SnH reactions

The number of similar cyclizations, including tandem and cascade sequences where an SnH reaction is a key step, has been considerably increased. As a rule, they are easily performed allowing at times the synthesis of complex polynuclear heterocycles in one step. The present paper, which summarizes about 130 articles on this topic, shows SnH cyclizations to be a very promising strategy for heterocyclic ring annulations. 

There are three groups of substrates for which SNH reactions are especially characteristic (i) neutral azines and azoles (ii) azinium and azolium salts and (iii) nitro-arenes. Their electron-deficiency and, thus, their ability to react with nucleophiles strongly differ from each other. Azinium salts are the more electrophilic and are able to add even neutral nucleophiles very easily. Triazines,. v-tetrazines and polynitro-arenes also possess high electrophilicity. At the same time substrates such as pyridine (82JHC1285, 72JA682) and cinnoline (03CHE87), at a low temperature (e.g. in liquid ammonia as a solvent), do not react even with sodium amide. It should also be... 

All heterocyclizations based on SnH reactions can be conveniently divided into... 

Tandem cyclizations initiated by an SnH reaction in which subsequent heteroring closure is realized by an intramolecular addition to a multiple bond, a condensation or an SN ipso substitution. 

Tandem SNH-SNH cyclizations when a hetero-ring annulation is a result of two consecutive SNH reactions. 

Complex multi-step cyclizations when the SNH reaction initiates several other processes sometimes including repeated SNH reactions, classified as cascade sequences (96CRV137). 

There are several examples of pyridine ring closure by an intramolecular oxidative SnH reaction in accordance with cyclization Schemes A and B ... 

B. Tandem Cyclizations Initiated by an SnH Reactions 1. Tandem S H Reactions and Addition to Multiple Bonds... 

As in the above tandem reactions, cascade sequences of this type are normally initiated by an SNH reaction. They differ from the former by having a larger number of stages and greater variety. Practically always this complexity is caused by involvement of functional groups, as a rule, via redox processes. For some time such cascades were known only for nitro derivatives of arenes and hetarenes. However, recently some novel substrates and cascade sequences have been discovered. 

T7669). Apparently, the first-formed intermediates 323 fail to cyclize into imidazolines 324 due to insufficient stability and steric hindrance. Instead, they lose a propylamine molecule giving enamine 325 that is then converted into pyrrole 236 via the oxidative SNH reaction. Interestingly, the sequence of steps leading to the pyrrole ring annulation in this case is opposite to that in the reaction of pyrimidopyridazine 227 with enamines (see Scheme 69). 

A.V. Gulevskaya and A.F. Pozharskii (Rostov State University, Russia) write on nucleophilic aromatic substitution of hydrogen, concentrated on the use of this reaction for heterocyclic ring annulation. It covers particularly the recent extension of the general SnH reaction to effect ring annulation. 

Amination of azaaromatic compounds using liquid ammonia-potassium permanganate (85S884 86MI1) has been found to be a successful method for preparing a number of 5-amino-l,2,4-triazines (Scheme 73). This SNH reaction is based on the ability of 3- and 6-substituted triazines to form amino adducts 22 at C-5 in liquid ammonia (see Section III,A,2 and Scheme 18). These adducts can be oxidized into 5-amino-1,2,4-triazines 126. A number of 1,2,4-triazines containing substituents at C-3 and C-6,... 

A rare example of an SNH reaction at C-6 has been found when triazin-ium salts 128 were reacted in alkaline solution in the presence of air oxygen. It yielded the l,2,4-triazin-6-ones 130, the formation of which must be initiated by the addition of the hydroxide ion at C-6, i.e., via the intermediacy of the C-6 adducts 129 (Scheme 74) (7ICC 1636). 

The specific nature of 1,2,4-triazine /V-oxides discussed in Section II,C is also manifested in the SNH reactions. Treatment of 1,2,4-triazine 2-oxides containing electron-donating groups at C-3 with methanol, ethanol, or isopropanol in the presence of hydrochloric acid results in 6-alkoxy-substituted 1,2,4-triazines 137 (Scheme 77) (77JOC3498). The reaction is proposed to involve the addition of alcohol to C-6 of the hydroxy-1,2,4-triazinium cation 135, followed by elimination of water. The presence of an electron-donating group at C-3 seems also to be important because it contributes considerably to the stabilization of the intermediate cationic species 136 (Scheme 77). 

A series of 5-substituted 3-methylisoxazole[5,4-cf]tl,2,3]triazin-4-one derivatives has been synthesized to test their potential immunological activity <04AP81>. The utility of l-N,N-dimethylaminopent-l-en-3-one in the synthesis of new l,2,4-triazolo[3,4-c]fl,2,4 triazines has been described <04JCR(S)174>. Synthesis of new 8-aryl-l,2,4-triazolo[l,5-. The synthesis of triazolotriazine 59 by a cyclization reaction of A-aminotriazole 58 and triethyl orthoformate has been achieved <04KGS130>. 

Regioselectivity in SnH reactions of some 3-nitro-l,5-naphthyridines with... 

The SnH reaction of C-nucleophiles with l,2,4-triazine-4-oxides has, in recent years, been extended to many other nucleophiles. For example, Kozhevnikov et al. (06TL869) have used the methodology to introduce aromatic- 50, heteroaromatic- 52 and carborane-substituted 51 triazines (Scheme 18). As discussed in Section 2.3 (Scheme 8) acetone cyanohydrin can be used to introduce a nitrile moiety by SnH (08JMC1703, 05IZV2122). 

The Chichibabin amination reaction, first reported by Chichibabin and Zeide in 1914, is simply a reaction for the introduction of an amino group to azines. This is one of the first examples of nucleophilic hydrogen substitution (SnH) reactions and is considered one of the most influential reactions in heterocyclic chemistry transformations of pyridines and azines in the 20th century. " ... 

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