Hydrolysis pyrazolines

In 2-pyrazolines [103] the conjugation involves N-1 and C-3 atoms. 2-Pyrazolines may be regarded as cyclic hydrazones, which have the advantage over non-cyclic products of being stable to hydrolysis. It has been shown by Elguero and Jacquier (1965) that protonation occurs at N-1, giving cation [104], while forms with the proton at N-2 and C-3 [105] may exist in amounts of less than 1-5%. 

V-acylaziridine-2-imides to oxazoline-4-imides, followed by hydrolysis of these latter compounds, has been used586 to afford chiral / -hydroxy-a-amino acid precursors. It has been suggested587 that the observed thermal rearrangement of c/.s-aziridinyl ketone tosylhydrazones (449) to 5-alkylamino-3,5-diphenyl-l-tosyl-2-pyrazolines (450) is... 

Azomethine imines obtained from 1,4-dichloro-l, 4-bis(trifluoromethyl)-azine and cycloalkenes or cyclodienes undergo [1.4] chlorotropy. Subsequent hydrolysis yields l-trifluoroacetyl-3-trifluoromethyl-2-pyrazolines (93CC9) (Scheme 65). 

Amino polystyrene pyrazolone linker resin 58 provided various amide products 59 with a high conversion rate and good purity under mild conditions the resin linker was stable under the reaction conditions, resistant to hydrolysis, and reused repeatedly without loss of activity <03TL8063>. The preparation of pyrazoline derivatives 61 was accomplished with traceless solid-phase sulfone linker 60 with phenylhydrazine <030L1067>. Aniline cellulose-bound enaminones 62 reacted with phenylhydrazine under microwave irradiation to produce pyrazolocarboxylic acid derivatives 63 in high yields <03JCO465>. 

Cyclopropyl aldehydes.2 The reagent is a more reactive 1,3-dipole than alkyl diazoacetates. It reacts with various olefins such as styrene, methyl acrylate, and 2 to form pyrazolines a, which on photolysis are converted into the cyclopropyl acetals b. The free aldehydes (3) are obtained by acid hydrolysis in overall yields greater than 80%. 

Although 2-pyrazolin-5-ones are relatively stable to acid hydrolysis, those having l-(dinitrophenyl) or l-(trinitrophenyl) substituents are decomposed, forming arylhydrazones (eq. 47).777... 

Acylation of 2-pyrazolin-5-ones leads to 4-acyl-2-pyrazolin-5-ones. This has been done by treatment with aromatic acid chlorides110 and with ethyl oxalate in the presence of potassium. A modification of this procedure is acylation of 2-pyrazolin-5-ones to give 4-acyl-5-acyloxy-pyrazoles 591,977 or 2,4-diacyl-3-pyrazolin-5-ones1058 followed by hydrolytic removal of the A-acyl or O-acyl groups. The 4-acyl compounds can also be prepared by hydrolysis of their Schiff bases as shown in eq. 215. 

A group of Italian workers has claimed that 1,3-disubstituted-2-methyl-5-oxo-3-pyrazolin-4-carboxaldehydes can be prepared through methylation of the Schiff bases derived from aromatic amines and l,3-disubstituted-2-pyrazolin-5-ones.1097 The methylation is carried out with methyl iodide which methylates the ring at N-2, and this is followed by hydrolysis of the Schiff bases with alkaline solutions (eq. 221). Passerini and Losco1092,1093-1097 and Ridi1181 claimed to have... 

The usual acid derivatives of 5-oxo-2-pyrazolin-3- and 4-carboxylic acids are known. Amides are prepared by reaction of esters and ammonia,1339 by the reaction of urea with 2-pyrazolin-5-ones, and by the reaction of azides with ammonia and amines. Hydrolysis of nitriles... 

Sulfur analogs of 5-oxo-3-pyrazolin-4-carboxylic acids, esters and amides are known. The usual synthesis of both thio and dithio acids is by alkaline hydrolysis of the dithioesters,109,831 as shown in eq. 234. 

Oxo-3-pyrazolin-4-sulfonic acids (Table XXXVI) are prepared by direct sulfonation738,745 with sulfuric acid and acetic anhydride or by chlorosulfonation with chlorosulfonic acid, followed by hydrolysis to the acid.1248,1249 The reaction of 2,3-dimethyl-l-phenyl-5-oxo-3-pyrazolin-4-sulfonyl chloride with urea forms a bis(5-oxo-2-pyrazolin-4-sulfonic acid) derivative,1249 the only such bis derivative reported. Reduction of the sulfonic acid chlorides with zinc and acid forms the corresponding mercapto compound.1249... 

For purposes of classification the 4-aminopyrazoles are considered to be 4-imino-2-pyrazolines and analogs of 2-pyrazolin-4-ones. These compounds are listed in Table XL. Such compounds can be prepared by direct cyclization using ethyl diazoacetate and ethyl cyanoacetate.92 This is the same as eq. 243, except that the malonic ester is replaced by ethyl cyanoacetate. Purines can be hydrolyzed to 4-imino-2-pyrazolines by using strong acid.1210 1846 By far the most frequently used preparation is reduction of appropriately substituted pyrazoles, such as 4-nitro,368,812,819,1015,1019,1049 4-nitroso1165 or 4-aryl-azo.671 974,995 The hydrolysis of the carbethoxy 4-imino-2-pyrazolines derived from ethyl cyanoacetate and ethyl diazoacetate forms 4-imino-2-pyrazolin-3-carboxylic acid which is readily decarboxylated to the parent compound.92... 

Only half-a-dozen of these compounds are known (Table XLI) and at least this number of methods of preparing them have been reported. Borsche and Manteuffel125 have found that 2-pyrazolin-4,5-diones are formed as the by-products when oc-ketoesters are treated with aryl-diazonium salts. The principal products are 4-arylazo-2-pyrazolin-5-ones. Nitric acid oxidation of 3-methyl-l-phenyl-2-pyrazolin-5-one forms the corresponding 4,5-dione.809 Wislicenus and Gtiz1842 heated 4 -bromo - 4 - nitro -1 - (4 - bromophenyl) - 3 - methyl - 2 -pyrazolin - 5 - one in water and obtained the analogous 4-oxo compound. Acid hydrolysis of rubazonic acids, which are 4-imino-2-pyrazolin-5-ones, leads to 2-pyrazolin-4,5-diones.424 809 Oxidation of 4,4 -bis(2-pyrazolin-5-ones) or of rubazonic acids with nitric acid809 forms the 4,5-diones. 

Synthetic methods involving conversion of other, but similar, ring systems to 3,5-pyrazolidinediones have been reduction of 1,2-diphenyl-3,4,5-pyrazolidinetrione with tin and hydrochloric acid63 and hydrolysis of 5-imino-3-pyrazolidinones (3-amino-2-pyrazolin-5-ones) with acid.1339,1596... 

The route can be modified to make optically active amino acids.Hence addition of diazomethane to the dioxopiperazine 14 [itself prepared from (Z)-4-benzylidene-2-methyloxazolone and L-proline] gave a 70% yield of the spiro-pyrazoline 15 (ratio of diastereomers 95 5). Separation of the major diastereomer and photolysis gave a 90% yield of the cyclopropane 16, which on hydrolysis gave (-l-)-17 in 70 % yield. 

The L-proline derived diketopiperazine 27 and diazomethane afford a 1-pyrazoline diastereo-mer which is photolyzed to give the cyclopropane derivative 28 in high yield. Acid hydrolysis then provides (+)-1-amino-2-phenylcyclopropanecarboxylic acid (29) [a] 5 +105 (c = 0.69, water) 81. The optical purity of this amino acid is not reported. Similarly the (—)-enantiomer of l-amino-2-phenylcyclopropanecarboxylic acid is available from a dehydroamino acid using (-)-Ar-methylephedrine as auxiliary81. 

Various ways of functionalization of the lactol 205 leading to C-nucleoside analogs were described.Compound 205 readily reacted with carboethoxymethylenetriphenylphosphorane with formation of trans ester 212, whereas the Wittig reagent prepared from pyruvate ester gave a product of an intramolecular Michael reaction (221). Acrylate ester 212 was converted on addition of diazomethane into pyrazoline 213, and further, by successive brom-ination-dehydrobromination followed by acid hydrolysis, was transformed into DL-3-(carboxamido)-4-P-ribofuranosylpyrazole 214. Another precursor of heterocyclic C-ribofuranosides (215) was obtained in the reaction of lactol 205 with... 

Hydrolysis or hydrogenolysis of 3-acetoxy-l-pyrazolines gives 3-hydroxy-l-pyrazolines (312), which are cyclic examples of a-azocarbinols, and undergo both acid- and base-catalysed ring opening to ketones (Scheme 17). The 3-hydroxy-group can be esterified or etherified under carefully controlled conditions. 

A somewhat different approach coupled acid chloride 2.154 with 2.155 to give 2.1S6J Treatment with 7-picoline led to the rearranged product 2.157 in 84% overall yield from 2.154. Acid hydrolysis gave 8-oxo-9-aminononanoic acid, 2.158. 2.5.B. Pyrazoline Derivatives... 

Pyrazoles such as 2.159 are formed by a [3+2]-cycloaddition reaction of an alkene with a diazoalkane7 Basic hydrolysis of such pyrazolines leads to an amino acid. Reaction of 2.159 with aqueous sodium hydroxide, for example, gave 2-methyl-3-aminopropanoic acid 2.160) Similarly, 2-methyl-3-aminobutanoic acid was prepared in 52% yield 2-ethyl-3-aminopropanoic acid in 81% yield and, 2-methyl-3-aminopentanoic acid in 52% yield, all from the appropriate pyrazoline. ... 

The reaction of diazomethane with dimethyl fumarate was reported by Von Pechmann to give the diester of 2-pyrazoline-4,5-dicarboxylic acid 25 (21,26) product was isolated as the acid after hydrolysis. 

---