Nitric acid with anhydrides

Nitration of pyrroles by the usual methods leads to extensive degradation. However, nitration can be achieved with an equimolar nitric acid—acetic anhydride mixture at low temperatures. In the case of pyrrole, the reaction leads predominandy to substitution at the -position (34), ie, in the following 51% 3-nitropyrrole [5930-94-9] (21) and 13% 2-nitropyrrole [5919-26-6] (22). 

Molybdenum Trioxide (Molybdenum Anhydride, Moiybdic Oxide, Moiybdic Acid Anhydride). Mo03, mw 143.95, white powd, mp 795°, bp 1155°, d 4.696g/cc at 26/4°, SI sol in w, sol in acids, alk sulfates and amm hydroxide. Prepn is by first boiling coned nitric acid with NH4... 

A number of secondary high explosives containing both nitramine and nitrate ester functionality have been reported. Aliphatic examples include A-nitrodiethanolamine dinitrate (DINA) (110), prepared from the nitration of diethanolamine with nitric acid-acetic anhydride in the presence of zinc chloride,and A,A -dinitro-A,A -bis(2-hydroxyethyl)oxamide dinitrate (NENO) (111), prepared from the mixed acid nitration of A,lV -bis(2-hydroxyethyl) oxamide . 

The reaction of fuming nitric acid with acetic anhydride can be violent, and therefore the components are usually mixed between 0 to 5 °C. Acetic anhydride in these mixtures acts as a dehydrating agent, reacting with water formed during the nitration to generate acetic acid. 

Wright illustrated the effectiveness of chloride-catalyzed nitration for a number of amines of different basicity. Wright showed that weakly basic amines like iminodiacetonitrile and its dimethyl and tetramethyl derivatives are all nitrated in high yield with nitric acid-acetic anhydride mixtures in the absence of chloride ion. In contrast, the slightly more basic 3,3 -iminodipropionitrile is not appreciably nitrated with acetic anhydride-nitric acid, but the inclusion of a catalytic amount of the hydrochloride salt of the amine base generates the corresponding nitramine in 71 % yield. ... 

Wright found it more suitable to use the nitrate salts of the more basic amines, like in the case of morpholine, which ignites at ambient temperature in the presence of nitric acid-acetic anhydride mixtures. Morpholine nitrate is not nitrated with acetic anhydride-nitric acid in the absence of chloride ion at room temperature, but the addition of 4 mole % of zinc chloride generates a 65 % yield of A-nitromorpholine, and this yield rises to 93 % if the hydrochloride salt of morpholine is directly nitrated. While morpholine nitrate is unaffected by treatment with acetic anhydride-nitric acid at room temperature, the same reaction in the presence of ammonium nitrate at 65 °C is reported to yield A-nitromorpholine in 48 % yield. ... 

Acetone cyanohydrin nitrate, a reagent prepared by treating acetone cyanohydrin with nitric acid-acetic anhydride, has been used for the At-nitration of aliphatic and alicyclic secondary... 

Nitric acid-acetic anhydride reagent has been used to synthesize N,N -Amitro-N,N -ethylenebisacetamide (58) from A, A -ethylenebisacetamide (57) the former is a secondary high explosive and a precursor to the powerful explosive ethylenedinitramine (Section 5.10). It is interesting to note that (58) is not formed when (57) is treated with nitric acid alone or with strong mixed acid. 

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. ... 

Chapman studied the nitrolysis of symmetrical methylenediamines. The nitrolysis of N, N, N, M-tetramethylmethylenediamine with nitric acid-acetic anhydride-ammonium nitrate mixtures gives both dimethylnitramine and RDX the latter probably arises from the nitroT ysis of hexamine formed from the reaction of ammonium nitrate and formaldehyde released from the hydrolysis of the methylenediamine. The same reaction with some morpholine-based methylenediamines (105) allows the synthesis of l,3,5-trinitro-l,3,5-triazacycloalkanes (106). 

The nitrolysis of (107) with nitric acid-trifluoroacetic anhydride yields 2,4,6-trinitro-2,4,6-triazaheptane (108). " ... 

The nitrolysis of cyclic polyamides offers a possible alternative industrial synthesis of HMX. The nitrolysis of l,3,5,7-tetraacetyl-l,3,5,7-tetraazacyclooctane (TAT) (79) and 1,5-diacetyl-3,7-dinitro-l,3,5,7-tetraazacyclooctane (DADN) (80) with a solution of dinitrogen pentoxide in anhydrous nitric acid gives HMX in 79 % and 98 % yields, respectively. Interestingly, the same reactions with nitric acid-acetic anhydride fail at room temperature. 

The above observations allow the selective formation of RDX, HMX or the two linear nitramines (247) and (248) by choosing the right reaction conditions. For the synthesis of the linear nitramine (247), with its three amino nitrogens, we would need high reaction acidity, but in the absence of ammonium nitrate. These conditions are achieved by adding a solution of hexamine in acetic acid to a solution of nitric acid in acetic anhydride and this leads to the isolation of (247) in 51 % yield. Bachmann and co-workers also noted that (247) was formed if the hexamine nitrolysis reaction was conducted at 0 °C even in the presence of ammonium nitrate. This result is because ammonium nitrate is essentially insoluble in the nitrolysis mixture at this temperature and, hence, the reaction is essentially between the hexamine and nitric acid-acetic anhydride. If we desire to form linear nitramine (248) the absence of ammonium nitrate should be coupled with low acidity. These conditions are satisfied by the simultaneous addition of a solution of hexamine in acetic acid and a solution of nitric acid in acetic anhydride, into a reactor vessel containing acetic acid. 

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. ... 

Agrawal and co-workers" " also conducted extensive studies into the synthesis, characterization and thermal and explosive behaviour of (113) (K-56, TNABN). 2,5,7,9-Tetraazabi-cyclo[4.3.0]nonane-8-one (112) was synthesized from the direct reaction of ethylenediamine with glyoxal, followed by reaction of the resulting cyclic imine with urea in concentrated hydrochloric acid nitration of (112) was achieved in 51 % yield with a mixture of nitric acid-acetic anhydride. Agrawal showed that K-56/TNABN is significantly more resistant to hydrolytic destruction than TNGU. 

Boyer and co-workers" also reported the synthesis of the guanidine tricycle (122), prepared as the tetrahydrochloride salt from the condensation of two equivalents of guanidine with 1,4-diformyl-2,3,5,6-tetrahydroxypiperazine in concentrated hydrochloric acid. Treatment of the tricycle (122) with absolute nitric acid yields thebis-nitrimine (123), whereas the same reaction with nitric acid-acetic anhydride yields HHTDD (117). 

It has been usual practice to introduce such explosophoric groups in the structure of a molecule with the use of conventional nitrating agents such as absolute nitric acid, sulfuric acid-nitric acid, acetic anhydride-nitric acid, ammonium nitrate-acetic anhydride-nitric acid... 

The nitrolysis of hexamine is a direct route to the military high explosives 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) and l,3,5,7-tetranitro-13,5,7-tetraazacyclooctane (HMX). " The direct nitrolysis of hexamine with dinitrogen pentoxide in absolute ifitric acid provides RDX in 57 % yield. RDX prepared by this process is exceptionally pure, but other reagents, like ammonium nitrate-nitric acid-acetic anhydride, give much higher yields, partly because they use ammonium nitrate to supplement for ammonium nitrogen deficiency in the reaction. 

These trends have been quantified for some reactions. Nitration studies showed carbazole to react 222,000 times faster than benzene, with nitric acid-acetic anhydride having partial rate factors of 32,100 (C-1), 1,100 (C-2), 77,600 (C-3), and too small to measure (C-4). Carbazole reacts about 20 times more slowly than diphenylamine. The partial rate factor for nitration at C-3 can be compared with a value of 50,100 found for the perchloric add protodesilylation of 3-trimethylsilylcarbazole. ... 

CA 70, 57139(1969) (Nitration of hydrocarbons with nitric acid—trifluoroacetic anhydride mixts)... 

Semenczuk and T. Urbanski also showed that dimethylaniline may be nitrated to tetryl by a mixture of nitric acid with acetic acid or acetic anhydride. As yet the only other results mentioned in the literature with reference to this method are those of Orton [11]. He asserted that dimethylaniline gives no N-nitro derivative when reacted with a mixture of nitric acid with acetic anhydride or acetic acid he obtained only 2,4-dinitromethylaniline. 

J) G.F. Wright Be W.J. Chute, USP 2678927 (1954) Si CA 49, 7606(1955) (Prepn of DPT and of HMX from DPT by treating with nitric acid or nitric acid-acetic anhydride-Ammonium Nitrate mixt)... 

According to Lenze and Rubens [38], the application of concentrated nitric acid with phosphoric anhydride P205 makes it possible to attain a nitrogen content close to 14.1%, i.e. approximately that of the pure trinitrate. 

Mesaconic acid has been prepared by heating citraconic acid with dilute nitric acid, with hydriodic acid,2 or with concentrated sodium hydroxide solution 3 by heating a concentrated water solution of itaconic or citraconic acid at 180-200° 4 by treating citradibromopyrotartaric acid and mesodibromopyrotartaric acid with potassium iodide and copper at 1500 5 and by heating citraconic anhydride with nitric acid.6... 

Chapman found that nitration of bistrimethylenedinitramine 217 (R = CH2-morpholinyl) with a mixture of nitric acid, acetic anhydride, and ammmonium nitrate afforded 1,3,5-triazocine 218 (R = NO2) along with 4-nitromorpholine (49JCS1631). In a related reaction, Mannich condensation of 217 (R = H) with formaldehyde in the presence of primary amines yielded 218 [R = Me (49JCS1638), var. alkoxyalk, alk (66JCS(C)870)]. Use... 

Wh solid, mp expl ca 98°. Was prepd by treating the previous compd with mixt of 99— 100% nitric acid, acetic anhydride and glac acetic acid(Ref 2)... 

For the nitration of aromatic hydrocarbons with acetylnitrate, there is a clearly linear correlation between the ionization potentials of these hydrocarbons and the rate constants relative to benzene (Pedersen and others 1973). Table 4-4 juxtaposes spin densities of the cation radicals and the partial rate factors of ring attacks in the case of the nitration of isomeric xylenes by means of the (nitric acid-acetic anhydride) mixture. 

The nitration of phenylfurans takes place in the furan ring very readily. The nitration of methyl 3,4-diphenylfuran-2-carboxylate using nitric acid acetic anhydride at low temperatures (-40 to 20°C) gives products due to nitration in the furan ring (20) and (21), up to 40% of (20) and 20% of (21) being obtained. With the addition of concentrated sulfuric acid to the nitrating mixture, compounds (22) and (23) (approx. 30 and 10%, respectively) are obtained and none of the products (20) and (21) (81CPB635). 

The nitration of 3-phenylpyrazole (26a) using nitric acid acetic anhydride gives a mixture of 3-(4-nitrophenyl)-l-acetylpyrazole (26b) and 1-nitro-3-phenylpyrazole (26c). Both then react with sulfuric acid to yield 3-(4-nitrophenyl)pyrazole (26d), which is the product of nitration using nitric acid sulfuric acid. In this case, even in acetic anhydride, nitration did not occur in the pyrazole ring [58AC(R)783]. 

Methyl-3-phenylisoxazole is also nitrated via the conjugate acid in mixed acid to yield the 3-nitrophenyl product and as the free base to give the 4-nitrophenyl product. The proportion of meta para nitration varies with the acidity of the medium. 5-Methyl-3-phenylisoxazole, in nitric acid acetic anhydride, yields 4-nitro-3-(4-nitrophenyl)isoxazole. The standard rates of nitration at 25°C and H0 -6.6 have been calculated [75 JCS(P2) 1627]. 

In another study of the nitration of 5-phenyl- and 3-methyl-5-phenylisox-azole the action of nitric acid sulfuric acid on 5-phenylisoxazoIe produced a 1 1 1 mixture of the ortho, meta, and para 5-(nitrophenyl) products with minor amounts of 4-nitro-5-(3-nitrophenyl)- and 4-nitro-5-(4-nitrophenyl)-dinitro products. The action of nitric acid acetic anhydride produced 4-nitro-5-phenylisoxazole as the major product with some nitrophenyl compounds as minor products. 3-Methyl-5-phenylisoxazole also gave a mixture of the ortho, meta, and para 5-(nitrophenyl) products when mixed acids were used, but no dinitro products were observed. The use of nitric acid acetic anhydride resulted in nitration at the 4-position of the isoxa-zole ring as the largely predominant product, with some phenyl ring substitution (89H1965). 

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