Pyridine 2-amino-, nitration

Chichibabin [28] and Razorenov observed that the amino derivatives of pyridine are nitrated in a similar way. For example, a mixture of nitric and sulphuric acids converts a-amino-pyridine into a-nitramino-pyridine. 

As in benzene chemistry, electron-releasing amino groups facilitate electrophilic substitution, so that, for example, 2-aminopyridine undergoes 5-bromination in acetic acid even at room temperature this product can then be nitrated, at room temperature, forming 2-amino-5-bromo-3-nitropyridine. Bromina-tion of all three amino-pyridines is best achieved with iV-bromosuccinimide at room temperature, products being 2-amino-5-bromo-, 3-amino-2-bromo- and 4-amino-3-bromopyridines. Similarly, chlorination of 3-amino-pyridines affords 3-amino-2-chloro-pyridines. Nitration of amino-pyridines in acid solution is also relatively easy, with selective attack of 2- and 4-isomers at P-positions. A mechanistic study of dialkylamino-pyridines showed nitration to involve attack on the salts. ... 

Nucleosides are first protected at the exocyclic amino groups with either the benzoyl (A, G, and C) (32), isobutyryl (G) (33,34), or phe-noxyacetyl (A and G) (27) groups through the transient procedure developed by Jones and coworkers for protection of deoxynucleosides (35). Following iV-protection the nucleosides are tiitylated (DMT or MMT) at the 5 -position by the standard pyridine (27) or pyridine-silver nitrate (30) procedures. Detailed NMR, UV, and TLC data of 5 -tritylated N-pro-tected ribonucleosides have appeared in the literature (6,27,29, JO, id-... 

Furo[3,4-d]pyridazine-1,4-diones synthesis, 4, 985 Furopyridazines, 4, 984 Furo[2,3-6]pyridine, 3-amino-synthesis, 4, 977 Furo[2,3-6]pyridine, 4-methyl-synthesis, 4, 976 Furo[2,3-6]pyridine, 6-methyl-synthesis, 4, 976 Furo[2,3-6]pyridine, 5-nitro-synthesis, 4, 977 Furo[3,2-c]pyridine, 4-allyl-synthesis, 4, 982 Furopyri dines H NMR, 4, 983 physical data, 4, 983 properties, 4, 982 synthesis, 4, 974-982 UV spectroscopy, 4, 983 Furo[6]pyri dines HMO data, 4, 975 Furo[2,3-6]pyri dines synthesis, 4, 974-977 7, 512 Furo[3,2-6]pyri dines C NMR, 4, 982 synthesis, 4, 648, 981 Furo[c]pyri dines HMO data, 4, 976 Furo[2,3-c]pyri dines synthesis, 4, 977 Furo[3,2-c]pyri dines nitration, 4, 983 synthesis, 4, 978-981 Furo[3,4-c]pyri dines synthesis, 4, 982 Furo[3,2-c]pyridin-3-ols synthesis, 4, 980 Furo[2,3-6]pyridin-6-ones synthesis, 4, 976 Furo[3,4-c]pyridin-4-ones synthesis, 4, 982... 

Thieno[3,2-c]pyridazine-3-carboxylic acid synthesis, 4, 819-820 Thienopyridazines, 4, 1015 Thieno[2,3- hjpyridazines nitration, 4, 1016 synthesis, 4, 791, 1015 Thieno[3,2-c]pyridazines synthesis, 4, 1016 Thieno[3,4-d]pyridazines synthesis, 4, 1016 Thieno[2,3-6]pyridine, 4-amino-synthesis, 4, 1005... 

Thieno[2,3-6]pyridine, 6-amino-2,3,4,5-tetracyano-synthesis, 4, 805 Thieno[2,3-6]pyridine, 5-ethyl-nitration, 4, 1014... 

Axenrod and co-workers reported a synthesis of TNAZ (18) starting from 3-amino-l,2-propanediol (28). Treatment of (28) with two equivalents of p-toluenesulfonyl chloride in the presence of pyridine yields the ditosylate (29), which on further protection as a TBS derivative, followed by treatment with lithium hydride in THF, induces ring closure to the azetidine (31) in excellent yield. Removal of the TBS protecting group from (31) with acetic acid at elevated temperature is followed by oxidation of the alcohol (32) to the ketone (33). Treatment of the ketone (33) with hydroxylamine hydrochloride in aqueous sodium acetate yields the oxime (34). The synthesis of TNAZ (18) is completed on treatment of the oxime (34) with pure nitric acid in methylene chloride, a reaction leading to oxidation-nitration of the oxime group to em-dinitro functionality and nitrolysis of the A-tosyl bond. This synthesis provides TNAZ in yields of 17-21 % over the seven steps. 

The product is 2-amino-5-nitropyridine because substitution occurs preferentially at the sterically less hindered position para to NH,. The conditions are milder than those for nitration of pyridine, because NH is activating. 

Similarly, primary aromatic amines undergo complex reactions when heated with nitric acid. The amine derivatives of anthraquinone, pyridine and thiazole are exceptions the amino group in these compounds is decomposed by the nitrating mixture. This was noticed by Scholl [27], who proposed the following method for nitrating / -aminoanthraquinone ... 

As expected, an amino group facilitates nitration strongly. 2-, 3- and 4-Aminopyridines are nitrated smoothly (H2S04-HN03 at 40-70°C to form mono- (5-, 2- and 3-, respectively) and dinitro- (3,5-, 2,6-and 3,5-, respectively) derivatives (Section 3.2.1.3.2). Alkylamino-, alkoxy- and 3-hydroxy-pyridines react analogously to the corresponding amino compounds. 

A-Aminopyridinium cations can be acylated or sulfonylated (with acid halides) and nitrated (H2S04 - HN03) to give the corresponding -(substituted amino)pyridines (972), often isolated as the imides (973 R = COR, S02R or N02). 

The results of nitration reactions depend on reagents and the acidity of the medium. Thus fuming nitric acid in concentrated sulfuric acid converts (410a) to the 3-nitro derivative while with acetyl nitrate reaction occurs exclusively at C-4 (equation 50). The nitration in the 4-position can also conveniently be done with nitronium tetrafluoroborate. The reduction of these nitro compounds by hydrazine in the presence of palladium on charcoal provides a versatile route to 4-amino-7,6-borazarothieno[3,2-c]pyridines (75ACS(B)46l>. In the nitration of 4,5-borazarothieno[2,3-c]pyridines (e.g. 409a), peri effects from the substituents on the boron atom lead to formation of a considerable amount of the 2-nitro derivatives. 

E. C. C. Baly and co-workers 2 showed that soln. of nitrates and carbonic acid are respectively converted into nitrite and formaldehyde in ultra-violet light, and these products then react to form formhydroxamic acid this acid then combines with more photosynthesized formaldehyde to give a variety of products —e.g. glyoxaline, free and substituted a-amino-acids, and substances of an alkaloidal nature. Methylamine and pyridine are produced by the action of... 

Nitraminopicolines, HjC(C, NJHjfNH NOj), mw 153.14, N 27.44%. The following isomers are described in the literature a-Nitramino-fi-picoline or 3-Nitro 3 methyl-pyridine. Lt yel ndls, mp 159° with decompn. Was prepd by nitrating 2-amino-3-methyl-pyridine with HNO,(d 1.4) in coned HaS04 in the cold... 

Note No higher nitrated derivs of amino-pyridine were found in Beil or CA through 1956... 

N 22.42%, OB to CO, -27.4%, OB to CO +5.5%. Lt yel crysts, mp 142-3° (with decomp) insol in w, ales, pet eth, chlf, CC14, benz col sol in acet, AcOH, NB pyridine. Can be prepd by nitrating either the corresponding dinicro- or trinitro- compds with fuming nitric acid (Ref 2). It is a powerful explosive Note According to Elderfield et al (Ref 3), the nitration of 2-(2, 4 -dinitrophenyl-amino)-1,3-propanediol with mixed nitric-sulfuric acid yielded a product which melted at 146.5° and exploded on further heating or on being struck with a hammer on an iron surface. No analysis was made but it seems that this product was identical with the one prepd by den Otter Refs l)Beil—not found 2)H.P.den... 

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