Steric effects with amines

Ten years ago Rorabacher (13) observed the substitution rate constants for aquonickel(II) ion with different amines (Table II). There is a decrease in the rate constants by a factor of 14 in going from ammonia to dimethylamine. If nickel-(II) substitution reactions are dissociative, then why is the effect this large Is this a steric effect with some associative contribution or is it an outer-sphere effect There has been surprisingly little investigation of the nature of the entering ligand so far as its bulk or its nucleophilicity is concerned even for what have been generally considered as simple substitution reactions. 

In conclusion, the use of amines for the characterization of adsorption and active sites raises the same problems as ammonia. The interaction of the amines, saturated aliphatic amines in particular, with oxide surfaces is certainly still less specific than that of ammonia because of their higher basicity and their larger molecular size. The influence of steric effects on amine adsorption has been discussed (172, 201b). Thus, Medema et al. (172) came to the conclusion that the adsorbed amount of an amine on 7-Al2 03 primarily depends on its molec-... 

A limited application of Lewis adds has been made in analyses of amines boron trifluoridetitanium tetrachloride, and tin tetrachloride were used to titrate heterocyclic bases in aprotic solvents. Other applications coimected with steric effects in amines will be discussed in section IV.C.4. 

The shade may be varied by choosing amines. For aromatic amines, the steric effect of substituents in the ortho position reduces the conjugation of the anibno group with the anthraquinone moiety, and the result is a hypsochromic shift and brighter shade. Thus Cl Acid Blue 129 (120) has a more reddish and brighter shade than Cl Acid Blue 25 (118). Cycloalkylamines have a similat effect on the shade. Cl Acid Blue 62 [5617-28-7] (125) Cl 62045) is an example. 

Some authors use O] instead of cr as the substituent constant in such correlations.) An example is provided by the aminolysis of phenyl esters in dioxane the substrates RCOOPh were reacted with -butylamine, and the observed first-order rate constants were related to amine concentration by = k2 [amine] kj [amine]. The rate constants kz and k could be correlated by means of Eq. (7-54), the reaction constants being p = +2.14, b = + 1.03 (for A 2) and p = -1-3.03,8 = -1-1.08 (for ks). Thus, the two reactions are about equally sensitive to steric effects, whereas the amine-catalyzed reaction is more susceptible to electronic effects than is the uncatalyzed reaction. 

The Bsmoc derivative is formed from the chloroformate or the A -hydroxy-succinimide ester. It is cleaved rapidly by a Michael addition with tris(2-aminoethyl)amine at a rate that leaves Fmoc derivatives intact. More hindered bases, such as A -methylcyclohexylamine or diisopropylamine, do not react with the Bsmoc group, but do cleave the Fmoc group, illustrating the importance of steric effects in additions to Michael acceptors. 

On the theoretical side, study of the dissociation of addition compounds of amines with trimethylborane, boron trifluoride, and borane provide a new quantitative approach to steric strains. These studies quickly removed doubts as to the importance of steric effects in chemical behavior. 

The enamines derived from cyclohexanones are of particular interest. The pyrrolidine enamine is most frequently used for synthetic applications. The enamine mixture formed from pyrrolidine and 2-methylcyclohexanone is predominantly isomer 17.106 A steric effect is responsible for this preference. Conjugation between the nitrogen atom and the tt orbitals of the double bond favors coplanarity of the bonds that are darkened in the structures. In isomer 17 the methyl group adopts a quasi-axial conformation to avoid steric interaction with the amine substituents.107 A serious nonbonded repulsion (A1,3 strain) in 18 destabilizes this isomer. 

The reaction of 5a-bromo-a-tocopherol (46) with amines was further elaborated into a procedure to use this compound as a protecting group Toe for amines and amino acids (Fig. 6.35).62 The protection effect was due to a steric blocking of the amino function by the bulky tocopheryl moiety rather than due to conversion into a non-nucleophilic amide derivative, and the Toc-protected amino acids were employed in the synthesis of dipeptides according to the dicyclohexylcarbodiimide (DCC) coupling method.64 The overall yield of the reaction sequence was reported to be largely dependent on the coupling reaction, since both installation and removal of the... 

The results obtained with different amines cannot be explained merely on the effects of amine basicity. Thus, to obtain complete hydrogenation of Q to DHQ, the basicity has to be tailored by other factors such as the steric hindrance of the amine and its electronic interaction with the catalyst active sites this seems to be favored by the presence of an electron-rich aromatic ring. Of note, the positive effect of substituted aromatic amines, with a 49% DHQ yield being obtained for ethylanilines, is independent of the substituent position of the alkyl group. 

Thus acid chlorides and anhydrides react readily with ROH and NH3 to yield esters and amides, respectively, while esters react with NH3 or amines to give amides, but the simple reversal of any of these reactions on an amide, though not impossible, is usually pretty difficult. The relative reactivity will also depend on both the electronic and, more particularly, the steric effect of R. A slightly unusual leaving group is eCX3 (e.g. eCI3) in the haloform (158) reaction (cf. p. 297) ... 

Angelici and Brink (40) have found that in the reactions of amine with trans-M(CO),(PPhMe2)2+ (M = Mn or Re), the rate of carbamoyl formation follows the order, n-butylamine > cyclohexyl-amine >, isopropylamine > sec-butylamine >> tert-butylamine, implying a strong steric effect in carbamoyl formation. A similar order has been observed in the rate of reaction of organic esters with amines to form amides (41). The data in Table III indicate that a steric effect may be operative in the Ru (CO) /NR3-catalyzed WGSR, since with tertiary amines the rate follows the order, NMeQ > MeNC.H > NEt > NBu0, which does not reflect the basicity of these amines. 

As pyramidal amides5,32 their Sn2 reactivity with neutral nucleophiles like /V-methylaniline parallels that of a-haloketones with amines, which, as described in an earlier section, are also strongly affected by steric effects on the a -carbon.183 SN2 reactions are in general strongly and adversely influenced by steric effects and branching / to the reactive centre and the same appears to be true for /V-acyloxy-/V-alkoxyamides 30b and 29a-e. Broadly speaking, their mutagenic activity is affected similarly. 

The lack of clear-cut hallucinogen-type activity for the 2-aminotetralins could be explained in several ways. The known deleterious effect of molecular bulk in the alpha-position would seem to direct attention to the steric effect of the reduced ring of the tetralins as detrimental to activity. In 18b, however, it has been noted (156) that the 5-methoxy group is forced out of plane by the adjacent 6-methyl and 4-methylene groups. The importance to activity of maintaining the methoxy groups coplanar with the aromatic ring has been emphasized earlier. Both substituent orientation and N-alkylation must also be important to activity, and it may not be realistic to make direct comparisons between the phenethyl-amines and the 2-aminotetralins. 

In one case, the intermolecular Heck reaction of 3-pyridyltriflate with ethyl acrylate was accelerated by LiCl to give 159 [127,128], Here, both electronic and steric effects all favored p-substitution. In another case, however, electronic effects prevailed and complete a-substitution was observed. In the presence of an electron-donating substituent (i.e., a protected amine), 3-bromopyridine 160 was coupled with f-butoxyethylene to give 3-pyridyl methyl ketone 162 [126]. The regiochemistry of the Heck reaction was governed by inductive effects, leading to intermediate 161. 

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