Nitrogen containing Organic compounds
Amines are moderately polar substances; they have bp that are higher than those of alkanes but generally lower than alcohols with similar molecular mass. Methanamine (CH3NH2) molecules form hydrogen to each other in a similar manner as it is ammonia. Gaseous amines possess a characteristic ammonia smell, while liquid amines have a distinctive fishy smell. Aromatically conjugated amines are often toxic and have the potential to be easily absorbed through the skin so should always be treated as hazardous.
However N-H---N hydrogen bonds are weaker than O-H---H hydrogen bonds because of the difference in the E.N between N and H is not as great as that between O and H. This difference account for the significantly lower bp of amines compared to that of the corresponding alcohols. Methyl, dimethyl, trimethyl and ethyl amines are gases under standard conditions. Most common alkyl amines are liquids and high molecular mass amines are solids at standard temperature.
In the gas phase the electron density of nitrogen in the family of methylamines increases with increasing methyl substitution.
However in aqueous solution: (CH3)2NH > CH3NH2 > (CH3)3N > NH3. The reason is that an alkylaminium ion in water is solvated and stabilised by hydrogen bonding via its hydrogen with water.
Uric acid is called an acid because it occurs tautomeric forms. In uricoletic animals, uric acid is the main form in which amino nitrogen is excreted.
Lactim form
The larger the value of Kb, the greater is the tendency of the amine to accept a proton from water and thus greater will be the concentration of RNH3+ and OH- in the solution.
Larger values of Kb are associated with those amines that are stronger bases than smaller values of Kb being weaker bases. An opposite relation is true for the pKb values: the lower is the pKb value the higher is the basicity of amine and conversely the higher is the pKb value the lower is the basicity.
Amines and heterocyclic nitrogen compounds.
Plants are able to make all their nitrogen containing compounds from inorganic nitrogen, CO2 and H2O. Animals however are more restricted in their ability to synthesise organic compounds and require some preformed nitrogen compounds in their diet. These must come from plants. Many but not all of the nitrogen containing compounds could be derived from ammonia.
Molecules of primary, secondary amines can form strong hydrogen bonds to each other while molecules of tertiary amines cannot form hydrogen bonds to each other because of lack of N-H bond and available hydrogen bonding.
Propylamine, bp 49oC forms 3 hydrogen bonds to other propylamine molecules whereas ethylmethlyamine, bp 34oC forms only 2 hydrogen bonds to other ethylmethlyamine molecules. No hydrogen are possible between trimethylamine, bp 2.9oC molecules and consequently it has the lowest bp among isomers.
Pteridine and alloxazin are more complex examples of heteroaromatic system obtained in this way. Alloxazine may be considered as a heterocyclic analogue of anthracene. Although the parent heterocyclic compounds do not occur naturally their derivatives are widespread in nature and of considerable importance.
Pyridoxin is derived from pyridine and it is a vitamin of B group. Pyridoxal phosphate includes a pyridine ring that is slightly basic as well as phenolic hydroxyl group that is slightly acidic. Thus pyridoxin phosphate derivative form stable tautomeric forms in which the pyridine nitrogen atom is protonated and positively charged while the hydroxyl group is deprotonated forming a phenolate. Pyridoxal phosphate is cofactor required for decarboxylation and transamination of amino acids.
Flavin Adenine Dinucleotide (FAD) is an electron carrier which consists of a flavin mono nucleotide (FMN) unit (riboflavin part with a phosphate part) and an AMP unit. The isoalloxizane ring of the molecule serves as a transient carrier of a pair of hydrogen atoms removed from the substrate molecule by the dehydrogenases.
Pyrimidine and purine derivatives are important in nucleic acids but they are also found as building blocks of several naturally occurring compounds. Purine is the skeleton of uric acid.
when nitrogen is part of a hero cyclic ring the basicity of these compounds is dependent upon hybrid state of nitrogen and whether the lone pair of electrons is involved in the formation of Pi election sextet.
Pyrrolidine and piperidine both include sp3 hybridised nitrogen which has a free available lone pair for accepting a proton: thus these 2 compounds have similar basicity to the secondary alkyl amines. Pyridine is a weaker base than the alkyl or cycloalkyl amines but much stronger base than pyrrole.
Heterocylcic nitrogen compounds: As with benzenoid aromatic system, fused heterocyclic aromatic compounds with nitrogen heteroatom are also possible.
Quinoline and isoquinoline are derived by fusion of benzene and pyridine rings. Indole the parent from which amino acid tryptophan is derived consists of benzene and pyrrole rings fused together.
Deficiency of folic acid causes a type of anaemia in which red blood cells do not mature properly. Derivative of folic acid, tetrahydrofolic acid functions as an intermediate carrier of 1C groups like methyl, formyl in a number of enzymatic reactions.
Riboflavin (vit B2) is derived from alloxazine. It occurs as the prosthetic group in a number of dehydrogenases generally coupled to nucleotides. A prosthetic group is the non protein constituent of an enzyme which is frequently involved chemically in the enzyme catalysed reaction.
Serotinine a neurotransmitter and vasoconstrictor in vertebrates is formed from tryptophan an amino acid derived from indole a heterocyclic amine formed by the fusion of benzene and pyrrole.
Serotinine plays an important role in modulation of anger aggression body temperature mood sleep human sexuality. Acetyl choline a quaternary amine is involved in nerve impulse conduction, it is formed by acylation of choline by acetyl CoA.
Papaverine morphine and codeine are all alkaloid obtained from the opium poppy. Morphine was first isolated from opium and its isolation represented one of the rest instances of the purification of an active drug. Morphine is one of the most potent analgesics known and is still used extensively in medicine to relive pain especially deep pain. its greatest drawbacks is its tendencies to lead to addiction and to depress respiration
Strychnine is a CNS stimulant and has been used medically to counteract poisoning by CNS depressants. Prontosil inhibited the growth of streptococci. Protonsil breaks down in human body to produce sulphanilamide and that sulphanilamide is the actual active agent against streptococci. Its inhibits the enzymatic steps of the bacteria that is involved in synthesis of folic acid Sulfapyridine is found to be effective against pneumonia.
Another important feature of NH3 molecule is that it behaves as a base in aqueous solution since the lone pair of electrons on the nitrogen can take up a proton forming NH4+ ion. The hydrogen bonding of ammonia to water molecules would contribute to the water solubility of the ammonia and of related organic compounds.
The 3rd important characteristic of ammonia which is also applicable to many of the nitrogen containing organic compound is that it contains highly polarised N-H bonds; thus it can form hydrogen bonding during molecular interactions with each other or with other molecules like water. The hydrogen bondings between the ammonia molecules contribute to its higher bp compared to other structural homologues such as PH3
The unshared pair of electrons on the nitrogen atom can be donated to positive ions such as hydrogen ion, thus making amines basic compounds. In primary, secondary and tertiary amines the bond angle will be close to , but slightly above of 107 because of the larger size of the alkyl groups (compared to hydrogen) needs more space and they also repulse each other more effectively. In quaternary amines when the lone pair is also shared between 2 atoms the bond angles would be close to the tetrahedral bond angle (109.5).
The amino group could be bonded to saturated or aromatic ring. In addition, the nitrogen could be part of the ring structure as a heteroatom in saturated 5 or 6-membered ring like piperidine and pyrrolidine respectively. One or two nitrogen atoms are involve as heteroatom in the aromatic ring structures of pyrrole and pyridine or imidazole and pyrimidine.
Like ammonia, amines act also as bases. Amines are relatively weak bases. They are stronger bases than water but are far weaker bases than hydroxide ions or alkoxide ions.
The basicity of amines varies by molecule and in general it largely depends on: availability of the lone pair of electrons from nitrogen; electronic properties of the attached substituent groups; degrees of salvation of the protonated amine, which depends mostly on the solvent used in the reaction.
When the basicity constants of the amines are examined it is seen that most aliphatic primary amines are somewhat stronger bases than ammonia. Examining the basicity constants of the aromatic amines it is seen that they are much weaker bases than either the alkyl- and cycloalkyl-amines or ammonia.
The difference in the basicity of alkyl- and aryl amines is due to the effect of the substituent group on the electron density of nitrogen and on the stabilisation of the alkyl-ammonium ion or the amine. In general, the electron-donating releasing groups increase whereas electron attracting withdrawing groups decrease the basicity of the amino nitrogen. The electron releasing ability of an alkyl group to stabilise the alkylaminium ion that results from the acid-base reaction by dispersing its positive charge. It stabilises the alkyl ammonium ion to a greater extent than it stabilises amine.
Spermine and spermidine are found in all bacteria and most animal cells. They are growth factors for some microorganism and serve to stabilise membrane structures in bacteria as well as structure of ribosomes some viruses and the DNA of many organisms.
The name alkaloid comes from the fact that these substances a alkali-like that is since alkaloids are amines they often react with acids to yield soluble salts. The nitrogen atoms of most alkaloids are present in heterocyclic rings.
In ground state nitrogen has 5 valence electrons in a configuration of 2s2 2px1 2py1 2pz1. Structural analyses of ammonia and other nitrogen containing compounds reveal an H-N-H bond angle of about 107. The lone pair is closer to the nitrogen (since its attracted by nitrogen only) than bonding pairs (which are attracted by both nitrogen and hydrogen) and it repels the bonding pairs resulting in a trigonal pyramidal geometry of NH molecules and a decrease of H-N-H to 107 from ideal 109.5
Unpaired electrons of px, py, pz orbitals do not form chemical bonding with hydrogen atoms directly since in this case the bond angle would be close to 90 because of the perpendicular orientation of the p orbital in the ground state. The 2s and 2 p orbitals are hybridised and form sp3 hybrid orbitals in the nitrogen. 3 of these of tetrahedrally oriented sp3 hybrid orbitals with unpaired electrons form covalent bonding with hydrogens in ammonia while one pair of electrons remains non bonded i.e. lone pair.
Beside the primary and secondary amines tertiary amines can also form hydrogen bonds to water, because the partial negative charge of its nitrogen together with the lone pair of electrons serves as an excellent hydrogen acceptor for hydrogen of water.
All low molecular mass amines are water soluble. Solubility decreases proportionally with the increase in the number of carbon atoms in the molecule- especially when the carbon atom number is 6 or greater and when amino group is bonded to a ring.
Amines are substituted ammonia in which one or more of the hydrogen have been replaced by a carbon chain. The -NH2 group like the parent compound ammonia has an unshared pair of electrons on the nitrogen making the group basic.
Amines are classified as primary, secondary, tertiary, or quaternary depending upon the number of carbon atoms bonded to the nitrogen. In primary, secondary and tertiary amines one, two or three carbon chains make covalent bonding to the nitrogen respectively. Quaternary nitrogen compounds are substituted NH4+ in which all hydrogen are replaced by carbon chains/rings. They bear a positive charge and exist as salts or hydroxides. The structure of primary, secondary and tertiary amines are similar to ammonia: 2 unshared electrons of nitrogen are at one apex of a pyramid and the alkyl groups and the hydrogens (in pri & sec amines) occupy one of the other 3 corners.
Cocaine is also a local anaesthetic and for a time it was used for these purposes. but when its tendency to cause addiction was recognised efforts were made to develop other local anaesthetics. This led to the synthesis of novocaine a compound the has the same structural features as cocaine.
Atropine is an intense poison used to dilate the pupil of eye in dilute solutions. 12 hour continuous release of capsules used to receive symptoms of the common cold.
Pyrimidine and Purine are the parent compounds of the 2 classes of nitrogenous bases found in nucleotides, the building blocks for nucleic acids, RNA and DNA. Purine may be regarded itself as a derivative of pyrimidine; it consists of a pyrimidine ring and an imidazole ring fused together. 3 pyrimidine derivatives uracil, thymine and cytosine and 2 purine derivatives adenine and guanine constitute the major nitrogenous bases found in nucleotides.
Caffeine
Lactim form <=> Uric acid <=> Lactam form
Caffeine is the principal stimulant and diuretic of coffee, is a simple purine derivative and theophylline and theobromine which occur in tea and cocoa respectively have very similar structures.
The predominant alkaloid of tobacco plant is nicotine. In very small doses nicotine acts as a stimulant but in larger doses it causes depression nausea and vomiting. In still larger doses it is a violent poison. Nicotine salts are used as insecticides.
Coniine is highly toxic, its ingestion may cause weakness drowsiness nausea laboured respiration paralysis and death. In small doses cocaine decreases fatigue increases mental activity and give a general feeling of well being. Prolonged use of cocaine however leads to physical addiction and to periods of deep depression.
A derivative of thiamine, thiamine pyrophosphate is required as a cofactor in the enzymic decarboxylation of Alpha ketoacids, thus its is an important coenzyme for example in the pyruvate dehydrogenase complex during the interconversion of pyruvate into acetyl-coenzyme A.
Deficiency of thymine in the human diet causes beriberi a disease characterised by neurological disorders paralysis and loss of weight.
Primary aliphatic amines react with nitrous act through reaction called diazotization to yield highly unstable aliphatic diazonium salts. Benzen sulfonamide and derivative of this compound used as sulpha drugs in medicine
Even at low temperatures, aliphatic diazonium spontaneously by losing nitrogen to produce alcohols. Aliphatic secondary amines react with nitrous acid to yield N-nitrosoamines. N-nitrosoamines usually separate from the reaction mixture as oil yellow liquids. No reaction of nitrous acid with tertiary amines occurs.
DNA base pairing: Purine: Guanine & Adenine Pyrimidine: Cytosine, Uracil & Thymine
Guanine + Cytosine & Adenine + Thymine
Pyrimidine and purine bases are weakly basic compounds and they may exist in 2 or more tautomeric forms depending on the pH. Uracil for example occurs in actual and lactim forms. At neutral pH (pH 7.0) the lactam form of uracil predominates.
Guanine can be paired with cytosine and adenine with thymine to form base pairs that have essentially the same shape. These base pairs that are held together by specific hydrogen bondings. This base pairing scheme was supported by studies of base composition of DNA from different species.
Dopamine, epinephrine and norepinephrine function physiologically in the regulation of heart rate and blood pressure. Epinephrine also is an activator of glycogen breakdown in liver and muscle. These hormones are formed from tyrosine.
Histidine is an amino acid derived from imidazole. Histamine an important vasodilator is from histidine by decarboxylation. Histamine is a biogenic amine involved in local immune response as well as regulating physiological function in the gut acting as a neurotransmitter. As part of an immune response to foreign pathogens histamine is produced by basophils and by mast cells found in nearby connective tissues.
