Inversion with amines

The SnI reactions do not proceed at bridgehead carbons in [2.2.1] bicyclic systems (p. 397) because planar carbocations cannot form at these carbons. However, carbanions not stabilized by resonance are probably not planar SeI reactions should readily occur with this type of substrate. This is the case. Indeed, the question of carbanion stracture is intimately tied into the problem of the stereochemistry of the SeI reaction. If a carbanion is planar, racemization should occur. If it is pyramidal and can hold its structure, the result should be retention of configuration. On the other hand, even a pyramidal carbanion will give racemization if it cannot hold its structure, that is, if there is pyramidal inversion as with amines (p. 129). Unfortunately, the only carbanions that can be studied easily are those stabilized by resonance, which makes them planar, as expected (p. 233). For simple alkyl carbanions, the main approach to determining structure has been to study the stereochemistry of SeI reactions rather than the other way around. What is found is almost always racemization. Whether this is caused by planar carbanions or by oscillating pyramidal carbanions is not known. In either case, racemization occurs whenever a carbanion is completely free or is symmetrically solvated. 

We conclude this section with a discussion of inversion of amines of the type NR.jR.2R375>76). In general this process is too rapid to be studied except in special circumstances 100). Nevertheless, Saunders and Yamada 101 were able to determine the very high rate of inversion of dibenzylmethylamine (Fig. 50) (k = 2x 10s sec-1 at 25 °C) by the elegant trick of partially neutralizing the amine with hydrochloric acid. Since the hydrochloride cannot invert, the benzylic protons in it are diastereotopic and hence anisochronous. Only the small amount of free amine in equilibrium with the salt at a given pH (the measurements were carried out on the acid side) inverts at the rate indicated and it can be easily shown i01) that kobs. = k [amine]/[salt + amine] where kobs. is the observed rate of site exchange of the diastereotopic protons at... 

The diazepinone (127) reacted with benzoyl chloride to give the A,Ar -dibenzoyl derivative137 and was brominated in acetic acid at 20°.138 Compounds 127 and 128 undergo the bis-semidine inversion when heated with 3% hydrochloric acid.117 The thione (128) is converted in high yield into the methylmercapto diazepine (126, R = SCH3) by reaction with methyl iodide in tetrahydrofuran.129 The thione does not react with amines, but the 6-methylmercapto compound on heating with amines or amine hydrochlorides gave rise to the 6-amino compounds (126, R = NR R")120 A number of these amino derivatives have exhibited some medicinal activity. With -butanol the 6-methylmercapto compound is quantitatively converted into 127.120... 

The oxonium ions are isoelectronic with amines and both have similar structures. The activation energy for the inversion of the isopropyloxiranium cation (AE" " =10 + 2 kcal mole ) is close to that of N-phenylaziridine (AE = 12 kcal mole ) X The angle between the aziridine ring and the phenyl substituent is 0 = 125 It agrees well with CNDO-2 calculations (0 = 124") for the methyloxiranium cation... 

Various amines were tested near neutrality for thiocarbamylation catalysis (Table IV). Amine pKa varied directly with reaction rate, and inversely with the percentage of correct product. Rapid reaction in the absence of tertiary amine suggested another activation pathway for thiocarbamylation. 

Ring openings of epoxides with various nucleophiles are catalyzed by acid or base and are accompanied by configurational inversion on the substituted carbon (23). Posner found that y-alumina facilitated nucleophilic ring openings of epoxides with amines, alcohols, and carboxylates to give P-functionalized alcohols stereospecihcally (trans) in good yields under mild reaction conditions (24). This catalytic behavior of alumina was assumed to be due to the cooperative function of acidic and basic sites on alumina. 

Third, the AH" and AS" valnes of many hydrogen-bonded complexes have been obtained from van t Hoff plots where the temperature range AT was nsnally too small. Enthalpies and entropies calcnlated with AT = 10° for the complexes of 4-nitrophenol with amines are inevitably less reliable than those calcnlated with AT = 78° for snbstitnted phenols hydrogen-bonded to dhnethylacetamide or with AT = 57° for snb-stimted phenols complexed with diphenyl snlfoxide , simply becanse the error in AH" is inversely related to AT. 

These are compounds that can be added to the electrolyte to alter the direction and rate of the electro-osmotic flow. Flow rate varies inversely with ionic strength and is independent of column diameter. The effect of pH between 2 and 12 and applied potential increase the electro-osmotic flow rate linearly. The flow can be reversed by adding quaternary amines, such as cetyltrimethylammonium bromide or tetradecyl-trimethylammonium bromide. Zero flow occurs when 5-benzyIthiouronium chloride is added to the buffer. Organic molecules such as methanol and putrescine reduce the flow, whereas acetonitrile increases the flow. Covalently bonded polyethylene glycol reduces the flow. 

Functionalized aziridines, especially optically active ones, are important intermediates in organic synthesis. The reaction of cyclic sulfates prepared from homochiral diols with amines or azide ion provides an efficient route to homochiral aziridines (equation 56). Formation of aziridines from cyclic sufates occurs with inversion at the stereogenic center. The reaction of the cyclic sulfates with an excess of a primary amine gives /2-... 

S )-0-Ethyl O-phenyl pho.sphorochloridothioate reacts with amines with inversion of configuration at phosphorus the resultant phosphorothioic amides undergo acid hydrolysis... 

In contrast with amines, the inversion at the phosphorus atom in phosphanes is much more hindered and, therefore, the influence of the lone pair of electrons at the phosphorus atom becomes more readily apparent if the substituents prefer a particular orientation. This can be enforced by using bulky substituents (Scheme 27). The effect has first been observed for /( P, C) in aminophosphanes, where the J values are large and positive for a sy/j-orientation and small and negative for anti-orientation of the respective N-C bonds and the assumed orientation of the lone electron pair at the phosphorus atom. The analogous stereochemical dependence is observed for V( P,N, Si) as shown for the A-silylaminophosphanes 135 and 136 (Scheme 27). ... 

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