Acetic anhydride, reaction with nitric acid

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. 

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). 

Compounds (49) undergo nitration in the heterocyclic ring on reaction with nitric acid acetic anhydride in nitromethane at - 15°C (77JHC1021). 

Combustible when exposed to heat or flame. Can react with oxidizing materials. Explosive reaction with acetic acid + acetic anhydride + ammonium nitrate + nitric acid, 1-bromopenta borane(9) (above 90°C), iodoform (at 178°C), iodine (at 138°C). Reaction with nitric acid + acetic anhydride forms the military explosives RDX and HMX. Reacts violently with Na202. When heated to decomposition it emits toxic fumes of formaldehyde and NOx. See also AMINES. 

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). 

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. ... 

For thiophene itself, conditions of type (1) tend to produce very fast reactions. However, work has shown that the explosively fast reaction with nitric acid-acetic acid, due to nitrosation, can be largely suppressed by using urea [71 JCS(B) 102] and sulfanilic acid would probably be even better in this respect [cf. 77JCS(P2)248, 77JCS(P2)1693]. Conditions (1) have therefore been confined mainly to deactivated thiophenes, with conditions (2) being preferred for activated thiophenes. It is believed that acetic anhydride suppresses side reactions preceeding via nitrosation under conditions (2) [71 JCS(B) 102]. 

Tetranitropropane diurea (TNPDU) has been prepared from the condensation reaction of urea with tetraethoxy-propane followed by nitration with nitric acid — acetic anhydride. The data on thermal analysis and preliminary... 

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). 

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. ... 

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. ... 

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. 

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. 

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. 

Nitration of pyridines in other than nitric or sulfuric acids is of little interest here because either no reaction or N-nitration takes place (see Section 2.05.2.10). However, pyridine 1-oxide is considerably more reactive and treatment with benzoyl nitrate ultimately leads to the 3-nitro derivative (Scheme 25) (60CPB28). Annelation of a benzene ring bestows greater reactivity on the 3-position in quinoline, compared with pyridine, and reaction with nitric acid in acetic anhydride furnishes the 3-nitro derivative (ca. 6%) (Scheme 26). This isomer has also been obtained, again at low yield (6-10%), by treatment of quinoline with tetranitratotitanium(IV) in carbon tetrachloride (74JCS(P1)1751>. Nitration of benzo analogues of pyridine occurs much more readily in the benzene ring, and Chapter 2.06 should be consulted for these reactions. 

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... 

The nitration of pyrrole has been investigated under a variety of experimental conditions.313 The reaction with nitric acid in acetic anhydride proceeds smoothly and both spectroscopic and kinetic results indicate that the acetyl nitrate is the effective electrophilic agent. The a. J3 ratio is about 4 for nitration in acetic anhydride over a wide temperature range. By using competitive procedures, the partial rate factors for a- and -positions of the pyrrole ring in the nitration were estimated by these authors to be 1.3 x 105 and 3 X 104, respectively. 

Compound (8), under Vilsmeier formylation and nitration (nitric acid-acetic anhydride) conditions, proceeded as might have been expected for electrophilic substitution reactions to give the 1-substituted products (142) and (143). Reduction of (143) gave predominantly the imidazopyridine (144) with a small amount of the tetrahydro derivative (145) (81JCS(P1)78). Heating (8) in D2O led to the 1-deutero derivative (78HCA1755) via deuter-ation-deprotonation or via the tautomeric 2-(diazomethyI)pyridine tautomer of (8). 

The key intermediate for the synthesis of various nitrofuran drugs is 5-nitro-furfural (45, isolated as diacetate), which is obtained by careful nitration of furfural (44) with a nitric acid-acetic anhydride mixture at low temperatures [30]. Reaction of 45 with various nucleophiles gives nitrofuran drugs of the general formula 46. 

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