Comprehensive Notes on Functional Derivatives of Carboxylic Acids, Amines, and Carbonyl Compounds

Acylhalogenidy

Acyl halides are represented by the general structure $R-C(=O)X$. They are characterized by their high reactivity toward nucleophilic agents, reacting significantly better than other functional derivatives of carboxylic acids. This increased reactivity is primarily due to the strong $-I$ effect of the halogen atom, which selectively lowers the electron density on the neighboring carbonyl carbon, making it a prime target for nucleophilic attack ($Nu^-$). Additionally, acyl halides can react with electrophiles, specifically through the substitution of hydrogen at the $\alpha$-carbon position. The primary reaction pathway for these compounds is the addition-elimination mechanism.

Specific examples include ethanoylchlorid ($CH_3COCl$) and benzoyl bromid ($C_6H_5COBr$). Acyl halides are systematically named as -oyl halides or halides of carboxylic acids ($halogenid\ harboxylové\ kyseliny$). The functional group itself is referred to as halogen karbonyl-.

In terms of specific chemical transformations, acyl halides react with water ($s\ vodou$), leading to the formation of carboxylic acids and the release of hydrogen chloride ($HCl$). When reacting with alcohols ($s\ alkoholy$), they yield esters. For example, the reaction of ethanoylchlorid with methanol ($CH_3-O-H$) produces an ester and $HCl$. They also react with nitrogen-based nucleophiles ($dusíkatými\ nukleofily$) such as amines or ammonia to form amides. A specialized reaction involves the reductive removal of the halogen ($reduktivni\ odstranění\ halogenu$); when treated with hydrogen ($H_2$) in the presence of a palladium on barium sulfate catalyst ($Pd/BaSO_4$), the acyl halide is converted into an aldehyde.

Anhydridy

Anhydrides consist of two carbonyl groups connected by an oxygen atom ($(RCO)_2O$). In these molecules, both carbonyl groups serve as potential reaction centers. Anhydrides are considered very weak C-acids ($velmi\ slabé\ C-kyseliny$). The reaction mechanism involves the addition of a nucleophile to one of the carbonyl groups, followed by the elimination of a carboxylate anion ($RCOO^-$) from the second carbonyl group.

Naming examples provided include ethananhydrid (acetic anhydride) and benzen-1,2-dikarboxanhydrid (phthalic anhydride). Reactions of anhydrides with water, alcohols, thiols, amines, and aromatic compounds generally yield the same primary products as acyl halides, with the specific addition of a carboxylic acid as a byproduct instead of a mineral acid like $HCl$. For example, the reaction of ethananhydrid with an amine ($CH_3-NH_2$) results in the formation of an amide and a carboxylate/carboxylic acid byproduct ($CH_3COO^-$).

Amidy

Amides ($R-CONH_2$) exhibit a lower reactivity toward nucleophilic agents at the carbonyl group compared to acyl halides or anhydrides. This addition is described as occurring with difficulty ($obtížně$). However, the nitrogen atom in the amide group is capable of reacting with electrophiles. Furthermore, the hydrogen atom attached to the nitrogen is acidic enough to be cleaved by a strong base ($vodík\ na\ dusíku\ může\ být\ silnou\ bází\ odštěpen$). Amides are described as both weak acids and weak bases.

In electrophilic aromatic substitution ($S_E Ar$), the amide group directs substitutes to the meta position ($m-$). Nucleophilic reactions involving amides typically include hydrolysis and reduction. Hydrolysis involves the addition of water or hydroxide to the carbonyl carbon. Reduction of amides using lithium aluminum hydride ($LiAlH_4$) results in the formation of an amine ($CH_3-CH_2-NH_2$). Amides also react with electrophiles such as sodium nitrite ($NaNO_2$) in the presence of $HCl$, which can lead to the formation of a carboxylic acid and nitrogen gas. Systematic naming uses the suffixes -amid or -karboxamid, and the substituent group is called karbamoyl.

Aminy

Amines ($NH_2$ group) act as both nucleophiles and bases due to the lone electron pair on the nitrogen atom. In aromatic systems, the amine group exhibits a $+M$ and $-I$ effect, acting as an ortho/para ($o-/p-$) directing group.

Nucleophilic reactions of amines include reactions with halogen derivatives ($halogenderiváty$) via an $S_N$ mechanism. This process can proceed sequentially from a primary amine to secondary and tertiary amines, ultimately forming a quaternary ammonium salt (tetra… as noted in the transcript). For example, reacting $CH_3-Br$ with ammonia ($NH_3$) yields methylammonium bromide, which can react further. Amines also react with aldehydes and ketones ($s\ aldehydy/ketony$). This involves an initial addition to form an aminoalkohol, followed by the elimination of water ($-H_2O$) to create an imine ($imin$).

With carboxylic acids, amines form amides, though this typically requires heat ($\Delta t$). They can also react with esters to produce amides and eliminate an alcohol. In aromatic systems ($SE\ Ar$), amines are highly reactive toward electrophiles like bromine ($Br_2$), which can lead to multiple substitutions on the ring (e.g., forming 2,4,6-tribromoaniline). The oxidation of aromatic amines can produce nitroso- ($-NO$) or nitro- ($-NO_2$) compounds using reagents like Caro's acid ($H_2SO_5$) for nitrosation or potassium permanganate ($KMnO_4$) for full oxidation to a nitro group.

Karboxylové kyseliny

Carboxylic acids ($R-COOH$) possess multiple reactive sites. Bases can remove the acidic proton from the hydroxyl group ($-O-H$), resulting in the formation of a salt. Nucleophiles target the carbonyl carbon, while electrophiles can attack the $\alpha$-carbon or the carbonyl oxygen. The carboxyl group exerts $-I$ and $-M$ effects, which makes it a meta-directing ($m-$) group in aromatic substitution reactions. Against very strong acids, carboxylic acids can behave as weak bases.

Reactions of carboxylic acids include additions to alkenes and alkynes. The reaction with alcohols, known as esterification ($esterifikace$), is an equilibrium process that produces an ester and water. Because alcohols are weak nucleophiles, a strong acid catalyst such as sulfuric acid ($H_2SO_4$) or phosphoric acid ($H_3PO_4$) is required. Carboxylic acids also react with halogenating agents ($halogenačními\ činidly$) to produce acyl halides like $CH_3-COCl$. On an aromatic ring, the carboxylic acid group facilitates substitution at the meta position, such as the nitration of benzoic acid using a mixture of $HNO_3$ and $H_2SO_4$ to form meta-nitrobenzoic acid.

Nitrily

Nitriles ($R-C \equiv N$) feature a carbon-nitrogen triple bond. Nucleophiles react at the carbon atom because it carries a partial positive charge ($\delta+$). The nitrogen atom, possessing a lone electron pair, is susceptible to protonation ($protonaci$). Nitriles exert $-I$ and $-M$ effects and are meta-directing ($m-$) groups. They are named as nitriles ($-nitril$), carbonitriles ($-karbonitril$), or identified by the cyano- ($kyan-$) prefix. Examples include benzenkarbonitril and propannitril ($CH_3CH_2C \equiv N$).

Key nucleophilic reactions include the reaction with alcohols to form imino compounds, though the transcript notes this may be difficult ($asi\ špatně...$). Their reaction with Grignard reagents ($CH_3-CH_2-MgBr$) produces magnesium salts of imines ($horečnaté\ soli\ iminů$), which upon acidic hydrolysis ($H_2O, H^+$) yield ketones. The complete hydrolysis of nitriles with water leads to the formation of carboxylic acids.

Nitrosloučeniny

Nitro compounds ($-NO_2$) are characterized by the $-I$ and $-M$ electronic effects, which make them deactivating and meta-directing in aromatic systems. They behave as weak acids because a base can remove a hydrogen atom from the $\alpha$-carbon.

The reduction of nitro groups leads to different products depending on the reaction conditions. Reduction with iron and hydrochloric acid ($Fe/HCl$) produces a primary amine ($-NH_2$). Reduction with zinc and ammonium chloride ($Zn/NH_4Cl$) results in a hydroxylamine ($-NH-OH$). Using zinc and sodium hydroxide ($Zn/NaOH$) leads to hydrazo compounds ($-NH-NH-$).

Specific examples cited include 2-nitropropan ($CH_3CH(NO_2)CH_3$) and 1-fenyl-2-nitroethen ($C_6H_5-CH=CH-NO_2$). Base-catalyzed reactions on the $\alpha$-carbon can lead to condensation reactions, such as the formation of nitroalkenes from nitroalkanes and aldehydes/ketones.

Diazoniové soli

Diazonium salts ($Ar-N_2^+ X^-$) are prepared via the diazotization of primary aromatic amines using sodium nitrite ($NaNO_2$) and a mineral acid at low temperatures. They undergo several types of reactions:

1. Nucleophilic and radical substitutions ($S_{N1}Ar$ and $S_{RN1}Ar$): These reactions allow for the replacement of the diazonium group with various nucleophiles to form phenols (with $H_2O/\Delta T$), halogen derivatives like fluorides (using $HBF_4$), or nitriles. The loss of nitrogen gas ($N_2$) is the driving force.
2. Electrophilic aromatic substitution ($S_E Ar$): The diazonium cation itself acts as a weak electrophile, reacting with activated aromatic rings (like phenols) to form azo compounds ($Ar-N=N-Ar'$).
3. Reduction: Treatment with hypophosphorous acid ($H_3PO_4$) can remove the diazo group entirely, replacing it with a hydrogen atom.

Aldehydy a hetony

Aldehydes ($R-CHO$) and ketones ($R-CO-R_2$) undergo reactions primarily at the carbonyl group and the $\alpha$-carbon. The carbonyl group reacts with both nucleophiles and electrophiles. These compounds are subject to oxidation to form carboxylic acids and are influenced by $-I$ and $-M$ effects. Examples given include ethanal ($CH_3CHO$), 1-fenylethanon (acetophenone), and benzenkarbaldehyd (benzaldehyde).

Nucleophilic reactions include the addition of Grignard reagents ($CH_3-MgBr$), which, after hydrolysis, produce alcohols ($CH_3-CH(OH)-CH_3$). Reaction with nitrogen nucleophiles like methylamine ($CH_3NH_2$) results in imines ($imin$) via an addition-elimination sequence. Aldolization is a crucial reaction where two carbonyl molecules combine to form an aldol (e.g., 3-hydroxy-2-methylpentanal).

Reduction of aldehydes and ketones can be achieved using complex hydrides like lithium aluminum hydride ($LiAlH_4$). This reduces aldehydes to primary alcohols and ketones to secondary alcohols. Reactions at the $\alpha$-carbon include halogenation. Under acidic catalysis, halogenation typically happens once. Under basic catalysis, polyhalogenation occurs, leading to the haloform reaction. For example, reacting acetone with iodine and base ($I_2, OH^-$) produces triiodomethane ($jodoform, CHI_3$) and an acetate ion. Nitrosation of the $\alpha$-carbon occurs exclusively in acidic environments using $NaNO_2/HCl$.

Ethery

Ethers ($R-O-R$) feature an oxygen atom with two lone pairs as their primary center of reactivity. The oxygen can be attacked by electrophiles, but ethers are generally weak nucleophiles themselves. Examples include diethylether ($CH_3-CH_2-O-CH_2-CH_3$) and fenyl(methyl)ether (anisole). The substituents are referred to as alkoxy- or aroxy- groups.

Ethers are generally unreactive toward nucleophiles under "classical" conditions. However, cyclic ethers like oxirane (ethylene oxide) are highly reactive due to ring strain and undergo ring-opening nucleophilic substitution ($S_N2$). For instance, reacting oxirane with a Grignard reagent ($CH_3MgI$) followed by hydrolysis ($H_2O$) yields a primary alcohol such as propan-1-ol ($CH_3-CH_2-CH_2-OH$). They can also be reduced to alcohols using $LiAlH_4$. Reactions with halogenated compounds like iodomethane ($CH_3-I$) can occur under specific conditions.