Nitromalonaldehyde

Sodium nitromalonaldehyde momo-iiydrate Warning), 46,104 Sodium sand, 46, 8 reaction with 2 carbomethoxy cyclo-pentanone, 45, 8... 

SODIUM NITROMALONALDEHYDE MONOHYDRATE (Malonaldehyde, nitro-, sodium derivative)... 

The slightly moist cake of crude product is transferred to a 1-1. flask and heated to boiling with a mixture of 400 ml. of 95% ethanol and 100 ml. of water. The hot solution is filtered to remove a fine yellow solid, and the clear red filtrate is cooled to 0-5°. The recrystallized product is collected on a Buchner funnel and dried in air at rpom temperature. The yield is 57-65 g. (36-41%) of pink or tan needles of sodium nitromalonaldehyde monohydrate (Note 3). 

It has been reported (Bruno Camerino, private communication) that, during the preparation of sodium nitromalonaldehyde monohydrate1 on a pilot-plant scale, two operators were so affected by the fumes evolved during the preparation that their immediate hospitalization was necessary. It was determined subsequently that hydrogen cyanide, up to approximately 1 g./kg. of muco-bromic acid utilized, was formed in the reaction mixture. It is essential that precautions specified in Note 1 of the procedure be followed carefully. 

The stereochemistry of the pentakisisocyanidecobalt(I) and (II) complexes is apparently a function of crystallization procedures. To date, four isomeric structures have been identified for isocyanide complexes of co-balt(l) (121) and three for those of cobalt(II) (284). Crystal structure determinations of [Co(CNPh)5]C104 CHCl3 (285) and [Co(CNPh)5]-(CI04)2 C1CH2CH2C1 (284) have shown the coordination around the cobalt to be square pyramidal, whereas with [Co(CNC6H4Me-p)5][Co(NM A)3] (NMA = nitromalonaldehyde) a trigonal bipyramidal structure was found for the cation (286). 

The 3-( 7-butylamino)-2-nitroacrylaldehyde is a synthetic equivalent to nitromalonaldehyde that reacts with substituted ethylenediamines in MeOH at 25 °C to provide the first examples of 6-nitro-2,3,4,5-tetrahydro-l//-l,4-diazepines in excellent yield (Scheme 54) <2004JOC8382, 2002H(56)425>. The slow addition of a solution of the diamine to the nitroenamine was required in order to minimize oligomer formation. 

Sodium iodide, 30, 11 Sodium methoxide, 32, 32 Sodium nitrite, 31, 14 32, 95 Sodium nitromalonaldehyde monohydrate, 32, 95 Sodium phenoxide, 32, 75 Sodium sulfhydrate, 31, 7 Sodium sulfide nonahydrate, 31, 6 Sorbic acid, 5-hydroxy-/3-methyl, 5-lactone, 32, 57... 

From this viewpoint, dinitropyridone 1 and nitropyrimidinone 2 would be supplementary synthetic equivalents of 4 treatable in organic media with considerable safety instead of sodium nitromalonaldehyde. Dinitropyridone 1 is a more suitable substrate for the RTF reaction compared to nitropyrimidinone 2 since the stable nitroacetamide anion is more readily ebminated than anionic urea. 

The 3-(/< r/-butylamino)-2-nitroacrylaldehyde 490 is a synthetic equivalent to nitromalonaldehyde and reacts with substituted ethylenediamines 491 in methanol to provide 6-nitro-2,3-dihydro- H- 1,4-diazepines 492 in excellent yields (Scheme 226) <2004JOC8382, 2002H425>. 

Salicylaldehydes give spirobenzo pyrans, often referred to simply as spiropyr-ans. In principle, true monocyclic spiropyrans would be prepared from 3-hydro-xyacrylaldehyde, which is the enol form of malonaldehyde. A reaction of Fischer s base with malonaldehyde or its chloro derivative gave complex mixtures containing the open form, but nitromalonaldehyde sodium salt gave with Fischer s base hydroiodide a 24% yield of beautiful orange crystals of the open form (3) (A. = 483 mm)7 Recently a series of 2-substituted malonaldehydes (4) became... 

This reaction was extended to other (i-dicarbonyl compounds containing a nitro group [474 176], The mechanism of the reaction of hydrazine with 1,3-dicarbonyl compounds is still largely unclear. Nevertheless, important evidence was obtained to indicate that a dihydroxypyrazolidine intermediate is formed in this reaction [477], If hydroxylamine is used instead of free hydrazine in the reaction with nitromalonaldehyde, the product is 4-nitroisoxazole [471], When a mixture of nitrocyanoacetic ester with one equivalent of hydrazine hydrate and a small amount of water is boiled, 5-amino-4-nitro-3-pyrazolone is formed [478],... 

Type 3 Nitromalonaldehyde, nitromalonic esters, ethoxymethyleneni-troacetic ester... 

Nitromalonaldehyde reacts with ethyl glycinate5-6 and j8-aminopropio-phenone7 in the presence of alkali to yield 6 (66%) and 7 (30%), respectively.5-8... 

Several reports are available on the condensation of nitromalonaldehyde with hydrazines to give 4-nitropyrazole derivatives (47) [Eq. (14)].39-41 The reaction of sodio-nitromalonaldehyde with aminoguanidine in the presence of acid directly yields l-guanyl-4-nitropyrazole (48 R = C(NH)NH2).42 43... 

In a typical /J-diketone reaction, nitromalonaldehyde reacts with hydroxyl-amine to produce the parent 4-nitroisoxazole,39-58 Similarly, dibenzoyl-nitromethane yields 3,5-diphenyl-4-nitroisoxazole 64.5 7... 

In an interesting sequence of reactions, Grundmann and co-workers have prepared 5-amino-4-nitroisoxazole (67) from the sodium salt of nitromalonaldehyde and hydroxylamine.59 The initially formed sodium malon-dialdoxime nitronate 65 is diacetylated and cyclized to the furazan oxide 66 acid hydrolysis, followed by rearrangement in alkali gives the 5-amino-4-nitroisoxazole (Scheme 13). The same product has also been detected in the decomposition of mercuric fulminate. 

The sodium salt of nitromalonaldehyde reacts with /J-aminocrotonic ester to give 2-methyl-5-nitronicotinate (82).7 3... 

Surprisingly, a preference for the formation of a pyridine rather than a pyrimidine ring is shown in the reaction of sodio-nitromalonaldehyde with ethyl formamidinoacetate the product is ethyl 2-amino-5-nitronicotinate (83).74... 

The condensation of sodio-nitromalonaldehyde with cyanoacetamide in the presence of Triton B gives 3-cyano-5-nitro-2-pyridone (84) (93%).75... 

The reaction of anilines with nitromalonaldehyde to form the 3-nitro-quinolines (96) is carried out in two steps. The cyclization is best catalyzed by the corresponding aniline hydrochloride in acetic acid (Scheme 19).89,90 The yields range from 40 to 77%, except in the case of o-toluidine, where the yield is very low. The tetracyclic compound 97 has been similarly prepared from 3-aminonaphthostyril.89... 

Nitromalonaldehyde has also been used in the syntheses of nitropyridines condensed to other heterocycles. The success of the reaction depends on the reactivity of the ortho position for cyclization. The 2-amino-4-cyanopyr-role 98 yields the pyrrolo [2,3-6] pyridine derivative 99.91... 

Diamino-6-hydroxypyrimidine condenses with nitromalonaldehyde in presence of alkali to give 2-amino-4-hydroxy-6-nitropyrido[2,3-d]pyrimi-dine (100) (75%).92 In a similar reaction 2,4-dioxo-l-hydroxy-6-nitro-lf/,3//-pyrido[2,3-d]pyrimidine is formed (101) [Eq. (32)].93... 

All the nitropyrimidine derivatives synthesized from open-chain nitro-containing precursors have the nitro group in the 5-position of the heteroring. Nitromalonaldehyde, nitromalonic ester, and ethoxymethylenenitroacetic ester are the common synthons employed. 

A variety of amidines react with nitromalonaldehyde in presence of Triton B or piperidine, to form the 5-nitropyrimidines 116 [Eq. (37)].106-110 Yields range from 30 to 90%. Acetamidine gives a very poor yield of the nitropyrimidine and formamidine does not give any isolable product. 

Guanidine reacts with nitromalonaldehyde in nearly quantitative yield to produce 2-amino-5-nitropyrimidine (116 R = NH2).106 107 111 N,N-Dimethylguanidine reacts similarly to produce the 2-dimethylamino compound (116 R = NMe2) in 33% yield.112 The reaction has been applied to a complex guanidine related to lysergic acid.113... 

Urea reacts with nitromalonaldehyde to yield the monoureide 117 which, with phosphorus oxychloride, undergoes ring closure and chlorination to give 2-chloro-5-nitropyrimidine (118) (14%) [Eq. (38)].114... 

Thiourea has also been reacted with nitromalonaldehyde. According to Hale and Brill, the condensation of sodio-nitromalonaldehyde with thiourea in presence of piperidine gives the thiazine 119.115 However, this observation could not be confirmed subsequent work has given only 5-nitro-2-piper-idinopyrimidine (120) under these conditions in 15% yield.116 These workers... 

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