Indian Journal of Chemistry Vol. 39B, March 2000, pp. 190 - 197

Chemistry of pyrones: Part i-Synthesis of triketones and triketoesters and related 4H-pyran-4-ones t

Aziz Shahrisa* & Salar Hemmati

D,epartment of o.rganic Chemistry, College of Chemistry, Tabriz University, Tabriz 51664 , Iran

Received 30 April 1997; accepted (revised) 6 November 1998

Variety of triketones 3a-d and triketoesters 3e-g have been synthesized, characterized and cyclized to the correspond­ing 4H-pyrones 4a-g.The pyronecarboxylates 4e-g have been converted to the corresponding pyronecarboxamides 5e-g. Dehydration of these carboxamides produces the cyanopyrones 6e-g. Finally cyanopyrones are converted to the tetrazolylpy­rones 7e,r.

4H-Pyran-4-ones are biologically active)a-e, syntheti­cally useful and important heterocyclic compounds . For these reasons the chemistry of pyrones has been the subject of many investigations2

. The present work is concerned with· the synthesis of 4-pyrones bearing various substituents at C-2 and C-6 positions. Our initial studies were focussed on the synthesis of tri­ketones 3a-d and triketoesters 3e-g which are impor­tant precursors in the preparation of 4-pyrone deriva­tives. It should be noted that some triketones bearing various aromatic and heterocyclic substituents at ter­minal carbons are known and possess antibacterial and fungicidal activities3a.b•

0 0.

R)~CH) + R2Co.2R

I 2

R) R2

CH) 2- Furyl

ii 2- Furyl ii 2-Thienyl

iii 2-Thienyl 1Il Co.2C2HS

iv 2-Pyridyl

As shown in Scheme I , the reaction of f3-diketones 1 with carboxylates 2 and sodium hydride in 1,2-dimetheoxyethane (DME) at reflux under ni­trogen atmosphere leads to the corresponding trike­tones 3a-d and triketoesters 3e-g in good yields. With the help of NMR, IR and mass spectral data and ele­mental analyses, stn' tures of the compounds were established. It can be seen from experimental section that for all the triketones 3a-d and triketoesters .3e-g the IR bands in the carbonyl and enol-chelate region from 1800 to 1540 were below 1640 cm') , indicating a considerable shift in the carbonyl absorption. The IR bands of ester groups of the triketoesters 3e-g ap-

0.

NaHlDMF D .. 67-95% R) 0. 0. R2

3

R) R) R2

CH) a .CH) 2-Furyl

CH3 b CH) 2-Thienyl

C2HS c 2-Thienyl 2-Furyl

d 2-Furyl 2-Furyl

e 2-Furyl Co.2C2H5

f 2-Thienyl Co.2C2H5

Scheme I g 2-Pyridy\ Co.2C2HS

t Presented in part at the fifth Eurasia Congress in Chemica l Sci­

ence, Dec 10-14, 1996 Guanghzou, China.

!

~

SHAHRISA et at.: CHEM ISTRY OF PYRONES : PART I 191

o 0 0

RlNUR2

3 a - d

RI R2 a 2-Furyl Me

b 2-Thienyl Me

c 2-Furyl 2-Furyl

d 2-Furyl 2-Thienyl Scheme II

o 0 0 OHII ···O·H' HO J:L\H .... .,O RI~COO·~_t __ ·b RINUcOOE::;t==~R .

I OOEt 3e-g 36-9 3 :'g'

e; R1= 2-Fury l

f; ~= 2-Thienyl

g; ~=2-Pyridyl Scheme III

pear in the region from 1755-1735 cm-I. Furthermore all the triketoesters studied here show a strong hydro­gen bonding in the region from 3200 to 2500 cm- I. These spectra suggest enol-chelate structures such as those outlined in Schemes II and III.These structures

are similar to those proposed for 1,3,5-triones5. The IH NMR spectra of the triketones 3a-d show

that the keto-from is in equilibrium with two dienolic forms4a

. For instance, the IHNMR spectrum of 1-(2-furyl)hexane-I,3,5-trione 3a shows three methyl sig­nals at 0 2_0 (enol), 2.05 (enol), and 2.3(ketone) and two methylene signals at 3.5 and 3.9 (keto-form). Four vinyl protons at 05.4 and 5.75 (enol), 5.85 and 6.26 (enol) (enols content 64% estimated from the ratios of methylene ,methyl and vinyl protons). Five signals appear at 0 6.55-6.7 (m, I H, H4-furan), 7.08 (d, h.4=4.0 Hz, H3-furan, enol), 7.28 (d, h.4=4.0 Hz, Hr furan , ketone), 7.4 (d, 13.4=4.0 Hz, Hr furan, ke­tone), 7.6-7 .8 (rri, IH, H5-furan) . Two broad signals also appear at 0 13.5 and 14.4 (strong enol-chelate, OH) which disappear in the presence of 0 20 . These NMR data are in full agreement with the equilibria outlined in Scheme II .

The I H NMR spectra of compounds 3e-g also show that except the triketoester 3g which exists ex­clusively in dienolic form 3g' in deuteriochloroform, the triketoesters 3e and 3f show dienolic form in equilibrium with monoenolic form4b

, (3e and 3f do not exist in keto-form at all). For example, thelH

NMR spectrum of the ethyl 6-(2-furyl)-2,4,6-trioxohexanoate 3e shows two signals at 0 1.35 (t, 3H, 1=7.5 Hz, CH3ester), 4.45 (q, 2H, 1 =7 .5Hz, CH2 ester) and four vinyl protons at 6.1 and 6.35 (dieilol), 4.05 and 6.6 (monoenol) in the ratio of 90: 10 respec­tively(estimated by NMR spectroscopy) .Two broad signals at 0 13.8 and 14.4 (disappear in the presence of 0 20,OH) and three furyl protons at 6.55-6.7 (m, IH, H4), 7.2 (d, IH, 13.4=3.8Hz, H3) and 7.65 (d, IH,

J4,5= 1.5 Hz).These NMR data are in full agreement with the proposed eqilibrium (cf Scheme III). In the next step, the triketones 3a-d and triketoesters 3e-g were cyclized with hot conc . sulfuric or hydrochloric acid to the corresponding 4H-pyran-4-ones 4a-d and 4e-g respectively. Cyclization of the triketones 3a-d to 4H-pyrones 4a-d was carried out following the literature procedure5. Better results were obtained when the triketones 3a-d or triketoesters 3e-g were dissolved in hot absolute ethanol and few drops of conc . hydrochloric acid were added to it. Cyclization was achieved within a few minutes (see Scheme IV).

3a-g

o

EtOH (,b,.) 1 Hel (OO"'! )l. 78-98% ~oA

RI R2

Scheme IV ( 4 a-g )

192 INDIA J CHEM, SEC B, MARCH 2000

o o

NH3 (g) I EtOH(abs.) I r.t. . . D 70-90 %

( 4e-g ) R, 2··Furyl 2 ~Thienyl

2-Pyridyl

o

R, 0 CONH2

( 5e-g )

(CF3 CO)P/Pyl

p-dioxane 60-80%

o

• "',I NHp 1 DMF 1 t ,t ,A, 90-92% )l_~

R, 0 CN

6 e-g

Scheme V

Treatment of the pyronecarboxylates 4e-g with gaseous ammonia in absolute ethanol resulted in the formation of the corresponding amides 5e-g in high yie lds (Scheme V). Structural assignments were bCl sed on mp, IR data and elemental analyses . 4-Pyrones bearing cyano and aryl substituents are the Important precursors in the synthesis of tetrazolyl derivatives of 4H-pyrones which act as antiallergic agents la.e. However synthesis of 4H-pyrones pos­sessing cyano and heteroaromatic substituents have not been reported as yet. In view of this , dehydration of 4-pyronecarboxamides 5e-g was carried out fol­lowing the standard method lO as shown in Scheme V. Spectral data ( IH NMR, IR, mass) and elemental analyses were in full agreement with the structures 6e_g7

.S

.II . Finally tetrazolyl-4H-pyrones 7e,f were

synthes ized following the standard method Ib, by the reaction of cyanopyrones 6e,f with sod1um azide and ammonium chloride in DMF at room temperature (Scheme V) . Structures of these tetrazolyl derivatives were establi shed on the basis of mp and mass spec­tral data and elemental analyses.

Experimental Section

General. Melting points were determined on an Electrothermal 910 instrument and are uncorrected . IR spectra were recorded on a Shimadzu IR-408 spectrometer using KBr pellets or chloroform solu-

tion . The nuclear maf'letic resonance spectra were measured on a Varian LM-390 (90 MHz) spectrome­ter in deuteriochloroform using tetramethylsilane as internal standard and chemica l shifts are reported in 8, ppm. Mass spectra were scanned on a FINNIGAN­MAT mass spectrometer GS-DS model 840 at 70 eV . Elemental analyses were performed by the Research Institute of Petroleum Company , Tehran, Iran.

General procedure for synthesis of 3a,b. To a slurry of sodium hydride (80%, 4 .5 g, 0.15 mole) in dry 1,2-dimethoxyethane (OME, 100 mL) at reflux under dry nitrogen, was added a solution of ace­tylacetone (5.0 g,0.06 mole) in 50 mL OME during 30 min. After 45 min, a solution of ·methyl 2-furoate (6 .3 g ,0.05 mole) in 50 mL of OME was added dur­ing 30 min . The reaction mixture was refluxed for 2.5 hr. Most of the solvent was then removed under re­duced pressure and the pasty orange residue cooled to o °C in an ice-water bath . Oiethyl ether ( 150 mL) was than added. After stirring for a few nUn , 100 mL of cold water was added; initially water was added dropwise till the excess of sodium hydride was de­stroyed . The two layers were separated. The organic layer was washed with cold water (2x I 00 mL) and then with 100 mL of cold I % aqueous sodium hy­droxide. The aqueous layers were combined with the original aqueous layer and then poured into a mixture of 40-50 mL of conc. hydrochloric ac id and 200g of

SHAHRISA e/ al.: CHEM ISTRY OF PYRONES: PART I 193

crushed ice. The mixture was kept for I hr and the resulting yellow precipitate was collected, washed with water and allowed to dry in air to give 3a .

1-(2-Furyl)hexane-l,3,S-trione 3a. Yellow nee­dles, 67 % yield, mp 49-50°C (pentane); IR (chloro­form) : 1595 and 1540 cm- I (carbonyl enol-chelate); IH NMR (COCh): 2.0(s, CH3 enol), 2 .05 (s, CH3

enol), 2.3 (s, CH] ketone) , 3.5 (s, CH2 ketone, C-4), 3.9 (s, CH2 ketone, C-2); 5.4(s, =CH enol), 5.7 (s, =CH enol), 5.85 (s, =CH enol), 6.2 (s, = CH enol) , 6.55-6.7 (m, I H, H4-furan) , 7 .08 (d, h.4 = 4.0 Hz, Hr fur!!n, enol) , 7 .28(d, h.4 = 4 .0 Hz, H]-furan, ketone), 7.4 (d, h .4=4.0 Hz, Hr furan , ketone), 7.6-7 .8 (m, IH, Hs-furan), 13.5 (broad s, disappeared on shaking with deuterium ox ide, OH) , 14.4 (broad s, disappeared on shaking with deuterium oxide, OH), (enol s content 64%), (keto-form is in equilibrium with two enol forms) (estimated from the ratios of methylene, methyl and vinyl protons); MS : mlz 194 (M+, 50%), 195 (M+I , 64), 179 (M-15 ,20), 176 (M-18,16) 153(40), 137(40), 110(48),95( 100),84( 14),69 (38), 43 (40). Anal. Calcd fo r C IOH IO0 4: C, 61.85;H, 5. 19%. Found: C, 61.70; H, 5.10%.

1-(2-Thienyl )hexane-l,3,S-trione 3b. Ye ll ow needles, 75 % yie ld , mp 59-60°C (hexane) ; IR (chlo­rofo rm) 1590 and 1550 cm- I (carbonyl enol-che late); IH NMR (CDCI]): 2.0 (s, CH] enol), 2 .05 (s, CH] enol), 2.30 (s, CH, ketone), 3.50 (s, CHz ketone, C-4), 3.90 (s , CH2 ketone, C-2), 5.3 (s, = CH enol ), 5.68 (s, = CH enol), 5.73 (s, =CH enol), 6.15 (s, =CH enol ), 7.1-7 .3 (m, IH H4-thiophene), 7.5-7 .9 (m, 2H, H)-and Hs-thiophene), 13.2 (broad, s, di sappeared on shaking with deuterium ox ide, OH), 14.5 (broad, s, disap­peared on shaking with deuterium oxide, OH), (enols content 62%: keto-form is in equilibrium with two eno l forms) (estimated from the ratios of methyl­ene, methyl and vinyl protons); MS :mlz 2 10 (M+, 26%), 21 1 (M+ I, I I) , 195 (M- 15, 42) , 192(M- 18,50), 169(28), 154(40), 111(100), 11 2(60),84(20),69(40), 43(88). Anal. Calcd for C1 0H IOO]S: C,57.13 ; H, 4.79%. Found: C, 57.00; H, 4.70%.

1-(2-Furyl)-S-(2-thienyl)pentane-l,3,S-trione 3c. To a slu rry of sodium hydride (80%, 3.0 g, 0. 1 mole) in 50 mL of dry DME, at reflux under dry nitrogen was added a so lu tion of 1-(2-thienyl)- 1,3- butane­dione (4 .1 g, 24 mmo les) and methyl 2-furoate (4.75 g, 38 mmoles) in 50 mL DME during 45 min . The react ion mi xture was re flux ed for 4 hr . Most of the solvent was removed under reduced pressure. After cooling followed by addit ion of ether and then water

gave a yellow precipitate which was filtered off. The filtrate was worked-up as described for the prepara­tion of 3a. The aqueous solution and the precipitate were added to a mixture of 20 mL conc . hydrochloric acid and 100 g crushed ice. After stirring the mixture for 20 min the yellow precipitate was collected on a funnel , washed with water and allowed to dry in air to give 5.5 g (87% yield) of the crude product. Recrys­tallization of the crude product from hexane, afforded the triketone 3c as small yellow needles mp 85-86°C;

'IR (chloroform): 158·5 and 1540 cm-I(carbonyl enol­chelate); IH NMR (COCl]): 3.9 (s, CHz ketone, C-2), 4 .0 (s, CH2 ketone, C-4) , 5.90 (s, =CH enol), 5.95 (s, =CH enol ), 6.2 (s, =CH enol ), 6.3 (s, =CI-i enol), 6.55-6.7 (m, IH, H4-furan) 7.0-7.4 (m, 2H, Hrfuran and H4-thiophene), 7 .5-7.95 (m, 3H, Hs-furan and H] and Hs-thiophene), 13 .8 (broad, s, disappeared on shaking with deuterium oxide, OH), 14.8 (broad, s, di sappeared on shaking with deuterium ox ide, OH) , (enols content 62%; keto -form is ex ist in equil ibriu m with two enol forms) (es timated from the ratios of methylene and vinyl protons); MS: mlz 262 (M+, 20%), 244 (M-18 ,20), 194(22), 168(30), 151(14) , 136( 18), 111 ( 100), 95(50), 83(20), 69(54). Anal. Calcd for C J3H100 4S: C, 59.53; H, 3.84%. Found: C, 59.40; H, 3.74%.

I,S-Di-(2-furyl)pentane-l,3,S-trione 3d. Under dry nitrogen atmosphere, a solution of 1.8 mL (25 mmoles) of acetone and 9.45 g (8 mL, 75 mmoles) of methyl 2-furoate 2 in 50 mL of DME was added to a suspension of s6dium hydride (80%, 2.4 g, 80 mmoles) in 50 mL of OME at reflux during 2 hr. Af­ter refluxing further for 3 hr, the solvent was re­moved in vacuum and the remaining orange paste carefully treated with water (100 mL). The resultant orange solution was filtered through Celite and poured into a mixture of 20 mL conc. hydrochloric ac id and 100 g crushed ice. The resultant ye llow solid was collected, washed with water, dried and recrys­talli zed from ethanol to give the triketone 3d as bril­li ant yellow need les in 65 % yie ld, mp 74-75°C. Thi s procedure in another run in dry THF as solvent af­forded the triketone 3d in 50% yield; IR (chl orofom): 1590 and 1545 cm- I (carbonyl enol-che late); IH NMR (CDCb): 3.9 (s, CHz ketone), 5.95 (s, =CH enol ), 6.25 (s, = CH enol), 6.55-6 .7 (m, 2H, H4-furans), 7 .08 (d, J ] .4 = 4.0 Hz, Hrfuran, enol form), 7.2 (d, h4 = 4.0 Hz, Hr furan, enol form), 7.4 (d, h .4 = 4 .0 Hz, Hr furan: ketone), 7 .5-7.75 (m, 2H, Hs-furans), 13.8 (broad, s, disappeared on shaking with deuterium

194 INDIAN J CHEM, SEC 8, MARCH 2000

oxide, OH), 14.8 (broad, s, disappeared on shaking with deuterium oxide, OH), (enols content 68%; keto­form is in equilibrium with two enol forms) (esti­mated from the ratios of methylene and vinyl pro­tons); MS:m/z 246 (M+, 28%), 247 (M+I, 46), 228 (M-18, 14),229 (30),137 (36),110 (52),95 (100),96 (52), 69 (40), 67 (18), 55 (39). Anal. Calcd for CJJHIOOs: C, 63.42; H, 4.09%. Found: C, 63.55; H, 4.20%.

General procedure for synthesis of 3e-g. To a stirred suspension of sodium hydride (80%, 1.1 g, 36 mmoles) in dry OME (20 mL) under dry nitrogen was added dropwise a solution of 1-(2-furyl)-1,3- butane­dione (1.5 g ,12 mmoles) and diethyl oxalate (3.32 mL, 24 mmoles) in 10 mL of OME in 30 min at re­flux. The reaction mixture was refluxed for:' hr, then cooled in an ice-bath and 40 mL 2N hydrochloric acid was added and after stirring for 10 min,the reaction mixture was allowed to stand for 30 min. The result­ing brownish-orange precipitate was filtered, washed with water and dried to give 3e-g.

Ethyl 6-(2-furyl)-2,4,6-trioxohexanoate 3e. Yel­low needles, 60% yield, mp 80-81 °C (hexane); IR (chloroform) : 2500-3200 (broad, OH enol-chelate), 1755 and 1735 (C=O, ester), 1615 and 1540 cm- I(carbonyl enol-chelate); IH NMR (COCI,): 1.35 (t, 3H, 1 = 7.5 Hz, CH, ester), 4.05 (s, CH2 ketone), 4.45 (q, 2H, 1 = 7.5 Hz, CH2 ester), 6.1 (s, =CH enol), 6.35 (s, = CH enol), 6.55-6.7 (m, H4-furan and =CH enol), 7.2 (d, I H, JJ.4 = 3.8 Hz, Hrfuran), 7.65 (d, I H, hs = 1.5 Hz,Hs-fman), 13.8 (broad, s, disappeared on shaking with deutf;!rium oxide, OH), 14.4 (broad, dis­appeared on shaking with deuterium oxide, OH) (the ratio of dienol form to monoenol is 90: 10) (estimated from the ratios of methylene and vinyl protons) ; MS:m/z 252 (M+, 18%),253 (M+I , 34), 179 (M-73, 80),180 (100),137 (42), 95 (70), 69 (34), 55 (39). Anal. Calcd for C1 2H1206: C, 57.14; H, 4.80%. Found: C, 57.25; H, 4.90%.

Ethyl 6-(2-thienyl)-2,4,6-trioxohexanotate 3f. Yellow needles, 87 % yield, mp 98-99°C (hexane); IR (chloroform): 2500-3200 (broad, weak, OH chelated), 1755 and 1735 (C=O, ester), 1605 and 1545 cm- I(carbonyl enol-chelate); IH NMR (COCl ,): 1.35 (t, 3H, 1= 7.5 Hz, CH, ester) , 4.10 (s, CH2 ketone), 4.45 (q, 2H, 1 = 7.5 Hz, CH2 ester), 6.1 (s, =CH enol) , 6.35 (s, =CH enol), 6.65 (s, =CH enol), 7.15-7.35 (m, I H, H4-thiophene), 7.6-7 .85 (m, 2H, H, - and Hs-thiophene), 12.5 (broad, s, disappeared on shaking with deuterium oxide, OH), 14.8 (broad, s, disap-

peared on shaking with deuterium oxide, OH) (the ratio of dienol to monoenol is 80:20) (estimated from the ratios of methylene and vinyl protons); MS:m/z 268 (M+, 14%) 269 (M+I, 26),195 (M-73,96),196 (70), 167 (10), 154 (28), II I (100), 112 (50), 83 (16), 69 (34). Anal. Ca\cd for CI2HI20SS: C, 53.72; H, 4.51 %. Found: C, 53.62; H,4.30%.

Ethyl 6-(2-pyridyl)-2,4,6-trioxohexanotate 3g. Small yellow needles, 65 % yield, mp 117-18°C (hex­ane or ethanol); IR (chloroform): 2500-3200 (broad, OH chelated), 1755 and 1735 (C=O, ester), 1605 and 1560 cm·l(carbonyl enol-chelate); IH NMR (COCI3):

1.4 (t, 3H, 1 =7 .5 Hz, CH, ester), 4.45 (q, 2H, 1 =7.5 Hz, CHz ester), 6.45 (s, I H, =CH enol), 6.9 (s, I H, =CH enol), 7.4-7.6 (m, IH, Hs-pyridine), 7.9-8 .2 (m, 2H, H3 and H4-pyridine), 8.8 (d, I H, ./s.6=6.3 Hz, H6-pyridine), 13 .0 (broad, s, disappeared on shaking with deuterium oxide, OH), 14.3 (broad, s, disappeared on shaking with deuterium oxide, OH) (enol content 100%); MS : m/z 263 (M+, 34%), 264 (M+I, 44),190 (M-73,100), 163 (34), 149 (84), 106 (70), 78 (54), 79 (32), 69 (22). Anal. Calcd fo r C1 , H1 ,NOs: C, 59 .31; H, 4.98%. Found: C, 59.45; H, 5.10%.

Cyclization of 1,3,5-triketones 3a-d to form 4H­pyrones 4a-d: General procedure. Conversion of triketones 3a-d to the corresponding 4-pyrones 4a-d was carried out according to the method described in the literatures: A sample of 0.98g (5 mmoles) of tri­ketone 3a was dissolved in 10 mL of conc. sulfuric acid at O°C, the solution kept for 20 min . and then poured into ice-water (30 mL). The resulting precipi­tate was filtered, washed with water and recrystal­lized from an appropriate solvent to give 4a.

2-(2-Furyl)-6-methylpyran-4H-one 4a. In the cyclization of triketone 3a a colloidal solution was obtained which was filtered through Celite and the filtrate extracted with dichloromethane (2x20 mL) and then with diethyl ether (20 mL) . The combined extracts were dried over sodium sulfate and the sol­vent evaporated. The residue was recrystallized from hexane as white need les , 80% yield, mp 106-7 °C; IR (KB r): 3100, 3050, 2965, 1660 (C=O, pyrone), 1615 cm·1 (C=C, pyrone); IH NMR (COCl ,) : 2.35 (s, 3H, CH,), 6.1 5 (d, I H, 1,.s =2 .2 Hz, H)-pyrone), 6.5-6.65 (m, 2H, H,- pyrone and H4-furan), 6.95 (d, I H, . hF3.7 Hz, Hduran), 7.6 (d, I H, 14.5 = 1.6 Hz, Hs­furan);MS:m/z 176 (M+, 80%), 177 (M+l, 100), 148 (M-28,10), 149 (70),95 (46), 92 (78),69(1 8), 43(14). Anal. Calcd for C1oHgOJ : C, 68.18; H, 4.58%. Found: C, 68.28; H, 4.64%.

SHAHRISA el al.: CHEMISTRY OF PYRONES: PART I 195

6-Methyl-2-(2-thienyl)pyran-4H-one 4b. The crude product was first crystallized from water and after drying dissolved in hot hexane and the hot solu­tion decanted. The solution was concentrated to a vo lume of 60 mL and then allowed to cool to give white plate crystals which were dried, 85% yield, mp

110- ll oC (hexane); IR (KBr): 3050,3 100,2960, 1650 (C=O, pyrone), 1605 cm·1 (C=C, pyrone); IH

NMR (COCI3): 2 .35 (s, 3H, CH3), 6 .2 (d, I H: h .5 = 2.3 Hz, Hr pyrone), 6 .65 (d, I H, J3.5 =2.3 Hz, Hs­pyrone), 7.25 (m, 1H, H4-thiophene), 7.5-7 .7 (m, 2H, Hr and Hs-thiophene) ; MS :mlz 192 (M+, 70%), 193 (M+I,100) , 164 (M-28, 70) , 165 (80),11 1 (48), 108 (92),84 (8),69 (2),43 (14) . Anal. Ca\cd fo r C IOHg0 2S : C, 62.49, H, 4.19%. Found: C ,62.60; H, 4 .26%.

2-(2-Furyl)-6-(2-thienyl)pyran-4H-one 4c. Thi s

compound was obtained in 87 % yield, mp 161-62°C (hexane); IR (KEr): 3075, 3025, 1655 (C=O, pyrone), 1625 cm·I(C=C, pyrone) ; IH NMR (COC1}): 6 .55-6.8 (m, 3H, H3-and Hs-pyrone and H4-furan), 7 .05 (d, I H, J3•4 =3.7 Hz, Hr furan), 7 . 15-7 .35 (m, IH, H4-

thiophene), 7 .5-7 .7 (m, 3H, Hs-furan and H3 and Hs­thiophene); MS:mlz 244 (M+ ,44%),245 (M+l, 90), 21 7 (M-29, 100),216 (M-28,60), 161 (28), 108 (54), 95 (24), 83 (14) , 69 (26) , 63 (41) . Anal. Calcd for C J3Hg0 3S : C ,63.92; H, 3 .30%. Found: C, 63.75; H, 3.18%.

2,6-Di-(2-furly)pyran-4H-one 4d. White needles

in 95 % yie ld, mp 2 13-14°C (ethanol); IR (KEr): 3100, 3050, 1665 (C=O, Pyrone), 1625 cm·1 (C=C, pyrone) ; 'H NMR (COCI}): 6 .5-6.6 (m, 2H, H4-

furans) , 6.7 (s, 2H, H)- and Hs-pyrone), 7 .0 (d, 2H, h.4 = 3.7 Hz, Hr furans), 7 .6 (d , 2H, J4,s = 1.6 Hz, H5-furans) ; MS : mlz 228 (M+, 46%), 229 (M+ I , 84), 200 (M-28 , 100), 201 (68), 144 (28), 116(44), lIS (32), 95 (50),92 (58) ,69 (20),57 (55). Anal. Cal cd for C J3Hg0 4 : C, 68 .42; H , 3.53%, Found: C, 68 .39; H , 3.50%.

Cyclization of 2,4,6-trioxohexanoates 3e-g to 4H-pyrones 4e-g: General procedure. The follow­ing simple method was applied for conversion of tri ­oxohexanoates to the corresponding 4H-pyrones . Tri­oxohexanoate 3e (I g, 4 mrnoles) was dissolved in 100 mL of hot absolute ethanol in a beaker, cone. hy­drochloric acid ( 10 drops ) added to it and heating continued. The volume of the solution was kept con­stant by the addition of absolute ethanol. The heating was continued (for-20 min) until TLC on silica gel using ether as irrigant showed no trioxohexanoate : (4-pyrone 4e under UV light gave a spot with Rr 0 .8 and

ye llow spot of trioxohexanoate 3e with Rr 0.2 disap­peared). The soluti on was concentrated to 30 mL, charcoal added to it and the whole mixture filtered off. The filtrate gave 4e.

Ethyl 6-(2-furyl)-4H-oxopyran-2-carboxylate 4e. Because of high so lubility of 4e in ethanol, the etha­nolic solution was poured into 200 mL of water, and the resultant white small needl es were collected, dried and recrysta llized from hexane (about 300 mL needed for 1.0 g). The product was obtained as white need les,

87% yie ld, mp 107-8°C (hexane),(1it.9, m.p. 103); IR

~KBr): 3 100, 3070, 2970, 2885 , 1740 (C=O, ester), 1660 (C=O, pyrone), 1652 c m·1 (C=C, pyrone) ; 'H NMR (CDCI 3) : 1.4 (t, 3H, J = 7.2 Hz, CH3 ester), 4.45 (q, 2H, J = 7 .2 Hz, CH2 ester), 6.6-6 .7 (m, IH , H4-furan), 6.8 (d, I H, h,s =2.7 Hz, H 5-pyrone), 7.1 (d, I H, h .5 =2 .7 Hz, H3-pyrone), 7.2 (d, I H, h A = 3.4 Hz, Hr furan ), 7 .65 (d , I H, J4 .5 = 1.5 Hz,Hs-furan); MS : mlz 234 (M+, 52%), 235 (M+ I, 100),206 (M-28, 38), 179 (48), 178 (40), 133 (38) , 95 (34) , 92 (58), 69 (44) . Anal. Ca\cd for CI 2H IOOS: C, 61.54 ; H, 4.30%. Found: C, 61.40; H, 4 .37% .

Ethyl 6-(2-thienyl)-4H-oxopyran-2-carboxylate 4f. Thi s compound was obtained as white pl ates in

95% yield, mp 141-41.5°C (ethanol ); IR (KB r): 3075,

3050, 2960, 2880, 1735 (C=O, ester) , 1655 (C=O, pyrone), 1620 em' ! (C=C, pyrone) ;!H NMR (COCI3) : 1.40 (t, 3H, J = 7 .2 Hz, CH3 ester) , 4.45 (q , 2H, J = 7 .2 Hz, CH2 ester) , 6 .75 (d , I H, J3.5 = 2.7 Hz, Hs­pyrone), 7.1 (d, I H, 1,,5 = 2 .7 Hz, Hr Pyrone), 7.2 (dd , IH, h s = J 3.4 = 4 .7 Hz, H4-thiophene) , 7 .6 (d , IH , h A = 4 .7 Hz, H3-thiophene), 7 .75 (d , I H, J4.S = 4 .7 Hz, Hs-thiophene); MS: mlz 250 (M+' 100%),251 (M+I , 68), 222 (M- 28, 32) , 194 (32), 195 (48), I I I (40),108 (58),83 (8), 69 (46). Anal. Ca\cd for C! 2H IO0 4S : C , 57 .59; H, 4 .03 %. Found: C, 57.39; H, 4 . 10%,

Ethll 6-(2-pyridyl)-4H-oxopyran-2-carboxylate 4g.This compound was obtained as white needles in

98% yield , mp I 12.5-13°C (ethanol ); IR (KBr) : 3050, 2965, 2880, 1725 (C=O, ester), 1655 (C=O, pyrone), 1625 em'! (C=C, pyrone), IH NMR (COCb) : 1.45 (t, 3H, J = 7.2 Hz, CH3 ester) , 4 .5 (q, 2H, J = 7.2 Hz, CH2 ester), 7 .2 (d , I H,h.5 = 2.8 Hz, Hr pyrone), 7.3-7 .55 (m, 2H, Hs-pyrone and Hs­pyridine), 7.8-8.2 (m, 2H, Hrand H4-pyridine), 8.8 (d , I H, J S,6 = 6 Hz, H6-pyridine) ; MS : mlz 245 (M+, 58%), 246 (M+I , 100), 2 18 (32), 219 (60) 189 (66), 172 (28), 173 (50), 144 (22), 145 (84), 103 ( 12), 104 (40), 78 (32), 79 (30), 69 (30). Anal. Ca\cd for

196 INDIA J CHEM, SEC B, MARCH 2000

C 13H"N04: C, 63. 67; H, 4.52%. Found: C, 63.56; H, 4.57%.

Conversion of 4-pyronecarboxylates 4e-g to the corresponding 4-pyronecarboxamides Se-g: Gen­eral procedure. A sample of 4e ( 2.34 g ,10 mmoles) was dissolved in absolute ethanol at room tempera­ture, and gaseous ammonia passed through the solu­tion ( for-20 min) until TLC on silica gel using ether as irrigant showed no spot of 4-pyronecarboxylate 4e (Rr 0.5). The resultant white solid was filtered , washed with ethanol and dried to give Se.

6-(2-Furyl)-4H -oxopyran-2-carboxamide Se. This compound was obtained in 90% yield, mp 305-6°C dec. (water); IR (KBr): 3390 and 3175 (broad, strong, NH), 3075, 3025, 1720 (C=O, amide), 1640 (C=O, pyrone), 1615 cm" (C=C, pyrone). Anal. Calcd for C,oH7NO: C, 58. 54; H, 3.44; N, 6.83 %. Found: C , 58.50; H, 3.40.N, 6.75%.

6-(2-Thienyl)-4H-oxopyran-2-carboxamide Sf. This compound was obtained in 97 % yield, mp 292-93°C dec. (water); lR (KBr): 3475 and 3200 (broad, strong, NH), 3075, 3050, 1720, (C=O, amide), 1640 (C=O, pyrone), 16 I 0 cm" (C=C, pyrone). Anal. Calcd for C IOH7NO,S: C, 54.30; H, 3. 19; N, 6.33 %. Found: C, 54.25 ; H,3. 18 ; N, 6.26% .

6-(2-pyridyl)-4H-oxopyran-2-carboxamide Sg. This compound was obtained in 92% yield , mp 301 -

2°C dec. (water); IR (KB r) : 3400 and 3200 (broad, strong ,NH), 3075, 1720 (C=O, amide), 1640 (C=O, pyrone), 1615 cm" (C=C, pyrone). Anal. Calcd for CllHsN10, : C, 61. 10; H, 3.73 ; N, 12.96%. Found: C, 61.0; H, 3.70;N, 12.90%.

Conversion of 4-pyronecarboxamides Se-g to cyano-4H-pyrones 6e-g: General procedure. To a cold suspension of 4-pyronecarboxamide ( 10 mmoles) in 20 mL of anhydrous dioxane, 2 mL (24 mmoles) of anhydrou s pyridine was added followed by the addit ion of 2 .52 mL (18 mmoles) of trifluQro­acetic anhydride at such a rate that the temprature was kept below 5°C" . Usualiy the addition was com­pleted within 30 min. The reaction mixture was then allowed to warm to room temperature and sti rred for 2.5 hr. The resulting thick slurry was worked-up ac­cording to one of the following methods :

Method-a. The pyrid inium salt was removed by filtration and the filtrate <;Iiluted with chloroform (40 mL) , was hed with water Ox5 mL) and saturated brine (2x5 mL) , dried over sodi um su lfate and the solvent evaporated under vacuum. The crude nitrile was then

crysta ll ized from an appropriate so l vent with the ad­dition of charcoa l and removing the impurities.

Method-b. lee-water (40 g) was added to the reac­tion mix ture and the so lid product filtered, washed with water, dri ed in a ir and crystallized from an ap­propriate sol vent.

2-Cyano-6-(2-furyl)pyran-4H-one 6e. This com­pound was obtained according to the method-b as white needles in 80% yield, mp I 83-84°C (ethanol); IR (KBr): 3125, 3050, absorption of CN bond is highly weak (see text), 1655 (C=O, pyrone), 1615 cm- ' (C=C, pryone);'H NMR (CDCl l ): 6.6-6.85 (m, 3H, Hr and H5-pyrone and H~-fu'ran), 7 . 15 (d, I H, /l,~ = 3.5 Hz, Hrfuran), 7.7 (d, I H, h5 = 1.6 Hz, H5-furan); MS: mJz 187 (M+, 76%), 188 (M+ I, 100), 161 (M-26, 62),160 (58), 95 (46), 92 (56), 69 (18), 57 (5 1) , 41 (39). Anal. Calcd for C IOH5NO, : C, 64.18 ; H, 2.69; N, 7.48%. Found: C, 64 .05; H, 2.70;N, 7.60%.

2-Cyano-6-(2-thienyl)pyran-4H-one 6f. This compound was obtained according to the method-b as white pl ates in 75% yie lJ , mp 194-95°C (isopropyl alcohol); IR (KBr): 3050, 3015, 2275 (was observed with 10% conc. in ch lorofo rm), 1640 (C=O, py­rone), 161 0 cm" (C=c, pyrone); 'H NMR (CDCI3):

6 .75 (d, I H, h .s = 2.6 Hz, Hs-pyrone), 6.85 (d, I H, h .s = 2.6 Hz, Hr pyrone), 7.1-7.25 (m, IH, H~­

thiophene), 7.6-7.8 (m, 2H, H l - and Hs-thiophene) ; MS : mJz 203 (M+, 66%),204 (M+ I, 100), 175 (M-28,96) , 147 (54),1 11 (40),108 (74),83 (8) ,69 (26), 45 (39). Anal. Calcd for C IOH5N01S : C, 59.10; H, 2.48; N, 6.89%. Found: C, 59.00; H, 2.58; N, 6,75%.

2-Cyano-6-(2-pyridyl)pyran-4H-one 6g. This compound was obta ined by the abo ve method as white needles , yield 60%, mp 189-90°C (isopropyl alcohol); IR (KBr): 3050, 3025, absorpt ion of C bond was highly weak, 1645 (C=O, pyrone), 1615 cm- ' (C=C, pyrone); 'H NMR (CDCI,) : 6.9 (d, I H, i.l.s = 2.8 Hz, HI-pyrone), 7.35-7.55 (m, 2H, Hs­pyrone and Hs-pyridine), 7.85-8.15 (m, 2H, H,rand H~-pyridine), 8.8 (d, I H, / ),6 = 6.2 Hz, H6-pyridine); MS: mlz 198 (M+ ,70%), 199 (M+ I, 100), 170 (M-28,50) ,171 (58), 147(26), 143(72),144 (72), 103 (24), 78 (36) , 69 (24), 51 (54), 50 (39). Anal. Calcd for C ll HoN20 2: C, 66.67; H, 3.05; N, 14.14%, Found : C, 66.78; H,3. 13; N, 14.22%.

Conversion of cyano-4H-pyrones 6e,f to the cor­responding tetrazolyl-4H-pyrones 7e,f: General procedure. In a 25 mL round bottomed fl ask

SHAHRISA et al.: CHEMISTRY OF PYRONES: PART I 197

equipped with a calcium chloride guard tube was placed 5 mL of dry dimethylfonnamide, and then 0.37 g (2 mmoles) of 6e (0.15 g, 2.25 mmoles) of sodium azide and 0.14 g (2.5 mmoles) of ammonium chloride were added to it. The mixture was stirred at room temperature until silica gel TLC (ether) showed no spot for cyano4-pyrone 6e (after about 1.5 hr). Thereafter 10 mL of IN hydrochloric acid was added and the mixture allowed to stand for 30 min. The re­sultant white precipitate was filtered, washed with water, dried at 60°C under vacuum, and recrystal­lized from DMF-ethanol mixture to give 7e.

6-(2-Furyl)-2-(tetrazol-5-yl)-4H-pyranone 7e. This cQmpound was obtained in 90% yield, mp 295-96°C (dec.) (DMF-ethanol); MS: rn/z 230 (M+, 56%), 231 (M+l, 100),202 (M-28, 30), 203 (38), 174 (M-56,58),160 (24), 119 (42), 95 (66), 92 (50), 69 (74), 53 (24), 39 (22). Anal. Calcd for ,CIOH~403: C, 52.18; H, 2.63; N, 24.34%. Found: C, 52.27; H, 2.70; N,24.28%.

2-(Tetrazol-5-yl)-6-(2-thienyl)-4H-pyrone 7f. This compound was obtained in 92% yield, mp 283-84°C (dec:) (DMF, ethanol); MS: rn/z 246 (M+ , 50%), 247 (M+l, 100), 218 (M-28, 32),190 (M-56, 58),135 (24),111 (46),108 (32),83 (12), 69 (44), 57 (45). Anal. Calcd for CIOH~402S : C, 48.78; H, 2.46; N, 22.75%. Found: C, 48.85; H.2.35: N. 22.60%.

Acknowledgement Financial support for this work by the Research

Council of Tabriz University is gratefully acknowl­edged. The authors are grateful to Dr Mehran Ghiaci

of Isfahan University of Technology for IH NMR spectra.

References & Notes I (a) Clark P B, Ross J W & Alec T, German Offen 3,012,584,

(1980); Chern Abstr, 94, 1981, 121322f. (b) Clark B P & Ross W J, German Offen, 3,012,597, (1980); Chern Abstr, 94, 1981, 83945b. (c) Abou ouf A, EI-kerdawy M M & Yousif M Y, Indian J Chern, 18B, 1979,168. (d) Kurary Co, Ltd Jpn Kolwi Tokkyo Koho, 80,102, 504, (1980); Chern Abstr, 93, 1980, 199231 z. (e) Yasushi H,Ysuo S, Tomiki H, Mikio T, Yasutoshi 0 & Kei T, Chern Pharrn Bull , 30, 1982, 4314.

2 Ellis G P, in : Comprehensive heterocyclic chernistry, Yol.3, edited by A J Boultoll and A Mckilloped, (Pergamon Press, Oxford) 1984, pp. 647-883 .

3 (a) Kuraray Co, Ltd, Jpn Kolwi Tokkyo Koho, 80, 11 8,434, (1980); Chern Abstr, 94, 1981, I9170k (b) Kuraray Co, Ltd, Jpn Kolwi Tokkyo Koho, 80, 108, 803 (1980); Chern Abstr, 93, 1980, 216680q.

4 (a) Miles M L,HarisT M & Hauser C R, J Arn Chern Soc, 85 , 1963,3884. (b) Marcus M, Chann J K & Strow S B, J Org Chern, 31 , 1966, 1369.

5 Synthesis of 3a-d were carried out according to the general procedure reported by Miles M L, Harris T M & Hauser C R, J Org Chern, 30, 1965, 1007.

6 Ellis I A, Gaines D F & Schaeffer R, J Arn Chem Soc, 85 , 1963,3885.

7 Light R J & Hauser C R, J Org Chern , 25, 1960, 538. 8 Ellis G P, in : Comprehensive heterocyclic chemistry, Yol. 3,

edited by A J Boulton and A Mckilloped, (Pergamon Press, Oxford) 1984, pp. 603-607.

9 Soliman G & Rateb L, J Chem Soc, 1956, 3663. 10 Ellis G P & Shaw D, J Chem Soc Perkin-I, 1972, 779. II Campagna F, Carotti A & Casini G, Tetrahedron Lett, 21,

1977,1813.