KERTÉSZETI ÉS ÉLELMISZERIPARI EGYETEM

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Organic Chemistry

Judit Kosáry (2016-1)

The lecture gives a basic knowledge about organic chemistry preparing the students to study food chemistry or plant biochemistry. The lectures present essential topics of organic chemistry: structure and hazards of organic molecules and mechanism of organic reactions. They are discussed in a pragmatic way based on electron density of organic molecules.

Biogenic elements

Building biomolecules: carbon (C), hydrogen (H), nitrogen (N), oxygen (O) (and P and S). They are in the first and second periods (high charge concentration on their surface unit), their atom are not susceptible to deformation and their form with own atoms and other biogenic elements strong (-bonds. All of atoms except carbon and hydrogen are called heteroatom (e.g. N, O, P and S). In organic chemistry halogen atoms e.g. chlorine (Cl) and bromine (Br) are also important.

Electronegativity can be characterized the atoms connected by a (-bond. The atom with higher electronegativity can collect a part of the electron density of the (-bond, this causes an electron surplus ((Ө) on it. This effect causes an electron deficiency ((() at the atom with lower electronegativity

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Position of biogenic elements and halogens in the periodical system and their electronegativity (EN)

Organic reactions

The reactivity of organic molecules and their reaction mechanism chemical reactions are influenced by their electron density characterized by the electronegativity of the atoms in the organic molecule. There are two phases of an organic reaction: attack and stabilization. A reagent molecule attacks the substrate molecule and at least one of the covalent bonds is disappeared. The type of this split is determined by the distribution of the electron concentration of this covalent bond.

Radical mechanism:

In the case of a reaction of radical mechanism an A–B the ( covalent bond of the substrate (the attacked molecule) with symmetric electron density (ENA(ENB – (EN=0 or very small) splits by homolysis: A(((B (( A( + (B forming two free radicals (containing unpaired electron). This kind of split needs a high energy (heat and/or pressure) or a presence of a free radical as reagent. A typical radical type reaction is the thermal decomposition of hexane.

Ionic mechanism:

In the case of a reaction of ionic mechanism the distribution of the A–B ( covalent bond of the substrate is asymmetric (ENA(ENB), this bond has a polarized electron density: an electron deficiency ((() on atom A and an electron surplus ((Ө) on atom B. This bond splits by heterolysis. The electron pair of the original ( bond transforms to a non-bonding electron pair of the atom B of higher electronegativity: ((()A((B((Ө) (( A( + B|Ө forming ions. It does not need extra energy therefore easily be carried out. Theoretically the atom of the bond with an electron deficiency ((() can be attacked by a nucleophilic reagent and the atom of the bond with an electron surplus ((Ө) can be attacked by an electrophilic reagent, but there are other important parameters to determine the real attack.

During the second phase of an organic reaction the intermediate formed in the first phase (attack) is stabilized either by an rearrangement or by a transfer of a small part of the intermediate.

Types of reactions (in these cases A–B is the substrate and C–D is the reagent):

Addition (A): A=B + C–D ( C–A–B–D (2 molecules ( 1 molecule, the substrate contains a double bond) AN, AE, AR

Elimination (E): C–A–B–D ( A=B + C–D (1 molecule ( 2 molecules, one of the reaction products contains a double bond) Eionic, ER

Substitution) (S): A–B + C–D ( [A–C–D + B] (intermediate and leaving group) ( A–C (product) + B–D (by-product). During stabilization a small part from the intermediate and the leaving group gives the by-product. (2 molecules ( 2 molecules) SN, SE, SR

Catalyzed reactions

Diagram of catalyzed reactions in an example of exothermic reaction. Catalyst forms a complex with the substrate or the reagent opening a new reaction route with low activation energy

In the case of high activity energy the reagent cannot attack the substrate. In this case a catalyst forms a complex with the substrate or the reagent opening a new, two-step reaction route with low activation energy. The formation of the complex with secondary bonds needs low activation energy. The properties of the complex make the reaction easy, therefore this step needs also low activity energy. At the end of the reaction the catalyst is regenerated. In the case of an exothermic reaction energy released, and in the case of an endothermic reaction energy absorbed can be found.

Solubility in organic solvents

Solvent – organic solvent – polar and apolar solvents

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Noble gases

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Electron saving property (ESP) of some elements in the periodical system

When an element is next to electron octet of noble gases (e.g. it is in 7. column), it does not incline to give an electron (no cation or H-bond formation), and this element has a large electron saving property (ESP). The closer is the electron system of an atom to the noble gas configuration; the larger is its ESP. An atom with a large ESP is unable to lose electron concentration even for a hydrogen bond.

The parts of organic molecules

The carbon skeleton part contains only carbon and hydrogen atoms, therefore the electron concentration of this part of the molecule is symmetric (low reactivity). The electron density of the part of a molecule contains heteroatom(s) with high electronegativity besides carbon and hydrogen is asymmetric. This part of the molecule can be easily attacked by nucleophilic or electrophilic reagent. This part (named functional group) of a molecule can determine the reactivity of the whole molecule.

In simple functional groups the heteroatom directly connects to the carbon skeleton, in combined functional groups a central carbon atom (wearing at least two simple functional groups) connects to the carbon skeleton.

Essential polar and apolar characters:

Polar character: H-bonds with water molecules (polarized bonds, e.g. methanol:

H3C–OH)

Apolar character: no H-bonds with water

a) non-polarized bonds (e.g. hydrocarbons)

b) polarized bond with a heteroatom of large ESP (e.g. methyl chloride: H3C–Cl)

In simple functional groups (the heteroatom directly connects to the carbon skeleton): amines – weak H-bonds, alcohols – strong H-bonds, ethers and chlorides – no H-bonds.

Essential polar and apolar characters of simple functional groups

In combined functional groups (a central carbon atom (wearing at least two simple functional groups) connects to the carbon skeleton): with carboxylic acids (e.g. acetate) – strong H-bonds, with esters (e.g. ethyl acetate) – no H-bonds, with carboxamides (e.g. acetamide) – very strong H-bonds.

Polar and apolar characters of combined functional groups

Carbon skeletons (hydrocarbons)

Saturated hydrocarbons (alkanes, paraffins): general formula (CnH2n+2) hybridization (sp3), angle of the bonds in hybridization: 109,5°, geometry is tetrahedral.

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Conformations of ethane: eclipsed and open structure

Conformation – the arrangement of the parts of a molecule (no direct connection by a (-bond). In saturated hydrocarbons there is a free rotation (eclipsed structure – hydrogen or other atoms are in the same position disturbing each other; open structure – hydrogen or other atoms are in the in a rotated position, minimal disturbance, therefore this structure means an advantage).

There is another phrase often used in organic chemistry: configuration. Configuration is used in two different meanings. On one hand the electron octet of a noble gas is called noble gas configuration. On the other hand the configuration means the arrangement of the substituents connected by covalent bonds to a central carbon atom. Substituent is an atom or a group of atoms connected to a carbon atom of an organic molecule instead of hydrogen.

Characteristic reaction mechanism of saturated hydrocarbons is radical mechanism because (ENC-C=0, (ENC-H is very small. An example – the thermal decomposition of hexane. Its practical use – increasing the light petrol phase during the fractioned condensation of mineral oil.

The thermal decomposition of hexane

Homologous series (unit methylene –CH2–). C1: CH4 – methane, C2: H3C–CH3 – ethane, C3 – propane, C4 – butane, C5 – pentane, C6 – hexane, etc. Fuels: gas (methane), petrol (C5-C11), diesel oil, etc. Liquid representatives are apolar solvents. The name of hydrocarbon groups: CH3– methyl, H3C–CH2 – ethyl, etc.

Isomerism in organic chemistry

When two molecules have some differences in their structure but their molecular formula (the composition of elements) is the same, they are called isomers. Isomers in which the atoms are bonded in a different order are called structural (constitutional) isomers e.g. structural isomers of hexane. The name of non-branched hexane is normal hexane, the name of the branched ones is isohexane.

The structural isomers of hexane

Stereoisomers have the same molecular formula and sequence of bonded atoms (constitution), but their atoms have different positions in their three-dimensional orientations in space. They are different stereoisomer types: optical isomers (enantiomers and diastereomers), geometrical isomers and conformers. Conformational isomers (conformers) have not only the same molecular but the same structural formula having different shapes due to rotations about one or more bonds (e.g. chair and sofa conformations of glucopyranoside – see later).

The consequence of the tetrahedral rearrangement of carbon atoms in saturated hydrocarbons – optical isomerism

Saturated carbon skeleton with four different substituents (marked by a star) called chiral carbon atom, hybridization (sp3), angle of the bonds in hybridization: 109,5°, geometry is tetrahedral. Chirality (on the basis of the Greek word kheir– hand), two enantiomers (antipodes), they are pairs of mirror-images. The chemical and physical properties of the enantiomers are the same, because the microenvironment of the atoms is the same. The only difference is in their optical rotation. An enantiomer can be named by the direction in which it rotates the plane of monochromatic and monopolarized light. If it rotates the light clockwise, that enantiomer is labeled (+). Its mirror-image is labeled (−).

Group of highest oxidation number

|

Smallest functional group–C–Characteristic functional group

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The application of Fischer’s convention on the D-enantiomer

Group of highest oxidation number

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Characteristic functional group–C–Smallest functional group

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Other group

The application of Fischer’s convention on the L-enantiomer

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The modified Fischer convention for the L-(-amino acids

Distinction of enantiomers can be carried out by Fischer’s convention that is shown here the simplest aldose glyceraldehyde. When the characteristic group is on right side in a Fischer projection, the chiral compound is called right-handed (D – after Latin word dexter) and the other enantiomer is left-handed variation (L – after Latin word laevus). D and L are typically typeset in small caps. For the description of chirality another more general (R/S) system (Cahn-Ingold-Prelog priority rules based on atomic number) is used in organic chemistry. In the case of glyceraldehyde D enantiomer is the clockwise (+) and L-enantiomer is the anti-clockwise (–) variation. For the L-(-amino acids a modified Fischer convention is used because it is better to illustrate the peptide bond.

The diastereomers contain at least two centers of chirality, and one of the centers in the two diastereomers is in the same while the other in the opposite position. The chemical and physical properties of the diastereomers are different, because the microenvironment of the atoms is not the same. This fact can serve as a basis for the separation of enantiomers from their mixture (called racemic mixture) by forming diastereomers. This process is called resolution.

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Diastereomers

In compounds containing two chiral centers and the carbon atoms have the same substituents of opposite chirality therefore the direction of the optical rotation of two carbon atoms is opposite (resultant optical rotation is zero) – this variation is called meso form (e.g. meso-tartarate).

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Meso-tartarate and (+)-tartarate are diastereomers

Many biologically active molecules are chiral, including the naturally occurring proteins, carbohydrates and nucleic acids. As enzymes are proteins and proteins are chiral, they can catalyze the transformation of only one of the enantiomers of a chiral substrate. Naturally occurring proteins are constituted of L-(-amino acids, carbohydrates mono- di-, oligo- and polysaccharides are made of D-sugars, and nucleic acids contain also D-sugars: D-ribose or D-deoxyribose – see later.

Unsaturated hydrocarbons (alkenes, olefins): general formula (CnH2n) hybridization (sp2), angle of the bonds in hybridization: 120°, not only (-bonds, double C=C bond, geometry is planar, that contains (-bond (its electron pair is perpendicular to the (-bond; therefore it can be attacked by an electrophilic reagent). The name of the group ethylene: H2C=CH – vinyl. Characteristic reaction is AE.

The bromine molecule is susceptible to deformation, therefore the effect of the strong electron density of the (-bond of ethylene can disproportionate the bromine molecule to bromine cation and bromide anion by repulsion.

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Bromination of ethylene and formation of ethylene from the product

General rule of the synthesis of unsaturated compounds: from a molecule formed by an addition of an unsaturated bond can be produced an unsaturated compound.

Polymerization of molecules containing an unsaturated C=C bond: polymerization is a special addition in that one double bond connected to another double bond –occurs several times: (n+1) CH2=CH2 ( H–(CH2–CH2)n–CH=CH2. Radical mechanism: it needs heat and pressure – expensive, good structural properties, pure polymer that can be used in food industry (e.g. polyethylene bags); ionic mechanism: at room temperature – cheap, not very good structural properties, because of the presence of toxic Ziegler catalyst it cannot be used in the food industry.

Polymerization of ethylene

Unsaturated hydrocarbons (alkines) with a (C(C) bond: general formula (CnHn) hybridization (sp), angle of the bonds in hybridization: 180°, geometry is linear, not only one but two (-bonds (their electron pairs are not only perpendicular to the (-bond, but to each another too. It can be easily attacked by an electrophilic reagent, but the intermediate is unstable (at the same carbon atom there is both a positive charge and a (-bond). The name HC(CH is acetylene. Characteristic reaction is AE. Bromination of acetylene leads to the formation of trans-1,2-dibromoacethylene that is an example for geometrical isomerism.

Bromination of acetylene

Geometrical isomerism

In the case of free rotation in saturated hydrocarbons (eclipsed structure – hydrogen or other atoms are in the same position disturbing each other; in the open structure – in which hydrogen or other atoms are in the in a staggered position, disturbance is minimal, therefore this structure is advantageous).

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Conformations of ethane: eclipsed and open structure

When there is a barrier to rotation (e.g. a ring system or a double bond) the large substituents can be on the same or on opposite sides. When large substituents are on the opposite side (trans isomer) the disturbance is less (therefore this isomer is more advantageous) than the cis isomer. For specific compounds in organic chemistry the E-Z notation based on priority rules is used.

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A simple example for geometric isomers: cisz- and trans-1,2- dibromoethylene

Compounds containing conjugated double bond system

In the case of conjugated double bond system C–C and C=C bonds are alternately, hybridization (sp2), angle of the bonds in hybridization 120°, geometry is plane. Two (-bonds are in parallel position, they can establish in an advantageous delocalized form that can be illustrated by mesomer structures. The differences in mesomer structures are only in the easy moving (-bond systems generally in the position of a double bond and charge(s). This is illustrated on 1,3-butadiene. The delocalized character is indicated by symbol ((). A positive or negative charge in the mesomer structure means an ((() or ((Ө) in the original molecule.

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Delocalization of 1,3-butadiene

Because of this delocalization the bromination of 1,3-butadiene leads to two isomers (structural isomers) of the product dibromobutene by AE (1,2AE.and 1,4AE.)

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Bromination of 1,3-butadiene

Aromatic carbon skeleton: hybridization (sp2), angle of the bonds in hybridization: 120°, circular conjugation, plane surface (Hückel’s rule – the number of ( electrons and/or easy moving electrons is 4n+2), total delocalization, high stability, characteristic reaction is SE, the reagent has to be always synthesized (because of delocalization the power of (-bonds is not strong enough for repulsion). Characteristic compound is benzene (C6H6), the group from benzene is (C6H5-) – phenyl group.

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The mesomeric structures of benzene and Hückel’s rule

The formation of reagent cation is carried out by Lewis acid catalysts (FeBr3, AlCl3) with electron sextet and the driving force of the reaction is the effort of iron or aluminum to acquire an electron octet by splitting off an anion from the reagent. In consequence of the electrophilic attack of the reagent cation a (-complex with a tetrahedral carbon atom is formed that has no aromatic character; therefore its stability is low. The stabilization of this intermediate is carried out by the splitting off of the hydrogen of the tetrahedral carbon atom in form of a proton as a leaving group and the aromatic character is restored by the electrons of this (-bond. Therefore the characteristic reaction of aromatic ring systems is electrophilic substitution (SE). When the reagent is an alkyl cation, the reaction is called Friedel-Crafts alkylation (in the case of methyl cation that is a methylation).

Formation of electrophilic reagent bromine cation and bromination of benzene to bromobenzene (intermediate (-complex has no aromatic character, therefore its stability is low)

Formation of electrophilic reagent methyl cation and synthesis of toluene by the methylation of benzene

Heteroaromatic ring systems: the properties of aromatic ring systems are altered by the presence of one or more heteroatoms in the ring (instead of CH can be N, O or S, but now only nitrogen heteroaromatic ring systems are discussed).

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Substitution of a CH by a nitrogen (ENC(ENN) in the benzene ring: The nitrogen collects the easy moving (-electrons, therefore the nitrogen has a strong basic character (it can be easily protonated), it can react as a nucleophilic reagent and pyridine can be attacked by electrophilic reagent less than benzene. When two nitrogens are in benzene ring (here is only the variation, pyrimidine that is current in living organisms, especially in nucleic acids), the delocalized (-electrons are distributed between two nitrogens, therefore pyrimidine has a less basic character than pyridine.

Five-membered heteroaromatic ring system containing nitrogen. Cyclopentadiene has no aromatic character (there are only four (-electrons and CH2 is saturated) but in pyrrole (CH2 is substituted by NH) the non-bonding electron pair of nitrogen can complete the mobile electron system to six. This delocalization can be characterized by mesomeric structures. The part of the electron density of nitrogen makes the carbon atoms richer in electrons than it was in benzene therefore SE can be carried out easier with pyrrole than with benzene. The reduced electron density at nitrogen changes its basic character to acidic character.

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In imidazole (a five-numbered ring system with two nitrogens) one of nitrogens is involved similar change therefore one nitrogen of imidazole remains acidic, but the second nitrogen got electron density from the first nitrogen therefore it has a really strong basic character. The part of the electron density of nitrogen makes the carbon atoms richer in electron than it was in benzene therefore the SE can be carried out easier in pyrrole than in benzene.

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The acidic-basic character of nitrogen heterocycles

There is a special condensed heteroaromatic ring system in nucleic acids called purine skeleton. Its acidic-basic character is a combination of pyrimidine and imidazole rings.

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The acidic-basic character of purine skeleton (nitrogen-1 and nitrogen-3 have weak basic character, nitrogen-7 is a strong base, NH-9 has an acidic character)

There are non-aromatic cyclic compounds containing heteroatoms called heterocycles. Their chemical properties are similar to compounds with a simple functional group. Some representatives of heterocyclic and heteroaromatic compounds exert marked physiological actions on animals and humans. Some of them are called alkaloids that can be used as medicines or poisons. Nicotine is an agent of tobacco that excites the nervous system. Coniine isolated from a medical plant (hemlock) paralyzes the nervous system; therefore it is a strong poison. The name of saturated pyridine ring is piperidine.

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Formulas of nicotine and coniine

Several compounds contain the indole heteroaromatic ring system e.g. an amino acid (tryptophan) and the most important plant growth hormone, heteroauxin.

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Compounds containing an indol skeleton

Functional groups

In organic chemistry functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of these molecules. The same functional groups can show same or similar chemical reactions but the type of the carbon skeleton, the size of the molecule and the presence of other functional groups in the molecule can influence their reactivity. Functional groups contain at least one heteroatom.

There are different classifications for functional groups. According to an old classification functional groups can be simple and combined. Nowadays this classification is not used anymore. When the heteroatom directly connects to the carbon skeleton, the reactivity of the compound is determined by the electron distribution of the covalent bond between the heteroatom and the carbon atom, the molecule has a simple functional group. In simple functional groups the heteroatom of high electronegativity can be connected to no atom within the group or only to atom(s) with low electronegativity (carbon skeleton–Ā–B) (ENA(ENB). According to this old classification the simple functional groups are: halogen atoms (–X), especially chlorine (–Cl), hydroxyl group (–OH), ether group (–O–), amino group (the formula of primary amino group: –NH2) and thiol group (–SH).

When simple functional groups are connected to a central carbon atom by covalent bonds, this molecule contains a combined functional group. The heteroatom of these simple functional groups can be nitrogen, oxygen or sulphur. There are combined functional groups that have only two simple functional groups. In these cases one heteroatom has to be connected by a double bond to the central carbon. This heteroatom can be oxygen (carbonyl earlier or oxo group C=O), nitrogen (imino group C=N–) or sulphur (thiocarbonyl earlier thioxo group C=S), but it is mostly oxygen. The combined functional groups of biomolecules always has a carbonyl part: carboxyl group (–COOH), ester group (e.g. the formula of a methyl ester: –COOCH3), carboxamide group (the formula of a carboxamide group with a primary amino group part: –CONH2), anhydride group (–CO–O–CO–) and acid chloride (–COCl). In the following only these combined functional groups will be discussed.

The carbonyl group is not a traditional simple group, because there is a double bond between carbon and oxygen and a carbon is part of the functional group. But it is not a traditional combined group also, because it does not contain two simple groups. The general formula of the functional groups containing C=O fraction (carbonyl group and combined functional groups that can be found in biomolecules) is:carbon skeleton–A=B (ENA(ENB).

According to another classification on the basis of the behaviour of the functional groups towards a double bond, two types can be distinguished. When the functional group is connected to an unsaturated carbon atom, a possibility for delocalization can be found: when the carbon atom is connected directly to a heteroatom (with at least one non-bonding electron pair) or the (-bond of the carbon skeleton is in conjugated position with a (-bond of the functional group. Delocalization can be illustrated by mesomer structures as it was introduced in the case of conjugated double bond systems. The two possibilities are illustrated by the vinyl derivatives.

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Effect +K and –K of the functional groups on the vinyl carbon skeleton

In the case of simple functional groups the delocalization causes an increase in electron density of the carbon skeleton, therefore it is called positive conjugation (+K). In the literature this effect is often called a positive mesomeric effect (+M). In consequence of +K effect the electron density at the heteroatom of the functional group decreases (this change can cause also a decrease in the basic character and an increase in the acidic character of a simple functional group).

In the case of carbonyl and combined functional groups delocalization can cause a decrease in electron density of the carbon skeleton, therefore it is called negative conjugation (-K). In the literature this effect is often called negative mesomeric effect (-M). In the functional groups containing a C=O fraction (carbonyl group and combined functional groups that can be found in biomolecules) the central carbon atom of the functional group is connected to the carbon atom of the carbon skeleton, therefore there is no electron surplus or deficiency at this carbon atom (C–C bond). It is noticed that these properties are valid for almost all of the functional groups with a –K effect.

Functional groups with a +K effect

In compounds containing functional groups with a +K effect the heteroatom directly connects to the carbon skeleton therefore the reactivity of the compounds is determined by the electron distribution of the covalent bond between the heteroatom and the carbon atom. In the case of chlorine (or other halogen) atom the carbon atom can be easily attacked by a nucleophilic reagent because the electronegativity (EN) of carbon is lower than that of chlorine; and the chloride anion is a good leaving group because of its high electron saving property (ESP).

Hydrolysis of ethyl chloride by sodium hydroxide

In hydroxyl (alcohol) and amine derivatives the heteroatom cannot cause an electron deficiency at carbon because of the attached hydrogen is of low EN. Inside the carbon skeleton carbon atoms have slightly increased electron density as compared to hydrogen (ENC(ENH). This electron surplus can be extracted by the heteroatom. Therefore hydroxyl and amine groups can be nucleophilic reagents.

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The attack of functional groups with +K by nucleophilic reagents

During a nucleophilic attack an intermediate with a positive charge can be formed. The stability of the intermediate can be estimated on the basis of the basic character of the reagent; and the role of the ESP of the heteroatom in it.

The role of the ESP of the heteroatom in the formation of the intermediate with positive charge

Because of its really high ESP the chloride can be neither a base nor a nucleophilic reagent. The hydroxyl group is a very weak acid; it can form a salt only with sodium metal but never with sodium hydroxide. It is hardly a base because of the high ESP of oxygen and its deformed tetrahedron (a non-bonding electron pair is larger than a covalent bond) it is difficult to form an oxonium cation when only hydrogen and carbon atoms are around it – and no another heteroatom is connected to the carbon atom. The compounds that can react as either an acid or a base are called amphoteric substances. The hydroxyl group can be considered an amphoteric functional group.

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The acid-base character of chlorine atom and hydroxyl group

A hydroxyl can attack an alkyl chloride only when first the hydrogen of the hydroxyl group is abstracted by the formation of a salt by means of sodium metal. In this case the nucleophilic reagent is the alkoxide anion. This reaction is illustrated by the example of the synthesis of ethyl methyl ether by the Williamson ether synthesis that can be used for the synthesis all kinds of ethers.

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Because acidic character of the thiol group is stronger than that of the hydroxyl group (because sulphur can be deformed easier than oxygen) thiolate salts can be formed not only by sodium metal but also by sodium hydroxide.

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Another difference between thiol and hydroxyl groups is their behaviour on oxidation. Oxidation of two thiol groups (e.g. methanethiol – its old name is methyl mercaptan) leads to a stable disulphide bond that plays an important role in proteins chemistry. Peroxides cannot be synthesized by the oxidation of hydroxyl groups but can be formed by the oxidation of ethers (e.g. diethyl ether) – sometimes spontaneously by the oxygen of the air. Peroxides are explosive and can disintegrate to very reactive free radicals therefore this process can be dangerous.

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Ethers can be neither nucleophilic reagents nor strong bases because of the high ESP of oxygen and the deformed tetrahedral structure of the oxonium cation as it was in the case of the protonation of a hydroxyl group. The different reactivity of the functional groups based on the high ESP of the oxygen atom causes that the names of the functional groups are different, when one or two hydrogen atoms of the water molecule are substituted by carbon substituents.

The reaction of methyl chloride and methylamine

In the amino group the electronegativity and electron saving property of nitrogen are lower than that of oxygen in the hydroxyl group; and the nitrogen is connected to three other atoms (H and C) of low electronegativity therefore the hydrogen(s) of the amino group is(are) not acidic hydrogen(s). The protonated amino group is a stable cation, because the ESP of nitrogen is not high and that the cation forms a symmetrical tetrahedron. It means that amines are strong bases. The more carbon atoms are connected to the nitrogen the stronger bases are the amines. The base of an amino group can be liberated from its salt by using a stronger base (e.g. sodium hydroxide) than the amine.

All kinds of amines can react with alkyl chlorides because the intermediate salts are stable even in the case of a tertiary amine. The alkylation reactions of amines are illustrated by three reactions. They are the reaction of methyl chloride with ammonia producing methylamine; with methylamine producing dimethylamine and with trimethylamine producing a quaternary ammonium salt. The similar reaction of amines with alkyl chlorides causes, that the names of the functional groups are the same (amino group), when one, two or three of hydrogen atoms of ammonia are substituted by carbon atoms.

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The synthesis of alkyl amines by alkylation

All kinds of amines can react with alkyl chlorides because the intermediate salts are stable even in the case of a tertiary amine. The alkylation reactions of amines are illustrated on three reactions. They are the reaction of methyl chloride with ammonia producing methylamine; with methylamine producing dimethylamine and with trimethylamine producing a quaternary ammonium salt. The similar reaction of amines with alkyl chlorides causes, that the names of the functional groups are the same (amino group), when one, two or three of hydrogen atoms of the ammonia molecule are substituted by carbon substituents.

The name of amines depends on the number of carbon atoms connected to the nitrogen. Primary amines contain one carbon skeleton (e.g. methylamine), secondary amines (e.g. dimethylamine), two, tertiary amines (e.g. trimethylamine) three, finally quaternary amines (e.g. tetramethylammonium chloride, that is a quaternary ammonium salt) four.

Representatives of molecules containing functional groups with +K effect

The molecules containing one or more hydroxyl groups connected to a saturated carbon skeleton are named alcohols. The name of an hydroxyl group connected to saturated carbon skeletons is alcoholic hydroxyl group. Their systematic name is based on the number of the carbon atoms with the ending “ol”. Alcohols are volatile, inflammable, colorless liquids; some of them are used in foods and industry. Primary, secondary and tertiary alcohols can be easily distinguished on the basis of the number of (-bonds connecting other carbon atoms to the carbon atom connected to the hydroxyl group. For example methanol, ethanol and ethylene glycol are primary alcohols; the middle hydroxyl group of glycerol is a secondary alcoholic hydroxyl group and tert-butanol (1,1-dimethylethanol (CH3)3C-OH) is a tertiary alcohol.

Methanol (methyl alcohol, wood alcohol, wood spirits) (H3C–OH, often abbreviated MeOH). It is used as an antifreeze, solvent, fuel and also used for producing biodiesel. Its properties are similar to that of ethanol, but it is far more toxic, it can cause blindness, even death.

Ethanol (ethyl alcohol, alcohol, drinking alcohol, spirit) (H3C–CH2–OH, often abbreviated EtOH) is a popular recreational drug used in alcoholic beverages. It is not as toxic as methanol, but it can cause addiction called alcoholism.

Ethylene glycol (HO–CH2–CH2–OH, ethane-1,2-diol) contains two hydroxyl groups. It is widely used as antifreeze and a precursor to polymers. It is often used for adulteration of wines. It is dangerous because ethylene glycol is toxic, it can cause death.

Glycerol

Glycerol (glycerine) contains three hydroxyl groups. It is sweet-tasting and of low toxicity. It is an important unit of lipids.

Because of the +K effect the acid-base character of the hydroxyl group connected to an unsaturated carbon atom (named enoles) is altered. The name of hydroxyl groups of enoles is enolic hydroxyl group. As this effect enhances the electron density at the carbon skeleton and decreases the electron density of the heteroatom; enols are stronger acids and weaker (practically no) bases than the alcohols. A special isomerism called keto-enol tautomerism (former name is oxo-enol tautomerism this name means that both aldehydes and ketones can take part in this kind of isomerism) caused by the effect of +K on enols is illustrated by the example of the simplest enol called vinyl alcohol (H2C=CH–OH). The differences between two tautomers are in the positions of one double bond and one hydrogen atom. Because of the delocalization caused by +K the hydrogen connected to the oxygen can split off as a proton (there is a positive charge at the oxygen in the mesomer that means, it is an acidic hydrogen) that attacks the negative charge of the carbon skeleton. The last step of the process is irreversible because hydrogen in a methyl group (or other alkyl groups) is not acidic and it cannot split off as a proton.

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Formation of acetaldehyde from vinyl alcohol by keto-enol tautomerism

+K effect in chlorobenzene and phenol

Because of the large delocalization a hydroxyl group connected to an aromatic ring system is definitely acidic, therefore its name is not alcoholic but phenolic hydroxyl group (the effect of a group with +K effect on the benzene ring can be illustrated by the example of chlorobenzene). When a hydroxyl groups is connected to a benzene ring, the name of the compound is phenol (carbolic acid) (C6H5–OH). Compounds containing phenolic hydroxyl groups are antimicrobial (antiseptic) materials.

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The effect of +K causes significant differences also in the reactivity of chlorine derivatives. It has been mentioned, that saturated alkyl chlorides can be attacked easily by nucleophilic reagents in a nucleophilic substitution. As +K effect enhances the electron density at the carbon skeleton and decreases the electron deficiency ((() at the carbon atom connected to chlorine atom (partial delocalization), this carbon atom can be attacked by the nucleophilic reagent with difficulty in unsaturated derivatives. Vinyl chloride (the starting material of polyvinyl chloride – plastic PVC) can be hydrolyzed with difficulty and the product vinyl alcohol forms acetaldehyde immediately by keto-enol tautomerism as it was presented earlier.

When a chlorine atom is connected to an aromatic ring system, this chlorine takes part in a total delocalization by +K effect resulting in a disappearance of the electron deficiency ((() at the carbon atom connected to the chlorine atom. In this way the carbon atom cannot be attacked by nucleophilic reagents.

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Hydrolysis of chlorine derivatives with different carbon substituents

As ethers contain two carbon substituents attached to an oxygen atom, earlier they were classified on the basis of the substituents. In simple ethers carbon substituents are identical; in mixed ethers they are different (e.g. diethyl ether is a simple ether; ethyl methyl ether is a mixed ether). The synthesis of both simple and mixed ethers was presented earlier (Williamson ether synthesis).

There is an alternative way for only the synthesis of simple ethers from alcohols that is illustrated by the example of the synthesis of diethyl ether. From sulphuric acid and ethanol ethyl hydrogen sulphate (an ester) can be synthesized by a proton catalyzed reaction. The thermal decomposition ethyl hydrogen sulphate depends on the temperature of the reaction mixture. At 130 oC two molecules produce diethyl ether and sulphuric acid. At higher temperature (160 oC) an ethyl hydrogen sulphate molecule gives ethylene and sulphuric acid in an elimination reaction.

CH3CH2–OH + HO–SO2–OH (H( catalyst) ( CH3CH2–O–SO2–OH + H2O

ethanol

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ethyl hydrogen sulphate

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diethyl ether

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ethyl hydrogene sulphate ethylene

Synthesis of diethyl ether from ethanol

Generally the ethers are dangerous, volatile, inflammable organic solvents, because between ether groups cannot be formed strong secondary bonds (e.g. hydrogen bonds). Ethers are prone to peroxide formation (it was presented earlier), and can form explosive peroxides, e.g. diethyl ether peroxide. Moreover ethers can build up electric charges causing a danger of sparks.

Diethyl ether, commonly referred to simply as "ether" (CH3CH2–O–CH2CH3) is a highly inflammable liquid of a very low boiling point and a characteristic odour. It is an organic solvent and was used earlier as a general anesthetic.

When the ether is connected to an aromatic ring system or some other kinds of complex molecule, it is described as an alkoxy substituent (e.g. –OCH3 can be named as methoxy group). The name of methoxybenzene is anisole: C6H5–OCH3 and the name of a molecule containing both hydroxyl and ether groups is 2-methoxyethanol (methyl cellosolve): CH3–O–CH2CH2–OH. Nowadays any ether can be named in this way: ethyl methyl ether – methoxyethane, diethyl ether – ethoxyethane, etc.

Amino compounds containing a small carbon skeleton are generally volatile liquids with a characteristic odour similar to that of ammonia. Biogenic amines are amino compounds of biological importance.

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The formation of biogenic amines from (-amino acids

Biogenic amines are formed from (-amino acids by decarboxylation. Foul-smelling diamines are formed during the deterioration of meat: putrescine (1,4-diaminobutane, H2N–(CH2)4–NH2 formed from ornithine) and cadaverine (1,5-diaminopentane, H2N–(CH2)5–NH2 formed from lysine). From etanolamine (cholamine, H2N–CH2CH2–OH formed from serine) choline an important unit of lecitine can be synthesized by methylation [(CH3)3N(–CH2CH2–OH]. Lecitine is one of the membrane building phospholipids that will be introduced later among biomolecules.

Functional groups with –K effect

In functional groups with –K effect two simple groups are connected to a central carbon atom and (as it was mentioned earlier) in the following we are going to study only that kinds of functional groups (the functional groups of biomolecules) in which one of the groups is a carbonyl group. According to the other simple functional groups connected to the carbon atom of the carbonyl group the combined functional groups are: carboxyl group (the second group is a hydroxyl group), ester group (the second group is an alkoxy group), carboxamide group (the second group is an amine group), anhydride group (two acyl groups connected by oxygen) and acid chloride (or other halogenide) group.

In the case of carbonyl and combined functional groups the delocalization can cause a decrease in electron density of the carbon skeleton, therefore it is called negative conjugation (-K). In the literature this effect is often called a negative mesomeric effect (-M) by some authors. In the functional groups containing C=O fraction (carbonyl group and combined functional groups that can be found in biomolecules) because of the higher electronegativity of oxygen the central carbon atom of the functional group is poor in electrons and therefore it can be attacked by nucleophilic reagents. The type of the reaction depends on the character of the substrate. In the case of a nucleophilic attack the electron pair of the new (-bond formed between the substrate and the reagent derives from the non-bonding electron pair (mostly of the heteroatom) of the reagent. Because of this dative bond a positive charge forms in the intermediate. The electron pair of the covalent bond ceased to exist around the carbon atom attacked has to migrate to an atom with higher electronegativity than that of carbon atom that was originally connected to the attacked carbon atom.

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Effect +K and –K of the functional groups on the vinyl carbon skeleton

In the case of the combined functional groups another heteroatom is connected to the central carbon atom that can give a possibility to form a leaving group as an anion therefore the characteristic reaction of the combined functional groups is nucleophilic substitution (SN). The degree of the electron deficiency at the central carbon atom of the combined functional groups depends on the possibility of a delocalization between the heteroatom components inside the functional group This kind of delocalization can increase the electron density at the central carbon atom – in this way it can decrease the ease of attack of the functional group by a nucleophilic reagent.

When simple functional groups are connected to a central carbon atom by covalent bonds, this molecule contains a combined functional group. The heteroatom of these simple functional groups can be nitrogen, oxygen or sulphur. There are combined functional groups that have only two simple functional groups. In these cases one heteroatom has to be connected by a double bond to the central carbon. This heteroatom can be oxygen (carbonyl earlier or oxo group C=O), nitrogen (imino group C=N–) or sulphur (thiocarbonyl earlier thioxo group C=S), but it is mostly oxygen. The combined functional groups of biomolecules always has a carbonyl part: carboxyl group (–COOH), ester group (e.g. the formula of a methyl ester: –COOCH3), carboxamide group (the formula of a carboxamide group with a primary amino group part: –CONH2), anhydride group (–CO–O–CO–) and acid chloride (–COCl). In the following only these combined functional groups will be discussed.

Combined functional groups (details are later)

The carbonyl group is not a traditional simple group, because there is a double bond between carbon and oxygen and a carbon is part of the functional group. But it is not a traditional combined group also, because it does not contain two simple groups. The general formula of the functional groups containing C=O fraction (carbonyl group and com