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Synthetic Communications: AnInternational Journal for RapidCommunication of SyntheticOrganic ChemistryPublication details, including instructions forauthors and subscription information:http://www.tandfonline.com/loi/lsyc20

Synthesis of 1-(2-Oxoalkyl)-2-acyltetrahydro-isoquinolinesby α-Amidoalkylation ofMethylene Active CarbonylCompounds with N-AcyliminiumIntermediatesAtanas P. Venkov a & Stela Statkova-Abeghe aa Department of Chemistry, University of Plovdiv,Plovdiv, 4000, BulgariaPublished online: 21 Aug 2006.

To cite this article: Atanas P. Venkov & Stela Statkova-Abeghe (1996) Synthesis of 1-(2-Oxoalkyl)-2-acyltetrahydro-isoquinolines by α-Amidoalkylation of Methylene ActiveCarbonyl Compounds with N-Acyliminium Intermediates, Synthetic Communications:An International Journal for Rapid Communication of Synthetic Organic Chemistry,26:11, 2135-2144, DOI: 10.1080/00397919608003572

To link to this article: http://dx.doi.org/10.1080/00397919608003572

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SYNTHETIC COMMUNICATIONS, 26(1 l), 2135-2144 (1996)

SYNTHESIS OF 1-(2-OXOALKYL)-2-ACY LTETRAHYDRO-

ISOQUINOLINES BY a-AMIDOALKY LATION OF METHYLENE

ACTIVE CARBONYL COMPOUNDS WITH

N-ACYLIMINIUM INTERMEDIATES

Atanas P. Venkov* and Stela Statkova-Abeghe

Department of Chemistry, University of Plovdiv, Plovdiv 4000, Bulgaria

Abstract: Intermolecular a-amidoalkylation reaction of methylene active carbonyl compounds with N-acyliminium salts of 3,4-dihydroisoquinolines and acyl chlorides has been used for synthesis of 1 -(2-oxoalkyl)- 2-acyltctrahydroisoquinolines.

The introduction of 2-oxoalkyl group into I-position of isoquinoline is important

for preparation of variety of isoquinoline alkaloids. Coupling a methylene active

carbonyl compound at C-1 position of the isoquinoline is one of the desirable

patterns for the synthesis of I-substituted derivatives. The intrinsic acceptor

reactivity in the I-position of isoquinolincs that is cnhanccd by lcaving groups such

as CI or MeS02 in the 1 -position or by quaternization of the nitrogen in the

2-position has so far been exploited most often. The classical preparation of the

*To whom correspondence should be addrcssed.

2135

Copyright @ 1996 by Marcel Dekker. Inc.

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2136 VENKOV AND STATKOVA-ABEGHE

isoquinoline nucleus for attack by 2-alkyl- or 2-acyl isoquinolinium salts arc

usually employed in the rcaction with kctoncs but the yields of 1 -(2-oxoalkyl)-

isoquinolines are low. An considerable improvement has bccn achieved by

application of boron enolates' or silyl cnol ethers of kctoncs, aldehydes and esters

in the reaction with 2-acylisoquinolinium

quinolines has been prepared also by reaction of 1 -ethoxy-2-methyI-tetrahydroiso-

quinolinc with active mcthylene compounds5, by reaction of 3,4-dihydroisoquino-

line with malonic acid6 and by cyclization of N-acylated cnamino kctones such as

4-~-acetyl-2-(3,4-dimethoxyphcnyl)ethylamino]- 1 , 1 , I -trichlor0-2-buten-2-one.~

N-acyliminium intermcdiatcs of 3,4-dihydroisoquinolines with acyl

chlorides display a considerablc clcctophilic activity and wcrc successhlly applied

for a-amidoalkylation of

intermediate 3a from 3,4-dihydroisoquinolinc and ethyl chlorofotmate with KMnO,

in acetone, we isolated 1 -acetonyI-2-carboxycthylltetrahydroisoquinoline 5a as a

side product of the reaction. The reaction of 3 with acetonc opcncd thc opportunity

for a convenient access to 1 -(2-oxoalkyl)-2-acyltctrahydroisoquinolincs 5 without

preliminary activation of ketones. Looking for farther application of N-acyliminium

intermediates 3 as clectrophilic reagcnts we invcstigatcd their reactions with other

ketones and methylenc active dicarbonyl compounds. It was found that N-acyl-

iminium intermediates 3 prepared from 3,4-dihydroisoquinolines and acyl chlorides

in acetone at reflw afforded 1 -acctonyl-2-acyItetrahydroisoqunolincs 5 (Table 1,

5a-e) in very good yields. The rcaction of 3 with acetophenoncs procecdcd in 1,2-

dichloroethane at reflux to the corresponding 142-0x0- phenylcthyl)-2-acyItctra-

hydroisoqunolines (Table 1,5f-I) including the analogues of alkaloid homo-

laudanosine" (Table 1,5k) and the analgetic drug mclhopholine (Vcrsidyne)"

(Table 1,51).

1 -(2-Oxoalkyl)-tetrahydroiso-

Recently, investigating the oxidation of

The reaction of 3 with unsaturatcd ketones and aldchydcs such as

benzy lidenacctone and hydrocinnamaldchyde proceeded at room temperature with

a rapid evolution of hydrogen chloride (Table 1,5m-q). The reaction of 3 with

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ISOQLJINOLINE ALKALOIDS 2137

Table 1 l-(2-oxoalkvl). 2-Acvltetrahvdroisoauinolines 5 Prepared

En- R R' R2 R3 React. conditions Yield Mp

tty Time Temp. (%) CC)

5a H

5b H

5c H

5d Me0

5e 7-N02

5f H

5g H 5h H

5i H

Sj Me0

5k Me0

51 Me0

5m H

5n H

50 H

5p Me0

5q H 5r H

5s H

5t H

5u H

5v H

COOEt

COC6Hs

COMe

COOEt

COOEt

COOEt

COOEt

COOEt

COC6Hs

COOEt

COOEt

COOEt

COOEt

COMe

COOEt

COOEt

COMe

COOEt

COMe

COOEt

COMe

COOEt

H

H

H

H

H

H

H

H

H

H

H

H

H

H

CH2C6H5

CH2C6H5

CH2C6H5

COMe

COMe

COMe

COMe

COOEt

- 85

80

70

70

70

83

80

70

60

85

82

83

87

54

74

34

58

70

50

72

58

40

oil

oil

oil

oil

108

86-87

oil

77-78

94-95

119

43-45

105

74-75

122-3

oil

oil

oil

oil

oil

oil

78-79

oil

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2138 VENKOV AND STATKOVA-ABEGHE

6p R=OMe, R1=Oh 6q R=H, R1=Me

H R' R2 R3 R4 7a H COOB H OH Me 7j Me0 COOB H OH CgH5 7t H COMe COOEt OH Me 8f H Me H H C&

hydrocinnamaldehydc led also to a side products 6 (6p in 22% and 6q in 23%

yield). Similar products with an open heterocyclic ring have becn obtained earlier

from the reaction of 3,Cdihydroisoquinolinc in AczO and methylene active

carbonyl compounds.'*

The scope of the reaction was farther cxtcnded to methylene active

dicarbonyl compounds such as diethyl malonate, acetylacctonc and cthyl accto-

acetate expecting that the reactions of 3 will dcpcnd on thc nucleophilic activity of

methylene group of 4. However, while the reaction with acetylacetone and ethyl

acetoacetate also proceeded at room temperature (Table 1,5r-u), the reaction with

diethyl malonate required reflux at 80"C(Tablc 1,Sv) and was low yiclded. The

intcrpretation of thcse results for the reaction of 3 with methylene active dicarbonyl

compounds leads to the assumption that the formation of enolate anion from 4 is

important for the success of the a-amidoalky lation rcaction. The reaction depended

also from the naturc of N-acyl group in 3, since thc yields of 5 obtaincd from

3,4-dihydroisoquinolines and ethyl chloroformatc arc better then those with acetyl

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ISOQUINOLINE ALKALOIDS 2139

Table 2 Ent- 'H-NMR (CDCI,/TMS), J (Hz), 6, ppm'"

5a 1 .22(ty3H,J=6),2.1 5(sY3H), 2.80(d,2H,J=6),2.82-2.95(m,2H), 261

5b 2.35(~,3H),2.63-2.87(m,2H),2.95(d,2H,J=5),3.50-3.80(m,2H), 293

MS(70eV) try m/e (M'L_

3.22-3.42 (my2H),4.08(q,2H,J=6)y5.52(t, 1 HyJ=6),6.92(s,4H), CI5HI9NO3

6.13(t, 1 H,J=6),7.03-7.20(m,4H),7.28(sy5H) lgH ISNO, 5c 2.05(s93H),2. 15(~,3H),2.70(d,2H,J=7),2.85(t,2H,J=6),3.45- 213

3.70(m,2H),5.27 and 5.80(t,t,I H,J=6),7.00(sY4H)* 17N02 5d 1 .23(t,3HYJ=7),2.1 5(~,3H),2.50-2.7O(m,2H),2.78(d,2H,J=7), 32 1

3.1 5-3.45(m,2H),3.75(~,6H),4.05(d,2H,J=6),5.30-5.53(m, 1 H), C,7H23N05 6.40(s, 1 H),6.46(sY 1 H)

5e 1.25(t,3H,J=7),2.23(~,3H),2.88(d,2H,J=8),3.05-3.1 5(mY2H), 306 3.1 8-3.58(mY2H),4. 1 O(q,2H,J=7),5.68(t, 1 H,J=6),7.15 IBN205 (d,lH,J=8),7.80 and 8.00(d,d,IH,J=7),7.90(s,lH)*

(mY2H),3 .72-4.20(m,2H),5.63(t, 1 H,J=7),6.95(sY4H),7.20-7.33 CZOHZ1NO3 (mY3H),7.67-7.85(m,2H)

5f 0.9- 1.25(m,3H),2.68-2.90(m,2H),3 .23(d,2HYJ=8),3 -30-3.55 323

5g 1 . O W .32(m,3H),2.86(t,2H,J=6),3.20(d,2H,J=6),3.27-3.48 383 (mY2H),3 .89(sY6H),3.92-4. 1 7(mY2H),5.57(t, 1 H,J=6),6.67 C22H25N05 (d, 1 H,J=8),6.92(~,4H),7.20-7.32(m,2H)

3.47-3.53(mY 1 H),3.75-4.1 O(mY2H),5 .62(t,2H,J=7),7.00(~,4H), 7.52(d,2H,J=8),8.02-8.27(mY 1 H),8.52(tY 1 H,J=8)*

(t, 1 H,J=7),6.52(d,2H,J=8),7.08(s,5H),7.20(s,4H),7.53(~, 1 H), 7.75(dy2H,J=8)

(m,2H),3.68(~,3H),3.74(~,3H),3.82-4.22(m,2H),5.52(t, 1 H,J=6), CZ2Hz5NO5 6.38(~,2H),7.19(~, 1 H),7.28(s,2H),7.62-7.79(mY2H)

5h 1 .OO-1 .28(m,3H),2.82(t,2H,J=6),3.32 and 3.57(d,dy2H,J=2), 368 C20H2&205

5i 2.68-2.92(m,2H),3.15-3.48(m,2H),3 .55-3.78(mY2H),6.08 37 1 CZ4H2,NO3

5j 0.98-1 .38(m,3H),2.62-2.92(m,2H),3.28(dy2H,J=8),3.35-3.56 383

5k 1 .25(ty3H,J=6), 2.65-2.90(mY2H), 3.1 7-3.56(mY2H), 3.75 443 (d,2H,J=4), 3.80(sY3H), 3.85(sY6H), 4.04(qy2H,J=6), 5.67 C24H29N07 (t,lH,J=6), 6.576.85(sY1H), 7.1 7(s,lH), 7.28-7.45(mY2H)

51 1.02-1.25(m,3H),2.62-2.90(m,2H),3.21(d,2H,J=7),3.28-3.55 495 (m,2H),3.68(~,3H),3.73(~,3H),3.85-4.07(m,2H),5.52 C22H24C1N05 (t, 1 H,J=6),6.40(~,2H),7.20(d,2H,J=8)~7.55-7.78(m,2H)

5m 1 .~5(t,3H,J=7),2.80(t,2H,J=6),3.02(d,2H,J=8),3.00-3.25(m,HH), 349 4.10(q,2H,J=7),5.75(t,l H,J=7),6.65(dY1 HYJ=2),6.87(d,1 H,J=4), C22H23N03 7. 10(s,4H),7.1 7-7.67(mY5H)

(42H,J=7),5.62 and 6.07(t,tY1 H,J=7),6.62(d,lH,J=l0),6.82 CzlH2,N02 (d, 1 H,J=8),7.1 2(sy4H),7.22-7.77(m,5H)*

5n 2.07 and 2.22(~,~,3H),2.95(d,2H,5=8),3.00-3.25(m,2H),3.75 319

(continued)

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2 140 VENKOV AND STATKOVA-ABEGHE

Table 2 continued

50 1.30(t,3H,J=7),2.60-2.8O(m,2H),2.90(d,2H,J=6),2.95-3.17 337 (m, 1 H),3.45-3.55(m,2H),4.07(q,2H,J=7),5 .56-5.70(m, 1 H), 6.95-7.1 5(m,9H),9.20(s,lH)

C2,H2,N0,

5p 1.30(t,3H,J=7),2.60-2.8O(m,2H),2.80-2.90(m,2H),3.55-3.70, 397 (m,lH),3.98(~,6H),4.15(q,2H,J=6),5.35-5.55(rn,l H),6.60 C23H27N05 (s,lH),6.70(s,l H),6.87-7.20(m,SH),9.32(s,lH)

5q 2.08(~,3H),2.77-2.83(m,2H).2.85(d,2H,J=4),3.05-3.25(m,lH), 307 3.60-3.72(m,2H),5.70(d, 1 H,J= 10),6.82-7.00(m,5H),7,20 C?0H21N03 (s,4H),9.55(~,1 H)

2.90(m,2H),3.12-3.50(m,2H),4.08(q.2H,J=7),5.98(d,1H,J=7), CI7H2,NO4 6.67-7.17(m,4H)

(m,2H),3.50-3.80(~,2H),5.40 and 6.05(t,t, 1 H,J=7),7.12(~,4H)* CI6Hl9NO3 5t 1 .lO(t,3H,J=7),1.32(t,3H,J=6),2.15(d,lH,J=6),2.32(~,3H),2.85 333

(t,2H,J=7),3.25-3.60(m,2H,m),3.97(q,2H,J=6),4.10(q,2H,J=7), C18H,,N05 6.07(d,l H,J=9),7.10(s,4H)

5r 1.23(t,3H,J=6),1.95(~,3H),2.01 (d,l H,J=5),2.22(~,3H),2.75- 303

5s 2.15(~,3H),2.23(~,3H),2.85(~,3H),2.90(d,2H,J~),2.90-3.10 273

5u 1 . I 5(t,3H,J=8),1.62(~,3H),2.25(d,I H,J=4),2.32(~,3H),2.95 303 (42H,J=5),3.70(t,2H,J=6),4.02(q,2H,J=7),6.37(d, 1 H,J=7), 1 7H2 I N04 6.92-7.32(m,4H)

(m,2H),3.72(d,lH,J=8),4.00(q,2H,J=7),4.1O(q,2H,J=7),4.13 C,3H25N06 (q,2H,J=7)5.77-5.97(m, 1 H),7.02(s,4H)

5~ 1.1 3(<3H,J=6),1.25(t,6H,J=7).2.87(t,2H,J=6),3.30-3.55 3 63

aSome of the signals are doubled because of stereoisomers

chloride. That can be contributed to the better salt formation of 3,4-dihydroiso- quinoline with ethyl chloroformate because of delocalization in 3.

Obtained 1 -(2-oxoalky1)-2-acyltetrahydroisoquinolines 5 were farther converted .to the corresponding alcohols 7 and 1 -phenylethyl-2-alkyltetrahydroisquinolines 8 by reduction with NaBH4 and LiAIH,. Thc reduction Of 5a, 5j and 5t with NaBH4 in methanol proceeded regioselectively to the corresponding 1 -(2-hydroxyalkyl)-2-acyl-

tetrahydroisoquinolines 7a, 7j, 7t with domination of onc of diastereomers that were separated by column chromatography. The reduction of 5f with LiAM, afforded the corresponding 1 -phenylethyl-2-mcthyltctrahydroisoquinolinc 8f.

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ISOQUINOLINE ALKALOIDS 2141

Spectral data of the obtained new compounds are given in Table 2 and the

experimental part.

EXPERIMENTAL

1-Acetonyl-2-acyltetrahydroisoquinolines 5a-e; Typical Procedure: To a

solution of 3,4-dihydroisoquinoline (3 mmol) in acetone (3 mL, dried overnight

over KMn04 and freshly distilled) was added acyl chloride (3 mmol) in acetone

(2mL) and the solution was refluxcd for the time given (Table 1). Water (20 mL)

was added and the solution was extracted with CH,C12 (3x20 A). The combined

extracts were dried (Na2S04) and after evaporation of the solvents, the products

were purified by filtration through a short column of neutral A1203 using p.ether

and Et,O as eluents.

l-(2-Oxo-phenylethyI)-2-acyltetrahydroisoqunolines 5f-I; Typical

Procedure: To a solution of 3,4-dihydroisoquinoline (3 mmol) in 1,2-dichloro-

ethane (3 mL) was added acyl chloride (3 mmol) and the mixture was stirred for 30

min at room temperature. The corresponding acetophenone 4 (4 mmol) in 1,2-di-

chloroethane (3 mL) was added and the mixture was refluxed for the time given

(Table 1). The reaction mixture was worked up as abovc and the products were

purified by recrystallization or filtration through a short column of neutral AlZO3

using p.ether and EtzO as eluents.

1-(2-Oxoalkyl)-2-acyltetrahydroisoqunolines 5m-v; Typical Procedure:

To a solution of 3,4-dihydroisoquinoline (3 mmol) in 1 ,Zdichloroethane (3 mL)

was added acyl chloride (3 mmol) and the mixture was stirred for 30 min at room

temperature. The corresponding dicarbonyl compound 4 (4 mmol) in 1,2-dichloro-

ethane (3 mL) was addcd and the mixture was stirred at room temperature, heated at

50°C (with acetylacetone for 5r), or refluxed (with diethyl malonate for 5v) for the

time given (Table 1). The reaction mixture was workcd up as above and the

products were purified by recrystallization or filtration through a short column of

neutral Al2O3 using p.ether and Et,O as eluents.

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2 142 VENKOV AND STATKOVA-ABEGHE

N-Carboxyethyl-2-[2-(2-benzyd2-formyl-vinyl~,5-dimethoxypheny~~-

ethylarnine 6p was isolated from the reaction mixture of 5p by column

chromatography in 22% yield; mp 76-77°C; IR (CHCI,), v(crn-'): 3376, 171 3,

1677, 1600; 'H-NMR (CDCl3/TMS), ppm: Ia28(t,2H,J=7),2.85(t,2H,J=7), 3.20

(t,2H,J=6), 3.30(s,2H),3.88 (s,6H), 4.05(q.2H,J=7), 4.54-4.80 (m,lH), 6.70 (s,lH),

6.73(s,l H), 6.95(s,lH), 7.05 (s,lH), 7.17(s,3H), 7.65(s,lH), 9.60(s,lH).

N-Acetyl-[2-(2-benzyl-2-formyI-vinyl)-phenyl]-ethylamine 6q: was isolated from the

reaction mixture of 5q by column chromatography in 23% yield; mp 128-129°C; lR (CHCI,), v(cm-'): 3274, 1673, 1627 1699; 'H-NMR (CDCI,/TMS), ppm: 1.88(s,3H),

2.80(t.2H,J=6), 3.25(t,2H,J=6), 3.75(s,2H), 5.50(m,lH), 6.90-7.20(m,4H), 7.25(s,5H),

7.62(s,IH), 9.65(s,lH).

1-(2-Hydroxyalkyl)-2-acyltetrahydroisoqunolines 7; Typical Procedure:

NaBH, (3 mmol) was added portionwise to a stirred solution of 1 -(2-Oxoalkyl)-

2-acyltetrahydroisoqunolines 5 (2 mmol) in MeOH ( 1 0 mL) at room temperature.

Water (30 mL) was added after 3 h and the solution was extracted with CH2Clz

(3x20 mL). The combined extracts were dried (Na,SO,) and after evaporation of

the solvent, the products were separated by column chromatography.

1-(2-Hydroxypropyl)-2-Carboxyethyltetrahydroisoquino~ne 7a was obtained as a

mixture of two diastereomers that were separated by column chromatography on

neutral Al,O, using p.ether and Et20 as eluents. First isomer was isolated using mixture

of p.ether/Et,O (8: 1) as oil in yield 15%; 'H-NMR (CDCI,/TMS), ppm: 1.17

(d,3H,J=6), le25(t,3H,J=7), 1.62-1.85(m,2H), 2.65-2.90(m,2H), 2.97-3.32 (m,lH),

4.20-4.42(m,2H), 4.07(q,2H,J=7), 4.40(s,lH,br.), 5.17(d,lH,J=7), 6.92(s,4H), MS, (M?

263 (Calc. for CI~H2,N03, 263.3).

The second isomer was isolated at eluent p.ether/ EtzO (2: 1) as oil in yield 74%;

H-NMR (CDCI,/TMS), ppm: 1.25(d,3H,J=6), 1.30(t,3H,J=7), 1.90 (q,2H,J=7), 2.57-

2.87(m,2H), 2.92-3.25(m,IH), 3.27-3.40(m,2H), 4.10(q,2H,J=7), 5.02(t,lH,J=6)

6.85(s,4H); MS,(M+) 263.

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ISOQUINOLINE ALKALOIDS 2143

1~2-HydroxyphenylethyI)-6,7-dimethoxy)-2-CarboxyethyItetrahydroiso-

quinotine 7j, obtained as a mixture of two diastereomers that were separated by

column chromatography on neutral A1203. First isomer was isolated using mixture

of p.ether/ Et20 (4: 1) in 16% yield ; crystals, mp 96-98°C; 'H-NMR (CDC13/TMS),

ppm: 1.27((t,3H,J=7), 2.02(t,2H,J=7), 2.55-2.85(m,2H), 2.95-3.27 (m,2H),

3.75(s,6H), 4.12(q,2H,J=7), 4.50(s,IH,br.),4.75 (t,lH,J=4), 5.17(t,lH, J=8), 6.32

(s,l H), 6.36(s,1 H), 6.86-7.12(m,5H); MS,(M') 385,(Calc. for C22H27N05,385.5).

The second isomer was isolated at eluent p.ether/Et,O ( I :2) in yield 72%; crystals,

mp 126°C; 'H-NMR (CDCI,/TMS), ppm: 1.27(t,3H,J=7), 2.15-2.45 (m,2H),2.55-

3.20(m,2H), 3.10-3.35(m,2H), 3.75(s,3H), 3.78(s,3H), 3.90(s,IH,br.), 4.10

(q,2H,J=7), 4.77-4.95(m,IH), 5.00-5.25(m,lH), 6.42(s,2H),7.10 (d,2H,J=2),

7.20(t,3H,J=2); MS, (M') 385.

l-(l-Carboxyethyl-2-hydroxypropyl)-2-Ace~ltetrahydroisoquinotine 6t

obtained as a mixture of four isomers, two of that were isolated by column

chromatography on neutral Al,O,. One of isomers was isolated using mixture of

p.ether/ Et,O (2: I ) as oil in 50% yield; 'H-NMR (CDCI,/TMS), ppm: 1.17

(t,3H,J=8), 1,30(d,3H,J=6), 2.02(~,3H), 2.55-2.70(111,2H), 2.90(t,2HgJ=6), 3.3 1 - 3.51(m,lH), 3.53-3.77(m,2H), 4.01(q,2H,J=7), 4.75(s,IH,br.), 5.95(d,IH,J=lO),

7.1 5(s,4H); MS,(M') 305,(Calc. for CI7H2,NO4, 305.4).

Another isomer was isolated using mixture of p.ether/Et,O (: 1) as oil in 30% yield;

H-NMR (CDCI,/TMS), ppm: 1.95(t,3H,J=8), 1.30(d,3H,J=5), 2. I2 (s,3H), 2.67-

2.85 (m,lH), 2.67-2.85(m,IH), 2.87-3.10(m,2H), 3.63(q,2H,J=8), 3.87 (t,2H,J=5),

4.00-4.22(s,IH,br.), 5.90(d,IH,J=6), 7.05(s,4H); MS, (M') 305.

1-Phenylethyl-2-methyltetrahydroisoquinolines 8f: A solution of 14243x0-

phenylethyl)-2-carboxyethyItetrahydroisoqunolines 5f (2 mmol) in Et20 (20 mL)

was added to a suspension of LiAIH4 (4 mmol) at 0°C and the mixture was stirred

for 3 h at room temperature, then workcd up us usual. The product was obtained as

oil in 90% yield; 'H-NMR (CDCI,/TMS), 6, ppm: 2. I7(t,1 H,J=5), 2.48(d,3H,J=3),

I

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2144 VENKOV AND STATKOVA-ABEGHE

2.67-2.87(m,2H), 2.92-3.20(m,2H), 3.54-3.80 (m,2H), 4.55(t,2H,J=5), 6.60-6.75

(m,4H), 6.90(s,SH); MS, (M') 249,(Calc. for C,sH,9N, 249.4).

REFERENCES

1. Recent review articles: Popp, F.D. Adv. Heterocyc. Chem. 1979,24, 187;

Heterocycles 1980,14, 1033.

2. Akiba,K., Araki,K., Nakatani,M., Wada,M. T. Letters 1981,4961.

3. Wada,M., Nakatani,M., Akiba,K. Chemistry Letters 1983,39.

4. Akiba,K., Araki,K., Nakatani,M., Wada,M.,Yamamoto,Y. J. Org. Chem.

1985,50,63.

5 . Hashigaki,K., Ishikava,S., Wan,W., Yarnato,M. Synthesis, 1988, 1001.

6. Pelletier,J.C., Cava,M.P. Synthesis 1987,474.

7. Tietze,L.F., Schimpf,R., Wichmann, J. Chem. Ber. 1992,125,2571.

8. Venkov,A., Statkova,S., Ivanov,l. Synth. Comrnun. 1992,22(1), 125.

9. Venkov,A., Statkova-Aghebe,S., Synth. Commun. 1995, in press.

10. Sugasawa,S., Yosh&awa,H., SOC. 1933, 1583; Hengell,F.R., Pass,M.C.

Austr. J. Chem. 1985,38(4), 293.

1 1. Brossi,A., Besendorf,H., Pelimont,B., Walter,M., Schnider,O. Helvetica

Chim. Acta, 1960, 1459.

12.Ziegler,E., Leitner,W., Sterk,H. Z. Naturforsch., 1978,33b, 640.

(Received in t he UK 11th October 1995)

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