Pyrazole phosphorylation

The decomposition of (536) with hydrogen sulfide yields pyrazole (76T1909). The 1-phosphorylpyrazoles (537) are suitable reagents for the phosphorylation of alcohols, amines, hydrazines and azides (76AG(E)378). 

Withasomnine Pyrazole, 1-phosphoryl-reactions, 5, 271 Pyrazole, 1-silyl-synthesis, 5, 236 Pyrazole, 1-stannyl-synthesis, 5, 236 Pyrazole, 1-styryl-synthesis, 5, 233 Pyrazole, 1-thienyl-reactions, 5, 268 Pyrazole, 4-(2 -thienyl)-nitration, 5, 238 Pyrazole, 4-(3 -thienyl)-nitration, 5, 238 Pyrazole, trifluoromethyl-synthesis, 5, 284... 

N-Hydroxypyrazoles are of interest as acylation and phosphorylation catalysts. Pyrazoles with strongly electron withdrawing groups (pKa < 9) 32 can be oxidized under buffered KHSO5 conditions to provide hydroxypyrazoles 33 in fair to good yields <96MC139>. 

Isolable pyrazolines (183) are obtained from the (1,3-butadiene)phosphonic acid esters (182 X=S02Me, COOalkyl R "=H or Me R2=Me or Ph) (products from (182 X=CN) are thermo-labile) and diazomethane. Pyrolysis of the phosphorylated pyrazolines affords phosphonopentadienes rather than phosphono-cyclopropanes (contrast (184)) and with NaH give pyrazoles or pyrazolephbsphonic acid esters. 

MethyM-cthoxycarbonyl-5-bcnzoyl-hydrazino-l //-pyrazole 274, prepared by reacting benzoyl chloride and 3-methyM-cthoxycarbonyl-5-bcnzoyl-hydrazino-l //-pyrazole hydrochloride 273, in the presence of pyridine in acetonitrile, has been cyclized with phosphoryl chloride in benzene or toluene to give 7-ethoxycarbonyl-6-methyl-3-phenyl-l //-pyrazolo[5,l -/ 1,2,4 triazolc 55. This compound has been also synthesized through cyclization of... 

Phosphorus oxychloride at 230-250° phosphorylates 1-substituted pyrazoles in the 4-position. By the action of alcohols, the phosphonodi-chlorides (58) are converted into esters.919 Phosphorylation here is presumably an electrophilic substitution. 

Eq. 5.17 shows ipso substitution of imidazoles (30) at the 2-position by an sp3 carbon-centered radical. Here, the tosyl group plays an important role in both activation of the ipso 2-position and as an effective leaving group, Ts [40-46]. The phosphoryl group also shows the same leaving ability as the tosyl group. Preparation of [1.2-b]-fused bicyclic pyrazoles (33) from l-(phenylselenoalkyl)pyrazoles (32) also works well, as shown in eq. 5.18. 

Diazo-l-phosphoryl-alkane reagieren mit Alkinen iiber die nicht isolierbaren 3-Phosphoryl-3H-pyrazole nach 1,5-sigmatroper Verschiebung des Phosphoryl-Restes zu 1-Phosphoryl-lH-pyrazolen, die extrem hydrolyseempfindlich sind unter Abspaltung des Phosphoryl-Restes1272 1409 141° ... 

Bis-[phosphoryl]-3H-pyrazole reagieren in konzentrierter Schwefelsaure bei 20° oder beim Erhitzen in Toluol unter Abspaltung des Phosphoryl-Restes aus der 4-Position z. B.1181 ... 

Phosphorsaure-chlorid-diester [s. Bd. E2, S. 601 (1982)], -chlorid-diamide1527 und -amid-di-chloride1628 [s. Bd. E2, S.653 (1982)] sind zur Herstellung von 1-Phosphoryl- bzw. 1,1 -Phosphoryliden-verbriickten lH-Pyrazolengeeignet. 5-Hydroxy-lH-pyrazole reagieren an der Hydroxy-Gruppe1628. 

Die aus 4-Diphenylphosphinyl-lH-pyrazol durch Reduktion mit Trichlorsilan zuganglichen Phosphane dienen als Startprodukte fur neue 4-Phosphoryl-lH-pyrazole754. 

Rockley and Summers (81AJC1117) (Scheme 41) presented the only example of a l,2-dihydropyrazol-3-one that underwent the Vilsmeier reaction. Thus treating pyrazole-3-one 129 with phosphoryl chloride and DMF in chloroform and toluene and heating at 60-65 °C afforded 4-formylpyrazol-3-one 130. 

Treatment of 2,4-dihydropyrazol-3-ones with phosphoryl oxychloride above 100 °C gives 4-chloropyrazoles. Thus pyrazol-3-ones 142a-g were converted into 4-chloropyrazoles 143a-g in yields of above 80% (68BSF5019, 79JPR127, 91JHC1837) (Scheme 45). 

Scheme 6 Catalyst-free synthesis of phosphorylated pyrazole derivatives via the Michael addition reaction.

Diazoalkanes (761) regiospecifically underwent 1,3-dipolar cycloaddition with dimethyl l-(formylamino)ethylenephosphonate (760) to alford 5-sub-stituted dimethyl 3-(formylamino)-4,5-dihydro-3//-pyrazole-3-phospho-nates (762) in high yields. Thermal decomposition of the latter followed by hydrolysis, provided a straightforward access to 2-substituted 1-amino-cyclopropanephosphonic acids (763). Aromatisation of (763) under acidic conditions led to 3-phosphorylated pyrazoles (764) (Scheme 193). ... 

Ab initio calculations and P NMR experimental studies on the magnetic shielding of the P nucleus in the phosphorylated A -vinylazoles, (11), and (12), show that intramolecular coordination of the P atom (in the chloro-phosphonium group) to the N atom (in the pyrazole ring) leads to an upfield shift of the phosphorus signal to Ssjp 170 ppm, and the contribution of the spin-orbital contribution to Ssip reaches 15%. Relativistic effects and effects of the medium are important factors in the theoretical calculation of... 

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