Substituent additivity

4)Isotope effects are cumulative (first rule of the geometric mean) 

5)Equivalent Isomers have the same Isotope chemistry. 

For the complete calculation of ln(s/s )f directly from atomic masses and molecular structure, G matrices, and molecular forces, F matrices. It is necessary to relate the modulating co- 

ACS Symposium Series American Chemical Society Washington, DC, 1975. 

Thus the C-C stretching force constant, 5.09 mdyne A , contributes 0.035 to ln(s/s )f in ethane at 300 K while each of the three C-H stretching force constants, 4.70 mdyne k, contributes but 0.016 to the same quantity. Up to terms in W A.Z6 u we can write  

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More convenient is the use of aryl a2ides which are readily converted into isocyanates upon heating in nonreactive solvents via the loss of nitrogen. The latter method is useful for the synthesis of isocyanates with additional substituents which could not be prepared with phosgene (20). 

When additional substituents ate bonded to other ahcycHc carbons, geometric isomers result. Table 2 fists primary (1°), secondary (2°), and tertiary (3°) amine derivatives of cyclohexane and includes CAS Registry Numbers for cis and trans isomers of the 2-, 3-, and 4-methylcyclohexylamines in addition to identification of the isomer mixtures usually sold commercially. For the 1,2- and 1,3-isomers, the racemic mixture of optical isomers is specified ultimate identification by CAS Registry Number is fisted for the (+) and (—) enantiomers of /n t-2-methylcyclohexylamine. The 1,4-isomer has a plane of symmetry and hence no chiral centers and no stereoisomers. The methylcyclohexylamine geometric isomers have different physical properties and are interconvertible by dehydrogenation—hydrogenation through the imine. 

Replacement of the benzene ring by other ring systems, or the introduction of additional substituents, decreases or aboHshes activity. 

Fischer projection formulas can be used to represent molecules with several stereogenic centers and are commonly used for caibohydrates. For other types of structures, a more common practice is to draw the molecule in an extended conformation witii the main chain horizontal. In this arrangement, each tetrahedral caibon has two additional substituents, one facing out and one in. The orientation is specified widi solid wedged bonds for substituents facing out and with dashed bonds for substituents that point in. 

Reductions by NaBKt are characterized by low enthalpies of activation (8-13kcal/mol) and large negative entropies of activation (—28 to —40eu). Aldehydes are substantially more reactive than ketones, as can be seen by comparison of the rate data for benzaldehyde and acetophenone. This relative reactivity is characteristic of nearly all carbonyl addition reactions. The reduced reactivity of ketones is attributed primarily to steric effects. Not only does the additional substituent increase the steric restrictions to approach of the nucleophile, but it also causes larger steric interaction in the tetrahedral product as the hybridization changes from trigonal to tetrahedral. 

Grignard reagents do react with epoxides 24 by an SN2-mechanism, resulting in a ring-opening reaction. An epoxide carbon bearing no additional substituent—i.e. a methylene group—is more reactive towards nucleophilic attack than a substituted one ... 

The Schiemann reaction seems to be the best method for the selective introduction of a fluorine substituent onto an aromatic ring. The reaction works with many aromatic amines, including condensed aromatic amines. It is however of limited synthetic importance, since the yield usually decreases with additional substituents present at the aromatic ring. 

When additional substituents are introduced in the 2- and/or 4-position, the thermal rearrangement gives products in which the substituents that were originally located in the 1- and 5-position of the quadricyclane are then located at C4 and C5 of the oxepin 7.30,123 In order to trap intermediates of this rearrangement reaction by intramolecular cycloaddition vinyl and acetylene groups were linked with different spacer groups to C2 of quadricyclane.123 In this manner two different intramolecular cycloadducts were isolated in addition to oxepin derivatives.123... 

Replacement of the carbaldehyde function by other carbonyl groups is successful and leads to the formation of bcnzazcpincs bearing additional substituents at the 1- and 5-positions.100 For example, 1,2-dibenzoylbenzene (69) and TV.A -bisIcyanomethyOisopropylamine yield the pentasubstituted 3/7-3-benzazcpinc 70. However, condensations with other bis(cyanomethyl)-alkylamines and with bis(cyanomethyl)arylamines produce only acyclic condensation products. 

Superphthalocyanines are the products of the cyclopentamerization of phthalonitrile212 or of phthalonitriles with additional substituents.70113 The formation of structural isomers occurs if these precursors are unsymmetrically substituted at the benzene nucleus, (cf. p736). 

The presence of an additional -substituent engenders the possibility of formation of the ( > and (Z)-isomers. The (F)-isomers, ( >3, are formed preferentially with E/Z ratios often exceeding 90 10. Both methoxy and acetoxy derivatives may be isolated and chromatograph-ically purified prior to the elimination reaction. 

The presence of additional substituents at the a- or [1-sites of the starting /i-methoxy or / -acetoxy complexes 4 has a somewhat detrimental effect upon the yield of the elimination step, but the reaction nevertheless proceeds to provide a,/J-unsaturated complexes28. 

Enhanced anti selectivity is observed in reactions of lithiated 4.5-dihydrooxazoles bearing an additional substituent which facilitates the formation of rigid azaenolates by internal chelation of lithium13. Thus, reaction of 2-ethyl-4,5-dihydro-4,4-dimethyloxazole (10) with 2-methylpropanal gives a 56 44 mixture of adducts while (R)-2-ethyl-4,5-dihydro-4-(methoxymethyl)-oxazolc (12) reacts with the same aldehyde to yield a 90 10 mixture of adducts 1313. 

Figure 2.74 Relationship between i/(C-0) for rrans-IrCl(CO)(PPhi)2 (in CHC13 solution) and Xi (Tolman s additivity substituent contribution for electronic effects in R3P). (See Chem.

The trend in relative effectiveness of RAFT agents with varying Z is rationalized in terms of interaction of Z with the C=S double bond to activate or deactivate that group towards free radical addition. Substituents that facilitate addition generally retard fragmentation. O-Alkyl xanthates (Z=0-alkyl, Table... 

A Diels-Alder reaction of arynes with 1,2,4-triazines 102 allows the preparation of isoquinolines substituted with electron-withdrawing groups in the nitrogen-containing ring. The isoquinoline-1-carboxylic esters bearing additional substituents are of particular interest because they are not readily available by the usual routes [100,101] (Scheme 2.42). 

From the and p values of Tables II, VI, and VIII, data for additional substituents may be used to obtain the various Or parameters. A number of secondary substituent parameters so derived are summarized in Table XXVI. The Or values are rounded values obtained from the indicated data. The oj parameters are based upon m-FC6H4X F-nmr shifts. The results in Table II are untested, of course, and should be used with due caution. 

The possibility of reticulating the materials by carefully introducing additional substituent groups in the polymer during the synthetic process (1-2% or less), prone to undergo selected reactions (e.g. allylic double bonds [576-579]), and/or by addition of appropriate external additives (e.g. sulfur [578] or hydroperoxides [531,576-578,580]) to these polymers... 

Further detailed investigations towards new chiral ruthenium catalysts that could enhance enantioselectivity and expand the substrate scope in asymmetric RCM were reported by Grubbs and co-workers in 2006 [70] (Fig. 3.24). Catalysts 59 and 61, which are close derivatives of 56 incorporating additional substituents on the aryl ring para to the ort/to-isopropyl group, maintained similar enantioselectivity than 56b. However, incorporation of an isopropyl group on the side chain ortho to the ortho-isopropyl group 60 led to an increase in enantioselectivity for a number of substrates. 

Introduction of an additional substituent such as alkyl, alkoxy, halogen, etc. at 3 -position has a large effect on color. That is, green color changes to red color when there is a tertiary amino group at 2 -position. Thus, 2 -dibenzylamino-6 -diethylamino-3 -methylfluoran (47 R1 = H, R2 = CH3 ),40 2 -dibenzylamino-6 -diethylamino-3 -ethylfluoran (47 R1 = H, R2 = C2H 5),34 3 -chloro-2 -dibenzylamino-6 -diethylaminofluoran (47 R1 = H, R2 = Cl),34 6 -((V-ethyl-4-methylanilino)-3 -methyl-2 -((V-methylanilino)flu-... 

An example of this reveals an additional substituent effect (Fig. 2.18).121 Ordinarily, the phenyl and carboxyl groups anchor the double bond approximately equally (notice the sixth entry in Table 2.3 and cinnamic acid in Fig. 

When the electron demand of a,p-unsaturated carbonyl compounds is weakened by additional substituents in P-position, the double bond returns to normal behavior as far as cyclopropanation is concerned. Some recent examples, displayed in Scheme 21, may illustrate this point. 

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