Mannich nitro

Cobb, A.J.A., Shaw, D.M., Longbottom, D.A., Gold, J.B. and Ley, S.V. (2005) Organocatalysis with proline derivatives improved catalysts for the asymmetric Mannich, nitro-Michael and aldol reactions. Org. Biomol. Chem., 3, 84. 

Pyrrolidin-2-yltetrazole 204 has been found to be a new, catalytic, and more soluble alternative to proline in a highly selective, organocatalytic route to chiral dihydro-1,2-oxazines <05OL4189> and as an asymmetric organocatalyst for Mannich, nitro-Michael and aldol... 

Primary nitroparaffins react with two moles of formaldehyde and two moles of amines to yield 2-nitro-l,3-propanediamines. With excess formaldehyde, Mannich bases from primary nitroparaffins and primary amines can react further to give nitro-substituted cycHc derivatives, such as tetrahydro-l,3-oxa2iaes or hexahydropyrimidines (38,39). Pyrolysis of salts of Mannich bases, particularly of the boron trifluoride complex (40), yields nitro olefins by loss of the amine moiety. Closely related to the Mannich reaction is the formation of sodium 2-nitrobutane-1-sulfonate [76794-27-9] by warming 1-nitropropane with formaldehyde and sodium sulfite (41). 

Purines, N-alkyl-N-phenyl-synthesis, 5, 576 Purines, alkylthio-hydrolysis, 5, 560 Mannich reaction, 5, 536 Michael addition reactions, 5, 536 Purines, S-alkylthio-hydrolysis, 5, 560 Purines, amino-alkylation, 5, 530, 551 IR spectra, 5, 518 reactions, 5, 551-553 with diazonium ions, 5, 538 reduction, 5, 541 UV spectra, 5, 517 Purines, N-amino-synthesis, 5, 595 Purines, aminohydroxy-hydrogenation, 5, 555 reactions, 5, 555 Purines, aminooxo-reactions, 5, 557 thiation, 5, 557 Purines, bromo-synthesis, 5, 557 Purines, chloro-synthesis, 5, 573 Purines, cyano-reactions, 5, 550 Purines, dialkoxy-rearrangement, 5, 558 Purines, diazoreactions, 5, 96 Purines, dioxo-alkylation, 5, 532 Purines, N-glycosyl-, 5, 536 Purines, halo-N-alkylation, 5, 529 hydrogenolysis, 5, 562 reactions, 5, 561-562, 564 with alkoxides, 5, 563 synthesis, 5, 556 Purines, hydrazino-reactions, 5, 553 Purines, hydroxyamino-reactions, 5, 556 Purines, 8-lithiotrimethylsilyl-nucleosides alkylation, 5, 537 Purines, N-methyl-magnetic circular dichroism, 5, 523 Purines, methylthio-bromination, 5, 559 Purines, nitro-reactions, 5, 550, 551 Purines, oxo-alkylation, 5, 532 amination, 5, 557 dipole moments, 5, 522 H NMR, 5, 512 pJfa, 5, 524 reactions, 5, 556-557 with diazonium ions, 5, 538 reduction, 5, 541 thiation, 5, 557 Purines, oxohydro-IR spectra, 5, 518 Purines, selenoxo-synthesis, 5, 597 Purines, thio-acylation, 5, 559 alkylation, 5, 559 Purines, thioxo-acetylation, 5, 559... 

The catrilydc asymmetric nitro Mannich-type reac blnaphthol gives the best result fsee Eq 4 141 The re a good ee, where nitromethane is added vety slowly ovei... 

The condensation of nitro compounds and imines, the so-called aza-Henry or nitro-Mannich reaction, has recently emerged as a powerful tool for the enantioselective synthesis of 1,2-diamines through the intermediate /3-amino nitro compounds. The method is based on the addition of a nitronate ion (a-nitro carbanion), generated from nitroalkanes, to an imine. The addition of a nitronate ion to an imine is thermodynamically disfavored, so that the presence of a protic species or a Lewis acid is required, to activate the imine and/or to quench the adduct. The acidic medium is compatible with the existence of the nitronate anion, as acetic acid and nitromethane have comparable acidities. Moreover, the products are often unstable, either for the reversibility of the addition or for the possible /3-elimination of the nitro group, and the crude products are generally reduced, avoiding purification to give the desired 1,2-diamines. Hence, the nitronate ion is an equivalent of an a-amino carbanion. 

Ph (SbFe)2 Ph Ph TIO OTf Ph 84 Scheme 14 Catalytic asymmetric aza-Henry (nitro-Mannich-type) reactions... 

Additions of stabilized carbanions to imines and hydrazones, respectively, have been used to initiate domino 1,2-addition/cyclization reactions. Thus, as described by Benetti and coworkers, 2-subshtuted 3-nitropyrrolidines are accessible via a nitro-Mannich (aza-Henry)/SN-type process [165]. Enders research group established a 1,2-addition/lactamization sequence using their well-known SAMP/ RAMP-hydrazones 2-308 and lithiated o-toluamides 2-307 as substrates to afford the lactams 2-309 in excellent diastereoselectivity (Scheme 2.72) [166]. These compounds can be further transformed into valuable, almost enantiopure, dihydro-2H-isoquinolin-l-ones, as well as dihydro- and tetrahydroisoquinolines. 

Nitration of 2-substituted 4/7-pyrido[l,2- ]pyrimidin-4-ones with 99% HN03 in cone. H2S04 gave 3-nitro derivatives <2000BMC751, 2001H(55)535>. Mannich reaction of 2-hydroxy-4//-pyrido[l,2-tf]pyrimidin-4-one afforded... 

In 2003, Williams and Mander reported a method designed to access the hetisine alkaloids (Scheme 1.3) [27]. This approach, based upon a previously disclosed strategy by Shimizu et al. [28], relied on arylation of a bridgehead carbon via a carbocation intermediate in the key step. Beginning with (1-keto ester 46, double Mannich reaction provided piperidine 47. Following a straightforward sequence, piperidine 47 was transformed to the pivotal bromide intermediate 48. In the key step, bromide 48 was treated with silver (I) 2,4,6-trinitrobenzenesulfonate in nitro-methane (optimized conditions) to provide 49 as the most advanced intermediate of the study, in 54 % yield. 

Bifunctional thiourea-catalysed enantioselective Michael reaction has been achieved. The thiourea moiety and an amino group of the catalyst activated a nitroolefin and a 1,3-dicarbonyl compound, respectively afford the Michael adduct with high enantioselectivity.177,178 Thioureas work as one of the most effective and general enantioselective nitro-Mannich reaction and carbonyl cyanation catalyst.179,180... 

Classical C,C-coupling reactions of AN anions (Henry, Michael, and Mannich) involve complex systems of equilibria and, consequently, generally not performed in protic solvents. The introduction of the silyl protecting group allows one to perform these reactions in an aprotic medium to prepare or retain products unstable in the presence of active protons. In addition, the use of nucleophiles which are specifically active toward silicon (e.g., the fluoride anion) enables one to design a process in which the effective concentration of a-nitro carbanions is maintained low. 

K. Yamada, S. J. Harwood, H. Groger, M. Shibasaki, The First Catalytic Asymmetric Nitro-Mannich-Type Reaction Promoted by a New Heterobimetallic Complex, Angew. Chem, 1999, 38, 3504-3506. 

Mannich bases derived from polynitroalkanes are usually unstable because of the facile reverse reaction leading to stabilized nitronate anions. The nitration of Mannich bases to nitramines enhances their stability by reducing the electron density on the amine nitrogen through delocalization with the nitro group. The nitration of Mannich bases has been exploited for the synthesis of numerous explosives, some containing both C-NO2 and N-NO2 functionality. Three such compounds, (163), (164) and (165), are illustrated below and others are discussed in Section 6.10. 

Adolph and Cichra prepared some A-nitroso-l,5-diazocines from the condensation of bis(2,2-dinitroethyl)nitrosoamine (49) with formaldehyde and various amines. 3,3,7,7-Tetranitro-1 -nitrosooctahydro-1,5-diazocine (50), the product obtained from the Mannich condensation of (49), formaldehyde and ammonia, was used to prepare nitro- and nitroso- 1,5-diazocines (52), (53), and (54). 

The Mannich reaction has been used to synthesize numerous heterocyclic nitramine explosives. Adolph and Cichra prepared a number of A-heterocycles containing ferf-butyl A-blocking groups. The nitrolysis of these f-butyl groups provides the corresponding A-nitro derivatives in excellent yields (Section 5.6.2.2). Some of the nitramine products from these reactions are powerful, energetic explosives with attractive properties. 

Oxidation of 3,6-diamino-1,2,4,5-tetrazine (198) with oxone in the presence of hydrogen peroxide yields 3,6-diamino-l,2,4,5-tetrazine-2,4-dioxide (201) (LAX-112). The same reaction with 90 % hydrogen peroxide in trifluoroacetic acid yields 3-amino-6-nitro-1,2,4,5-tetrazine-2,4-dioxide (202). Treatment of 3,6-diamino-1,2,4,5-tetrazine (198) with 2,2,2-trinitroethanol and 2,2-dinitro-2-fluoroethanol generates the Mannich condensation products (203) and (204) respectively. 

Enamine nucleophiles react readily with soft conjugated electrophiles, such as a, 3-unsaturated carbonyl, nitro, and sulfonyl compounds [20-22], Both aldehydes and ketones can be used as donors (Schemes 27 and 28). These Michael-type reactions are highly useful for the construction of carbon skeletons and often the yields are very high. The problem, however, is the enantioselectivity of the process. Unlike the aldol and Mannich reactions, where even simple proline catalyst can effectively direct the addition to the C = O or C = N bond by its carboxylic acid moiety, in conjugate additions the charge develops further away from the catalyst (Scheme 26) ... 

Bicyclic ester 100 forms in analogy to isomeric ester 65 (Section 2.4.1.1) (07JOC5608). /l-Phenylethylamine 101 undergoes palladium-catalyzed direct aromatic carbonylation, thus providing another synthesis of benzo-lactam 78b (06JOC5951). A stereoselective nitro-Mannich/lactamization cascade of y-nitro ester and cyclic imine affords polysubstituted lactam 102 (08OL4267). 

Takemoto et al. discovered N-phosphinoyl-protected aldimines as suitable electrophilic substrates for the enantioselective aza-Henry [224] (nitro-Mannich) reaction [72] with nitromethane, when utilizing thiourea 12 (10mol%) as the catalyst in dichloromethane at room temperature [225]. The (S)-favored 1,2-addition of nitromethane to the electron-deficient C=N double bond allowed access to various P-aryl substituted N-phosphinoyl-protected adducts 1-5 in consistently moderate to good yields (72-87%) and moderate enantioselectivities (63-76%) as depicted in Scheme 6.73. Employing nitroethane under unchanged reaction conditions gave adduct 6 as a mixture of diastereomers (dr 73 27) at an ee value of 67% (83% yield) of the major isomer (Scheme 6.73). 

Scheme 6.73 Typical products of the enantioselective aza-Henry (nitro-Mannich) reaction between nitroalkanes and N-phosphinoylimines proceeding in the presence of catalyst 12.

Figure 6.29 Acetamide (thio)urea derivatives evaluated for catalytic efficiency in the nitro-Mannich reaction between N-Boc-protected benzaldimine and nitroethane.

Scheme 6.122 Products of the 122-catalyzed aza-Henry (nitro-Mannich) addition of nitromethane and nitroethane to acylated aldimines.

In 2008, Tang and co-workers reported the utilization of tertiary amine-functionalized saccharide-thiourea 211 as a bifunctional hydrogen-bonding catalyst for the enantioselective aza-Henry [224] (nitro-Mannich) addition [72] of... 

The N-sulfinyl (thio)ureas are modular and easily accessible in one step by condensing tert-butanesulfinamide with the appropriate isocyanate or isothiocyanate. Figure 6.64 shows a representative selection of the prepared N-sulfinyl (thio)ureas evaluated for their catalytic activity in the aza-Henry (nitro-Mannich) reaction of N-Boc-protected benzaldimine and nitroethane producing adduct 1. 

Die Mannich-Reaktion mit Nitro-benzimidazolen verlauft dagegen isomerenrein492 (s.S. 343). 

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