Reduction of some esters of pyrazole-3,4-dicarboxylic acid

摘要

720 J.C.S. Perkin IReduction of Some Esters of Pyrazole-3,4-dicarboxylic AcidBy C. V. Greco and F. Pellegrini, Department of Chemistry, St. John's University, Jamaica, New York 114323,4-Bishydroxyrnethylpyrazole was prepared by reduction of diethyl pyrazole-3.4-dicarboxylate and of SS-diethylpyrazole-3.4-dicarbothioate. A reduction of dimethyl pyrazole-3.4-dicarboxylate to methyl 4-formylpyrazole-3-carboxylate is also described.IN connection with another study, we had need of3,4-bishydroxymethylpyrazole (I). We describe hereseveral preparations and a novel reduction of dimethylpyrazole-3,4-dicarboxylat e.A 1,3-dipolar cyclo-addition of diazomethane todimethyl acetylenedicarboxylate (see Scheme) at lowtemperature gave dimethyl pyrazole-3,4-dicarboxylate(IIa). This was a more convenient preparation than thecyclization of ethyl ethoxymethyleneoxalacetate withhydrazine hydrate which we had initially employed forobtaining the diethyl ester (IIb).Treatment of di-isobutylaluminium hydride (DIBAL-H) with the diethyl ester (IIb) in toluene between -75and -65" gave the diol (I) in 36--43 yield.SinceDIBAL-H is very pyrophoric, the dimethyl ester (IIa)was treated with a 10 molar excess of sodium orlithium aluminium hydride (LAH) in tetrahydrofuran(THF) at low temperature. Instead of the diol (I),the previously unknown methyl 4-formylpyrazole-3-carboxylate (111) was obtained. The best yields ofcompound (111) (41-60) were obtained in the tem-perature range from -73 to -70". Attempts toproduce pyrazole-3,4-dicarbaldehyde (X) from thediester (IIa) consistently led to the formation of theformyl ester (111) or decomposition products at highertemperatures. We were unable to reduce further eitherthe aldehyde group (at -78 to -70") or the carboxylategroup (at -65 to -50") of (111): either (111) wasrecovered unchanged or decomposition resulted.The structure of (111) was determined by elemental,i.r., and mass spectral evidence.The compound wasdistinguished from the isomeric 3-formylpyrazole byhydrolysis to the fonnylpyrazole-carboxylic acid (IV),which subsequently was decarboxylated with copper inquinoline. Comparison of the product with the knownpyrazole-3-carbaldehyde indicated that it was the4-carbaldehyde (V) . This was verified by oxidationwith moist silver oxide to pyrazole-4-carboxylic acid(VI) -Since thioesters are reduced more readily thanordinary esters with LAH,5 we applied this reagent toSS-diethyl pyrazole-3,4-dicarbothioate (IX) .The thio-ester was prepared from the ester (IIa), which, afterhydrolysis to pyrazole-3,4-dicarboxylic acid (VII), washeated under reflux with thionyl chloride (or heated withR. G. Jones and C. W. Whitehead, J . Org. Chem., 1955, 20,K. Henkel and F. Weygand, Ber., 1943, 76, 812.R. Huttel, Ber., 1941, 74B, 1681.R. Huttel and M. E. Schon, Annalen, 1959, 625, 55.M. L. Wolfram and J. V. Karabinos, J . Amer. Chem. Soc.,1342.1944, 66, 909.phosphorous pentachloride) to afford the acid chloride(VIII). Treatment of (VIII) with ethanethiol inpyridine gave the thioate (IX).The reduction of (IX)Nq co. SE t 2 HN3"" c 1" c 0.s E t " COCL Qc":2:00 (YI 1 (V)SCHEMEReagents: i, ether, 10"; ii, DIBAL-H, from -65 to -75";iii, ~ N - H C ~ ; iv, NaAlH, or LiAlH,-THF, from -73 to -70";v, H,O+; vi, Cu-quinoline; vii, Ag20; viii, SOCl, or PC1,;ix, EtSH-pyridine; x, Raney Ni or LiAlH,.with LAH in THF at -75" produced only low yields ofthe diol (I). However, the use of Raney nickel ofvarying activities 697 led to the diol (I) in yields of36-50y0. The best yields were obtained with amodified W-2 catalyst .8We subjected the acid chloride (VIII) to treatmentwith lithium tri-t-butoxyaluminium hydride under con-6 H. Adkins and J. Pavlic, J . Anzev. Chem. Soc., 1947, 69,R.Mozingo, H. Adkins, and L. Richard, Org. Synth., 1941,* R. Mozingo, D. Wolf, S. Harris, and K. Folkers, J. Amev.3039.21, 15.Chem. SOC., 1943, 65, 10151972 721ditions described by Brown and his co-workers for the acid, was evaporated at reduced pressure to give the acidreduction of terephthaloyl and isophthaloyl chlorides to (VI) as a white powder, m.p. 273-275" (lit.,' 275-276"),the corresponding dialdehydes. However, this pro- v,, 3210 (OH), 3150 (NH), 1680 (CO,H), and 1430 (C-OH)cedure did-not afford pyrazole-3,4-dicarbaldehyde -(X)but only the hydrolysis product, the acid (VII).cm-l*Pyrazole-3,4-dicarboxylic Acid (VII) .-The ester (IIa)(18.4 g) in G~-hydrochloric acid (380 ml) was heated underEXPERIMENTAL reflux for 4 h and cooled. The gelatinous precipitate wascarbaldehyde (V) (0.1 g) was stirred for 10 min at 0" andfiltered. The filtrate, acidified to pH 5 with hydrochloricH. C. Brown and R. F. McFarlin, J . Amer. Chem. SOC.,1956,78, 252; 1958,80, 5372; H. C. Brown and B. C. Subba Rao, l1 E. A. Falco and G. H. Hitchings, J . Amer. Chem. SOC.,ibid., p . 5377.1/1474 Received, 16th August, 19711l o H. V. Peckmann and E. Steal, Bev., 1899, 32, 2292.1956, 78, 3143