Synthesis of some heterocyclic compounds from enamines of 3-acetylfuran-2(5 H)-ones

Article abstract of DOI:10.1080/00397911.2011.555591

The interaction of different 3-acetylfuran-2(5H)-ones (1, 4) with dimethylformamide dimethyl acetal (DMF/DMA) has been investigated, and the condensed furopyridine system 3 was obtained. By means of interaction of compounds 4 and DMF/DMA via the 3-acetylfuran-2(5H)-one enamines, the heterocyclic substituted furanones are obtained. The condensation of 3-acetyl-4,5,5-trimethylfuran-2(5H)-one (1a) with veratraldehyde was realized. Through the interaction of 1a with malononitrile and further intramolecular condensation of the product, 6-amino-dihydroisobenzofuran-5-carbonitrile was also synthesized.

Full text of DOI:10.1080/00397911.2011.555591

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Synthesis of Some Heterocyclic
Compounds from Enamines of 3-
Acetylfuran-2(5 H)-ones
Gagik S. Melikyan a , Anna A. Hovhannisyan a & Sargis S. Hayotsyan a
a Department of Organic Chemistry , Yerevan State University ,
Yerevan , Armenia
Accepted author version posted online: 15 Dec 2011.Published
online: 09 Apr 2012.
To cite this article: Gagik S. Melikyan , Anna A. Hovhannisyan & Sargis S. Hayotsyan (2012)
Synthesis of Some Heterocyclic Compounds from Enamines of 3-Acetylfuran-2(5 H)-ones, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
42:15, 2267-2276, DOI: 10.1080/00397911.2011.555591
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Synthetic Communications1, 42: 2267–2276, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.555591
SYNTHESIS OF SOME HETEROCYCLIC COMPOUNDS
FROM ENAMINES OF 3-ACETYLFURAN-2(5 H)-ONES
Gagik S. Melikyan, Anna A. Hovhannisyan, and
Sargis S. Hayotsyan
Department of Organic Chemistry, Yerevan State University,
Yerevan, Armenia
GRAPHICAL ABSTRACT
Abstract The interaction of different 3-acetylfuran-2(5H)-ones (1, 4) with dimethylforma-
mide dimethyl acetal (DMF=DMA) has been investigated, and the condensed furopyridine
system 3 was obtained. By means of interaction of compounds 4 and DMF=DMA via the
3-acetylfuran-2(5H)-one enamines, the heterocyclic substituted furanones are obtained.
The condensation of 3-acetyl-4,5,5-trimethylfuran-2(5H)-one (1a) with veratraldehyde
was realized. Through the interaction of 1a with malononitrile and further intramolecular con-
densation of the product, 6-amino-dihydroisobenzofuran-5-carbonitrile was also synthesized.
Keywords 3-Acetylfuran-2(5 h)-ones; 6-amino-dihydroisobenzofuran-5-carbonitrile;
enamines of 3-acetylfuran-2(5 H)-ones; furopyridines; 3-heterocyclyl-furan-2-ones
INTRODUCTION
A symmetrical 3,4-disubstituted 2(5H)-furanones are not common in nature,
though some of their derivatives feature in literature sources as drugs and biocides.[1]
Their natural representatives, gymnoascolides, recently isolated from Australian soil
Received December 27, 2010.
Address correspondence to Gagik S. Melikyan, Department of Organic Chemistry, Yerevan State
University, Alex Manoogian 1, 0025 Yerevan, Armenia. E-mail: suren@netsys.am
2267

2268
G. S. MELIKYAN, A. A. HOVHANNISYAN, AND S. S. HAYOTSYAN
ascomycete Gimnoascus reessii and Malbranchea filamentosa IFM41300, possess
antifungal and vasodilatory activities, and their structural analog, eutopoid A, was
isolated from the South China Sea marine fungus of the genus Eutipa.[2]
Compounds with similar structures are also used in medicine and agrochemistry.[3–5]
According to some authors, the presence of aromatic substituents in furan-2-ones is an
important factor for development of biological activity, and these works are devoted
mainly to the synthesis of substituted furanones.[6]
Some of our earlier published works[7–10] were dedicated to the synthesis of
unsaturated c-lactones with heterocyclic substituents. Particularly, those possessing
biological activity (benzimidazolyl-, benzothiazolyl- and benzoxazolyl substituted
furan-2-ones) were synthesized.
In continuation of our work in the field of enamine-based heterocyclic system
synthesis[11] and for the purpose of getting compounds combining furanone and
nitrogen-containing heterocycles, 3-acetyl-4-methyl-5,5-dialkylfuran-2(5H)-one-
s[12](1a,b) were chosen as initial objects. For the synthesis of corresponding
enamines, the condensation of 1a,b with DMF=DMA in refluxing anhydrous xylene
was carried out Scheme 1. The reaction yields were up to 96%.
The presence of two potentially reactive methyl groups in the initial compound
1 allowed an assumption of two possible methods of condensation (A and B) with
the formation of corresponding products. The structures of obtained compounds 2
1
have been investigated using H, 13C, and nuclear Overhauser effect (2D-NOESY)
NMR spectroscopy.
In the 1H NMR spectrum of the compound 1a, there are two signals of methyl
groups at 2.46 and 2.36 ppm, which correspond to the acetyl group and 4-methyl
group of the furanone ring, whereas in the spectrum of 2a there is only one signal
in this region, at 2.31 ppm.
The 13C NMR spectrum of 1a shows two signals of methyl groups at 12.4 and
29.3 ppm, and for the compound 2a there is only one signal at 29.2 ppm which is

HETEROCYCLES FROM 3-ACETYLFURANONES
2269
Scheme 1.
typical for the methyl group of acetone derivatives (i.e., there is acetyl group in
compound 2a).
For more certainty, the 2D-NOESY spectrum of 2a was gathered, which shows
the presence of crosspeaks between the signals of equivalent protons of two methyl
groups at the position 5 of furanone ring and vinyl protons of dimethylaminovinyl
fragment. This indicates the steric adjacency of these fragments, which means that
in the reaction of 1a and DMF=DMA the 4-methyl group of the ring is involved,
leaving the acetyl group unaffected (i.e., the reaction course is A).
Furthermore, there are no cross peaks between acetyl fragment’s methyl pro-
tons and vinyl protons, which indicates the steric remoteness of these groups.
An interaction of enamine 2b with 20% ammonia solution leads to a condensed
furopyridine system 3, which could be related to alkaloid serpegin.[13] The compound
3 could not be received from the enamine B, which is a chemical confirmation of struc-
ture 2. It also worth mentioning that the reaction pathway A leads to the conjugated
system, while according to the alternative pathway B the proposed compound
represents a concurrently conjugated system. This may be the reason for the realiza-
tion of condensation of furanone 1a and DMF=DMA by the pathway A.
It is well known from the literature that the compounds containing N,N-
dimethylaminovinylketone fragment are convenient starting materials for the synthesis
of various nitrogen-containing heterocyclic systems.[14,15] To the desired fragment, the
methyl group of acetyl substituent should be involved in the condensation with DMF=
DMA, which as we showed is not the case for 4-methyl substituted furanones in these
conditions. Therefore, for that purpose 3-acetyl-4-phenyl-5,5-dimethyl-furan-2(5H)-
one (4a) was chosen,[16] which under the same conditions leads to the desired com-
pound 5a with dimethylaminovinylketone substituent Scheme 2.
Existence of the N,N-dimethylaminovinylketone fragment allows a number of
condensations (with hydroxylamine hydrochloride, hydrazine hydrate, and guanidine
nitrate) to obtain corresponding compounds, as shown in Scheme 3. Syntheses are
carried out according to known methods,[14,15] with adaption to our systems. Yields
were 67–90%.
Taking into account that, among substituted furanones spiro-compounds are
especially interesting from the point of view of biological activity,[16] these reactions
were also carried out also for furanone 5b, and corresponding spiro-derivatives were

2270
G. S. MELIKYAN, A. A. HOVHANNISYAN, AND S. S. HAYOTSYAN
Scheme 2.
obtained in good yields. It is also noteworthy that compounds 8a,b could be used as
condensation agents, because of the primary amino group in their molecule.
The greater activity of the 4-methyl group of furanone ring in the condensation
reaction with DMF=DMA allowed us to assume that 1a will behave similarly in
other reaction conditions. Earlier we researched condensation of 3-cyano- and
3-ethoxycarbonyl-furan-2(5H)-ones with different aldehydes on many samples.[18]
However, reaction was not spread to 3-acetylfuran-2(5H)-one (1) because of the
existence of two competitive reaction centers. On the basis of our new investigation
and with the purpose of synthesizing novel aromatic derivatives of furan-2(5H)-ones,
similar interaction held for 1a and veratraldehyde, as shown in Scheme 4.
The 13C NMR spectrum of compound 9 showed an existence of the signal at
29.93 ppm corresponding to the methyl group of acetyl moiety (i.e., in this case also
the condensation occurred by pathway A). Such course of the reactions could be
explained as with the greater activity of the 4-methyl group of furanone ring either
in apolar nonprotic or polar protic solvents as well as with the stability of products
(2a, b, 9) due to the conjugation effect.
Scheme 3.

HETEROCYCLES FROM 3-ACETYLFURANONES
2271
Scheme 4.
Scheme 5.
An interesting continuation of the synthesis of enamines on the basis of
3-acetyl-4,5,5-trimethyl-furan-2(5H)-one (1a) became a two-step synthesis of dihydroi-
sobenzofuranones. In Knoevenagel condensation conditions, from 1a and malononi-
trile, the 2-(1-(4,5,5-trimethyl-2-oxo-2,5-dihydrofuran-3-yl)ethylidene)malononitrile
(10) was synthesized,[19] which in sodium hydroxide ethanol solution undergoes further
intramolecular condensation to give target product 11[20] Scheme 5. Formed
6-amino-1,1,4-trimethyl-3-oxo-1,3-dihydroisobenzofuran-5-carbonitrile (11) is inter-
esting either by itself or as a potential starting compound for further transformations.
EXPERIMENTAL
All melting points were determined on a Kofler hot-stage microscope and are
1
uncorrected. HNMR and 13CNMR spectra were obtained on a Varian Mercury
300 spectrometer at 300 and 75MHz in DMSO-d6 solution at 303 K with tetramethyl-
silane (TMS) as internal reference, assignment of signals is done on the basis of
2D-NOESY data. Initial compounds 3-acetyl-4-methyl-5,5-dialkylfuran-2(5H)-one[19]
(1a,b) and 3-acetyl-4-phenyl-5,5-dialkylfuran-2(5H)-one[16] (4a,b) were synthesized by
corresponding methods.
Initial Compounds
3-Acetyl-4,5,5-trimethylfuran-2(5H)-one (1a). Yield 70%; Mp 50–51 ꢀC
1
(Ref.[19] 50–51 ꢀC); H-NMR: 1.48 (s, 6H, 2CH3); 2.31 (s, 3H, CH3); 2.46 (s, 3H,

2272
G. S. MELIKYAN, A. A. HOVHANNISYAN, AND S. S. HAYOTSYAN
CH3CO); 13C NMR: 12.43 (CH3); 23.8 (2C, 2CH3), 29.3 (C(O)CH3); 84.5 (O-C);
122.9 (C(O)-C-C(O)); 167.8 (OC(O)); 179.4 (C-CH3); 193.5 (C(O)CH3). Calculated
for C9H12O3(%): C, 64.27; H, 7.19. Found (%): C, 64.44; H, 7.05.
3-Acetyl-4-methyl-1-oxaspiro[4,5]dec-3-en-2-one (1b). Mp 99–101 ꢀC
(Ref[19] 99–101 ꢀC).
3-Acetyl-5,5-dimethyl-4-phenyl-5H-furan-2-one (4a). Yield 50%, Mp
76–77 ꢀC (Ref.[16] 76–77 ꢀC).
3-Acetyl-4-phenyl-1-oxaspiro[4,5]dec-3-en-2-one (4b). Yield 52%, Mp
137–139 ꢀC (Ref.[16] 137–139 ꢀC).
3-Acetyl-4-(2-dimethylaminovinyl-) (2a,b) and 3-(3-Dimethyl-
aminoacriloyl)-4-phenyl-(5a,b) 5, 5-Dialkyl-furan-2(5H)-ones
A solution of each initial compound (0.02 mol) in anhydrous xylene (20 ml) was
treated with 3 ml (0,0214 mol) of DMF=DMA. The reaction mixture was refluxed for
4.5 h and then left to cool. Light petroleum (20 ml, bp 60–80 ꢀC) was added to the
reaction mixture at room temperature. The formed solid products were collected
by filtration, washed with light petroleum and dried.
3-Acetyl-4-(2-(dimethylamino)vinyl)-5,5-dimethylfuran-2(5H)-one (2a).
1
Yield 96%; mp 140 ꢀC; HNMR: 1.54 (s, 6H, 2CH3), 2.36 (s, 3H, COCH3), 3.04
(s, 3H, NCH3), 3.30 (s, 3H, NCH3), 6.29 (br, 1H, ¼CH), 8.16 (br, 1H, ¼CHN).
13C NMR: 27.7 (2C,CH3), 29.2 [C(O]CH3), 36.5 (NCH3), 44.9 (NCH3), 81.0
(O-C), 105.9; 155.5, 169.9, 174.8, 193.2 (COCH3). Calculated for C12H17NO3 (%):
C, 64.56; H, 7.68; N, 6.27. Found (%): C, 64.15; H, 7.82; N, 6.33.
3-Acetyl-4-(2-(dimethylamino)vinyl)-1-oxaspiro[4,5]dec-3-en-2-one (2b).
Yield 83%; mp 135–136 ꢀC; 1HNMR: 1.45–1.92 [m, 10H, (CH2)5], 2.35 (s, 3H,
COCH3), 3.02 (br, 3H, NCH3), 3.27 (br, 3H, NCH3), 5.84 (d, J ¼ 13.5 Hz, 1H,
¼CH), 7.99 (d, J ¼ 13.5 Hz, 1H, ¼CHN). Calculated for C15H21NO3(%): C, 68.42;
H, 8.04; N, 5.32. Found (%): C, 68.76; H, 8.28; N, 5,48.
3-(3-(Dimethylamino)acryloyl)-5,5-dimethyl-4-phenylfuran-2(5H)-one (5a).
1
Yield 71%; mp 146–147 ꢀC; HNMR: 1.57 (s, 6H, 2CH3), 2.79 (s, 3H, NCH3), 3.12
(s, 3H, NCH3), 5.18 (d, 1H, J ¼ 13.0 Hz, ¼ CH), 7.31 (m, 2H) and 7.37–7.42 (m, 4H,
¼CHN, C6H5). Calculated for C17H19NO3 (%): C, 71.56; H, 6.71; N, 4.91. Found
(%): C, 71.34; H, 6.85; N, 4.93.
3-(3-(Dimethylamino)acryloyl)-4-phenyl-1-oxaspiro[4,5]dec-3-en-2-one
1
(5b). Yield 86%; mp 150–151 ꢀC; HNMR: 1.16 (m, 1H) and 1.62–1.82 [m, 9H,
(CH2)5], 2.77 (br, 3H, NCH3), 3.11 (br, 3H, NCH3), 5.18 (d, 1H, J ¼ 12.0 Hz,
¼CH) 7.18–7.24 (m, 2H) and 7.32–7.42 (m, 4H, C6H5, ¼CHN). Calculated for
C20H23NO3 (%): C, 73.82; H, 7.12; N, 4.30. Found (%): C, 73.56; H, 7.07; N, 4.32.

HETEROCYCLES FROM 3-ACETYLFURANONES
2273
4’-Methyl-3’H-spiro[cyclohexane-1,1’-furo[3,4-c]-pyridin]-3’-one (3)
The solution of 0.710 g (0.0027 mol) of (E)-3-acetyl-4-(2-(dimethylamino)
vinyl)-1-oxaspiro[4,5]dec-3-en-2-one (2b) in 49 ml of 20% ammonia was refluxed for
5 h. The third part of solvent was removed by evaporation under reduced pressure,
and the reaction mixture was left to cool. The formed solid product was collected
by filtration, washed with light petroleum, and dried. Yield 83%; mp 135–136 ꢀC;
1HNMR: 1.46 (m, 1H) and 1.66 (m, 2H) and 1.75–1.98 [s, 7H, (CH2rsqb;5], 2.78 (s,
=
3H, CH3), 7.39 (d, 1H, J ¼ 5.1 Hz, ¼CH), 8.60 (d, 1H, J ¼ 5.1 Hz, N CH). Calculated
for C13H15NO2 (%): C, 71.87; H, 6.96; N, 6.45. Found (%): C, 71.52; H, 6.81; N, 6.36.
3-(Isoxazol-5-yl)-4-phenyl-5,5-dialkyl-furan-2(5H)-ones (6a,b)
The solution of 0.0015 mol of each 3-(3-dimethylaminoacriloyl)-4-phenyl-5,5-
dialkylfuran-2(5H)-one (5a,b) and 0.0016 mol of hydroxylamine hydrochloride in
1.5 ml of methyl alcohol was refluxed for 5 h and left to cool. Formed solid products
were filtered, crystallized from ethanol, and dried.
3-(Isoxazol-5-yl)-5,5-dimethyl-4-phenylfuran-2(5H)-one (6a). Yield 65%;
1
mp 139–140 ꢀC; HNMR: 1.60 (s, 6H, 2CH3), 6.90 (d, 1H, J ¼ 1.8 Hz, 40-H),
7.31–7.37 (m, 2H) and 7.49–7.54 (m, 3H, C6H5), 8.32 (d, 1H, J ¼ 1.8 Hz, 30-H);
13C NMR: 24.4 (2C, CH3), 86.1 (O-C), 103.8 (4-C), 114.5, 126.7 (2C) and 128.1
(2C, C6H5), 129.1 (C-para), 130.9, 149.4 (3-C), 159.6; 166.6, 167.8. Calculated for
C15H13NO3(%): C, 70.56; H, 5.13; N, 5.49. Found (%): C, 70.32; H, 5.21; N, 5.35.
3-(Isoxazol-5-yl)-4-phenyl-1-oxaspiro[4,5]dec-3-en-2-one (6b). Yield 72%;
1
mp 154–155 ꢀC; HNMR: 1.16 (m, 1H) and 1.77 [m, 9H, (CH2)5], 6.88 (d, 1H,
J ¼ 1.8 Hz, 4-H); 7.25–7.29 (m, 2H) and 7.49-7.52 (m, 3H, C6H5); 8.30 (d, 1H,
J¼1.8 Hz, 3-H). Calculated for C18H17NO3 (%): C, 73.20; H, 5.80; N, 4.74. Found
(%): C, 73.47; H, 5.68; N, 4.80.
3-(1H-Pyrazol-5-yl)-4-phenyl-5,5-dialkyl-furan-2(5H)-ones (7a,b)
A solution of 0.0015 mol of each 3-(3-dimethylaminoacriloyl)-4-phenyl-5,5-
dialkylfuran-2(5H)-one (5a,b) and 0.0022 mol of 80% hydrazine hydrate in 1 ml of
ethanol was refluxed for 20–30 min and left to cool. The formed solid products were
filtered, washed with light petroleum, and dried.
5,5-Dimethyl-4-phenyl-3-(1H-pyrazol-5-yl)furan-2(5H)-one (7a). Yield 89%;
1
mp 209–201 ꢀC; HNMR: 1.56 (s, 6H, 2CH3), 5.64 (br, 0.35H) and 6.57 (br, 0.65H,
4-H), 7.28 (m, 2H) and 7.42 (br, 4H, 3-H and C6H5), 12.40 (br, 0.35H) and 12.75 (br,
0.65H, NH). Calculated for C15H14N2O2 (%): C, 70.85; H, 5.55; N, 11.02. Found
(%): C, 70.60; H, 5.71; N, 11.13.
4-Phenyl-3-(1H-pyrazol-5-yl)-1-oxaspiro[4,5]dec-3-en-2-one (7b). Yield
1
92%; mp 195–197 ꢀC; HNMR: 1.15 (m, 1H) and 1.75 [m, 9H, (CH2)5], 6.07 (br,
1H, 4-H), 7.22 (m, 2H) and 7.38–7.47 (m, 3H, C6H5), 7.34 (br, 1H, 3-H), 12.65
(br, 1H, NH). Calculated for C18H18N2O2 (%): C, 73.45; H, 6.16; N, 9.52. Found
(%): C, 73.24; H, 6.10; N, 9.43.

2274
G. S. MELIKYAN, A. A. HOVHANNISYAN, AND S. S. HAYOTSYAN
3-(2’Aminopyrimidine-4’-yl)-4-phenyl-5,5-dialkyl-
furan-2(5H)-ones (8a,b)
A solution of sodium ethoxide (0.002 mol sodium=5 ml of anhydrous ethanol)
was added to the solution of 0.0015 mol of each 3-(3-dimethylaminoacriloyl)-4-
phenyl-5,5-dialkylfuran-2(5H)-one (5a,b) and 0.002 mol of guanidine nitrate in 5 ml
of anhydrous ethanol under conditions of stirring and reflux. In 2 h of reflux, the
precipitated sodium nitrate was filtered, and the filtrate was left to cool. The formed
solid products were collected by filtration, crystallized from ethanol, and dried.
3-(2-Aminopyrimidin-4-yl)-5,5-dimethyl-4-phenylfuran-2(5H)-one (8a).
1
Yield 68%; mp 213–215 ꢀC; HNMR: 1.60 (s, 6H, 2CH3), 5.92 (br, 2H, NH2), 6.66
(d, 1H, J ¼ 5.0 Hz, 2-H), 7.24–7.29 (m, 2H) and 7.37–7.41 (m, 3H, C6H5), 8.14 (d,
1H, J ¼ 5.0 Hz, 3-H). Calculated for C16H15N3O2 (%): C, 68.31; H, 5.37; N, 14.94.
Found (%): C, 68.03; H, 5.20; N, 14.81.
3-(2-Aminopyrimidin-4-yl)-4-phenyl-1-oxaspiro[4,5]dec-3-en-2-one (8b).
1
Yield 58%; mp 189–190 ꢀC; HNMR: 1.16 (m, 1H) and 1.76 [m, 9H, (CH2]5), 5.83
(br, 2H, NH2), 6.68 (d, 1H, J ¼ 5.1 Hz, 2-H), 7.17–7.21 (m, 2H) and 7.36–7.40 (m,
3H, C6H5), 8.11 (d, 1H, J ¼ 5.1 Hz, 3-H). Calculated for C19H19N3O2 (%): C,
71.01; H, 5.96; N, 13.08. Found (%): C, 71.26; H, 5.95; N, 13.24.
3-Acetyl-4-(2-(3,4-dimethoxyphenyl)vinyl)-5,5-dimethyl-
furan-2(5H)-one (9)
The solution of 0.01 mol 3-acetyl-4,5,5-trimethylfuran-2(5H)-one (1a) and
0.11 mol of veratraldehyde in the n-butanol (30 ml) with catalytic amount of piperidine
(0.05 ml) was refluxed for 5 h and left to cool. The formed solid product was collected
by filtration, washed with ether, and dried. Yield 79%; mp 209–210 ꢀC; 1HNMR: 1.74
(s, 6H, 2CH3), 2.52 (s, 3H, COCH3), 3.87 (s, 3H, OCH3), 3.88 (s, 3H, OCH3), 6.93 (d,
1H, J ¼ 8.3 Hz, 5H-Ar), 7.22 (d, 1H, J¼ 1.7 Hz, 2H-Ar), 7.27 (dd, 1H, J¼ 8.3 Hz,
J ¼ 1.7 Hz, 6H-Ar), 7.43 (d, 1H, J ¼ 17.0 Hz, ¼CH), 7.84 (d, 1H, J ¼ 17.0 Hz, ¼ CH),
13C NMR: 26.7 (2C, 2CH3), 29.9 (COCH3), 55.2 (2C, OCH3), 83.4 (O-C), 111.1 (CH),
111.4 (CH), 115.1 (CH), 119.4; 122.2 (CH), 128.1; 144.4 (CH), 149.0, 151.5, 168.3,
171.8, 194.7 (COCH3). Calculated for C18H20O5(%): C, 68.34; H, 6.37. Found (%):
C, 68.18; H, 6.23.
2-(1-(4,5,5-Trimethyl-2-oxo-2,5-dihydrofuran-3-yl)ethylidene)
malononitrile (10)
In a flask fitted with a Dean–Stark trap, 0.02 mol of 3-acetyl-4,5,5-
trimethylfuran-2(5H)-one (1a) and 0.02 mol malononitrile were mixed in 16 ml of
anhydrous benzene in the presence of a catalytic amount (0.07 g) of b-alanine and
2 ml of anhydrous acetic acid. The reaction mixture was refluxed for 6 h and cooled
to the room temperature. The reaction mixture was washed with semiconcentric
sodium chloride water solution (6 ml); the organic layer was isolated and cooled.
The formed solid product was collected by filtration, washed with water and ether
1
and dried. Yield 71%; mp 115 ꢀC; HNMR: 1.54 (s, 6H, 2CH3), 2.13 (s, 3H, CH3),

HETEROCYCLES FROM 3-ACETYLFURANONES
2275
2.52 (s, 3H, CH3). Calculated for C12H12N2O2 (%): C, 66.65; H, 5.56; N, 12.44.
Found (%): C, 66.32; H, 5.78; N, 12.59.
6-Amino-1,1,4-trimethyl-3-oxo-1,3-dihydroisobenzofuran-5-
carbonitrile (11)
2-(1-(4,5,5-Trimethyl-2-oxo-2,5-dihydrofuran-3-yl)ethylidene)malononitrile (10)
(0.01 mol) in 50 ml of 0.6% sodium hydroxide ethanol solution was refluxed for 20 h
and left to cool. The formed solid product was collected by filtration, washed with
1
ethanol, and dried. Yield 54%; mp 255 ꢀC; HNMR: 1.55 (s, 6H, 2CH3), 2.67 (s,
3H, CH3), 6.56 (s, 1H, ¼CH), 6.58 (br, 2H, NH2), IR, n, cmꢁ1: 1720, 2226, 3243,
3349, 3408. Calculated for C12H14N2O2 (%): C, 66.04; H, 6.47; N, 12.84. Found
(%): C, 65.86; H, 6.31; N, 12.63.
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