Hydrazinolysis

Suprizingly enough, hydrazine and its hydrate in diluted solutions of alcohols, dimethylformamide, and mixtures of both have not often been used to cleave the benzyl ester type linkage of peptides bound to the common Merrifield support, though this cleavage was found more effective than the transesterification method of detachment [178,179]. This effect can be explained by a more sufficient solvation of the peptide on polymer by the cleaving reagent and by the distinct nucleophilicity of hydrazine. In this way fully pro- 

Since phenacylesters show an enhanced electrophilicity, this type of anchoring function on a polystyrene gel phase is very rapidly and quantitatively cleaved by hydrazinolysis within 2 hours at 8-12 °C. On 0.5% cross-linked supports we are applying a 10% (v) solution of hydrazine hydrate in dioxane/methanol 9 1 (v v). The detachment filtrates are immediately neutralized with solid carbon dioxide as described in the transesterification procedure. 

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Regioselectivity becomes important, if unsymmetric difunctional nitrogen components are used. In such cases two different reactions of the nitrogen nucleophile with the open-chain educt may be possible, one of which must be faster than the other. Hydrazone formation, for example, occurs more readily than hydrazinoLysis of an ester. In the second example, on the other hand, the amide is formed very rapidly from the acyl chloride, and only one cyclization product is observed. 

In a study aimed at identifying thiazole derivatives, Travagli (485) obtained the ring cleavage of 2-aminothiazoIes (205) by their phenyl-hydrazinolysis in acetic acid. 

Alkylation of phthalimide The Gabriel synthesis (Section 22 8) The potassium salt of phthalimide reacts with alkyl hal ides to give N alkylphthalimide deriva fives Hydrolysis or hydrazinolysis of this derivative yields a primary alkylamine... 

Hydrazinolysis of the ethoxypyrazolone (399) leads to the hydrazino derivative (400) (70ZC224). A probable mechanism involves intermediates (401 R = OEt) and (401 R = NHNH2). 

Pyrazolo[3,4-d][l,2]diazepines synthesis, 7, 597 Pyrazolop, 4- 6][ 1,4]diazepines synthesis, 5, 272 Pyrazolo[l, 4]diazepinones as anticonvulsant, 1, 170 Pyrazolo[2,3-e]diazepinones synthesis, 5, 272 1 H-Pyrazolo[l,5-6]imidazoles synthesis, 6, 992 Pyrazolo[2,3-a]imidazoles biological activity, 6, 1024 Pyrazolo[2,3-c]imidazoles reactions, 6, 1041 synthesis, 6, 1047 Pyrazolo[2,3-imidazoles synthesis, 6, 991 Pyrazolo[3,2- njisoquinolines synthesis, 5, 339 Pyrazolop, 4-c]isoquinolines synthesis, 5, 273 Pyrazolonaphthyri dines synthesis, 5, 339 Pyrazolone, diazophotolysis, 5, 252 Pyrazolone, 4,4-dihalo-rearrangements, 5, 250 Pyrazolone, ethoxy-hydrazinolysis, 5, 253 Pyrazolone, 4-halo-... 

The crotonate esters, prepared to protect a primary hydroxyl group in nucleosides, are cleaved by hydrazi ne (MeOH, Pyr, 2 h). The methoxycrotonate is 100-fold more reactive to hydrazinolysis and 2-fold less reactive to alkaline hydrolysis than the corresponding acetate. ... 

Sulfobenzyl esters were prepared (cesium salt or dicyclohexylammonium salt, Na03SC6H4CH2Br, DMF, 37-95% yield) from A -protected amino acids. They are cleaved by hydrogenolysis (H2/Pd), or hydrolysis (NaOH, dioxane/water). Treatment with ammonia-or hydrazine results in formation of the amide or hydrazide. The ester is stable to 2 M HBr/AcOH and to CF3SO3H in CF3CO2H. The relative rates of hydrolysis and hydrazinolysis for different esters are as follows ... 

The diphenylmaleimide is prepared from the anhydride, 33-87 % yield, and cleaved by hydrazinolysis, 65-75% yield. It is stable to acid (HBr, AcOH, 48 h) and to mercuric cyanide. It is colored and easily located during chromatography, and has been prepared to protect steroidal amines and amino sugars. " ... 

This reaction forms the basis of one method of terminal residue analysis. A peptide is treated with excess hydrazine in order to cleave all the peptide linkages. One of the terminal amino acids is cleaved as the free amino acid and identified all the other amino acid residues are converted to acylhydrazides. Which amino acid is identified by hydrazinolysis, the N terminus or the C terminus ... 

Hydrolysis NO2C6H4CH2O- C6H4CH2O- > O3SC6H4CH2O- > MeO-Hydrazinolysis NO2C6H4CH2O- > O3SC6H4CH2O— > C6H5CH2O- > MeO-... 

A useful reaction sequence has been developed for conversion of an aromatic aldehyde into the next higher homologous acid. The nitro analog of 45, prepared from m-nitrobenzaldehyde, is converted into the azide 51 by hydrazinolysis and treatment with nitrous acid. The... 

The hydrazinolysis is usually conducted in refluxing ethanol, and is a fast process in many cases. Functional groups, that would be affected under hydrolytic conditions, may be stable under hydrazinolysis conditions. The primary amine is often obtained in high yield. The Gabriel synthesis is for example recommended for the synthesis of isotopically labeled amines and amino acids. a-Amino acids 9 can be prepared by the Gabriel route, if a halomalonic ester—e.g. diethyl bromomalonate 7—is employed as the starting material instead of the alkyl halide ... 

Pi peridinobenzimidazole also serves as starting material for the antipsychotic agent halopemide (69). In the absence of a specific reference, one may speculate that the first step involves alkylation with bromochloro-ethane to give halide The chlorine may then be converted to the primary amine by any of several methods such as reaction with phthalimide anion followed by hydrazinolysis. Acylation with j -fluorobenzoyl chloride then gives the desired product. 

Triazinopurinyl derivative 612 was prepared (91S625) by hydrazinolysis of 610, followed by cyclization of the presumably formed hydrazine derivative 611 (Scheme 125). 

Destructive hydrazinolysis is of importance for the establishment of the structure of the PCS main chain, since the reaction products can easily be identified. The importance of this reaction also results from the fact that C=C bonds do not undergo hydrazinolysis. A general scheme of the process of destructive hydrazinolysis may be given as follows ... 

RAFT agents (211,224,232), which can be subsequently deprotected by hydrazinolysis.420... 

The lead tetraacetate reaction between jV-aminophthalimide and (E) stilbene was first described by Rees,5 and the hydrazinolysis of the addition product by Carpino.6 The procedures described here incorporate their methods, with improvements. The dimesylate-hydrazine reaction was first described by Paulsen7 in the carbohydrate series. 

Hydrazides (RCONHNH2) are highly useful starting materials and intermediates in the synthesis of heterocyclic molecules.2 They can be synthesized by hydrazinolysis of amides, esters and thioesters.3 The reaction of hydrazine with acyl chlorides or anhydrides is also well known,4 but it is complicated by the formation of 1,2-diacylhydrazines, and often requires the use of anhydrous hydrazine which presents a high thermal hazard. Diacylation products predominate when hydrazine reacts with low molecular weight aliphatic acyl chlorides, which makes the reaction impractical for preparatory purposes.5... 

The major preparative routes to hydrazinoquinoxalines, by primary synthesis (Chapter 1) and by hydrazinolysis of halogenoquinoxalines (Sections 3.2.1 and 3.4.1) have been covered already minor routes by hydrazinolysis of alkoxy-, alkylthio-, alkylsulhnyl-, or alkylsulfonylquinoxalines do not appear to have been used recently. 

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