Heterocyclic synthesis with activated nitriles: An expeditious synthetic approach to polyfunctionally substituted pyrroles, heterocyclopyrimidines and coumarins

Article abstract of DOI:10.1081/SCC-120018775

The applicability and synthetic potency of the new reagent N-(2,2-dicyanoethenyl)aminoacetonitrile (3) to develop an expeditious convenient synthetic route of unique polyfunctionally substituted pyrroles, heterocyclopyrimidines, and 2H-1-benzopyran-2-ones

Full text of DOI:10.1081/SCC-120018775

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Heterocyclic Synthesis with Activated Nitriles: An
Expeditious Synthetic Approach to Polyfunctionally
Substituted Pyrroles, Heterocyclopyrimidines and
Coumarins
Ayman W. Erian a , Sherif M. Sherif a & Nadia R. Mohamed b
a Department of Chemistry , Faculty of Science , Cairo University , Giza, Egypt
b Department of Photochemistry , National Research Center , Dokki, Giza, Egypt
Published online: 16 Aug 2006.
To cite this article: Ayman W. Erian , Sherif M. Sherif & Nadia R. Mohamed (2003) Heterocyclic Synthesis with Activated
Nitriles: An Expeditious Synthetic Approach to Polyfunctionally Substituted Pyrroles, Heterocyclopyrimidines and Coumarins,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:9,
1563-1573, DOI: 10.1081/SCC-120018775
To link to this article: http://dx.doi.org/10.1081/SCC-120018775
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 9, pp. 1563–1573, 2003
Heterocyclic Synthesis with Activated Nitriles:
An Expeditious Synthetic Approach to
Polyfunctionally Substituted Pyrroles,
Heterocyclopyrimidines and Coumarins
1,
1
Sherif M.Sherif, and
*
Ayman W.Erian,
2
Nadia R.Mohamed
1Department of Chemistry, Faculty of Science,
Cairo University, Giza, Egypt
2Department of Photochemistry,
National Research Center, Dokki, Giza, Egypt
ABSTRACT
The applicability and synthetic potency of the new reagent N-(2,2-
dicyanoethenyl)aminoacetonitrile (3) to develop an expeditious
convenient synthetic route of unique polyfunctionally substituted
pyrroles, heterocyclopyrimidines, and 2H-1-benzopyran-2-ones is
reported. Chemical and spectroscopic evidence for the structures of
the newly synthesized compounds are described.
*Correspondence: Ayman W. Erian, Department of Chemistry, Faculty of
Science, Cairo University, Giza, Egypt; E-mail: erian10@yahoo.com.
1563
DOI: 10.1081/SCC-120018775
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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1564
Erian, Sherif, and Mohamed
a,b-p-Deficient nitrile reagents are highly reactive and are extensively
utilized as unique synthons for the construction of a variety of unique
heterocyclic ring systems.[1–5] In continuation with ourmedicinal chem-
istry program directed towards the development of new procedures for
the synthesis of azoles, azines, and theircondensed derivatives utilizing
readily obtainable polyfunctional nitriles,[6–10] we report herein, an easy,
facile, and new synthetic methodology forthe synthesis of N-(2,2-dicya-
noethenyl)aminoacetonitrile (3). The latterporved to be a new key
precursor for the synthesis of some polyfunctionally substituted pyrroles,
thiazolo[1,2-a]pyrimidines, pyrido[1,2-a]pyrimidines, and coumarins.
The importance of those compounds is due to their diverse potential
biological and physiological expected broad spectrum.[11–14]
RESULTS AND DISCUSSION
The key precursor N-(2,2-dicyanoethenyl)aminoacetonitrile (3) was
prepared, in a facile high yield reaction, upon treatment of aminoaceto-
nitrile hydrogen sulphate (1) with an equimolaramount of ethyl 2-cyano-
3-ethoxypropenonitrile (2) in an aqueous alcoholic NaOH solution at
room temperature. Assignment of structure 3 for the reaction product
was based on its correct elemental analyses and compatible spectroscopic
data. Thus, its mass spectrum revealed a molecular ion peak at m/z
(%) ¼ 132 (18%) corresponding to the molecular formula C6H4N4. Its
IR spectrum showed absorption peaks at ꢀ 3340 (NH), and 2220, 2216,
1
2208 cmÀ1 (3CN). Its H-NMR spectrum (DMSO-d6) showed a singlet
signal (2H) at ꢁ 4.12 ppm assigned forthe CH protons, a singlet at ꢁ
2
7.32 ppm assigned for the CH proton, and a broad signal at ꢁ 9.11 ppm
assigned for the NH proton which underwent a facile hydrogen deute-
rium exchange and disappeared upon addition of D2O to the NMR
sample. The structure of 3 was further confirmed on the basis of its
chemical behavior towards different chemical reagents.
Compound 3 reacted with an equimolar amount of diazomethane in
dry ether at ice bath to yield the corresponding N-methyl derivative 4.
The active methylene group in compound 4 underwent an electrophilic
substitution upon coupling with equimolaramounts of ayrldiazonium
chloride salts to yield the corresponding hydrazone coupling products
5a,b. Compound 5 proved to exist predominantly in the hydrazone
1
form rather than the azo form on the basis of H-NMR data. Thus,
e.g., 5a revealed, besides the expected signals, the presence of a singlet
signal exchangeable with D2O at ꢁ 8.21 ppm attributed to the hydrazone
NH function. Furthermore, its UV spectrum showed absorption maxima

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Heterocyclic Synthesis with Activated Nitriles
1565
at ꢂ 420 (" ¼ 35,280) and 330 nm (" ¼ 23,470) in accordance with those for
[15,16]
hydrazo functions which are reported to exhibit strong absorption at
wavelengths higherthan 310 nm.
Compound 4 underwent an intramolecular heterocyclization, upon
boiling under reflux in dry pyridine, to afford 3-amino-2,4-dicyano-1-
methylpyrrole (6). Compound 3 readily reacted with an equimolar
amount of ethyl chloroacetate in aqueous Na2CO3 solution, under
reflux, to yield ethyl 3-amino-4-cyano-1-cyanomethylpyrrole-2-carboxy-
late (7) (Sch. 1). Formation of 7 is assumed to proceed via an initial
N-alkylation and a subsequent intramolecular heterocyclization via
nucleophilic addition of the CH2 protons to the cyano function.
The base-promoted nucleophilic addition of phenyl isothiocyanate to
3 has been achieved, upon boiling underreflux in an aqueous ethanolic
NaOH solution, to yield the corresponding 1-cyanomethyl-4-oxo-2-
thioxopyrimidine derivative 8 (Sch. 2). The reaction apparently involves
an intramolecular heterocyclization via the addition of the amine nitro-
gen of 3 to the carbon of isothiocyanate function and a subsequent alka-
line hydrolysis of the imino function under the reaction conditions.[17]
Reaction of 8 with an equimolaramount of N,N-dimethylformamide
Scheme 1.

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1566
Erian, Sherif, and Mohamed
dimethylacetal (DMF–DMA) in dry dioxane, under reflux, furnished
5-cyano-1-[10 -cyano-20 -dimethylaminoethenyl)-4-oxo-3-phenyl-1,2,3,4-
tetra-hydro-2-thioxopyrimidine (9) in an acceptable yield. Treatment of 9
with an equimolar amount of hydrazine hydrate in refluxing ethanol
furnished exclusively a single product that could be formulated as 1-[30-
amino-pyrazol-40-yl]-5-cyano-4-oxo-3-phenyl-1,2,3,4-tetrahydro-2-thioxo-
pyrimidine (10). Characterization of 10 is consistent with its elemental
analysis and spectral data. However, compound 10 was an unstable
yellow product that decomposed automatically at 25ꢀC within two
days, therefore, it should be stored in a refrigerator. When compound
3 was treated with an equimolar amount of N,N-dimethylformamide
dimethylacetal (DMF–DMA) in dry dioxane, under reflux, the corres-
ponding 2,2-dimethylaminoethenyl derivative 11 was isolated. Elucida-
tion of the proposed structure 11 was based on its correct elemental
analyses and compatible spectroscopic data.
Next, it was of interest to explore the scope, limitations, and general-
ity of 11 as a precursor for the synthesis of some difficult to access poly-
functionally substituted fused pyrimidine or benzopyranone derivatives
forwhich we might expect a wide specturm of bioersponses. Thus,
reaction of 11 with equimolaramounts of N-nucleophiles; namely,
2-aminopyridine or 2-aminothiazole, upon reflux in glacial acetic acid,
afforded the corresponding 4H-pyrido[1,2-a]pyrimidin-4-one 13 and
Scheme 2.

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Heterocyclic Synthesis with Activated Nitriles
1567
5H-thiazolo[1,2-a]pyrimidin-5-one 15 derivatives, respectively, in reason-
able yields (Sch. 3). The identity of the product was established on the
basis of elemental analyses and spectral background in each case.
Analogously, compound 11 reacted with C-nucleophiles e.g.,
dimedone, underthe same expeimr ental conditions to yield the
corresponding 5,6,7,8-tetrahydro-2H-1-benzopyran-2-one derivative 17.
The free amino heterocycles 18–20 could be achieved on treatment of
the appropriate 2,2-dicyanoethenylamino heterocycles 13, 15, or 17 with
hydrazine hydrate in ethanol at reflux temperature, respectively.
In conclusion, the results presented in this article, indirectly extend
and broaden the knowledge in the area of activated nitriles and demon-
Scheme 3.

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1568
Erian, Sherif, and Mohamed
strate a general applicable methodology for the construction of a wide
variety of polyfunctionally substituted annelated pyrimidines and 2H-1-
benzopyranones of expected wide spectrum of potential bioresponses.
Work along the expansion of such synthetic approach is now in
progress.
EXPERIMENTAL SECTION
Melting points are uncorrected. IR spectra were recorded (KBr disc)
1
on a Pye Unicam SP-1000 spectrophotometer. H-NMR spectra were
obtained on a Varian Gemini 200 MHz spectrophotometer using TMS
as an internal reference. Chemical shifts are expressed as ꢁ (ppm). Mass
spectra were recorded on a GCMS-QP 1000 Ex spectra mass spectro-
meter operating at 70 eV. Microanalytical data were performed by the
Microanalytical Data Unit, Cairo University.
N-(2,2-Dicyanoethenyl)aminoacetonitrile (3): To a solution of amino-
acetonitrile hydrogen sulphate (1) (100 mmol, 15.4 g) in water(60 mL)
containing sodium hydroxide (100 mmol, 4.0 g), a solution of ethyl 2-
cyano-3-ethoxypropenoate (2) (100 mmol, 12.2 g) in EtOH (50 mL) was
added portionwise. The reaction mixture was stirred for 2 h and left aside
overnight at room temperature. The solid product that separated was
collected by filtration and crystallized from ethanol to give 10.04 g
(76%); m.p. 45–47ꢀC. IR (KBr): 3340 (NH), 2220, 2216, 2208 cmÀ1
1
(3CN). H-NMR (DMSO-d6): ꢁ 4.12 (s, 2H, CH2), 7.32 (s, 1H, CH),
9.11 (brs, 1H, NH, exchangeable).
m/z (%) 132 (Mþ, 18%).
Anal. calcd. forC H4N4: C, 54.5; H, 3.05; N, 42.4. Found: C, 54.4; H,
3.0; N, 42.2.
6
N-(2,2-Dicyanoethenyl)-N-methylaminoacetonitrile (4): To a solution
of 3 (20 mmol, 2.64 g) in dry ether (50 mL), diazomethane (20 mmol,
0.84 g) was added. The reaction mixture was stirred at ice-bath tempera-
ture 0–5ꢀC for2 h, then left aside ovenright at 0 ꢀC. The mixture was
evaporated under reduced pressure at 25ꢀC, whereby the residue that
precipitated was collected by filtration and crystallized from ether.
Yield 2.07 g (71%); m.p. 49ꢀC. IR (KBr): 2220, 2214, 2210 cmÀ1
1
(3CN). H-NMR (DMSO-d6): ꢁ 2.12 (s, 3H, CH3), 4.08 (s, 2H, CH2),
7.18 (s, 1H, CH). Anal. calcd. forC H6N4: C, 57.5; H, 4.1; N, 38.3.
Found: C, 57.4; H, 4.1; N, 38.2.
7
Arylhydrazono-N-(2,2-dicyanoethenyl)-N-methylaminoacetonitriles (5a,b):
(General Procedure). To a stirred solution of 4 (5 mmol, 0.73 g) in ethanol
(50 mL) containing NaOAc (1.0 g), the appropriate aryldiazonium chlo-
ride (5 mmol) [prepared by adding NaNO2 (5 mmol, 0.35 g) to the appro-

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Heterocyclic Synthesis with Activated Nitriles
1569
priate primary aromatic amine (5 mmol) in concentrated HCl (2 mL) at
0–5ꢀC while stirring] was added dropwise while cooling at 0–5ꢀC and
stirring. The reaction mixture was left aside at room temperature for
3 h, whereby the solid product that separated was collected by filtration,
dried, and crystallized from the appropriate solvent.
N-(2,2-Dicyanoethenyl)-N-methylphenylhydrazonoaminoacetonitriles
(5a): 0.70 g (56%); m.p. 105ꢀC (EtOH). IR (KBr): 2222, 2218, 2209 cmÀ1
1
(3CN). H-NMR (DMSO-d6): ꢁ 2.05 (s, 3H, CH3), 7.16 (s, 1H, CH),
7.32–7.39 (m, 5H, aromatic protons), 8.21 (s, 1H, NH, exchangeable).
m/z (%) 250 (Mþ, 22%). Anal. calcd. forC 13H10N6: C, 62.4; H, 4.0; N,
33.6. Found: C, 62.2; H, 4.0; N, 33.5.
p-Chlorophenylhydrazono-N-(20,20-dicyanoethenyl)-N-methylamino-
acetonitriles (5b): 0.88 g (62%); m.p. 121ꢀC (EtOH). IR (KBr):
3342 (NH), 2220, 2218, 2210 cmÀ1 (3CN). 1H-NMR (DMSO-d6): ꢁ
2.08 (s, 3H, CH3), 7.14 (s, 1H, CH), 7.30–7.36 (m, 4H, aromatic pro-
tons), 8.52 (s, 1H, NH, exchangeable). Anal. calcd. forC 13H9ClN6: C,
54.8; H, 3.2; Cl, 12.45; N, 29.5. Found: C, 54.8; H, 3.0; Cl, 12.3; N,
29.5.
3-Amino-2,4-dicyano-1-methylpyrrole (6): A solution of 4 (5 mmol,
0.73 g) in dry pyridine (30 mL) was refluxed for 3 h. The reaction mixture
was cooled at room temperatures triturated with water, whereby the
resulted solid product was collected by filtration, dried, and crystallized
from AcOH. Yield 0.39 g (54%); m.p. 152–154ꢀC (EtOH). IR (KBr):
3450–3380 (NH2), 2218, 2212 cmÀ1 (2 CN). 1H-NMR (DMSO-d6):
ꢁ 2.31 (s, 3H, CH3), 6.33 (s, 1H, pyrrole 5-H), 10.71 (br s, 2H, NH2,
exchangeable). Anal. calcd. forC 7H6N4: C, 57.5; H, 4.1; N, 38.3.
Found: C, 57.4; H, 4.0; N, 38.2.
Ethyl 3-amino-4-cyano-1-cyanomethylpyrrole-2-carboxylate (7): To a
warm solution of 3 (5 mmol, 0.66 g) in ethanol (30 mL), ethyl chloro-
acetate (5 mmol, 0.61 g) in an aqueous Na2CO3 solution [5 mmol, 0.28 g
in H2O (10 mL)] was added. The reaction mixture was refluxed for 2 h,
left to cool at room temperature, poured onto cold water, and neutralized
with dilute HCl. The solid product separated was filtered off, dried, and
crystallized from AcOH. Yield 0.60 g (55%); m.p. 142ꢀC (EtOH). IR
1
(KBr): 3445–3380 (NH2), 2218, 2210 cmÀ1 (2CN). H-NMR (DMSO-
d6): ꢁ 1.10 (t, 3H, CH3, J ¼ 7.2 Hz), 4.00 (q, 2H, CH2, J ¼ 7.2 Hz), 4.12
(s, 2H, CH2), 6.31 (s, 1H, pyrrole 5-H), 10.62 (br s, 2H, NH2, exchange-
able). m/z (%) 218 (Mþ, 18%). Anal. calcd. forC 10H10N4O2: C, 55.0; H,
4.6; N, 25.7. Found: C, 55.0; H, 4.5; N, 25.6.
1-Cyanomethyl-4-oxo-3-phenyl-1,2,3,4-tetrahydro-2-thioxopyrimidine
(8): To a solution of 3 (5 mmol, 0.66 g) in ethanol (30 mL), phenyl iso-
thiocyanate (5 mmol, 0.67 g) in aqueous solution of NaOH (5 mmol,

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1570
Erian, Sherif, and Mohamed
0.20 g in 10 mL H2O) was added. The reaction mixture was refluxed for
3 h, left to cool at room temperature, poured onto cold water and neu-
tralized with dilute HCl. The formed precipitate was filtered off, dried
and crystallized from AcOH. Yield 0.86 g (64%); m.p. 163ꢀC (EtOH). IR
(KBr): 2220, 2216 (2CN), 1690 (CO) cmÀ1. 1H-NMR (DMSO-d6): ꢁ 4.08
(s, 2H, CH2), 6.18 (s, 1H, pyrimidine 4-H), 7.28–7.34 (m, 5H, aromatic
protons). Anal. calcd. for C13H8N4OS: C, 58.2; H, 3.0; N, 20.9; S, 11.95.
Found: C, 58.0; H, 2.9; N, 20.7; S, 11.8.
5-Cyano-1-[10-cyano-20-dimethylaminoethenyl)-4-oxo-3-phenyl-1,2,3,4-
tetrahydro-2-thioxopyrimidine (9): To a solution of 8 (5 mmol, 1.34 g) in
dry dioxane (30 mL), dimethylformamide dimethylacetal (DMF–DMA)
(5 mmol, 0.6 g) was added. The reaction mixture was refluxed for 3 h,
evaporated in vacuo and triturated with ethanol. The resulting solid
product was collected by filtration, dried and crystallized from dioxane.
Yield 0.79 g (49%); m.p. 175ꢀC (EtOH). IR (KBr): 2218, 2215 (2CN),
1686 cmÀ1 (CO). 1H-NMR (DMSO-d6): ꢁ 2.86 (s, 6H, 2CH3), 6.12 (s, 1H,
pyrimidine 4-H), 7.26–7.31 (m, 5H, aromatic protons), 8.22 (s, 1H, CH).
Anal. calcd. forC 16H13N5OS: C, 59.4; H, 4.05; N, 21.65; S, 9.9. Found:
C, 59.4; H, 3.8; N, 21.4; S, 9.8.
1-[30-Aminopyrazol-40-yl]-5-cyano-4-oxo-3-phenyl-1,2,3,4-tetrahydro-
2-thioxopyrimidine (10): A mixture of 9 (3 mmol, 0.97 g) and hydrazine
hydrate (3 mmol, 0.97 g) in ethanol (30 mL) was boiled under reflux for
30 min and then left aside at room temperature overnight. The mixture
was poured onto cold water, whereby the solid product was filtered
off and crystallized from EtOH. Yield 0.52 g (56%); m.p. 138ꢀC
(EtOH). IR (KBr): 3445–3210 (NH and NH2), 2218 (CN), 1690 cmÀ1
1
(CO). H-NMR (DMSO-d6): ꢁ 6.05 (s, 1H, pyrazole 5-H), 6.22 (s, 1H,
pyrimidine 4-H), 7.26–7.31 (m, 5H, aromatic protons), 8.46 (s, 1H, NH,
exchangeable), 9.62 (brs, 2H, NH 2, exchangeable). Anal. calcd. for
C14H10N6OS: C, 54.2; H, 3.25; N, 27.1; S, 10.3. Found: C, 54.0; H, 3.2;
N, 26.9; S, 10.2.
N-(2,2-Dicyanoethenyl)-2,2-dimethylaminoethenyl aminoacetonitrile (11):
To a solution of 3 (10 mmol, 1.32 g) in dry dioxane (30 mL), dimethyl-
formamide dimethylacetal (DMF–DMA) (10 mmol, 1.2 g) was added.
The reaction mixture was refluxed for 3 h, evaporated in vacuo and trit-
urated with ethanol. The resulting solid product was filtered, dried, and
crystallized from dioxane. Yield 1.01 g (54%); m.p. 135ꢀC (EtOH). IR
(KBr): 3345 (NH), 2218, 2216, 2210 cmÀ1 (3 CN). 1H-NMR (DMSO-d6):
ꢁ 2.81 (s, 6H, 2CH3), 7.15 (d, 1H, CH), 8.16 (brs, 1H, NH, exchangeable),
8.22 (s, 1H, CH). Anal. calcd. forC H9N5: C, 57.7; H, 4.8; N, 37.4.
9
Found: C, 57.6; H, 4.8; N, 37.3.

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Heterocyclic Synthesis with Activated Nitriles
1571
Reaction of 11 with Heteroaryl Amines 12, 14 and with
C-Nucleophile 16 (General Procedure)
To a solution of 11 (4 mmol, 0.75 g) in glacial AcOH (30 mL), the
appropriate heteroaryl amine or C-nucleophile (4 mmol) was added. The
reaction mixture was refluxed for 3 h and then left aside at room tem-
perature overnight. The mixture was evaporated under reduced pressure,
the residue was triturated with ethanol, whereby the solid precipitated
so-formed was collected by filtration, dried, and crystallized from the
appropriate solvent.
3-(2,2-Dicyanoethenyl)amino-4H-pyrido[1,2-a]pyrimidin-4-one (13):
Yield 0.39 g (41%); m.p. 171ꢀC (EtOH). IR (KBr): 3420, 3415 (NH),
1
2220, 2218 (2CN), 1695 cmÀ1 (CO). H-NMR (DMSO-d6): ꢁ 7.21–7.32
(m, 6H, aromatic protons þCH), 8.95 (s, 1H, NH, exchangeable). m/z
(%) 237 (Mþ, 16%). Anal. calcd. forC 12H7N5O: C, 60.8; H, 3.0; N, 29.5.
Found: C, 60.6; H, 2.9; N, 29.3.
6-(2,2-Dicyanoethenyl)amino-5H-thiazolo[1,2-a]pyrimidin-5-one (15):
Yield 0.38 g (49%); m.p. 193ꢀC (EtOH). IR (KBr): 3435 (NH), 2220,
2216 (2 CN), 1690 cmÀ1 (CO). 1H-NMR (DMSO-d6): ꢁ 7.08 (s, 1H,
pyrimidine H-4), 7.16 (d, 2H, thiazole H-4, H-5), 7.28 (s, 1H, CH),
8.92 (s, 1H, NH, exchangeable). Anal. calcd. forC 10H5N5OS: C, 49.4;
H, 2.1; N, 28.8; S, 13.2. Found: C, 49.3; H, 1.9; N, 28.6; S, 13.0.
3-(2,2-Dicyanoethenyl)amino-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-
2H-1-benzopyran-2-one (17): Yield 0.49 g (43%); m.p. 210ꢀC (EtOH). IR
(KBr): 3435 (NH), 2220, 2216 (2CN), 1690, 1682 cmÀ1 (2 CO). 1H-NMR
(DMSO-d6): ꢁ 1.24 (s, 6H, 2CH3), 2.48 (s, 2H, CH2), 2.73 (s, 2H, CH2),
7.58 (s, 1H, H-4), 7.72 (d, 1H, CHNH), 10.52 (d, 1H, NH, exchangeable).
Anal. calcd. forC 15H13N3O3: C, 63.6, H, 4.6; N, 14.8. Found: C, 63.5; H,
4.6; N, 14.7.
Preparation of the Free Aminoheterocycles 18, 19, and 20
(General Procedure)
A mixture of the N-(2,2-dicyanoethenyl)amino heterocyclic com-
pound 13, 15, or 17 (2 mmol) and hydrazine hydrate (2 mmol, 0.1 g) in
ethanol (15 mL) was refluxed for 1 h, and then left aside at room
temperature overnight. The precipitated resulted was filtered off and
crystallized from the appropriate solvent.
3-Amino-4H-pyrido[1,2-a]pyrimidin-4-one (18): Yield 0.17 g (52%);
m.p. 178–180ꢀC (EtOH) (Lit.[18] m.p. 180–182ꢀC). IR (KBr): 3450–3375

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1572
Erian, Sherif, and Mohamed
1
(NH2), 1690 cmÀ1 (CO). H-NMR (DMSO-d6): ꢁ 5.57 (brs, 2H, NH ,
2
exchangeable), 7.21–7.38 (m, 5H, aromatic protons). m/z (%) 161 (Mþ,
14%). Anal. calcd. forC H7N3O: C, 59.6; H, 4.4; N, 26.1. Found: C,
59.5; H, 4.3; N, 25.9.
8
6-Amino-5H-thiazolo[3,2-a]pyrimidin-5-one (19): Yield 0.22 g (66%);
m.p. 170–172ꢀC (EtOH). IR (KBr): 3454–3375 (NH2), 1688 cmÀ1 (CO).
1H-NMR (DMSO-d6): ꢁ 5.14 (brs, 2H, NH 2, exchangeable), 7.15 (s, 1H,
pyrimidine 4-H), 7.23 (d, 2H, thiazole H-4, H-5). Anal. calcd. for
C6H5N3OS: C, 43.1; H, 3.0; N, 25.1; S, 19.2. Found: C, 43.0; H, 2.8;
N, 24.9; S, 19.0.
3-Amino-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-2H-1-benzopyran-2-one
(20): Yield 0.20 g (49%); m.p. 149ꢀC (EtOH). IR (KBr): 3450–3364 (NH2),
1695, 1688 cmÀ1 (2 CO). 1H-NMR (DMSO-d6): ꢁ 1.26 (s, 6H, 2CH3), 2.44
(s, 2H, CH2), 2.63 (s, 2H, CH2), 5.35 (brs, 2H, NH 2, exchangeable), 7.40
(s, 1H, H-4). Anal. calcd. forC 11H13NO3: C, 63.75; H, 6.3; N, 6.8. Found:
C, 63.6; H, 6.3; N, 6.6.
REFERENCES
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Heterocyclic Synthesis with Activated Nitriles
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49, 133.
Received in the UK May 15, 2002

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©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.