CHM 219 Module 7 exam with complete solutions

Define Heterocyle as it applies to organic molecules. Cyclic molecules in which one or mroe carbon atoms are replaced by heteratoms - elements other than carbon or hydrogen. What are two main sub-groups of heterocyclic compounds? Aliphatic and Aromatic Previous Play Next Rewind 10 seconds Move forward 10 seconds Unmute 0:02 / 0:15 Full screen Brainpower Read More Explain why pyridine is soluble in water. First - the ability of pyridine to accept Hydrogen bonding interactions from water molecules due to the lone pair of electrons in the nitrogen atom. In addition, the electronegative nitrogen creates a relatively strong dipole moment in the pyridine molecule, thus making pyridine a polar compound overall. Is pyridine more likely to act as an acid or base? Explain. Pyridine, like all amines, is a weak base. Amines use the lone pair on the nitrogen atom to accept protons and thus act as bases. Name the two main classes of reactions that the pyridine molecule will undergo - EAS - Electrophilic Aromatic Substitution NAS - Nucleophilic Aromatic Substitution Heterocyclic six-membered rings with two or more N atoms present as a part of the ring system are known as what type of heterocycles? Azines Why are pyrimidines the most biologically important members of the diazene family of molecules? Derivatives of pyrimidines are important bases in the nucleic acids DNA and RNA , namely cytosine, thymine and uracil. Name the most important five-membered heterocyclic compounds containing a single heteroatom substitution and state which element is the heteroatom in each. Furan (Oxygen based) Pyrrole (Nitrogen based) Thiophene (sulfur based) What is the most important difference between five and six membered heterocycles in terms of the bonding a the heteroatom? The heteroatom of a five-membered ring contributes two electrons (one lone pair) to the aromatic pi system of the ring to make the molecule aromatic. This is in sharp contrast to six membered heterocycles where the heteroatom only contributes one electron to the aromatic pi system. Explain why Pyrrole is a weaker base than pyridine, even though both are aromatic, heterocyclic amines. This is due to the availability of the lone pair. In pyridine, the lone pair is available (not part of the aromatic pi system) to accept an acidic proton. In Pyrrole, this is not the case. Protonation of the lone pair of pyrrole destroys the aromatic pi system and the special stability of aromaticity; thus, pyrrole is much less likely to accept an acidic proton on its nitrogen atom. Introduction of a nitrogen to the ring of furan, pyrrole, or Thiophene creates a family of heterocyclic compounds known as what? Azoles What is the definition of a fused ring? In a fused ring system, two (or more) rings are fused together to form a larger molecule. To be fused means that each ring shares two (or more) common atoms as a part of the structure of each ring. The molecule Indole has what ring fused to the C2-C3 bond of a pyrrole ring? Benzene Adenine and guanine, two of the nitrogenous bases present in DNA and RNA , contain what fused ring heterocycle? Purine Heterocycles Cyclic organic molecules in which one or more carbon atoms are replaced by heteroatoms - elements other than C or H. Largest class of organic compounds known. Most common heteroatoms... O, N, S Two subgroups of heterocyclic compounds Aromatic and Alliphatic (Non-Aromatic) Examples of Non-Aromatic (Aliphatic) Heterocycles Epoxides, Glucose Pyridine Six membered heterocyclic analog of benzene. One of the CH units of the (benzene) ring is replaced by a N atom. Aromatic Tends to undergo substitution reactions rather than addition (which would destroy aromaticity). The substitution of the N atom in the ring changes many properties of the molecule. Pyridine Properties Miscible in most organic solvents, and completely miscible with water. Boiling point is 35 degrees above that of Benzene due to dipole-dipole attractive forces. Weak base and will react with strong acids to form pyridinium salts. The ability if pyridine to act as a base makes it suited to act as a proton scavenger in acid producing reactions, like the conversion of alcohols to alkyl chlorides using thionyl chloride. Electrophilic Aromatic Substitution (EAS) An H is replaced by an electrophile. Requires very harsh conditions and occurs very slowly. Can be nitrated or brominated at very high temperatures and with ver strong acid catalysis. Electron withdrawal by the N makes the ring partially positive and this not as receptive to attack by electrophiles like NO2 or Br. The strongly acidic conditions cause protonation of the N atom and positive pyridinium ion is even less attatractive to electrophiles. When EAS does occur it happens at C3 Why is C3 preferred in EAS? It is preferred as the positive charge that forms on the carbon during the reaction is the one position that does not put the positive charge on the electronegative nitrogen via resonance (especially unstable if the N is already protonated). Nucleophilic Aromatic Substitution (NAS) Pyridine undergoes this more easily. Nucleophile displaces a hydride ion or a halide ion (on a substituted pyridine) from the aromatic ring. Due to the presence of the N heteroatom the ring is partially positive and therefore is more attractive to nucleophile rahter than electrophiles. Strong nucleophiles like Alkoxide ions (RO-) and amide ions (NH2-) hello to facilitate the reaction. Azines Heterocyclic six membered rings with two or more N atoms present as a part of the ring system. Diazenes Heterocyclic six membered rings with two N atoms. Three constitutional isometric forms - pyridazine (1,2 N disubstitution) pyrimidine (1,3 N Disubstitution), pyrazine (1,4 N disubstitution) Pyrimidines Most important of the diazenes (1,3 disubstitution) Important bases that are derivatives - DNA and RNA (specifically cytosine, thymine and uracil). Highest Subsitution Tri and Tetrazenes Five-Membered Heterocycles Furan (O based) Pyrrole (N based) Thiophene (S based) These molecules contain a C ring with a single heteroatom substitution. Aromatic. Planar. Tend to undergo EAS One important difference in 5 and 6 membered heterocycles... The heteroatom of a five membered ring contributes two electrons (one lone pair) to the aromatic pi system of the ring to make the molecule aromatic. This is in sharp contrast to six-membered heterocycles where the heteroatom only contributes one elytron to the aromatic pi system. Pyrrole Much weaker base than pyridine due to the availability of the lone pair. In pyridine the lone pair is available (not part of the aromatic pi system) to accept an acidic proton. In Pyrrole, this is not the case. Protonation of the lone pair of pyrrole destroys the romantic pi system and special stability of aromaticity; this pyrrole is much less likely to accept an acidic proton on its nitrogen atom. Bonding of Thiophene and Furan They have two lone pairs of their respective heteroatoms. While one pair is involved in the aromatic pi system, the other is in the same plane as the atoms of the ring and is available for protonation. Pyridine-Like Atoms When the nitrogen atom of an aromatic heterocycle is participating in a pi bond, then the lone pair occupies an sp2 orbital in the same plane as the ring and is available to react as a weak base. Pyrrole-like Atoms When the nitrogen atom of an aromatic heterocycle has single binds only then the lone pair participates in the conjugated pi system to create aromaticity and is not available to react as a weak base. Substitution at C2 is preferred... As the carbocation intermediate that forms during the reaction is delocalized over mroe atoms (and hence, more stable) when substitution occurs at this position. Azoles N in the place of C3 in Furan, pyrrole or Thiophene. Oxazole , Imidazole, Thiazole Inclusion of the N at C3 results in a pyridine-like nitrogen, which is involved in a pi bond. The lone pair on this N is this available for bonding to acidic proton. Imidazole Very good base... the positive charge obtained from protonation of the N at C3 can be delocalized via resonance over both N atoms. Present in the amino acid histidine and is important in the reasons of many enzymes AThiazole Occurs naturally as thiamin (vitamin b1) a coenzyme required for many biochemical processes essential to human life. Fused Ring Heterocycles Two or more rings are fused together to form a larger molecule. To be fused means that each ring shares two or more common atoms as a part of the structure of each ring. Indole Made by fusing a benzene ring to the C2-C3 bond of pyrrole results in a bicyclic , fused ring compound. Component in many biologically active compounds including the amino acid , tryptophan. Purines Contains a pyrimidine ring fused to an imidazole ring. Uric acid (present in urine of all carnivores), caffeine (found in chocolate) are all based on the structure of purine. ADenine and guanine. Add or remove terms Choose a st