Amines from hydrazides

Curtius transformation An alternative to the Hofmann transformation for obtaining an amine from an ester via the hydrazide, azide and isocyanate. Thus ethyl ethanoate is converted into melhylamine by the following series of reactions ... 

Another approach to the synthesis of simultaneously b- and e-fused heterosystems containing l,3-thiazin-4-one fragments is based on the use of a thiazinone ring prepared in advance. Thus, 2-imino-3-amino-TA 79, obtained from hydrazide 198, was applied to the syntheses of triazolobenzo-TAs 199,200, and 201 (75MI1). Amine 201 may be obtained from hydrazide... 

Aromatic aUazines and ketazines. Polyphosphoric acid is an excellent catalyst and solvent for production of amines from aromatic aldehydes and ketones in the presence of various carbonyl reagents, for example, hydrazine, its salts, semicarbazide hydrochloride, toluene/i-sulfonohydrazide, and acid hydrazides. The reaction is usually complete at 100° within 15 min. The reaction is not useful in the case of aliphatic carbonyl compounds. 

Waldmann s safety-catch hydrazide linker is also part of the class of traceless linkers [55]. Starting from hydrazide resin 126, which is converted into an activated species by oxidation with Cu(OAc)2, the molecules are cleaved by the addition of nucleophiles like amines to give arenes 127 (Scheme 16.30). 

In another example, BSA, as a model protein, vras entrapped in biodegradable shell crosslinked nanocapsules via layer-by-layer assembly of tertiary amine and hydrazide grafted poly(aspartamide) and carboryl and aldehyde grafted poly(aspartamide) on amino-fiinetionalized silica spheres, by hydrazone crosslinking and with a silica core. Tbe BSA release rate increased significantiy as tbe ambient pH dropped from tbe physiological pH to acidic endosomal pH, and cell experiments showed that the obtained polymerie nanocapsules possessed good uptake properties and biocompatibility. ... 

Sulfonic acid amides from sulfonic acid hydrazides Amines from hydrazones... 

Lithium tetrahydridoaluminate Amines from carboxylic acid hydrazides... 

Di- and Poly-carboxylic Acids. Preparation of Diamines. The presence of more than one carboxyl group does not interfere with the conversion of the acids to the amines. Adipyl hydrazide is formed from the... 

The independent preparation of potassium phthabmide (from a solution of phthalimide in absolute ethanol and potassium hydroxide in 75 per cent, ethanol) may be avoided in many cases by boiling phthalimide with the halide in the presence of anhydrous potassium carbonate. The N-substituted phthalimide (I) is frequently cleav with difficulty this is often facilitated by reaction with hydrazine hydrate to give an intermediate product, which is easily decomposed by hydrochloric acid to 3deld the insoluble hydrazide of phthaUc acid (II) and the primary amine (III) ... 

A special problem arises in the preparation of secondary amines. These compounds are highly nucleophilic, and alkylation of an amine with alkyl halides cannot be expected to stop at any specifle stage. Secondary amides, however, can be monoalkylated and lydrolyzed or be reduced to secondary amines (p. 11 If.). In the elegant synthesis of phenyl- phrine an intermediate -hydroxy isocyanate (from a hydrazide and nitrous acid) cyclizes to pve an oxazolidinone which is monomethylated. Treatment with strong acid cleaves the cyclic irethan. 

The aminolysis of esters of pyrimidine occurs normally to yield amides. The reagent is commonly alcoholic ammonia or alcoholic amine, usually at room temperature for 20-24 hours, but occasionally under refiux aqueous amine or even undiluted amine are used sometimes. The process is exemplified in the conversion of methyl pyrimidine-5-carboxylate (193 R = Me) or its 4-isomer by methanolic ammonia at 25 °C into the amide (196) or pyrimidine-4-carboxamide, respectively (60MI21300), and in the butylaminolysis of butyl ttracil-6-carboxylate (butyl orotate) by ethanolic butylamine to give A-butyluracil-5-carboxamide (187) (60JOC1950). Hydrazides are made similarly from esters with ethanolic hydrazine hydrate. 

Classically, amides and hydrazides have been prepared from an ester or an acid chloride and an amine or hydrazine, respectively they can also be prepared directly from the acid as shown in eqs. 1-3. 

The A-substituted derivatives of 4-oxo-4//-pyrido[l,2-n]pyrimidine-3-carboxamides and -3-acetamides and l,6-dimethyl-4-oxo-1,6,7,8-tetrahy-dro-4//-pyrido[l,2-n]pyrimidine-3-carboxamide were prepared by treatment of the appropriate 3-carboxylic acids and acetic acid, first with an alkyl chloroformate in the presence ofNEt3 in CHCI3 below — 10°C, then with an amine (98ACH515). A-Phenethyl and A-[2-(3,4-dimethoxyphenyl)ethyl] derivatives of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetamide were obtained in the reaction of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-3-acetic acid and phenethylamines in boiling xylene under a H2O separator. Hydrazides of 4-oxo-4//- and 4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic acid were prepared from the appropriate ester with H2NNH2 H2O in EtOH. Heating 4-oxo-4//- and 6-methyl-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic hydrazides in EtOH in the presence of excess Raney Ni afforded fhe appropriafe 4-oxo-6,7,8,9-fefrahydro-4//-pyrido[l,2-n]pyrimidine-3-acefa-mide. In the case of the 4-oxo-4// derivative, in addition to N-N bond... 

As in 10-55 hydrazides and hydroxamic acids can be prepared from carboxylic esters, with hydrazine and hydroxylamine, respectively. Both hydrazine and hydroxylamine react more rapidly than ammonia or primary amines (the alpha effect, p. 445). Imidates, RC(=NH)OR, give amidines, RC(=NH)NH2. Lactones, when treated with ammonia or primary amines, give lactams. Lactams are also produced from y- and 5-amino esters in an internal example of this reaction. 

Acyl hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. Reaction of acyl hydrazides 149 with imidoylbenzotriazoles 148 in the presence of catalytic amounts of acetic acid under microwave irradiation afforded 3,4,5-trisubstituted triazoles 150 <06JOC9051>. Treatment of A-substituted acetamides with oxalyl chloride generated imidoyl chlorides, which reacted readily with aryl hydrazides to give 3-aryl-5-methyl-4-substituted[ 1,2,4]triazoles <06SC2217>. 5-Methyl triazoles could be further functionalized through a-lithiation and subsequent reaction with electrophiles. ( )-A -(Ethoxymethylene)hydrazinecarboxylic acid methyl ester 152 was applied to the one-pot synthesis of 4-substituted-2,4-dihydro-3//-1,2,4-triazolin-3-ones 153 from readily available primary alkyl and aryl amines 151 <06TL6743>. An efficient synthesis of substituted 1,2,4-triazoles involved condensation of benzoylhydrazides with thioamides under microwave irradiation <06JCR293>. 

Aldehyde-containing macromolecules will react spontaneously with hydrazide compounds to form hydrazone linkages. The hydrazone bond is a form of Schiff base that is more stable than the Schiff base formed from the interaction of an aldehyde and an amine. The hydrazone, however, may be reduced and further stabilized by the same reductants utilized for reductive amination purposes (Chapter 3, Section 4.8). The addition of sodium cyanoborohydride to a hydrazide-aldehyde reaction drives the equilibrium toward formation of a stable covalent complex. Mallia (1992) found that adipic acid dihydrazide derivatization of periodate-oxidized dextran (containing multiple formyl functionalities) proceeds with much greater yield when sodium cyanoborohydride is present. 

Derivatives of hydrazine, especially the hydrazide compounds formed from carboxylate groups, can react specifically with aldehyde or ketone functional groups in target molecules. Reaction with either group creates a hydrazone linkage (Reaction 44)—a type of Schiff base. This bond is relatively stable if it is formed with a ketone, but somewhat labile if the reaction is with an aldehyde group. However, the reaction rate of hydrazine derivatives with aldehydes typically is faster than the rate with ketones. Hydrazone formation with aldehydes, however, results in much more stable bonds than the easily reversible Schiff base interaction of an amine with an aldehyde. To further stabilize the bond between a hydrazide and an aldehyde, the hydrazone may be reacted with sodium cyanoborohydride to reduce the double bond and form a secure covalent linkage. 

Related (diisopropoxyphosphoryl)- and (diisobutoxyphosphoryl)formonitrile oxides (114), generated in basic media from the corresponding oximes react in situ with alcohols, phenols, alkanethiols, thiophenols, aliphatic and aromatic primary amines, hydrazines and hydrazides as well as 4-aminoantipyryne to give hydroxymates, thiohydroxymates, and amidoximes, respectively. It is important to note that the addition is stereoselective and gives E-adducts with the exception of (i-Pr0)2P(0)C( N0H)0Me, which is formed as a 1 1 mixture of E and Z isomers. 

Closure of the triazole ring can be achieved either by oxidative formation of the N-N bond, or condensation of an fV-aminopyridone. The latter was formed by iV-amination of pyridines with mesitylhydroxylamine (MSH), or by forming the pyridine ring, starting from cyanoacetic hydrazide with malononitrile or 2-cyanoacrylates. 

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