Silatranes reactions

Table 8 shows that at concentrations of 10-7 — 10 8M l-(chloromethyl)sila-trane does not affect phosphodiesterase of the rat brain and monoamine oxidase of the rat liver. At the same time, at 10 4M concentration the preparation weakly inhibits the acetylcholinesterase of the rat brain. Therefore, 1-(chloromethyl)sila-trane may be expected to produce a gentle stimulatory effect on the processes in the central and peripheral nervous system which are mediated by acetylcholine. l-(Chloromethyl)silatrane activates mildly the preparation of summarized ATP values of the rat liver. No reaction is observed with SH-groups of glutathione. 

Thus, healing of wounds treated with silatranes is accompanied by a normal reaction of the organism which is expressed by rapidly progressive anaemia and moderate leucocytosis. However, in this case all the processes advance more quickly. Furthermore, the silatranes studied suppress inflammatory processes. This is proved by the normal leucocyte content by the time of wound healing. 

The data obtained have shown that l-(chloromethyl)silatrane produces a favourable effect on the physiological processes in the organism of fowl. It increases the viability, stimulates the function of haemopoiesis thus raising the number of erythrocytes and the amount of haemoglobin. Administration of 1-(chloromethyl)silatrane stimulates metabolic reactions in the organism thus increasing the metabolism of protein, lipids, carbohydrates and phosphorus-calcium. 

The most common and convenient methods for the preparation of a variety of Si- and C-substituted silatranes are the reactions of trifunctional silanes with tris(2-hydroxyalkyl)amines (equation 1). Halo, alkoxy, acyloxy and dialkylamino groups can... 

It should be emphasized that these reactions involving two trifunctional reagents afford monomeric compounds in high yields instead of polymeric products. There is no question that the driving force of these reactions which generate the tricyclic silatrane skeleton is the formation of the transannular Si- —N bond. 

As an organosilicon component for the reaction shown in equation 1, trial-koxysilanes are used predominantly since these are widely available. The transetherihcation of phenyltriethoxysilane and tetraethoxysilane with triethanolamine [tris(2-hydroxyethyl)amine, THEA] in the presence of the basic catalyst has led to the first silatranes (equation 2)1,32. 

The exchange reactions of organyltrialkoxysilanes with THEA mostly require heating of the components in an appropriate inert solvent (benzene, toluene, xylene, anisole, chloroform, methanol, ethanol etc.) for a long time. However, in some cases the reactions can be carried out at room temperature or, if necessary, with cooling. The transetherification rates and silatrane yields increase in the presence of an alkali metal hydroxide or alkoxide as a basic catalyst. 

Organyltrialkoxysilanes can be converted to the corresponding silatranes by a one-pot reaction with bis(2-hydroxyalkyl)amines and epoxides52,69. According to Frye and... 

The reaction given in equation 2 cannot be applied for the preparation of l-(2/-haloethyl)silatranes because of -elimination leading to cleavage of the Si—C bond (equation 23)76. 

Reaction 24 does not occur with the protonated amine (i.e. with the zwitterionic form of the dihydroxyethylated amino acid) in the absence of pyridine. It seems most likely that the catalytic role of pyridine involves release of the lone-pair electrons of the nitrogen atom, that facilitates the formation of the transannular Si- —N bond and, consequently, the silatrane ring110. 

By using organyltriacetoxysilanes, which are considerably more reactive than organyltrialkoxysilanes, it is possible to obtain the corresponding silatranes by the reaction shown in equation 1 in almost quantitative yields. This method has some advantages, namely mild reaction conditions, no need for a catalyst and convenient isolation of pure products. For example, 1-alkyl- or 1-alkenylsilatranes are formed by treatment of alkyl- or alkenyltriace-toxysilanes with tris(2-hydroxyalkyl)amines in chloroform at 0°C (equation 26)37,118,119. 

A potentially more direct route to 1-organylsilatranes as compared with the conversion of organylalkoxysilanes (or organyltriacetoxysilanes) is the reaction of organyltrichlorosilanes with tris(2-hydroxyalkyl)amines or their hydrochlorides (equation 28)13,62. Thus, l-chloromethyl-3-(2, 2, 2 -trifluoroethyl)silatrane is obtained in 69% yield from chloromethyltrichlorosilane and the corresponding trialkanolamine at 10-15 °C62. 

An alternative synthetic route to silatranes is the reaction of organyl-tris(dialkylamino)silanes with tris(2-hydroxyalkyl)amines52 125. Examples are given in equation 3452. 

In wet acetonitrile electrochemical oxidation of silatranes becomes a multielectron, completely irreversible process. Participation of H2O molecules in the electrochemical reaction leads to a product of a total hydrolysis of the silatrane molecule, i.e. to Si(OH)4281. 

Kinetic studies show that hydrolysis of 1-organyl- and 1-alkoxysilatranes in neutral aqueous solutions is a first-order reaction catalyzed by the formed tris(2-hydroxyalkyl)amine13 294. As a rule, electron release and steric effects of the substituent X hinder the reaction. However, the hydrolytic stability of 1-methylsilatrane is just below that of 1-chloromethylsilatrane294. Successive introduction of methyl groups into the 3, 7 and 10 sites of the silatrane skeleton13,294 and substitution with ethyl group on C-459 retard sharply the hydrolysis rate. It was proposed294 that nucleophilic attack at silicon by water proceeds via formation of the four-centered intermediate 57 (equation 56). 

The reaction of 51 with alkali thiolates or thiols without a HI acceptor yields silatranes having a S—Si bond (equation 91)320. 

Silatrane 51 reacts with acetylenes having an electron-withdrawing substituent to give 1-alkynylsilatranes (equation 92). No reaction takes place with butylacetylene321. 

This reaction allowed one to prepare the first of the spin-labeled silatranes, (l -oxy-2, 2, 6, 6 -tetramethyl-3, 4 -dehydropiperidinyl-4 )silatrane323. 

The Si—C bond in 1-organylsilatranes is easily cleaved by bromine or iodine chloride even at — 50 °C (equation 106)329. This route is observed in CH2CI2 or CHCI3 as a solvent. By using diethyl ether-bromine, THF-bromine or dioxane-bromine adducts, a mixture of 1-halo- and 1-haloalkoxysilatranes is formed. For example, the reaction of 1-phenylsilatrane (21) with dioxane-bromine results in 1-bromosilatrane (50) and l-[2 -(2"-bromoethoxy)ethoxy]silatrane (73) in 39% and 12% yield, respectively (equation 107)329. 

The reaction of 1-allylsilatrane (76) with 0,0-diethyldithiophosphoric acid in CHCI3 at room temperature gave 0,0-diethyl S-(silatran-l-yl)dithiophosphate (81) in low yield (15%) instead of the terminal adduct (equation 116)109. 

Both l-(butadien-l, 3 -yl)silatrane (93) and -trialkoxysilane can react by a Diels-Alder-type reaction with tetracyanoethylene (TCNE) or maleic anhydride (MA) to give the corresponding adducts (equations 129 and 130). However, a higher temperature is required for effective conversion of trialkoxysilane355. 

A variety of onium salts (101-103) are formed by reaction of l-(iodomethyl)silatrane with tertiary amines358, triorganylphosphines360 or diorganylchalcogenides (equation 137)92,361,362 ... 

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