Amides nitrations, nitric acid

Secondary nitramides are relatively stable in highly acidic media and so their synthesis from the direct nitration of A -substituted amides with nitric acid and its mixtures is feasible. The synthesis of primary nitramides from the nitration of A -unsubstituted amides is usually not possible in acidic media, although this class of compounds have no practical value as explosives anyway. 

ISOTHIOCYANATE de METHYLE (French) (556-61-6) Forms explosive mixture with air (flash point 90°F/32°C). Incompatible with strong acids, caustics, chlorates (e.g., potassium chlorate, sodium chlorate), ammonia, amines, amides, alcohols, glycols, caprolactam solution, nitrates, nitric acid, organic peroxides, peroxides, strong oxidizers. 

Amides, azides, nitrites, nitrates, nitric acid... 

Nitroiminodiacetic Acid Diamide (Nitrodiglycol-amidic Acid). C4H8N404,02N.N(CH2.C0.NH2)2, mw 176.16, N 31.81%, OB to C02 -72.66%, clear platelets, mp 190-218° (decompn). Prepd by nitration of iminodiacetic acid amide with anhydrous nitric acid at RT Ref 1) Beil 4, (488)... 

Amines and amides can be N-nitrated with nitric acid, or and... 

Examples of the so-called chaperon effect involving interaction between the electrophile and an appropriate substituent at the a-position in an alkyl chain prior to ring substitution at the ortAo-position have been explored in nitrations involving dilute solutions of nitric acid in dichloromethane. Aldehydic or ketonic carbonyl groups are most effective, but carboxyl, alkoxycarboxyl, and amide groups also work well. l-Phenylpropan-2-one, for example, forms 85% of l-(2-nitrophenyl)propan-2-one (5). 

The energetic nitramide (60) has been prepared from the nitration of the tris-acetamide (59) with nitric acid and acetic anhydride or trifluoroacetic anhydride. Nitric acid-trifluoroacetic anhydride mixtures are powerful nitrating agents and well suited for amide and urea A-nitration. 

Nitric acid-acetic anhydride mixtures give poor yields for the nitration of amides with groups that hinder the amide nitrogen against electrophilic attack. The use of higher temperatures in these reactions leads to variable amounts of the A-nitroso compound as a by-product. ... 

A mixture of concentrated sulfuric and nitric acids has been used for the A-nitration of amides and ureas. A, A -Dinitro-A,A -bis(2-hydroxyethyl)oxamide dinitrate (NENO) (11) is prepared from the action of mixed acid on A, A -bis(2-hydroxyethyl)oxamide (61), itself prepared from the condensation of diethyloxalate with two equivalents of ethanolamine. Niuo-sylsulfuric acid is an inhibitor of A-nitration and so nitrous acid should be rigorously excluded. The reaction of (61) with absolute nitric acid results in 6>-nitration of the hydroxy groups but no A-nitration, and consequently, (62) is isolated as the sole product. 

Von Runge and Triebs used a solution of dinitrogen pentoxide in chloroform for the N-nitration of both amides and imides. Solutions of dinitrogen pentoxide in chlorinated solvents are not neutral nitrating agents when amides and imides are nitrated - the presence of acidic N-H protons in these substrates leads to the formation of nitric acid. Sodium fluoride acts like a base towards nitric acid and so its addition to these reactions can increase product yield. Sodium acetate has been used for the same purpose during the nitration of n-butyl-V, V -dimethylurea. The effectiveness of dinitrogen pentoxide for the V-nitration of ureas is further illustrated by its use in the conversion of 2-imidazolidinone to N, V -dinitro-2-imidazolidinone in 90 % yield. In the presence of sodium fluoride the yield for this reaction exceeds 90 %. 

Inductive effects can have very pronounced effects on the reactivity of amides and similar substrates towards nitrolysis. Chemists at the Naval Air Warfare Center (NAWC) have reported an extreme case encountered during the synthesis of the energetic 1,5-diazocine known as HNFX (86). A key step in this synthesis involves a very difficult nitrolysis of the electron deficient N-nosyl (4-nitrobenzenesulfonyl) bonds of (85). Nitrolysis with strong mixed acid requires a temperature of 70 °C for 6 weeks to achieve a yield of 16 %. The same reaction with nitric acid-triflic acid requires a temperature of 55 °C for 40 hours to achieve a 65 % yield of HNFX. The same chemists reported a similar case of N-nosyl bond nitrolysis which needed a nitrating agent composed of nitric acid-triflic acid-antimony pentafluoride. ... 

The instability of primary nitramines in acidic solution means that the nitration of the parent amine with nitric acid or its mixtures is not a feasible route to these compounds. The hydrolysis of secondary nitramides is probably the single most important route to primary nitramines. Accordingly, primary nitramines are often prepared by an indirect four step route (1) acylation of a primary amine to an amide, (2) A-nitration to a secondary nitramide, (3) hydrolysis or ammonolysis with aqueous base and (4) subsequent acidification to release the free nitramine (Equation 5.17). Substrates used in these reactions include sulfonamides, carbamates (urethanes), ureas and carboxylic acid amides like acetamides and formamides etc. The nitration of amides and related compounds has been discussed in Section 5.5. 

Eaton and co-workers ° synthesized the cubane-based dinitrourea (42) via iV-nitration of the cyclic urea (41) with nitric acid-acetic anhydride. Cubane-based nitramide (43) is prepared from the IV-nitration of the corresponding bis-amide with acetic anhydride-nitric acid. Bis-nitramine (44) is prepared from the IV-nitration of the corresponding diamine with TFAA-nitric acid. ... 

The Af-nitration of urea and imide functionality is usually quite difficult compared to the analogous amides. Solutions of dinitrogen pentoxide in nitric acid are frequently employed to synthesize energetic Af, Af -dinitroureas. Yields are often very high and go to completion unlike with many conventional nitrating agents which frequently yield partially nitrated products. Energetic bicycles K-56 (16)" and K-55 (17)" have been prepared from the dihydrochloride salts (14) and (15) respectively. 

Direct nitration with anhydrous nitric acid (98%) can be accomplished most conveniently in the presence of monosubfctituted N-alkylamides. A secondary nitr-amide is then formed ... 

Generally, reaction (1) is not successful with non N-substituted, i.e. primary amides, most of which undergo decomposition when nitrated. Primary aliphatic amines also decompose under the action of concentrated nitric acid. 

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