Hydrazides reaction with alcohols

The acyl-azide method of coupling (Figure 2.13) has been available for about a century, but it is not attractive for routine use because it involves four distinct steps that include two stable intermediates that require purification. In addition, aminolysis of the azide is slow. The first step involves preparation of the ester (see Section 3.17), which can be methyl, ethyl, or benzyl. The ester is converted to the hydrazide by reaction in alcohol with excess hydrazine at ambient or higher... 

In general the synthesis of suitably protected amino acid and peptide hydrazides from the corresponding alkyl or aryl esters by reaction with hydrazine hydrate is carried out in alcohols or DMF at ambient temperature.P However, with C-terminal branched amino acids such as valine or isoleucine, or larger peptides, more vigorous conditions are required, i.e. higher temperature (25-80°C) and longer reaction times. To avoid formation of symmetrical bis(A-acyl-aminoacyl)hydrazides an excess of hydrazine hydrate or hydrazine is recommended, which also enhances the reaction rates. In this context, the solvent is known to play an important role, with alcohols being more appropriate than DMFP 0 or solvent mixtures such as dioxane/methanol.f l The use of hydrazine hydrate without any solvent has also been reported. ... 

Syntheses of quaternary l-alkyl-3-perfluoroalkyl-4,5-dimethyl-l,2,4-triazolium iodides have led to the disclosure of a variety of new quaternary salts <04JOC1397>. Arylation of 3-alkylthio-5-aryl-l,2,4-triazoles under basic conditions gave 5-alkylthio-l,3-diaryl-l,2,4-triazoles in moderate yields <04JHC201>. Acyl hydrazides 155 reacted with imidates 156 to yield 1,2,4-triazoles 157 followed by Mitsunobu reactions with amino alcohols 158 to give regioisomeric... 

MALEIC ACID HYDRAZIDE (123-33-1) C4H4N2O2 Deconqjoses above 500°F/260°C. Violent reaction with strong oxidizers nitric acid cellulose nitrate (of high surface area) 1 -chloro-2,3-epoxypropane (exothermic). May form heat-sensitive explosive materials with digold ketenide. Incompatible with acids, acid halides alcohols, aldehydes, alkylene oxides anhydrides, including... 

An incorrect choice of base with which to carry out the decomposition of the hydrazide may also lead to unwanted reactions. Whilst the treatment of the hydrazide 12a with NaOEt in dme affords the diazo ester 12b (but which then undergoes a further intramolecular reaction), the use of aqueous Na2C03 leads to the phosphorylated secondary alcohol 13. Compound 12b, however, undergoes cyclization to 14 and this, under the influence of more ethoxide, tautomerizes to 15 ... 

The preparation of hydrazides from acid chlorides is an uncertain procedure which frequently ves rise to large quantities of secondary hydrazide." Indeed, the secondaiy hydrazide may be the only product if an unsuitable procedure is followed. The most successful method is to add slowly a chilled solution of the add chloride in ether to a well-stirred, chilled alcoholic solution of hydrazine hydrate containing considerably more than the 2 moles theoretic y required. The product is usually separated from the hydrazine hydrochloride formed at the same time by extracting the latter with water. Where the ester is extremely unreactive, this may be the only practicable method for preparing the hydrazide. On the other hand, if the acid chloride must be made, it is usually more expedient to convert it directly to the azide by reaction with sodium azide. 

Hydrazides. Acyl halides, esters, and amides react with hydrazine to form hydrazides which are themselves useful synthetic intermediates. Treatment of the hydrazide with nitrous acid yields the acyl azide which, upon heating, gives isocyanates (Curtius rearrangement). Di- or trichlorides are obtained upon reaction with Phosphorus(V) Chloride Crotonate and other esters have been cleaved with hydrazine to liberate the free alcohol (eq 10). ... 

MeAlCl2 has been used as the catalyst for epoxide-initiated cation-alkene cyclizations. A tertiary alcohol has been converted to a hydrazide by reaction with MeAlC in the presence of MesitylenesulfonyUiydroTide. a-Trimethylsilyl enones can be prepared by isomerization of l-(trimethylsilyl)-2-propynyl trimethylsilyl ethers with MeAICl2. ... 

Thiazole carboxylic acid hydrazides were prepared in a similar way (444, 445). Thus by refluxing thioacetamide or thiobenzamide with y-bromoaceto acetic ester arylhydrazones (83) for several hours in alcohol the 4-carboxythiazole derivatives (84) listed in Table II-ll were obtained (Scheme 36) (656). This reaction is presumed to proceed via dehydration of the intermediate, thiazoline-S-oxide. 

The Cunius degradation of acyl azides prepared either by treatment of acyl halides with sodium azide or trimethylsilyl azide [47] or by treatment of acyl hydrazides with nitrous acid [f J yields pnmarily alkyl isocyanates, which can be isolated when the reaction is earned out in aptotic solvents If alcohols are used as solvents, urethanes are formed Hydrolysis of the isocyanates and the urethanes yields primary amines. 

Much more important than these reactions, however, are the reactions of CDI and its analogues with carboxylic acids, leading to AAacylazoles, from which (by acyl transfer) esters, amides, peptides, hydrazides, hydroxamic acids, as well as anhydrides and various C-acylation products may be obtained. The potential of these and other reactions will be shown in the following chapters. In most of these reactions it is not necessary to isolate the intermediate AAacylazoles. Instead, in the normal procedure the appropriate nucleophile reactant (an alcohol in the ester synthesis, or an amino acid in the peptide synthesis) is added to a solution of an AAacylimidazole, formed by reaction of a carboxylic acid with CDI. Thus, CDI and its analogues offer an especially convenient vehicle for activation of... 

Primary, secondary and tertiary thioamides and thionreas are readily converted to their corresponding 0x0 analogs with Oxone in refinxing CH3CN . Thiono esters were converted to esters, while thioketones remained intact nnder these reaction conditions. Hydrazines can be selectively converted to esters and acids in high yields by nsing Oxone in an alcohol and a water, respectively . However, Mane and coworkers showed that hydrazides can be smoothly converted into the corresponding Af,Af -diacylhydrazines in excellent yields with Oxone in water (equation 67) . ... 

If the cation introduced by ion exchange is capable of multiple valence, the clay may serve as a catalyst for oxidation or reduction reactions. For example, montmorillonite treated with iron(III) nitrate is so reactive that it has to be stored under an inert atmosphere the clay catalyzes reactions of the nitrate ion, such as oxidation of secondary alcohols to ketones (via nitrite ester intermediates) and organic hydrazides to azides, and the nitration of phenols. 

Hydrazine attacks indiarubber, and cork and, when boiled in aq. soln.) glass is eroded. Hydrazine hydrate and sodium develop much heat, with the expulsion of hydrogen and ammonia. When the liquid cools, a crystalline substance is formed which is soluble in water and alcohol, and which is thought to be sodium hydrazide hydroxide, N2H5ONa. The aq. soln. gives the reactions for hydrazine. T. Weich-selfelder prepared the derivatives ... 

---