Ring closure by nucleophilic attack

Heating 4-amino-3-azido-4//-1,2,4-triazoles (229) in chlorobenzene to 110 °C gives the 3-amino-l,2,4,5-tetrazines (232). This reaction is explained by the intermediate formation of the nitrene (230) which opens to the formazane (231) and subsequent ring closure by nucleophilic attack of the hydrazono group on the nitrile function (66TL5369). 

The cycloaddition of alkenylidenecyclopropanes 5 with chlorosulfonyl isocyanate is described via electrophilic attack at C4, disrotatory opening of the cyclopropane ring to form a dipolar intermediate 8, and ring closure by nucleophilic attack of nitrogen or oxygen on either end of the allyl cation portion of the intermediate 8 which gives adducts 9-12. [27t -I- 2tc] Products 13 were also obtained. 

A 5-endo reaction takes place when 4-methyl-4-dcccnal is treated with tin(IV) chloride. After ring closure by nucleophilic attack of the olefin on the polarized carbonyl group, the resulting tertiary cation is stabilized by a sequence of two consecutive suprafacial [1,2] hydride shifts and ra . -2,3-dialkylated cyclopentanone 1 is formed stereoselectively2Q. 

Finally, the aminal undergoes an internal condensation involving ring closure by nucleophilic attack of the primary amine group on the carbon of the carbonyl followed by dehydration of the hemiaminal to yield the diazabicyclo[3.1.0]hex-3-ene ring system, again catalyzed by ammonium bromide. A reasonable scheme is shown below ... 

The calabar bean (the seed of Physostigma venenosum, Fa-baceae) was formerly used for trial by ordeal in Eastern Nigeria in an area known as the Calabar Coast (Holmstedt, 1972). By this method, the guilt or innocence of the accused is determined by whether that person survives after ingesting extracts or concoctions prepared from the plant. The seeds of the calabar bean contain a number of indole alkaloids derived from tryptamine and 5-adenosyl methionine. A concerted ring closure and nucleophilic attack on 5-adenosyl-methionine appears reasonable, but neither this mechanism nor the origin of the carbamate group have been well studied (Fig. 35.11). 

A useful method to synthesize ten and fourteen-membered ring imides 346 involved an initial condensation of macrocyclic -ketoestes 343 with alkyl or aryl isocyanates and carbodiimides, respectively, in the presence of a base [68]. After a nucleophilic attack of the enolate on the isocyanate C, the resultant amide N anion 344 induced a ring closure by addition to the keto group. Then, the intermediately formed four-membered ring 345 underwent a fragmentation... 

The reaction of 9 (generated thermally from 7 in toluene) with tetraphenyl-cyclopentadienone is more complex. Both the [6 + 2]-cycloadduct 3416), for which an X-ray structure analysis is available, and the [12 + 2]-cycloadduct 3516), whose constitution has been assigned primarily on the basis of H-NMR evidence, are obtained. The two cycloadducts presumably have a common intermediate which, in accord with the general reactivity of 9, should possess betaine character (.31 - 32) it is caused by nucleophilic attack by the carbonyl oxygen atom on the phosphorus of the heterocumulene. Ring closure of the carbanionic carbon atom... 

Whereas heating [Pt(terpy)(N3)]+ in the gas phase gives dinitrogen, heating in solution in acetonitrile or benzonitrile gives the tetrazolato complexes 14 (R = Me, Ph), presumably by nucleophilic attack by RCN at coordinated azide and subsequent closure of the N4C ring (401). 

The two reaction modes of the Michael adducts 145 demonstrate two general principles for the possible preparation of ordinary size heterocyclic compounds from the chlorocyclopropylideneacetates 1,2. Thus, either the heterocycles 153 can be formed by Michael addition of a bidentate nucleophile 150 onto the chloro ester 1-Me and subsequent ring closure of the intermediate 151 [26] by nucleophilic substitution of the chlorine atom at the newly formed sp carbon center adjacent to both the carbonyl and the cyclopropyl group (Route B in Scheme 48). Alternatively, the intermediate 151 can cyclize by nucleophilic attack on the ester moiety to give heterocycles of type 152 (Route A in Scheme 48) [26]. 

In the first proposal of a mechanism for chemiluminescent luminol oxidation, Albrecht postulates a bicyclic endoperoxide as the high-energy intermediate. The endoperoxide is presumably formed by nucleophilic attack of hydrogen peroxide monoanion on one of the diazaquinone 27 carbonylic groups to form 28, followed, after deprotonation to 29, by ring closure to 30 (Scheme 21) . 

The mechanism of the reductive ring closure by formation of a nitrogen-nitrogen bond is often closely related to the mechanism of the formation of azoxy compounds. This has mostly been formulated as an attack of the nucleophilic hydroxylamino group on the positive center in the nitroso group, followed by loss of water. Inasmuch as the system ArNO + 2 e + 2 H + ArNHOH generally is electrochemically reversible, it is not unlikely... 

Hydroxy aldehydes or ketones normally exist in equilibrium with the corresponding 2-hydroxytetrahydrofurans, which afford 2,3-dihydrofurans on dehydration. Similarly, 7-aminoketones spontaneously yield pyrrolines. From a mechanistic viewpoint the-initial cyclizations may be regarded as being initiated by nucleophilic attack of the heteroatom upon the carbonyl group. While such reactions occur with facility, their synthetic applicability is largely determined by the accessibility of appropriate precursors. A selection of examples of this type of ring closure is provided in Scheme 12. 

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