Organic Chemistry Fundamentals for Biochem Part 2 PDF

Resonance In certain cases, molecules can be represented by more than one reasonable Lewis structure that differ only in the location of π electrons. Electrons in σ bonds have a fixed location and so they are said to be localized. In contrast, π electrons that can be drawn in different locations ar...

Resonance In certain cases, molecules can be represented by more than one reasonable Lewis structure that differ only in the location of π electrons. Electrons in σ bonds have a fixed location and so they are said to be localized. In contrast, π electrons that can be drawn in different locations are said to be delocalized. Collectively these Lewis diagrams are then known as resonance structures or resonance contributors. The "real" structure has characteristics of each of the contributors, and is often represented as the resonance hybrid. The resonance hybrid is a mixture of the contributors. oxygen hybridization sp2 Noteworthy: none of Lewis diagrams are consistent with the observed properties of the nitrate ion and, therefore, does not correctly depict the nitrate! The nitrate ion, according to its Lewis diagram, has two types of nitrogen-oxygen bonds, one double bond and two single bonds, suggesting that one nitrogen-oxygen bond in the nitrate ion is shorter and stronger than each of the other two. Also, the Lewis structure implies, with respect to formal charge, that there are two types of oxygen atoms in the nitrate ion, one formally neutral and each of the other two bearing a formal charge of –1. Experimentally, however, the three nitrogen-oxygen bonds in the nitrate ion have the same bond length and the same bond energy, and the three oxygen atoms are indistinguishable. The Lewis diagram fails to explain the structure and bonding of the nitrate ion satisfactorily.  What you obtain after the sp2 hybridization is: 3 sp2 orbitals.The p orbital, namely the one that was not used in the sp2 hybridization, is perpendicular to the sp2 plane. Most importantly it is available to join other p orbitals: conjugation This is not used in + the sp2 hybridization! Again, this is the p orbital not used in the sp2 hybridization. It is perpendicular to the sp2 plane. It is available to create π bonds and, most importantly, it can develop extensive delocalized electon systems sp2 orbitals are trigonal and planar. They give rise to three sigma (head to head) bonds and they constitute the molecular skeleton of conjugated systems as benzene.  Sp2 carbons, thanks to the p orbitals create a «road» for electron circulation (delocalization). In this view, a sp3 carbon acts as a road block! Sp3 carbon display exclusively sigma bonds which are localized in a limited region between two atoms. This carbon do not possess any p orbital which can partecipate to the conjugation. In other words it interupts the π delocalization! Nitrogen and Oxygen are atoms with lone pairs hence they can partecipate to the π delocalization DRAW THE LEWIS RESONANCE STRUCTURES OF THE FOLLOWING MOLECULES Add electron pairs and hydrogens where is necessary To draw resonant structures you have to Identify: 1) sp2 hybridized carbons (carbons sharing a double bond) 2) atoms with lone electron pairs (e.g. O,N) 3) carbocations and carbanions Remember that in a Lewis diagram, conjugated π system has double bonds and single bonds in an alternating pattern. Check atom charges. Charge= Valence electrons – Molecular electrons. Molecular electrons= 2 electron for a lone pair, 1,2,3 electrons for single, double and triple bond respectively. Consider the contribution of each resonance form. Remember that π delocalization stabilizes both carbocations and carbanions. As a consequence it displays a great influence on organic compounds reactivity and on reaction mechanisms. Always ask whether a resonance structure BF3 has a total of 24 valence electrons, 3 from boron and 3x7 = 21 from the fluorines. There are four possible ways is plausible: the strange case of boron to allocate the electrons in the molecule: fluoride The structure on the left (the “electron-deficient” one) has octets on the fluorines, but only three electron pairs on boron, while the ones on the right have octets on all the atoms. So, why not choose the structures with octets on all the atoms? There are two competing things to consider. If you calculate formal charges for the electron-deficient structure, all the atoms are neutral (= zero charge). However, the structures on the right all have a -1 charge on boron and +1 charge on one fluorine. Boron has a very low electronegativity and does not tolerate a negative charge, while fluorine has a very high electronegativity and does no tolerate positive charges. The question is, is it better to have more bonds with “inappropriate” charges, or fewer bonds but with no charges. On balance, it’s better for boron to remain electron deficient (electrophile) than to put charges on atoms that cannot tolerate them. Tautomers are structural isomers that readily interconvert. This reaction commonly results in the relocation of a hydrogen atom. The chemical reaction interconverting the two is called tautomerization. Care should be taken not to confuse tautomers with depictions of "contributing structures" in chemical resonance. Tautomers are distinct chemical species that can be distinguished by their differing atomic connectivities, molecular geometries, and physicochemical and spectroscopic properties, whereas resonance forms are alternative Lewis structure of a specie, whose true structure is best described as the "average" of the geometries implied by these resonance forms. Double arrows: this represents an actual equilibrium π electrons provide strenght and rigidity to double bonds. Double bonds can not rotate because of the presence of π electrons. Differently from the electrons of σ bonds, which are protected, being concetrated between two atoms π electrons are exposed to the attack of electrophiles. A sigma bond is a localized chemical bond. It is not free to move! These bonds are concentrated on a limited region of a molecule. These regions have a concentrated electron distribution. In other words, the electron density of this region is very high. Delocalization occurs in conjugated π system. In a Lewis diagram, conjugated π system has double bonds and single bonds in an alternating pattern. Markovnikov's Rule states that with the addition of an electrophile as the proton of as strong acid as HX (where X is some atom more electronegative than H bearing lone pairs) to an asymmetric alkene, the acid hydrogen (H) (the electrophile) gets attached to the carbon with more hydrogen substituents, and the halide (X) group (the nucleophile) gets attached to the carbon with more alkyl substituents. The same is true when an alkene reacts with water in an addition reaction to form an alcohol which involve formation of carbocations. The hydroxyl group (OH) bonds to the carbon that has the greater number of carbon–carbon bonds, while the hydrogen bonds to the carbon on the other end of the double bond, that has more carbon–hydrogen bonds. The chemical basis for Markovnikov's Rule is the formation of the most stable carbocation during the addition process. The addition of the hydrogen ion to one carbon atom in the alkene creates a positive charge on the other carbon, forming a carbocation intermediate. The more substituted the carbocation, the more stable it is, due to induction and hyperconjugation. The major product of the addition reaction will be the one formed from the more stable intermediate. Therefore, the major product of the addition of HX to an alkene has the hydrogen atom in the less substituted position and X in the more substituted position. But the other less substituted, less stable carbocation will still be formed at some concentration, and will proceed to be the minor product with the opposite, conjugate attachment of X. Nucleophilic Acyl Substitution and the nucleophilic addition at carbonyl are of fundamental importance in biochemistry Cyclization of Monosaccharides Nucleophilic Acyl Substitution: The fact that one of the atoms adjacent to the carbonyl carbon in carboxylic acid derivatives is an electronegative heteroatom – rather than a carbon in ketones or a hydrogen in aldehydes - is critical to understanding the reactivity of carboxylic acid derivatives. The most significant difference between a ketone/aldehyde and a carboxylic acid derivative is that the latter has a potential leaving group - what we are calling the 'acyl X group' - bonded to the carbonyl carbon. As a result, carboxylic acid derivatives undergo nucleophilic acyl substitution reactions, rather than nucleophilic additions like ketones and aldehydes. A nucleophilic acyl substitution reaction starts with nucleophilic attack at the carbonyl, leading to a tetrahedral intermediate (step 1 below). In step 2, the tetrahedral intermediate collapses and the acyl X group is expelled, usually accepting a proton from an acid (used as a catalyst) in the process. Mechanism for a nucleophilic acyl substitution reaction: Notice that in the product, the nucleophile becomes the new acyl X group. This is why this reaction type is called a nucleophilic acyl substitution: one acyl X group is substituted for another. For example, in the reaction below, one alcohol 'X group' (methanol), substitutes for by another alcohol 'X group' (3-methyl-1-butanol) as one ester is converted to another. Another way of looking at this reaction is to picture the acyl group being transferred from one acyl X group to another: in the example above, the acetyl group (in green) is transferred from 3-methyl-1-butanol (blue) to methanol (red). For this reason, nucleophilic acyl substitutions are also commonly referred to as acyl transfer reactions. Enzymes catalyzing nucleophilic acyl substitution reactions have evolved ways to stabilize the negatively charged, tetrahedral intermediate, thus lowering the activation energy of the first, rate-determining step (nucleophilic attack). In many cases, for example, enzymatic amino acid residues are positioned in the active site so as to provide stabilizing hydrogen bond donating interactions with the negatively-charged oxygen. This arrangement is sometimes referred to in the biochemistry literature as an oxanion hole. The figure below shows a tetrahedral intermediate stabilized by hydrogen bond donation from two main chain (amide) nitrogen atoms.  one two three INCREASING NUMBER OF CARBON OXYGEN BONDS Can carbon be further oxidized? What is the molecule in which C and O share 4 bonds (2 double bonds)? When decarboxylation occurs an electron pair of the broken bond is left on the molecule. In the enzymatic processes this electron pair is captured by NAD+ and FAD The formation of a peptide bond is a nucleophilic acyl substitution reaction Mechanism of a peptide bond synthesis on a ribosome