JOURNALꢀOFꢀCHEMICALꢀRESEARCHꢀ2007ꢀ 393
O
O
R
O
O
R
O
C
R
R
NHR'
O
O
- Me2CO
3
O
1 + 2
4
O
N
R''NHNH
R
C
N
O
R
R'
R'
5
7
6
Scheme 2
1711,ꢀ1653ꢀ(C=O);ꢀ1348,ꢀ1291.ꢀ1HꢀNMR:ꢀ1.05ꢀ(9ꢀH,ꢀs,ꢀCMe3);ꢀ1.44ꢀ
(6ꢀH,ꢀs,ꢀ2ꢀMe);ꢀ1.62ꢀ(2ꢀH,ꢀs,ꢀCH2);ꢀ1.42ꢀ(3ꢀH,ꢀs,ꢀMe);ꢀ1.47ꢀ(3ꢀH,ꢀs,ꢀ
Me);ꢀ3.44ꢀ(1ꢀH,ꢀs,ꢀCH);ꢀ6.93ꢀ(1ꢀH,ꢀs,ꢀNH);ꢀ8.02ꢀ(1ꢀH,ꢀd,ꢀ3JHHꢀ=ꢀ9.1,ꢀ
CH);ꢀ8.50ꢀ(1ꢀH,ꢀdd,ꢀ3JHHꢀ=ꢀ9.1,ꢀ4JHHꢀ=ꢀ2.1ꢀHzꢀCH);ꢀ8.81ꢀ(1ꢀH,ꢀd,ꢀ4JHHꢀ
=ꢀ2.1,ꢀCH);ꢀ9.13ꢀ(1ꢀH,ꢀbroadꢀs,ꢀNH).ꢀ13CꢀNMR:ꢀ23.1,ꢀ23.9ꢀ(2ꢀCH3);ꢀ
29.6ꢀ(CMe2);ꢀ32.0ꢀ(CMe3);ꢀ35.2,ꢀ46.3ꢀ(2ꢀCMe2);ꢀ52.0ꢀ(CMe3);ꢀ52.5ꢀ
(CH2);ꢀ57.2ꢀ(CH);ꢀ121.7,ꢀ124.7,ꢀ128.2ꢀ(3ꢀCH);ꢀ134.6,ꢀ142.1,ꢀ144.4ꢀ
(3ꢀC);ꢀ166.6,ꢀ168.2,ꢀ177.7ꢀ(3ꢀC=O).ꢀEI–MS:ꢀ463ꢀ(M+,ꢀ5),ꢀ266ꢀ(48),ꢀ
198ꢀ(52),ꢀ157ꢀ(100),ꢀ57ꢀ(52).ꢀAnal.ꢀCalcdꢀforꢀC21H29N5O7ꢀ(463.5):ꢀ
Cꢀ54.42,ꢀHꢀ6.31,ꢀNꢀ15.11;ꢀFound:ꢀCꢀ54.21,ꢀHꢀ6.35,ꢀNꢀ15.09.
N-(tert-butyl)-1-[1-(2,4-dinitrophenyl)-3,5-dioxo-1-
phenyltetrahydro-1H-pyrazol-4-yl)-1-cyclohexanecarboxamide
(4d):ꢀ Yield:ꢀ 0.25ꢀ gꢀ (56%).ꢀ Yellowꢀ powder,ꢀ m.p.ꢀ 170–172°C.ꢀ
IRꢀ(KBr):ꢀ3400,ꢀ3150ꢀ(NH);ꢀ1731ꢀandꢀ1685ꢀ(C=O),ꢀ1531,ꢀ1342ꢀ(C-O).ꢀ
1HꢀNMR:ꢀ0.92–0.95ꢀ(4ꢀH,ꢀm,ꢀ2ꢀCH2);ꢀ1.59–1.74ꢀ(6ꢀH,ꢀm,ꢀ3ꢀCH2);ꢀ
1.38ꢀ(9ꢀH,ꢀs,ꢀCMe3);ꢀ3.44ꢀ(1ꢀH,ꢀs,ꢀCH);ꢀ5.63ꢀ(1ꢀH,ꢀs,ꢀNH);ꢀ8.04ꢀ(1ꢀH,ꢀ
d,ꢀ3JHHꢀ=ꢀ9.1,ꢀCH);ꢀ8.47ꢀ(1ꢀH,ꢀdd,ꢀ3JHHꢀ=ꢀ9.1,ꢀ4JHHꢀ=ꢀ2.5,ꢀCH);ꢀ8.79ꢀ
(1ꢀH,ꢀd,ꢀ4JHHꢀ=ꢀ2.0,ꢀCH);ꢀ10.9ꢀ(1ꢀH,ꢀbroadꢀs,ꢀNH).ꢀ13CꢀNMR:ꢀ25.2ꢀ
(CH2);ꢀ28.5ꢀ(CMe3);ꢀ28.6,ꢀ28.8,ꢀ29.6,ꢀ30.7ꢀ(4ꢀCH2);ꢀ41.9ꢀ(C);ꢀ52.7ꢀ
(CMe3);ꢀ65.3ꢀ(CH);ꢀ121.1,ꢀ123.6,ꢀ127.7ꢀ(3ꢀCH);ꢀ134.5,ꢀ142.2,ꢀ144.2ꢀ
(3ꢀC);ꢀ168.3,ꢀ170.9,ꢀ174.1ꢀ(3ꢀC=O).ꢀEI-MS:ꢀ447ꢀ(M+,ꢀ2),ꢀ127ꢀ(65),ꢀ73ꢀ
(100),ꢀ86ꢀ(55),ꢀ57ꢀ(32).ꢀAnal.ꢀCalcdꢀforꢀC20H25N5O7ꢀ(447.4):ꢀC53.69,ꢀ
Hꢀ5.62,ꢀNꢀ15.65;ꢀFound:ꢀCꢀ53.74,ꢀHꢀ5.54,ꢀNꢀ15.47.
Inꢀ summary,ꢀ theꢀ reactionꢀ betweenꢀ alkylꢀ isocyanidesꢀ andꢀ
alkylideneꢀMeldrum’sꢀacidꢀinꢀtheꢀpresenceꢀofꢀarylhydrazinesꢀ
leadsꢀtoꢀfunctionalisedꢀpyrazols.ꢀTheꢀpresentedꢀreactionsꢀcarryꢀ
theꢀadvantageꢀthatꢀnotꢀonlyꢀisꢀtheꢀreactionꢀperformedꢀunderꢀ
neutralꢀconditions,ꢀbutꢀtheꢀsubstancesꢀcanꢀbeꢀmixedꢀwithoutꢀ
any activation or modification.
Experimental
General.ꢀ Isopropylideneꢀ Meldrum’sꢀ acidꢀ wasꢀ preparedꢀ
byꢀ additionꢀ ofꢀ Meldrum’sꢀ acidꢀ toꢀ acetoneꢀ inꢀ presenceꢀ ofꢀ
piperidineꢀandꢀglacialꢀaceticꢀacid.6ꢀM.p.:ꢀElectrothermal-9100ꢀ
apparatus.ꢀIRꢀSpectra:ꢀShimadzuꢀIR-460ꢀspectrometer.ꢀ1Hꢀandꢀ
13Cꢀ NMRꢀ spectra:ꢀ Brukerꢀ DRX-500ꢀ AVANCEꢀ instrument;ꢀ
inꢀCDCl3ꢀatꢀ500.1ꢀandꢀ125.7ꢀMHz,ꢀrespectively;ꢀdꢀinꢀppm,ꢀJꢀinꢀ
Hz.ꢀEI-MSꢀ(70ꢀeV):ꢀFinnigan-MAT-8430ꢀmassꢀspectrometer,ꢀ
inꢀm/z.ꢀElementalꢀanalysesꢀ(C,ꢀH,ꢀN)ꢀwereꢀperformedꢀwithꢀaꢀ
HeraeusꢀCHN–O–Rapidꢀanalyser.
General procedure for the preparation of compounds 4.ꢀ
ToꢀaꢀmagneticallyꢀstirredꢀsolutionꢀofꢀisopropylideneꢀMeldrum’sꢀacidꢀ
(0.18ꢀg,ꢀ1ꢀmmol)ꢀandꢀphenylhydrazineꢀ(0.11ꢀg,ꢀ1ꢀmmol)ꢀinꢀCH2Cl2ꢀ
(15ꢀml)ꢀwasꢀaddedꢀtert-butylꢀisocyanideꢀ(0.12ꢀml,ꢀ1ꢀmmol)ꢀatꢀ0°Cꢀ
overꢀ 5ꢀ min.ꢀ Theꢀ reactionꢀ mixtureꢀ wasꢀ thenꢀ stirredꢀ forꢀ 24ꢀ h.ꢀ Theꢀ
solventꢀwasꢀremovedꢀunderꢀreducedꢀpressureꢀandꢀtheꢀviscousꢀresidueꢀ
was purified by diethyl ether.
N-(tert-butyl)-2-(3,5-dioxo-1-phenyltetrahydro-1H-pyrazol-4-
yl)-methylpropanamide (4a):ꢀYield:ꢀ 0.31ꢀ gꢀ (98%).ꢀYellowꢀ powder,ꢀ
m.p.ꢀ 140–142°C.ꢀ IRꢀ (KBr):ꢀ 3355,ꢀ 3055ꢀ (NH);ꢀ 1727,ꢀ 1697ꢀ (C=O);ꢀ
1361,ꢀ 1297.ꢀ 1Hꢀ NMR:ꢀ 1.36ꢀ (9ꢀ H,ꢀ s,ꢀ CMe3);ꢀ 1.51,ꢀ 1.61ꢀ (6ꢀ H,ꢀ 2ꢀ s,ꢀ
2ꢀMe);ꢀ3.34ꢀ(1ꢀH,ꢀs,ꢀCH);ꢀ5.60ꢀ(1ꢀH,ꢀs,ꢀNH);ꢀ7.22ꢀ(1ꢀH,ꢀt,ꢀ3JHHꢀ=ꢀ7.4,ꢀ
CH);ꢀ 7.41ꢀ (2ꢀ H,ꢀ t,ꢀ 3JHHꢀ =ꢀ 7.7,ꢀ 2ꢀ CH);ꢀ 7.71ꢀ (2ꢀ H,ꢀ d,ꢀ 3JHHꢀ =ꢀ 7.9,ꢀ
2ꢀCH);ꢀ8.30ꢀ(1ꢀH,ꢀbroadꢀs,ꢀNH).ꢀ13CꢀNMR:ꢀ24.5,ꢀ24.6ꢀ(2ꢀMe);ꢀ28.8ꢀ
(CMe3);ꢀ 46.9ꢀ (C);ꢀ 52.1ꢀ (CMe3);ꢀ 53.3ꢀ (CH);ꢀ 119.8ꢀ (2ꢀ CH);ꢀ 125.9ꢀ
(CH);ꢀ129.6ꢀ(2ꢀCH);ꢀ136.7ꢀ(C);ꢀ166.7,ꢀ170.7,ꢀ175.5ꢀ(3ꢀC=O).ꢀEI-MS:ꢀ
317ꢀ(M+,ꢀ5),ꢀ217ꢀ(10),ꢀ88ꢀ(100),ꢀ77ꢀ(20),ꢀ59ꢀ(40),ꢀ39ꢀ(27).ꢀAnal.ꢀCalc.ꢀ
forꢀC17H23N3O3ꢀ(317.4):ꢀCꢀ64.33,ꢀHꢀ7.30,ꢀNꢀ13.24;ꢀFound:ꢀCꢀ63.93,ꢀ
Hꢀ7.08,ꢀNꢀ13.20.
N-(tert-butyl)-2-[1-(2,4-dinitrophenyl)-3,5-dioxotetrahydro-1H-
pyrazol-4-yl]-2-methylpropanamideꢀ(4b):ꢀYield:ꢀ0.40ꢀgꢀ(98%).ꢀRedꢀ
powder,ꢀm.p.ꢀ184–186°C,ꢀIRꢀ(KBr):ꢀ3410,ꢀ3075ꢀ(NH);ꢀ1714,ꢀ1652ꢀ
(C=O),ꢀ1368,ꢀ1342.ꢀ1HꢀNMR:ꢀ1.30ꢀ(9 H, s,ꢀCMe3);ꢀ1.52,ꢀ1.63ꢀ(6ꢀH,ꢀ
2ꢀs,ꢀ2ꢀCH3);ꢀ3.47ꢀ(1ꢀH,ꢀs,ꢀCH);ꢀ6.62ꢀ(1ꢀH, s,ꢀNH);ꢀ8.11ꢀ(1ꢀH, d,ꢀ3JHHꢀ
=ꢀ9.1,ꢀCH);ꢀ8.63ꢀ(1ꢀH,ꢀdd,ꢀ3JHHꢀ=ꢀ9.1,ꢀ4JHHꢀ=ꢀ2.5,ꢀCH);ꢀ8.76ꢀ(1ꢀH,ꢀ
d,ꢀ4JHHꢀ=ꢀ2.5,ꢀCH);ꢀ10.9ꢀ(1ꢀH,ꢀbroadꢀs,ꢀNH).ꢀ13CꢀNMR:ꢀ23.7,ꢀ24.1ꢀ
(2ꢀ CH3);ꢀ 28.2ꢀ (CMe3);ꢀ 48.3ꢀ (C);ꢀ 51.7ꢀ (CMe3);ꢀ 51.8ꢀ (CH);ꢀ 121.4,ꢀ
123.9,ꢀ128.2ꢀ(3ꢀCH);ꢀ135.2,ꢀ142.4,ꢀ144.4ꢀ(C);ꢀ169.2,ꢀ170.0,ꢀ176.1ꢀ
(3ꢀC=O).ꢀEI-MS:ꢀ407ꢀ(M+,ꢀ5),ꢀ307ꢀ(5),ꢀ84ꢀ(72),ꢀ59ꢀ(84),ꢀ58ꢀ(100).ꢀAnal.ꢀ
Calcdꢀ forꢀ C17H21N5O7ꢀ (407.4):ꢀ Cꢀ 50.12,ꢀ Hꢀ 5.20,ꢀ Nꢀ 17.19;ꢀ Found:ꢀ
Cꢀ50.21,ꢀHꢀ5.12,ꢀNꢀ17.30.
Received 10 May 2007; accepted 9 July 2007
Paper 07/4640 doi: 10.3184/030823407X228812
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2-[1-(2,4-Dinitrophenyl)-3,5-dioxotetrahydro-1H-pyrazol-4-yl]-2-
methyl-N-(1,1,3,3-tetramethylbutyl)propanamide (4c):ꢀYield:ꢀ0.43ꢀgꢀ
(94%).ꢀ Redꢀ powder,ꢀ m.p.ꢀ 90–92°C.ꢀ IRꢀ (KBr):ꢀ 3410,ꢀ 3210ꢀ (NH);ꢀ
PAPER: 07/4640