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Synthesis of 2(3H)-imidazolethiones and 2(3H)-imidazolones from β,γ-alkynyl carbanilides
T~!de&ua
Leaers. Vol. 35. No. IO, pp 158%1586.1994 Ekevii scimee Ltd l’rinted in Gmu Britain @040-4039/94 $6.004.~
0040-4039(94)EOO84-B
Synthesis of 2(3H)-Imidazolethiones and 2(3II)dmidazolones from B,y-Alkyoyl Carbanilides Balachori
Devan and Krishnsmoortlty
Xqjagopalon*
Department of Organic Chemistry, University of Madras, Guindy Campus, Madras - 600 025. India.
Ahtract
: 8, y-Aatyknic
arbnilida
alH$ mhncnt with ammonia
md
cyclize aad sub6cqutn1ly isomer& KOH int-BuOH rcspcctively.
Base catalysed inttamolecular addition-cyclization
to 2(3Ii)-lmib~ktbioncs
have at&acted amsiderable
upon
strategy has heen receiving a great dea1 of attention
as a potential methodologyfor constructionof five membered heterocycles.ls imidaaAethionw
and 2(3H)-lmidazobnes
A
number
of 2(3H)-
attention because of their ptonounced antithyroid activity,3 thus
setting them apart aa important synthetic targets. This prompted the comtnunicstion of our fittd@s viz, an expedient synthesis of 2(3H)-imidazokthion
and 2(3H)-imidazolones
from compounds la-c.
N-propargyl cartmnilide Is was ptepared in almost quantitative yield from catbanilide with propargyl bromideand K&G,
in a&one or acetonitrile.?
adjusted to #I=10 by adding NH,OH.
Compound lo was dissolved in methanol and the solution
H$3 was passed at room temperature until a sample of the mixture no
longer showed TLC spot correspatding to the starting material. Tlte mixture was then poured onto ice and the solid which separated was filtered, dried and recrystalhsed from chloroform to afford 2(3H)-imidazolethione
4n (m.p: 22@‘C, CHC13, 82% yield) (equation 1). The general applicability of this reaction was established with R=CI and R=GCH, Addition of few drops of 1N NaOH during the reaction enhances the rate and the reaction goes to completion in one hour. n I
”
Critical analysis of 13C NMR data, appearance of an NH proton in ‘H NMR at 8 12.0 and failure to get the Educed product with NaBH, clearly showed the product to have structure 4. The reaction shows the
initial attack of -SH on the nitrile carbon and cyclization occurs in a Sew-dig
pathway leading to intermediate
3 which on subsequent isomerization affords compound 4. The presence of the NH proton was confirmed by D, 0 exchange in ‘H NMR. 1585
1586
Extension prepared
following
equation
1,
of this reaction to the B-allenyl system was investigated conventional
methods.45
This system
H-C-H ,CuBr
t+S,NH,,OH
p
pH=IO, 042 OH,
(iPr, Mi,THF, A, 12 hr
The cyclization
and the propensity
of compounds
temperature
for 2 h.
quantitative
yield (Eq.3).
described
as in
-
la-c
were also effected
After work up, it afforded All the
to isomerization
compounds
la,b&
c
warrant further exploration
with
2(3H)-’ nnidazolones
gave satisfactory H\
1x1conclusion, in t-BuOH
powdered 7a-c
resulting
in t-B&H’
as the only products
compound
at reflux in almost
data.
KOH ,l -B&l-l
A.Ph
0 43
in formation
(aq.3)
N
70-c
with compounds
operates
of 2(3H)- imidamlethionw
derivatives respectively under mild conditions and could therefore Further work is in pmgress
of
N
this study demonstrate-s that the S-~XO-digcyclization thereby
KOH
spectral6 and analytical
:r and KOH
under conditions
50 was
r.t
The drive for cyclization la-c.
to cyclize
failed
compound
but resulted in the thio urea 69 in 70% yield.6 i
la.
(eq2). The allenyl
both
in ammoniacal
and
find useful applications
H,S
2(3H)-imidazolone in organic
synthesis.
bearing good leaving group at the termini carbon of the alkyne
in compound 1. hhlOWh&Mclltr
BD th* UGC, NCW Delhi for the fellowship. We are thankful to Dr.B.Go@mt, Mr.SJanrrdhanam and Dr.T.Rajmnmmar for tt&itI tliscttssiotct: DrS.P.Gatt~~lt bj (Zurich), Dr.R.BaIasubramrnian (University of Madras) md I-k& RSIC, IlT, Madras for spcctnl data. References 1. Sbott, KM.; Zie@er. C&Jr. Terrult&on Len., 1993, 34.75-78. 2. Mmshm, J* DuB8y, WJ. J. or& them.. 1993,58,3435-3443. a. 3. Jackmu, M.; Kknk, M.: Fsbbum, B.: Tullar. B.F.; Archer, S. J. Am. Cltem. Sac., 1948,70, 2884. b. Stanley. MU; Ilrtwood, E.B. EndocrLtology 1949.4$, 588-589. c. For a comprehensive review on 2@I)-itnidazolone and 2(3H)-imidrzolctkionc. see KJaus Hofttunn, “The Chemistry of Heterocycliccompounds” Itnidszole and its derivative, part 1: Interscience Publishers. Inc., London. 1953. pp.63-91. 4. &van, B.; Rajagopalrn, K. S~!I. Commun, 1993, in Press. a. 5. Janmdhanam, S.; Dcvmt, B.; Rajagopalrn, K. Tetmlredrort. Lerr.. 1993. +). 6761-6764. b. Balakumar, A.; h~rdbr~m. S.; Rajagopalan. K. J. Org. Chem. 1993. 5%. 5482-5487. c. DilrJbit, D.K. Ind 1. Chem.. Sect. B.. 1983. 22, 1144. 6. Spcctnl data of sonx selcctcd compountk : 4h : Solid (m.p. 208”C, CHCQ IR (Kerr, u,,,cm -I’*, 1630, 1390, 1330, 1250, 1120, 1090, 1070. lH NMR (90 MHz, CDCI,), & 12.0 @r s, lH,-NH) (disappears on exchange with D?O), 7.42 (ABq. 4H. Ar-H), 6.55 (s. 1H. vinylic l-I). 2.1Y (ssJH.-CH3). % NMR (CDClp. 22.5 MHr) 6 : 160. 32 (s,C& 136.09 (s), 133.95 (x), 129.17 (d), 127.07 (d), 125.95 (s). 115.32 (d), 9.81 (q). 6r : IR (CHClg. ~,,,cm-~); 3500.3380. 1950, 1585, 1460, 1360. ‘H NMR (300 MHz, CDCI,) 6; 7.2 (ABq, 4H, Ar-H). 5.73-5.46 @r I, W, -NH& 5.44-5.13 (m, I H.‘*= ), 4.77-4.73 (m, 2H, =Z ), 4.70-4.66 (tn. 2H. -N-CH,), 2.39 (s-3H. ArCH,). 13C NMR (CDCI, 22.5 Mtl~) 209.44. 182.19. 139.02. 138.26, 130.78, 127.37, 85.76, 70.01, 54.34, 20.92. 7c : Solid (m.p.218”C, CHCI,-McOH), IR (CHCI,, u,,,,,cn~~~‘: 3450, 1680. 1510, 1400 ’ H NMR (90 MHz, CDCI,) b; 10.2 @r.s, 1H, NH) (cxcbange with DZO),7.1 (ABq, 4H, Ar-H). 6.08 (s, IH, vinylic H), 3.8 (s, 3H,-OCH3). 2.03 (s, 3H,CH& “C NMR (DMSO+, 225 MHz), 156.13, 152.07, 130.72. 121.84. 117.83. 113.88. 105.97. 55.04. 1035. 7. Hall. J.H., Gislcr, M., 1. Org. Cbcm., 1976. 41. 3769-3770.
(Received in UK 11 November 1993; revised 21 December 1993; accepted 7 J~uary
1994)
Leaers. Vol. 35. No. IO, pp 158%1586.1994 Ekevii scimee Ltd l’rinted in Gmu Britain @040-4039/94 $6.004.~
0040-4039(94)EOO84-B
Synthesis of 2(3H)-Imidazolethiones and 2(3II)dmidazolones from B,y-Alkyoyl Carbanilides Balachori
Devan and Krishnsmoortlty
Xqjagopalon*
Department of Organic Chemistry, University of Madras, Guindy Campus, Madras - 600 025. India.
Ahtract
: 8, y-Aatyknic
arbnilida
alH$ mhncnt with ammonia
md
cyclize aad sub6cqutn1ly isomer& KOH int-BuOH rcspcctively.
Base catalysed inttamolecular addition-cyclization
to 2(3Ii)-lmib~ktbioncs
have at&acted amsiderable
upon
strategy has heen receiving a great dea1 of attention
as a potential methodologyfor constructionof five membered heterocycles.ls imidaaAethionw
and 2(3H)-lmidazobnes
A
number
of 2(3H)-
attention because of their ptonounced antithyroid activity,3 thus
setting them apart aa important synthetic targets. This prompted the comtnunicstion of our fittd@s viz, an expedient synthesis of 2(3H)-imidazokthion
and 2(3H)-imidazolones
from compounds la-c.
N-propargyl cartmnilide Is was ptepared in almost quantitative yield from catbanilide with propargyl bromideand K&G,
in a&one or acetonitrile.?
adjusted to #I=10 by adding NH,OH.
Compound lo was dissolved in methanol and the solution
H$3 was passed at room temperature until a sample of the mixture no
longer showed TLC spot correspatding to the starting material. Tlte mixture was then poured onto ice and the solid which separated was filtered, dried and recrystalhsed from chloroform to afford 2(3H)-imidazolethione
4n (m.p: 22@‘C, CHC13, 82% yield) (equation 1). The general applicability of this reaction was established with R=CI and R=GCH, Addition of few drops of 1N NaOH during the reaction enhances the rate and the reaction goes to completion in one hour. n I
”
Critical analysis of 13C NMR data, appearance of an NH proton in ‘H NMR at 8 12.0 and failure to get the Educed product with NaBH, clearly showed the product to have structure 4. The reaction shows the
initial attack of -SH on the nitrile carbon and cyclization occurs in a Sew-dig
pathway leading to intermediate
3 which on subsequent isomerization affords compound 4. The presence of the NH proton was confirmed by D, 0 exchange in ‘H NMR. 1585
1586
Extension prepared
following
equation
1,
of this reaction to the B-allenyl system was investigated conventional
methods.45
This system
H-C-H ,CuBr
t+S,NH,,OH
p
pH=IO, 042 OH,
(iPr, Mi,THF, A, 12 hr
The cyclization
and the propensity
of compounds
temperature
for 2 h.
quantitative
yield (Eq.3).
described
as in
-
la-c
were also effected
After work up, it afforded All the
to isomerization
compounds
la,b&
c
warrant further exploration
with
2(3H)-’ nnidazolones
gave satisfactory H\
1x1conclusion, in t-BuOH
powdered 7a-c
resulting
in t-B&H’
as the only products
compound
at reflux in almost
data.
KOH ,l -B&l-l
A.Ph
0 43
in formation
(aq.3)
N
70-c
with compounds
operates
of 2(3H)- imidamlethionw
derivatives respectively under mild conditions and could therefore Further work is in pmgress
of
N
this study demonstrate-s that the S-~XO-digcyclization thereby
KOH
spectral6 and analytical
:r and KOH
under conditions
50 was
r.t
The drive for cyclization la-c.
to cyclize
failed
compound
but resulted in the thio urea 69 in 70% yield.6 i
la.
(eq2). The allenyl
both
in ammoniacal
and
find useful applications
H,S
2(3H)-imidazolone in organic
synthesis.
bearing good leaving group at the termini carbon of the alkyne
in compound 1. hhlOWh&Mclltr
BD th* UGC, NCW Delhi for the fellowship. We are thankful to Dr.B.Go@mt, Mr.SJanrrdhanam and Dr.T.Rajmnmmar for tt&itI tliscttssiotct: DrS.P.Gatt~~lt bj (Zurich), Dr.R.BaIasubramrnian (University of Madras) md I-k& RSIC, IlT, Madras for spcctnl data. References 1. Sbott, KM.; Zie@er. C&Jr. Terrult&on Len., 1993, 34.75-78. 2. Mmshm, J* DuB8y, WJ. J. or& them.. 1993,58,3435-3443. a. 3. Jackmu, M.; Kknk, M.: Fsbbum, B.: Tullar. B.F.; Archer, S. J. Am. Cltem. Sac., 1948,70, 2884. b. Stanley. MU; Ilrtwood, E.B. EndocrLtology 1949.4$, 588-589. c. For a comprehensive review on 2@I)-itnidazolone and 2(3H)-imidrzolctkionc. see KJaus Hofttunn, “The Chemistry of Heterocycliccompounds” Itnidszole and its derivative, part 1: Interscience Publishers. Inc., London. 1953. pp.63-91. 4. &van, B.; Rajagopalrn, K. S~!I. Commun, 1993, in Press. a. 5. Janmdhanam, S.; Dcvmt, B.; Rajagopalrn, K. Tetmlredrort. Lerr.. 1993. +). 6761-6764. b. Balakumar, A.; h~rdbr~m. S.; Rajagopalan. K. J. Org. Chem. 1993. 5%. 5482-5487. c. DilrJbit, D.K. Ind 1. Chem.. Sect. B.. 1983. 22, 1144. 6. Spcctnl data of sonx selcctcd compountk : 4h : Solid (m.p. 208”C, CHCQ IR (Kerr, u,,,cm -I’*, 1630, 1390, 1330, 1250, 1120, 1090, 1070. lH NMR (90 MHz, CDCI,), & 12.0 @r s, lH,-NH) (disappears on exchange with D?O), 7.42 (ABq. 4H. Ar-H), 6.55 (s. 1H. vinylic l-I). 2.1Y (ssJH.-CH3). % NMR (CDClp. 22.5 MHr) 6 : 160. 32 (s,C& 136.09 (s), 133.95 (x), 129.17 (d), 127.07 (d), 125.95 (s). 115.32 (d), 9.81 (q). 6r : IR (CHClg. ~,,,cm-~); 3500.3380. 1950, 1585, 1460, 1360. ‘H NMR (300 MHz, CDCI,) 6; 7.2 (ABq, 4H, Ar-H). 5.73-5.46 @r I, W, -NH& 5.44-5.13 (m, I H.‘*= ), 4.77-4.73 (m, 2H, =Z ), 4.70-4.66 (tn. 2H. -N-CH,), 2.39 (s-3H. ArCH,). 13C NMR (CDCI, 22.5 Mtl~) 209.44. 182.19. 139.02. 138.26, 130.78, 127.37, 85.76, 70.01, 54.34, 20.92. 7c : Solid (m.p.218”C, CHCI,-McOH), IR (CHCI,, u,,,,,cn~~~‘: 3450, 1680. 1510, 1400 ’ H NMR (90 MHz, CDCI,) b; 10.2 @r.s, 1H, NH) (cxcbange with DZO),7.1 (ABq, 4H, Ar-H). 6.08 (s, IH, vinylic H), 3.8 (s, 3H,-OCH3). 2.03 (s, 3H,CH& “C NMR (DMSO+, 225 MHz), 156.13, 152.07, 130.72. 121.84. 117.83. 113.88. 105.97. 55.04. 1035. 7. Hall. J.H., Gislcr, M., 1. Org. Cbcm., 1976. 41. 3769-3770.
(Received in UK 11 November 1993; revised 21 December 1993; accepted 7 J~uary
1994)