Ortho effect refers to the interaction between adjacent substituents in the benzene ring, which significantly changes the activity of the group and the physical and chemical properties of the molecule.This effect does not exist in meta and para compounds.Neighborhood effects include spatial hindrance, inductive effect, field effect and bonding ability between substituents.
Ortho effect refers to the interaction between adjacent substituents in the benzene ring, which significantly changes the activity of the group and the physical and chemical properties of the molecule.This effect does not exist in meta and para compounds.Neighborhood effects include spatial hindrance, inductive effect, field effect and bonding ability between substituents.[1]
Substitution reaction
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1. Nucleophilic substitution reaction.It is called SN for short.There are many nucleophilic substitution reactions on saturated carbon.For example,HaloalkaneCan be separated fromsodium hydroxide, sodium alkoxide or sodium phenolate, thiourea, sodium mercaptanCarboxylateNucleophilic substitution reaction with ammonia or amine to produce alcohol, ethermercaptan、Thioether, carboxylic acid ester and amine, etc.Alcohols can react with hydrohalide acid, phosphorus halide or sulfoxide chloride to generate halogenated hydrocarbons.Haloalkanes are reduced to alkanes by lithium aluminum hydride, which is also the substitution of negative hydrogen ions for halogens in the reactants.When the nucleophilic atom of the reagent is carbon, the substitution result forms a carbon carbon bond, thus obtaining a carbon chain growth product, such as haloalkanes andSodium cyanide, sodium alkyne or enolate.Due to the difference in the structure of reactants and reaction conditions, SN has two mechanisms, namely, single molecule nucleophilic substitution reaction SN1 and bimolecular nucleophilic substitution reaction SN2.
2. The process of SN1 is divided into two steps: the first step is bond cracking of reactants（ionization）To generate active intermediate carbonium ion and leaving group;In the second step, positive carbon ions quickly combine with reagents to form products.The total reaction rate is only proportional to the concentration of reactants, and has nothing to do with the concentration of reagents.SN2 is a synergetic process of old bond breaking and new bond formation.The reaction rate is proportional to the concentration of reactants and reagents.The reactants that can generate relatively stable positive carbon ions and leaving groups are prone to SN1, and the reactants with small space hindrance of central carbon atoms are prone to SN2.If the nucleophile showsalkalinity, nucleophilic substitution reaction is often accompanied by elimination reaction, and the ratio of the two depends on the structure of reactantsreagentProperties and reaction conditions.Low temperature and weak alkalinity are favorable for SN substitution.
3. Aromatic substitution reaction.There are two types of aromatic electrophilic substitution reaction SEAr and aromatic nucleophilic substitution reaction SNAr. Ar represents an aryl group.Aromatics can be introduced into the aromatic ring through nitration, halogenation, sulfonation, alkylation or acylationNitro, halogen atomSulfonic groupandalkyloracyl, these are SEAr.Compounds with substituents on the aromatic ring, and substituents can locate the attack of reagents.When the substituents on the benzene ring are electron donating groups and halogen atoms, the electrophilic reagents are more likely to enter their ortho and para positions;When the substituent is electron withdrawing group, it is mainly to obtain meta product.In addition, in addition to these normal reactions, sometimes the reagent can attack the position of the original substituent and replace it, which is called in situ substitution.SNAr can only be performed under certain conditions.For example, halogenated aromatics are generally not prone to SNAr, but when halogen atoms are activated by ortho or para nitro groups, they are easy to be replaced.Halogenated aromatic hydrocarbons can also be substituted under strong alkali conditions.In addition, the aromatic diazonium salts become stable molecular nitrogen due to the cleavage of the leaving group, which is conducive to the formation of phenyl positive ions, and can also undergo a reaction similar to SN1.
4. Homolytic substitution reaction.It is called SH for short.It refers to the reaction between a free radical and an atom in the reactant molecule to generate a product and a new free radical.This reaction is usually a chain transfer step of free radical chain reaction.Some organic substances will be automatically oxidized in the air, and the process is also homolytic substitution, such as benzeneformaldehyde、CumeneandTetralinAnd oxygen can generate corresponding organic peroxides respectively.[1]
Steric effect
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The steric hindrance effect mainly refers to the steric hindrance caused by the proximity of some atoms or groups in molecules.For example, steric hindrance in enzyme reaction will reduce its catalytic activity.In coordination compounds, when some large groups are introduced into a ligand, the steric hindrance will affect its formation of coordination compounds with the central atoms.The fact that space has an impact, each atom occupies a certain space in the molecule.If the atoms are too close, two adjacent atoms will form overlapping electron clouds (shown as repulsion), which may affect the reaction of molecules and preferred shapes (structures).
The effect of affecting the molecular reaction activity because the atoms or groups near the reaction center occupy a certain space position.The space effect of reducing molecular reaction activity is called "space obstruction".For example, the esterification of ortho disubstituted benzoic acids is much more difficult than that of unsubstituted benzoic acids.Similarly, ortho disubstituted benzoates are also difficult to hydrolyze.This is because the adjacent group occupies a large space position, which hinders the attack of reagents (water, alcohol, etc.) on carboxyl carbon atoms.On the contrary, in the process of transforming reactants into active intermediates, if the space crowding degree of reactants is reduced, the reaction speed can be improved.This spatial effect is called "spatial synergy".For example, tert butyl cation is easier to form than methyl cation, because the space crowding degree is much lower in the reaction of forming tert butyl cation, while the space crowding degree is relatively lower in the reaction of forming methyl cation.Spatial effect is an important factor affecting the organic reaction process.Steric hindrance effect is also called stereoscopic effect.It mainly refers to the space obstruction caused by the proximity of some atoms or groups in the molecule and the tension in the molecule caused by the deviation from the normal bond angle.For example, steric hindrance in enzyme reaction will reduce its catalytic activity.In coordination compounds, when some large groups are introduced into a ligand, the steric hindrance will affect its formation of coordination compounds with the central atoms.For example, ethylenediamine (abbreviated as en in coordination chemistry) is easy to generate diethylenediamine copper (II) ion [Cu (en)two]2+, but N, N, N ', N' - tetramethylethylenediamine (tmen) cannot generate [Cu (tmen)] due to the large steric hindrance of two methyl groups on each Ntwo]2+。Space hindrance will generally reduce the reaction rate. For example, in the bimolecular nucleophilic substitution reaction of bromoalkanes, the increase of alkyl volume will cause space hindrance and reduce the reaction rate.However, in some reactions, the steric effect may increase the reaction rate. For example, in the single molecule nucleophilic substitution reaction, when the alkyl of trialkyl substituted haloalkanes increases, due to the space repulsion between substituents, the heterolysis of the carbon halogen bond will occur, leading to the formation of carbon positive ions, thus improving the reaction rate.
The spatial hindrance of adjacent groups can affect the symmetry of molecules.The spatial hindrance of adjacent groups can transform - NHtwo、─NOtwoIsoconjugated groups are excluded from the conjugated system of benzene ring, which greatly changes the static physical and chemical properties of molecules such as bond length, polarity, acidity and alkalinity of the compound.[1]
Induced effect
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To replace benzene ring carbon atomschemical shiftBased on the parameters of methyl induction effect and conjugation effect that were set and initially confirmed, the induction effect, conjugation effect and localization effect of methyl substituents were discussed.The induced effect parameter indicated by the chemical shift value indicates that methyl has electron absorption induced effect, and the corrected chemical shift value indicates the conjugation effectParameter tableMingmethyl has weak electron donorConjugate effect, and even its conjugation effect may be in the critical state of electron donor and electron acceptor. In short, relative to the hydrogen atom,methylIt has electron absorption effect.Methyl has strong para positioning effect and weak ortho positioning effect, and under appropriate conditions, substitution reaction may also occur in the meta position.
Due to the inductive effect of chlorine atom, the acidity of compound e is greater than that of compounds f and g.In compound h and i, because compound h is mainly intermolecular hydrogen bond, its boiling point can reach 295 ℃, while compound i is mainly intramolecular hydrogen bond, its boiling point is only 214 ℃.Neighborhood effect also affects the reaction rate and mechanism.For example, compound j can react with iodomethane to formQuaternary ammonium salt, but in compound k, due to the space hindrance of two adjacent methyl groups, - N (CHthree）twoThe group plane deviates from the benzene ring plane, making it extremely difficult for compound k to form quaternary ammonium salt.Under normal conditions, the esterification rate of compound 1 is much slower than that of compounds m and n.However, in concentrated sulfuric acid, due to the formation of positive carbon ions, the attacking group can attack the reaction center from the direction perpendicular to the benzene ring, so the esterification reaction of compounds can proceed smoothly.At this time, the esterification mechanism has changed.
In a certain reaction process, adjacent groups are partially or completely bonded to the reaction center, which significantly increases the reaction rate. This neighborhood effect is attributed to the participation of adjacent groups.Because of the involvement of adjacent groups, the chlorine in compound p is easily hydrolyzed in boiling water, but compound q is stable under the same conditions.
Because of this special effect of neighboring groups, the influence of neighboring groups on molecular properties does not followHamitt equation。[1]
field effect
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Transferred directly through space and solvent moleculesElectronic effect。Field effect is a kind of long distance polar interaction, which is the polar effect when the distance exceeds two C-C bond lengths.The action direction of field effect is often the same as that of induced effect, so it is difficult to distinguish the two effects.R. Gordon and LM. Stoke measured the ionization constants [kg] of the following polycyclic acidstwo]p: When X=H, p is 6.04;When X=Cl, p is 6.25;When X=COOCH, p is 6.20.In the above molecules, there are four single bonds between X group and COOH group, and the induction effect of X group has little effect on the change of p.In addition, intramolecular formationhydrogen bondIt is also very unlikely.Therefore, the difference in p of the above compounds can be explained by the field effect.When X=Cl and COOCH, their p is greater than that when X=H. The reason is that the group X absorbs electrons and forms a dipole C-X field effect, which directly affects the ionization of COOH through space or solvent molecules.The field effect is also related to the moleculargeometryofFor example, the p and esterification reaction rate constants of the following two compounds are different, and their order is a>b.In compounds a and b, the induction effect of chlorine atoms on COOH is the same, and the same number of C-C bonds are inserted between the two groups.But their field effects are different. The interaction distance between the chlorine atom in compound b and COOH through space is closer than that of compound a, so the interaction distance of aacidityLarger.This shows that the field effect does exist.[2]
application
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Application of benzoic acid: the effect of benzoic acid on the activity of monophenolase and diphenolase of mushroom tyrosinase and the inhibition mechanism.The research results show that benzoic acid hasMushroomBoth monophenolase and diphenolase activities of tyrosinase are inhibited, and the effect is reversibleInhibitory effect。Determine the inhibitor concentration (IC) that leads to 50% reduction of monophenolase activity and diphenolase activityfifty）1.20 and 1.00mmol/L respectively.Benzoic acid significantly prolonged the delay time of the monophenolase of mushroom tyrosinase, and 4 mmol/L benzoic acid prolonged the delay time of the monophenolase from 42 s to 200 s.The inhibition of benzoic acid on diphenolase was determined to be noncompetitiveconstant0.95mmol/L.The combination of benzoic acid and enzyme leads to the endogenous of natural enzymefluorescenceHowever, the fluorescence emission peak did not shift.The authors propose a model of the interaction between inhibitors and enzyme molecules.[2]
influence
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Proton effect: use o-chlorobenzaldehyde, p-chlorobenzaldehydeChlorobenzaldehyde、O-methoxybenzaldehyde, p-methoxybenzaldehyde and cyclohexanone diethyl acetal, respectivelyα，α'-Bisbenzylidene naphthenic ketones.By means of 1H NMR, the influence of neighborhood effect on the chemical shift of proton is expounded through the analysis of the chemical shift of H on double bond carbonElectronic effectandSpatial effectAnd so on.The spatial hindrance of adjacent groups can affect the symmetry of molecules, for example, compound a is a chiral molecule, while compound b is a non chiral molecule.
The steric hindrance of adjacent groups can exclude the conjugated groups such as - NH, - NO from the conjugated system of benzene ring, thus greatly changing the static physical and chemical properties of molecules such as bond length polarity and acid-base property of the compound.For example, in compound c, because the nitro group is conjugated with the para amino group, the lone electron pair on the amino group can be transferred to the nitro group (c), and its dipole moment is 6.18D.However, in compound d, due to the space obstruction of ortho methyl group, the plane of - NH and - NO group deviates from the plane of benzene ring, and the electron pair on the amino group cannot be transferred to the nitro group. Its dipole moment is only 4.89D.
For another example, due to the induction effect of chlorine atom, the acidity of compound e is greater than that of compounds f and g.In compound h and i, because compound h is mainly intermolecular hydrogen bond, its boiling point can reach 295 ℃, while compound i is mainly intramolecular hydrogen bond, its boiling point is only 214 ℃.
The ortho effect also has an impact on the reaction rate and reaction mechanism. For example, compound j can react with methyl iodide to form quaternary ammonium salt, but in compound k, the plane of the - N (CH) group deviates from the plane of the benzene ring due to the space obstruction of the two methyl groups on the ortho position, making it extremely difficult for compound k to form quaternary ammonium salt.
Under normal conditions, the esterification rate of compound 1 is much slower than that of compounds m and n.However, in concentrated sulfuric acid, due to the formation of positive carbon ions, the attacking group can attack the reaction center from the direction perpendicular to the benzene ring, so the esterification reaction of compounds can proceed smoothly.At this time, the esterification mechanism has changed.
In a certain reaction process, adjacent groups are partially or completely bonded to the reaction center, which significantly increases the reaction rate. This neighborhood effect belongs to the participation of adjacent groups.For example, due to the involvement of adjacent groups, the chlorine in compound p is easily hydrolyzed in boiling water, but compound q is stable under the same conditions.
Because of this special effect of the adjacent group, the influence of the adjacent group on the molecular properties does not follow the Hamit equation.[2]
