witha previously prepared sample.[13] Bands due to MeSH[8] were

also present.Iminopropadienones always exhibit extremely strong

absorptions due to the cumulenic stretching vibrations in

the 2200–2300 cm�1 range. Consequently, the signal at2244 cm�1 in Fig. 2 corresponds to only a minor amount ofthe 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

N

N N

O

N

H

N

N C C C O

N

H2N

�

16a 6 15a

N

N N

O

N

H

N

N N

N

O18

H

16a�

H

Scheme 6.

N

NHN

O

N

NH

NH

N

H2N

16b, c

15b, c 15a

R5

R5

R4

R4

N

NH2

HN

HN

R5

R4

NH C

NHN

N

20

R5

R4

C

O

N

N C C C O

6N

NCCCO

19+ �

b: R4 � Me, R5 � Hc: R4 � H, R5 � Me

R4

R5

Scheme 7.

N

NHN

O

N

NH

NH

16b, c

R5

R4

HN

HN

R5

R4

N CH

HN N

N

22

R5

R4

N

N C C C O

6

N

NCCCO

19b: R4 � Me, R5 � Hc: R4 � H, R5 � Me

R4

R5

CO

N

HN

HN

O21

HN

R4

R5

FVT

�

�

Scheme 8.

N

NS

O

SMe

24

N

NS

O

SMe

COOH

23

FVT

FVT

25 29

26 28

N CH

NS SMe

CO

N

CNS

CH~1,3-SMe

NH C

NS SMe

C

O

N C C C

S

N

O

–MeSH

O SMe

~1,5-H

�CO2

MeSH

27

NH

SN

SMe

CC

O

Scheme 9.

RNCCCO 107

iminopropadienone decreases at high temperature, and that

of cyanoketene increases.[3,7] Therefore, it is reasonable tosuggest 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 typealkene 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 shiftsgenerate 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-etene 39. Thus, the several ketenes 37]39, together with theketenimine 33, each of which can exist in at least two

conformeric forms, may be responsible for the peaks in the2000–2100 cm�1 region seen in Fig. 2. The conformer 39 can

now generate cyanoketene 26 by elimination of the stabilizedS,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 notstable 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] (3509and 1982 cm�1) and acetylene[20] (3304, 3288, 1328 and

737 cm�1) (Scheme 12). Fragmentation of the molecular ionof 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 ascribableto ethylene in our spectra confirms that the fragmentationhappens after the hydrogen shifts generating the thiazole ring(Scheme 12).

Thus, in summary, the FVT of the dihydrothiazolopyrimidi-none 31 affords the iminopropadienone 35, which howeverrearranges in a series of H-shifts to finally fragment to cyano-

ketene and thiazol-2-ylidene 40, the latter fragmenting to HNCSand acetylene.

Conclusion and Outlook

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 regeneratethe starting material.

FVT of the picolinylpyridopyrimidinones 16b and 16c

generated mixtures of pyridyliminopropadienone 6 and picoli-nyliminopropadienones 19b and 19c, respectively, due toprocesses that make the two pyridine rings equivalent.

2-Thiazoyliminopropadienone 28 was obtained in an analo-gous manner by FVT of the 2-methylthiothiazolopyrimidinone24. However, the corresponding dihydro derivative 31 gave onlya small yield of an iminopropadienone; instead, cyanoketene

36, isothiocyanic acid and acetylene were formed as majorproducts, and this is interpreted in terms of fragmentation ofthe keteneimine 39 to cyanoketene and thiazol-2-ylidene 40.

0.04000 3000 2000 1500 1000 400

KS

I

K

K

I

0.2

0.4

0.6

0.8

1.0Ar

1.2

1.4

1.6

1.8

2.0

Fig. 1. FTIR spectrum of (2-thiazolyl)iminopropadienone 28 and ketenimine 29 in Ar at 7K, generated by FVT of 24 at 9908C.

I¼ iminopropadienone 28, K¼ ketenimine 29, S¼ starting material 24 (1704, 1536, 1464 cm�1).

S

N

N

NS

O

SMe

NH2

31

N

NS

O

SMe

COOH

30

FVTO

O

O

O

MeS

MeS

FVT

32 33

34 35

N CH

NS SMe

CO

N

CNS

CH~1,3-SMe

NH C

NS SMe

C

O

N C C C

S

N

O

�MeSH

O SMe

~1,5-H

�MeSH�Me2CO

�CO2

CC

H

O

N

36

Scheme 10.

108 H. G. Andersen and C. Wentrup

The further use of arylimine derivatives of chloro-

pyridopyrimidinones and chlorothiazolopyrimidinones forgeneration of the little-known class of bisiminopropadienesAr-N¼C¼C¼C¼N-Ar by FVT is under investigation. Pyrido-

pyrimidinones are of interest in their own right as potentialinhibitors of DNA-dependent protein kinase,[22] and an evalua-tion of new derivatives is of interest.

Experimental

Matrix Isolation Procedure

The general procedure has been reported.[23,24] The startingmaterials (,10-mg portions) were placed in a quartz

thermolysis tube in a oven directly attached to the vacuum

system. After evacuating the system, the cryostat was turned onand the pressure brought to 10�5 hPa while the spectroscopicwindow reached a temperature of 7K. Argon was passed overthe sample while it was sublimed through the thermolysis

tube maintained at various temperatures. The products wereco-deposited with Ar at 7K for FTIR spectroscopy.

Preparative Flash Vacuum Thermolysis

The starting materials were sublimed and subjected topreparative FVT[24] at 8608C and 10�4 hPa. The products werecollected on a liquid nitrogen-cooled cold finger. Upon com-

pletion of the thermolysis, the system was isolated from thepump and brought to atmospheric pressure with nitrogen gas.The liquid nitrogen was removed from the cold finger, whichwas rinsed with dichloromethane.

2-(2-Pyridylamino)-4H-pyrido[1,2-a]pyrimidin-4-one 16a

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 (0.005mol, 0.90 g) and 2-aminopyridine 15a

(0.050mol, 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 unreacted2-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, 28K)/cm�1 3429w), 1719m, 1646w,1592m, 1587s, 1578m, 1540s, 1517s, 1497m, 1481s, 1462m,

1444v., 1417m, 1376w, 1321m, 1232m, 1187w, 1151w, 774w.dH (400.1MHz, DMSO-d6) 9.96 (s, 1H, NH), 8.84 (dd,

3J6,7 7.0,5 J6,9 0.8, 1H,H-6), 8.30 (ddd,

3J60,50 5.0,4J60,40 1.9,

5J60,30 0.8, 1H,H-60), 7.85 (ddd, 3J40,30 9.0,

3J40,50 6.8,4J40,60 1.8, 1H, H-4

0), 7.70(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, 3J30,40 9.0,

4J30,50 1.0,5J30,60 0.5, 1H, H-3

0) 7.15(ddd, 3J7,8 6.9,

3J7,6 6.9,4J7,9 1.3, 1H, H-7), 6.98 (s, 1H, H-3),

6.96 (ddd, 3J50,40 7.2, 3J50,60 5.0, 4J50,30 1.0, 1H, H-50).

N

R

H3C

H

C C C O

>300�CC

C

H

O

N�RC(CH3)CH2

36

Scheme 11.

3735

S C

NN H

C

O

N C C C

S

N

O

~1,5-H

38

S C

NH

N H

C

O

S CH

NN H

C

O

~1,5-H

~1,3-H

S

NN

H CH

CO

S

N

S

HN

C ONC

H 36

40

H-C C-H

H-N=C=S

41

39

Scheme 12.

2280

IC

800�C 850�C 900�C 1000�C

K

S

I

C

K

S

I

C

K

S

I

C

K

S

1970 2280 1970 2280 1970 2280 1970

Fig. 2. Partial FTIR spectra (Ar, 7K) of the products of FVT of 31. I¼ iminopropadienone 35 (2244 cm�1), K¼ ketenes and ketenimines (see text),

C¼ cyanoketene 36 (2164, 2239 cm�1), S¼HNCS (1982 cm�1 (also 3509 cm�1)).

RNCCCO 109

dC (100.6MHz, 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.

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

(0.008mol, 1.53 g) and 2-amino-4-picoline 15b (0.08mol,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. Aftercrystallisation in ethyl acetate white crystals were obtained:

yield 0.70 g (33%);mp 2098C. nmax (Argon, 23K)/cm�1 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(400.1MHz, DMSO-d6) 9.90 (s, 1H, NH), 8.73 (d,

3J6,7 7.2, 1H,H-6), 8.29 (ddd, 3J60,50 5.0,

4J60,40 1.9,5J60,30 0.8, 1H, H-6

0), 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

(ddd, 3J50,40 7.1,3J50,60 5.0,

4J50,30 1.1, 1H, H-50) 6.85 (s, 1H, H-3),

2.42 (s, 3H, CH3-40). dC (100.6MHz, 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 (CH3-4

0). 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%.

2-(2-(5-Picolinyl)-amino)-4H-pyrido[1,2-a]pyrimidin-4-one 16c

A mixture of 2-chloro-4H-pyrido[1,2-a]pyrimidin-4-one 14

(0.008mol, 1.50 g) and 2-amino-5-picoline 15c (0.08mol,9.05 g) was melted and heated in a sealed Schlenk vessel undervacuum 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: yield0.77 g (37%); mp 2168C. nmax (Argon, 23K)/cm�1 3732w,3431w, 1716m, 1707s, 1647w, 1591s, 1540s, 1518s, 1494v.,

1466s, 1441m, 1422w, 1388m, 1374m, 1319m, 1302w, 1283w,1231m, 1186w, 1135w, 1028w, 836w, 772w. dH (400.1MHz,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),7.52 (d, 3J9,8 8.4, 1H, H-9), 7.49 (d, 3J40,30 8.4, 1H, H-4

0), 7.40(d, 3J30,40 8.9, 1H, H-3

0), 7.13 (dd, 3J7,8 6.9,3J7,6 6.9, 1H, H-7),

6.91 (s, 1H, H-3), 2.21 (s, 3H, CH3-50). dC (100.6MHz, 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 (CH3-5

0).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%.

Thermolysis of 2-(2-pyridylamino)-4H-pyrido[1,2-a]pyrimidin-4-one 16a

2-(2-Pyridylamino)-4H-pyrido[1,2-a]pyrimidin-4-one 16a wassublimed at 105–1158C and subjected to FVT over the tem-

perature range 700–9808C. At 7008C, starting material(1719 cm�1) and a small amount of (2-pyridyl)iminopropadie-none 6 (2250, 1433, 776 cm�1)[3] were observed. In the range

from 800–9008C, a mixture of 16a and 6 was obtained. At9808C, the formation of 6 was essentially complete. Bandsbelonging to 2-aminopyridine (1484 and 1445 cm�1) appeared

together with those of 6. (2-Pyridyl)iminopropadienone 6: nmax

(Argon, 7K)/cm�1 2250v., 2128m, 1611m, 1587m, 1567w,1459w, 1433m, 1293w, 1261w, 1220w, 776w.

In a separate experiment, the pyridopyrimidinone 16a

(,50mg portion) was sublimed in a stream of Ar through theFVT tube at 9008C/10�5 hPa, and the products were depositedon thewindow at 50K (i.e. Ar was not condensing). The cryostatwas turned off, and IR spectra were recorded for every 10K

temperature increase until room temperature. Observation of thepeak at 2239 cm�1 (corresponding to 2249 cm�1 in the matrix)showed that reaction of 6 commenced at ,�1008C, and the

reaction was essentially complete at �408C.

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 16bwas subjected to FVT at 860 and 9808C with a sublimation

temperature of 1108C. At 8608C, there were still traces of 16b(1711 cm�1) in the IR spectrum of the thermolysate. The ther-molysis was essentially complete at 9008C. Bands belonging to2-aminopyridine (1484 and 1445 cm�1), 2-amino-4-picoline(1424 and 1307 cm�1), (2-pyridyl)iminopropadienone 6 (2249,1433, 777 cm�1; see above) and (2-(4-picolinyl))iminopropa-

dienone 19 (2249 and 1397, 1189 cm�1) were observed. 19: nmax

(Argon, 7K)/cm�1 2249v., 2149m, 1617m, 1593m, 1562w,1477w, 1451w, 1397w, 1381w, 1261w, 1189w, 1130w, 823w.

Thermolysis of 2-(2-(5-methylpyridyl)amino)-4H-pyrido[1,2-a]pyrimidin-4-one 16c

Compound 16cwas subjected to FVTat 8608Cwith a sublimationtemperature of 1108C. Bands belonging to 2-aminopyridine(1484 and 1445 cm�1), 2-amino-5-picoline (1500, 1394 cm�1),

(2-pyridyl)iminopropadienon 6 (2249, 1433, 777 cm�1; seeabove) and (2-(5-picolinyl))iminopropadienone 23 (2249 and1470, 1376 cm�1) were observed. 23: nmax (Argon, 7K)/cm

�1

2249v., 2128m, 1611m, 1591m, 1540w, 1470m, 1375w, 1260w,1228w, 833w.

Reference Spectra

2-Aminopyridine 15a

Sublimation temperature: 208C. nmax (Argon, 23K)/cm�1

3535m, 3429m, 3074w, 3031w, 1611v., 1608v., 1586w, 1575m,

1497w, 1484s, 1445s, 1317m, 1273w, 1149w, 987w, 846w,803w, 785w, 772w, 765w, 735w, 519w, 419w, 403m.

2-Amino-4-picoline 15b

Sublimation temperature: 508C. nmax (Argon, 23K)/cm�1

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

Sublimation temperature: 458C. nmax (Argon, 23K)/cm�1

3732w, 3694w, 3526w, 3424w, 3022w, 2956w, 2935w, 1622s,

1594w, 1577w, 1501v., 1462w, 1394s, 1310w, 1264w, 1140w,1020w, 818w.

3-(Dimethylamino)-3-(2-pyridylimino)-N,N-dimethylpropanamide 17

2-(2-Pyridylamino)-4H-pyrido[1,2-a]pyrimidin-4-one 16a

(0.43mmol, 103mg) was sublimed at 130–1408C and

110 H. G. Andersen and C. Wentrup

thermolysed at 8608C in the preparative FVT apparatus. The

cold finger was rinsed with a solution of dimethylamine indichloromethane. After warm-up to room temperature, thesolvent 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 (18mg) 18%. dH(400.1MHz, 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,CH2-3

0), 3.07 (s, 6H, N(CH3)2-20), 2.88 (s, 3H, N(CH3)-4

0), 2.76(s, 3H, N(CH3)-4

0). The compound was identical to a previously

prepared sample.[3]

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 (0,41mmol, 100mg)was sublimed at 175–2008Candsubjected to preparative FVT at 6008C and 10�4 hPa. The coldthermolysate was dissolved in dichloromethane. After warming

to room temperature, the solvent was evaporated giving 25 aspale yellow crystals: yield 65mg (79%); mp 1388C. nmax

(Argon, 23K)/cm�1 2941w, 1704v., 1688m, 1600w, 1565w,1536m, 1526m, 1486w, 1470m, 1464m, 1434w, 1363w, 1315w,

1181w, 1100m, 1082w, 970w, 890w, 819w, 777w, 697w. dH(400.1MHz, DMSO-d6) 7.94 (d, 3J3,2 4.9, 1H, H-3), 7.45(d, 3J2,3 4.7, 1H, H-2), 6.04 (s, 1H, H-6) 2.46 (s, 3H, SCH3).

dC (100.6MHz, DMSO-d6) 167.5, 162.4 (quat. C-5, C-7)155.9C-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%.

2,3-Dihydro-7-methylthio-5-oxo-5H-thiazolo[3,2-a]pyrimidin-6-carboxylic acid 30

This compound was prepared by adaptation of the procedurereported for 23,[12] but with substitution of 2-aminothiazoline

(0.016mol, 1.6 g) for 2-aminothiazole: yield 3.2 g (81%); mp2788C. nmax (Argon, 23K)/cm�1 3702w, 1745m, 1734m,1712m, 1622m, 1600m, 1542v., 1475v., 1468v., 1432m,

1387w, 1337w, 1314w, 1273w, 1242w, 1194w, 1125w,1042w, 1001w, 955w, 866w, 803w, 689w. dH (400.1MHz,DMSO-d6) 4.44 (t, 3J3,2 7.9, 2H, H-3), 3.63 (t, 3J2,3 7.9, 2H,

H-2), 2.38 (s, 3H, SCH3). dC (100.6MHz, 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%.

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 (0.42mmol, 103mg) was sublimed at 150–2008C and subjected to preparative FVT at 6008C and 10�4 hPa.

The procedure used for the workup of 25was followed, yielding31 as white crystals: yield 72mg (85%); mp 136–1388C. nmax

(Argon, 23K)/cm�1 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 (400.1MHz, DMSO-d6) 5.87 (s, 1H,

H-6), 4.29 (t, 3J3,2 7.7Hz, 2H, H-3), 3.50 (t, 3J2,3 7.7Hz, 2H,H-2), 2.37 (s, 3H, SCH3). dC (100.6MHz, DMSO-d6) 168.5,164.8 (quat. C-5, C-7) 158.8 (C-8a), 101.3 (C-6), 48.5 (C-3),

26.3 (C-2), 13.4 (SCH3). m/z 200. Anal. Calc. for C7H8N2OS2C 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 temperaturerange 800–10008C. The sublimation temperature was 60–708C.At 8008C, only the precursor 24 (1709, 1536 and 1464 cm�1)was observed. In the range from 850–10008C, a mixture of 24(1709 cm�1), a keteneimine (assigned as 29) (2050 cm�1), and

signals ascribed to s-Z- and s-E-(2-thiazolyl)iminopropadienone28 (2250 and 2245 cm�1) were observed. 29: nmax (Argon 7K)/cm�1 2050v., 1706s, 1486w, 1426w, 1413w, 1363w, 1281w,

1212w, 1152w, 1105m, 1060w, 1049w, 970w, 859w, 737m,721m, 714w, 694w, 603w. s-Z-28: nmax (Argon 7K)/cm�1

2250v., 2164w, 1641w, 1486w, 1413w, 1276w, 1212w,1105w, 1060w, 818w, 694w, 603w. s-E-28: nmax (Argon 7K)/

cm�1 2245v., 2127w, 1621m, 1480w, 1396w, 1276w, 1223w,1118w, 1060w, 818w, 694w, 666w. Bands due to methanethiolwere observed at 963w, 1331w, 1434w, 2550vw, 2941w and

3007w cm�1 in agreement with literature data.[8]

Thermolysis of 2,3-dihydro-7-methylthio-5H-thiazolo[3,2-a]pyrimidine-5-one 31

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 cm�1) was theonly compound observed in the IR-spectra. From 800–9008C,a mixture of 31, cyanoketene 36 (2164, 2239 cm�1),[13] and

signals tentatively assigned to (4,5-dihydro-2-thiazolyl)imino-propadienone 35 (2244 cm�1) and keteneimine 33 (2044 cm�1)were observed. Cyanoketene (2164v., 2239m cm�1) was the

major product observed at 10008C. Bands due tomethanethiol[8] were observed at 962, 1327, 1436, 1447, 2550and 3007 cm�1, bands due to HNCS[19] at 1982 and 3509 cm�1,

and bands due to acetylene[20] at 737, 1328, 3288 and3304 cm�1. Very weak bands assignable to thiazole[18] wererecorded at 799, 864, 881, 1041, 1239, 1322, 1383, 1484 and3095 cm�1.

Accessory Publication

Ar matrix IR spectra and observed and calculated wavenumbersof iminopropadienones 6, 19b, 19c, and 28 and full-scale IRspectra 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.

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