Weak N-0 bond

Although a number of reagents can be used to reduce an isoxazole ring, molybdenum hexacarbonyl31 was selected for use in this synthesis. The action of this reagent on 24 reduces the weak N-0 bond of the isoxazole ring and produces a //-amino-a,//-unsaturated aldehyde (i.e. a vinylogous formamide) (see Scheme 19). Intermediate 87 forms smoothly upon deprotection of the terminal acetylene carbon with basic methanol-THF. 

Elimination Reactions with Silyl Nitronates Most elimination reactions of SENA involve cleavage of the weak N-0 bond or cleavage of the O-Si bond. In the latter case, the reactions could occur with the participation of hyper-valent silicon in the transition state, that requires the presence of an external nucleophile. 

If you don t want to be bothered with the oxidation, you can use hydroxylamine instead of ammonia. The intermediate is now unstable and eliminates water 54 very easily. One of the two marked Hs at C-4 is lost as a proton with cleavage of the weak N-0 bond to give the pyridine 50 and water. 

Photohomolysis of the weak N-0 bond of a nitrite ester A forms a pair of radicals B and NO. The oxy radical B abstracts a hydrogen atom from a nearby carbon and the resulting radical C and NO couples to give a nitroso compound D. Tautomerism of the nitroso product D followed by treatment with nitrous acid converts this to the carbonyl group (Scheme 2.41). 

The reaction leading to amides is more complex. It was early proposed that thermal gas-phase reactions involved biradical intermediates formed by cleavage of the weak N-0 bond. In solution, a spectrum of transition states have been suggested ranging from radical to concerted to ionic. An extensive and detailed exposition of the merits of various mechanisms has been made by Lamchen, who favors dipolar intermediates or transition states. 

For branched chain primary amines (20), oximes (19) are good intermediates since they can be made easily from ketones and reduction cleaves the weak N-0 bond as well as reducing the C-N bond. FGI is again required before disconnection. 

The base does not attack at the C-3 atom but at the H-atom. Via an E2-type mechanism, facilitated by the weak N-0 bond, a (Z)-cyano enolate is formed leading to an a-cyano ketone. 

The reactions of isoxazoles differ considerably from those of oxazoles, although both systems are aromatic. The reason for this lies in the relatively weak N-0 bond in the isoxazole molecule, which is cleaved in all ring-opening reactions. Moreover isoxazoles, unlike oxazoles, do not react with dieno-philes to form Diels-Alder adducts [82]. 

Evidently, the cleavage of the weak endocyclic N-0 bond is the driving force of the ring opening. The nucleophilicity of the /V-oxide oxygen atom in nitronates facilitates the backward cyclization reaction (in the case of minimization of steric hindrance). With regard to the above mentioned one cannot exclude the tautomerism between cyclic nitronates 100 and open (or chain) isomers 101. 

N02 has also been shown to react with 1,1-dimethyl-hydrazine in air, forming HONO and tetramethyltetra-zine-2, (CH3)2NN=NN(CH3)2 (Tuazon et al., 1983b). The reaction is also proposed to involve abstraction of a hydrogen from the weak N-H bond by N02, forming HONO. The tetramethyltetrazine-2 is hypothesized to be formed by the addition of N02 to the (CH3)2NNH radical, followed by decomposition to (CH3)2N2 + HONO and the self-recombination of the (CH3)2N2 radicals (Tuazon et al., 1982). The apparent overall rate constant for the reaction was 2.3 X 10 17 cm3 molecule-1 s-1 so that the lifetime of 1,1-dimethylhy-drazine at an N02 concentration of 0.1 ppm would be 5 h. Since the lifetimes with respect to 0.1 ppm 03 or 1 X 106 OH radicals cm-3 are 7 min and 6 h, respectively, the reaction of N02 can contribute to the atmospheric reactions of the hydrazine only at low 03 levels. 

The reduction is straightforward the N-0 bond is weak and is reduced by catalytic hydrogenation but the hydrolysis needs some comments. Early and violent methods included the Nef reaction1—the hydrolysis of the enol form 8 in strong acid, probably via the intermediate 10 with liberation of nitrous oxide N2O. 

Alkali-metals are frequently used in heterogeneous catalysis to modify adsorption of diatomic molecules over transition metals through the alteration of relative surface coverages and dissociation probabilities of these molecules.21 Alkali-metals are electropositive promoters for red-ox reactions they are electron donors due to the presence of a weakly bonded s electron, and thus they enhance the chemisorption of electron acceptor adsorbates and weaken chemisorption of electron donor adsorbates.22 The effect of alkali-metal promotion over transition metal surfaces was observed as the facilitation of dissociation of diatomic molecules, originating from alkali mediated electron enrichment of the metal phase and increased basic strength of the surface.23 The increased electron density on the transition metal results in enhanced back-donation of electrons from Pd-3d orbitals to the antibonding jr-molecular orbitals of adsorbed CO, and this effect has been observed as a downward shift in the IR spectra of CO adsorbed on Na-promoted Pd catalysts.24 Alkali-metal-promotion has previously been applied to a number of supported transition metal systems, and it was observed to facilitate the weakening of C-0 and N-0 bonds, upon the chemisorption of these diatomic molecules over alkali-metal promoted surfaces.25,26... 

The product is a very unstable compound. The 0-0 single bond (bond energy 140 kj mol-i) is a very weak bond—much weaker than the N-0 bond (180 kj mol-1) we have been describing as weak in previous examples—and this heterocycle has two of them. It immediately decomposes—by a reverse 1,3-dipolar cycloaddition. 

Zard has developed the use of N-amidyl radicals. The precursors of the radical intermediates are 0-benzoyl hydroxyamines such as 37. Addition of a tributylstannyl radical to the carbonyl group of the benzoate moiety is followed by the cleavage of the weak N - O bond. A subsequent 5-exol6-endo tandem cyclization takes place to yield the skeleton of the natural product deoxyserratine (Scheme 12) [49]. Later, the same group disclosed a tin-free source of amidyl radicals that relies on the use of M-(0-ethyl thiocarbonyl-sulfanyl) amides and lauryl peroxide as initiator. Examples of polycyclization were also given [50]. On the occasion of a model study toward the synthesis of kirkine, the use of thiosemicarbazide precursors gave access to the tetracyclic structure of the natural product [51]. 

The 4,5-dihydroisoxazole ring is usually sufficiently stable to allow the introduction or manipulation of substituents (see Section 4.03.7.2). However ring opening can be smoothly achieved by cleavage of the weak N-O bond and less frequently of the C(5)-0 bond using suitable reagents. 

When oxime benzoates, prepared by benzoylation of dialkyl 1-hydroxyiminophosphonates in the presence of Py, are submitted to the action of tin hydrides under radical conditions, the weakness of the N-0 bond is responsible for the fast formation of the reactive iminyl radical. In the example displayed in Scheme 7.71, the intermediate iminyl radical undergoes cyclization faster than the P-scission to nitrile to give a cyclic aminophosphonale. "- The reaction has also been explored with dialkyl l-benzoyloxyimino-2,2-dimethyl-3,4-pentadienylphosphonate and BujSnH/AIBN in refluxing cyclohexane. In this case, the iminyl radical generated by stannyl radical addition on the benzoyl moiety leads to the sole formation of phosphonylated dihydropyridine in quantitative yield. ... 

Since the intramolecular reactions are so much the best, others have linked the alkene and the alkyne by a weak bond that can later be sacrificed. This is the tether strategy you will meet in chapter 36. An N-0 bond is ideal and with the alkyne additionally blocked with a silyl group 124, good yields of Pauson-Khand product 125 and of the amino alcohol 126 could be achieved even with an amine A-oxide as promoter. Samarium(II) iodide was used as the reducing agent.35... 

The instability of the iso- compounds comes from the weak O-N or S-N bond. These bonds can be cleaved by reducing agents, which then usually reduce the remaining functional groups further, he first product from reduction of the N-0 bond is an unstable imino-enol. The enol tautomerizes the ketone and the imine may be reduced further to the amine. We used this sort of chemistry on products of 1,3-dipolar cycloadditions in Chapter 35 and isoxazoles are usually formed by such... 

The reaction between CragOO " " and NO2 appears to be the only documented study of the interaction of a superoxometal complex with NO2. The 0-0 bond in the product CraqOONO + is weak and cleaves in the reverse process, the overall formation constant being 10 M . In comparison, the reaction of NO2 with HO2 is faster in the forward direction, = 1.8x10 M s (190) and slower in the reverse, /j = 0.005-0.05 s (225-227), yielding a much larger equilibrium constant, 7 66 = (3-6 x 10 ° —3.6 x 10 ) The weakening of the N-0 bond upon coordination of peroxynitrate can be traced to increased thermodynamic stability of the metal-superoxo fragment over H02-... 

On the C- and N-covered surfaces, the disruption is overcompensated by the formation of strong adsorbate-Ni bonds and by new Ni-Ni surface bonds resulting from the clock reconstruction. When O is forced into a coplanar site, however, both the higher electron count and increased electronegativity of the O atoms lead to severe disruption of the surface bonding and the formation of weak Ni-0 bonds. When O atoms sit above the surface, they form more polar Ni-0 bonds, contribute less electron density to the Ni surface bands, and cause less disruption to the Ni-Ni surface bonds. These results suggest that similar to the organometallic clusters, the... 

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