Carbonyl Compounds and Carboxylic Acids

Carbonyl Compounds

Structure and Properties

• Carbonyl compounds feature a carbon-oxygen double bond (C=O), which is fundamental to their reactivity and properties.

• The carbon-oxygen double bond is polar due to the significant difference in electronegativity between carbon and oxygen. Oxygen, being more electronegative, attracts electrons more strongly, resulting in a partial positive charge (\delta+) on carbon and a partial negative charge (\delta-) on oxygen. This polarity influences the compound's reactivity and intermolecular interactions.

• The general formula for carbonyl compounds is R_2C=O, where R represents various substituents. This formula encompasses a wide range of compounds, including aldehydes, ketones, carboxylic acids, and esters.

• Each atom (C, O) in the carbonyl group has 3 electronic regions, dictating the spatial arrangement and reactivity of the molecule.

• The arrangement of bonds at the carbon is trigonal planar. This geometry affects the molecule's overall shape and how it interacts with other molecules.

Carbonyl Compound Characteristics

• The carbonyl group is planar, meaning all atoms directly bonded to the carbonyl carbon lie in the same plane. This planarity is critical for understanding the stereochemistry and reactivity of carbonyl compounds.

• Carbon and oxygen atoms in the carbonyl group are sp^2 hybridized. This hybridization results in the trigonal planar geometry and influences the types of reactions the carbonyl group can undergo.

• The angle between the three atoms bonded to the carbonyl carbon is approximately 120° because electronic geometries are trigonal planar. This affects the molecule's physical and chemical properties.

Aldehydes and Ketones

• An aldehyde features a carbonyl group (C=O) bonded to a hydrogen atom (H) and a hydrocarbon group (RCHO). The presence of the hydrogen atom is a distinguishing feature of aldehydes, affecting their oxidation and reduction reactions.

• A ketone has a carbonyl group (C=O) bonded to two hydrocarbon groups (R_2C=O). The two hydrocarbon groups influence the ketone's stability and reactivity.

• Common names and examples:

  • Acetaldehyde (CH_3CHO) is involved in the cellular oxidation of ethanol. Understanding its role in metabolic pathways is essential in biochemistry.

  • Formaldehyde (HCHO) is used as a formalin preservative. Its ability to cross-link proteins makes it useful for preserving biological specimens.

  • Acetone (CH3C(=O)CH3) is found in nail polish remover and cassava (which also contains HCN). Acetone's solvency properties make it a common ingredient in various industrial and cosmetic products.

Aldehydes and Ketones: Properties

• Aldehydes with one carbon atom (C1) are gases, while those with more than two carbon atoms (> C2) are liquids at room temperature. Ketones are generally liquids, influencing their handling and applications in various chemical processes.

• Most aldehydes and ketones have a distinct odor, which can be attributed to their volatility and interaction with olfactory receptors.

• Due to the higher electronegativity of oxygen (3.5) compared to carbon (2.5), the C=O group is polar. This polarity leads to dipole-dipole interactions, affecting boiling points and solubility.

• They interact in the pure state via dipole-dipole interactions, leading to relatively high boiling points compared to nonpolar compounds. This affects their use in industrial applications and as solvents.

• They exhibit higher water solubility than hydrocarbons due to their ability to form hydrogen bonds. This property is essential in biological systems, where water is the primary solvent.

• Electronegativity values: O (3.5), C (2.5), H (2.1). These values help explain the polarity of various bonds in organic molecules.

Aldehydes / Ketones: Naming

• The parent chain is the longest chain containing the carbonyl group, which is critical for systematically naming organic compounds.

• In ketones, the position of the carbonyl group must be numbered to distinguish between different isomers.

• In aldehydes, the carbonyl carbon is C1 by default due to its terminal position in the carbon chain.

• Aldehydes have the suffix -al, which denotes the presence of an aldehyde functional group in the molecule.

• Ketones have the suffix -one, indicating the presence of a ketone functional group.

Carboxylic Acids

• Carboxylic acids contain a carboxyl group (carbonyl + hydroxyl), which gives them acidic properties.

• The general formula for an aliphatic carboxylic acid is RCOOH, where R is an alkyl group. This formula represents a broad class of organic acids.

• The general formula for an aromatic carboxylic acid is ArCOOH, where Ar is an aryl group, indicating the presence of an aromatic ring.

• Examples:

  • Acetic acid (ethanoic acid) is a common carboxylic acid found in vinegar.

  • Formic acid (methanoic acid) is found in ant stings and is the simplest carboxylic acid.

• Formation: Oxidation of primary alcohols (RCH_2OH) yields carboxylic acids (RCOOH), passing through an intermediate aldehyde with the use of an oxidizing agent [O]. This is a common method for synthesizing carboxylic acids in the lab.

Carboxylic Acids II

• Weak acids with a pKa around 5: RCOOH + H2O \rightleftharpoons RCOO^- + H_3O^+. The equilibrium indicates the partial dissociation of carboxylic acids in water.

• Fatty acids are long-chain carboxylic acids found in living cells, serving as building blocks for lipids and playing a vital role in energy storage and cell structure.

• Animal fatty acids are saturated, whereas many plant fatty acids are unsaturated (contain double bonds). This difference affects their physical properties and health implications.

  • Example: Oleic acid (C{17}H{33}COOH) makes up about 80% of olive oil. Its monounsaturated nature is associated with various health benefits.

Carboxylic Acids III

• Examples of saturated carboxylic acids and fatty acids:

  • Formic acid (HCO_2H) was first obtained by distilling ants; some ant species use it as a defense mechanism.

  • Acetic acid (CH3CO2H) is obtained by distilling vinegar.

  • Butyric acid (CH3(CH2)2CO2H) is found in rancid butter and sweat. The odour becomes worse as chain length increases.

  • Caproic acid (CH3(CH2)4CO2H) is found in goat fat.

  • Stearic acid (CH3(CH2){16}CO2H) is found in cow's milk (10%).

Carboxylic Acids III

• Common unsaturated fatty acids:

  • Oleic acid: CH3(CH2)7CH=CH(CH2)7CO2H (monounsaturated).

  • Linoleic acid: CH3(CH2)3(CH2CH=CH)2(CH2)7CO2H (polyunsaturated, an essential fatty acid in the human diet), found in corn oil (60%).

• Common dicarboxylic acids:

  • Oxalic acid: HO2CCO2H (found in rhubarb). Its presence in certain foods can affect mineral absorption.

  • Succinic acid: HO2CCH2CH2CO2H (intermediate in the TCA cycle S5, the oxidation of C6H{12}O6 to CO2 & H_2O).

  • Tartaric acid: A diprotic acid found in plants such as grapes, contributing to their tart taste.

Carboxylic Acid Salts

• A common tricarboxylic acid is citric acid, which gives characteristic acidity to fruit juices and is an intermediate in the TCA cycle (S1).

• Water-soluble carboxylic acid salts are formed by the reaction of the acid with an alkaline base.

  • Example: CH3COOH + NaOH \rightarrow Na^+CH3COO^-

• The name is derived from the carboxylic acid, where the suffix -ate replaces -ic acid.

  • Example: Sodium acetate or sodium ethanoate, commonly used in various applications, including food preservation.

Carboxylic Acid Derivatives

• Three main carboxylic acid derivatives:

  • The “hydroxyl” group is replaced by either a chloro, alkoxy, or amino/ammonia group, leading to diverse compounds with varied properties.

Esters

• The functional group is an acyl group RC(=O) bonded to an –OR or an –OAr group, with general formulas RCO2R' or RCO2Ar.

• Formation: RCOOH + R'OH [H^+] \rightarrow RCOOR' + H_2O. This reaction is an esterification, typically catalyzed by an acid.

• Esters often have sweet smells; for example, C4H9COOCH_3 smells like pineapple. Another example is ethyl ethanoate (ethyl acetate), used as a solvent and flavoring agent.

Lipids

• Lipids are a complex group of molecules found in plants and animals, extracted using non-polar solvents (e.g., Et_2O, hexane). Their solubility in non-polar solvents defines their classification.

• Triacyl esters are a common class of lipid, found in living organisms as fats (saturated fatty acids) or oils (more unsaturated fatty acids) and used as an energy storage source. They are crucial for energy metabolism and insulation.

• Simple lipids may be formed by linking several fatty acids to a common alkanol chain. For example, tristearin is glycerol linked to 3 stearic acids.

• Breaking the many C-C bonds releases a lot of energy, making lipids an efficient energy storage form in living organisms.

Soaps

• Soaps are fatty acid salts (formed by hydrolysis of triacyl esters with a strong base) and are generally complexed to cations of Groups 1A or 2A. The process is known as saponification.

Acid Halides

• The functional group is an acyl group RC(=O) bonded to a halogen, typically –Cl, RCO_2Cl (chlorine is the usual halogen). These are highly reactive compounds used in organic synthesis.

• Formation: RCOOH + ClSOCl \rightarrow RCOCl + HCl + SO2 [thionyl chloride SO2Cl_2]. This method is commonly used to convert carboxylic acids into acid chlorides.

Amides

• The functional group is an acyl group RC(=O) bonded to an –NH2, –NRH, or –NR2 group (a trivalent N - one that has 3 covalent bonds). Amides are important in peptides and proteins.

• Formation: RCOOH + 'NH2H' \rightarrow RCONH2 + H_2O. This reaction involves the condensation of a carboxylic acid and an amine.

• Amides can be classified as primary (RCONH2), secondary (RCONHR’), or tertiary (RCONR’2), based on the number of alkyl groups attached to the nitrogen atom.

Anhydrides

• The functional group of an anhydride is formed when two carbonyl groups are bonded to the same oxygen. Anhydrides are highly reactive acylating agents.

• Symmetrical anhydrides are derived from two identical acyl groups, whereas mixed anhydrides are derived from two different acyl groups, leading to different reactivity patterns.

• IUPAC naming: Drop the word "acid" from the name of the carboxylic acid and add the word "anhydride”.

• N.B. the acyl group is –RC(=O)

• Example: acetic anhydride (IUPAC: ethanoic anhydride) has the structure (CH3CO)2O.

Carboxylic Acid Derivatives: Character & Properties

• Carboxylic acids are polar compounds due to the presence of the carboxyl group (COOH).

• Carboxylic acids have significantly high boiling points compared to alkanes (e.g., acetic acid: 118^oC) because they form strong hydrogen bonds.

• They are associated by hydrogen bonding into dimers, affecting their physical properties and behavior in solutions.

• Carboxylic acids are more soluble in water than alcohols, ethers, aldehydes, and ketones of comparable molecular weight (MW) because they form hydrogen bonds with H_2O through C=O and OH groups. This solubility is essential in biological systems.

• Water solubility decreases with increasing parent chain length due to the increasing hydrophobic character of the alkyl chain.

Carboxylic Acid Derivatives: Naming

• Carboxylic acids: For the IUPAC name, drop the final –e from the parent alkane and replace it with the suffix –oic acid. The carboxyl carbon is by definition number 1, simplifying nomenclature.

Naming Acid Chlorides

• Acid halides are named by replacing the suffix –oic acid in the name of the parent carboxylic acid and changing it to –oyl halide. This systematic nomenclature aids in identifying and classifying these compounds.

• Acid chlorides are highly reactive with water! They undergo rapid hydrolysis, making them useful in various chemical syntheses where controlled reactions are crucial.

Naming Esters and Lactones

• For naming esters and lactones (cyclic esters):

  • The alkyl or aryl group bonded to O is named first, indicating the substituent attached to the oxygen atom.

  • Followed by the name of the acid, in which the suffix –oic acid is replaced by the suffix –oate (as a separate word). This nomenclature reflects the ester's origin from a carboxylic acid and an alcohol.

  • Cyclic esters are given the common name lactone.

    • Example: gamma -hexalactone [IUPAC: (5S)-5-ethyldihydro-2(3H)-furanone], showcasing the systematic naming of complex cyclic structures.

• Ethyl ethanoate (ethyl acetate) has a sweet, coconut, cream, herbaceous, hay, woody scent, making it a common ingredient in fragrances and flavorings.

Naming Amides and Lactams

• Named by dropping the suffix –oic acid from the name of the parent acid and replacing it with –amide, reflecting their origin from carboxylic acids.

• Substituents bonded to N are placed first in the name, using N in italics in front of the name to indicate substitution on the nitrogen atom.

• Cyclic amides are given the common name lactams (e.g., beta β-propiolactam or 3-propanolactam [IUPAC: 2-azetidinone]).

• Example: N,N-dimethylmethanamide (N,N-dimethylformamide), commonly used as a polar aprotic solvent in organic chemistry.

Analysis of Oseltamivir (Tamiflu) API

• Active Pharmaceutical Ingredient (API) of Tamiflu (Oseltamivir) is ethyl (3R,4R,5S)-4-acetamido-5-amino-3-(pentan-3-yloxy)-cyclohex-1-ene-1-carboxylate. Analyzing its structure provides insights into its pharmacological activity.

• Questions to consider:

  • What are the main functional groups present in Oseltamivir? Identifying these groups helps understand its chemical properties and reactivity.

  • What are the ‘characteristics’ (polarity, acidity) of the functional groups? These characteristics influence its solubility, bioavailability, and interactions with biological targets.

  • Is there any stereochemistry (cis/trans, E/Z or R/S) involved? Stereochemistry is crucial for understanding its binding affinity and selectivity towards its target enzyme.

  • Stereocenters are 3R, 4R, and 5S, indicating the three-dimensional arrangement of atoms around these centers, which is critical for its biological activity.