Organic Compounds Containing Nitrogen — Practice Questions with Answers

Alkyl groups are electron-donating (exhibit a $+I$ inductive effect) relative to hydrogen — when an alkyl group replaces a hydrogen on ammonia's nitrogen, this electron-donating effect increases the electron density available on nitrogen's lone pair.

This increased electron density makes the nitrogen's lone pair more available/reactive for accepting an incoming proton, thereby increasing basicity — this is why aliphatic amines (with one or more alkyl groups attached to nitrogen) are generally more basic than ammonia itself, which lacks any such electron-donating alkyl substituents.

Diazotisation converts an aromatic primary amine into a diazonium salt, by treating it with nitrous acid (generated in situ from sodium nitrite and a mineral acid, typically HCl), at low temperature (0-5°C).

$ArNH_2 + NaNO_2 + 2HCl \xrightarrow{0-5°C} ArN_2^+Cl^- + NaCl + 2H_2O$

The low temperature is essential, since diazonium salts are thermally unstable and decompose readily above about 5°C in aqueous solution.

In the carbylamine test, a primary amine is heated with chloroform and alcoholic potassium hydroxide, producing a foul-smelling isocyanide (carbylamine): $RNH_2 + CHCl_3 + 3KOH \rightarrow RNC + 3KCl + 3H_2O$.

This reaction specifically requires a primary amine's nitrogen to have two available N-H bonds (needed for the mechanistic steps forming the isocyanide's characteristic $-N\equiv C$ triple bond arrangement) — since secondary amines have only one N-H bond, and tertiary amines have none at all, only primary amines can undergo this specific reaction and produce the characteristic foul odour, making this test diagnostic specifically for primary amines.

The Friedel-Crafts reaction requires a Lewis acid catalyst (typically $AlCl_3$), which is itself a strong electron-pair acceptor.

Aniline's nitrogen, possessing a highly available lone pair of electrons, readily reacts directly with this Lewis acid catalyst, forming a stable acid-base adduct/complex ($C_6H_5NH_2\cdot AlCl_3$) — this effectively deactivates/consumes the Lewis acid catalyst (rendering it unavailable to perform its intended catalytic function), and the resulting positively-charged nitrogen (now bonded to the Lewis acid) becomes strongly electron-withdrawing/deactivating towards the ring, rather than activating — this combination of catalyst poisoning and resulting ring deactivation is precisely why aniline does not undergo efficient Friedel-Crafts reactions under standard conditions.

Cyanides (nitriles, $R-C\equiv N$): The alkyl/aryl group is bonded directly to the carbon atom of the cyano group, with a carbon-nitrogen triple bond.

Isocyanides (carbylamines, $R-N\equiv C$): The alkyl/aryl group is instead bonded directly to the nitrogen atom, with the carbon-nitrogen triple bond oriented in the opposite sense — the terminal carbon atom in an isocyanide is divalent, formally carrying a lone pair and a negative formal charge, balanced by a positive formal charge on nitrogen.

Both aliphatic and aromatic primary amines initially react with nitrous acid to form an unstable diazonium salt intermediate.

Aliphatic diazonium salts are extremely unstable, even at low temperature, and decompose almost immediately, releasing nitrogen gas and forming a carbocation, which typically reacts further with water (or undergoes rearrangement) to give a mixture of alcohols, alkenes, and alkyl halides as products.

Aromatic diazonium salts (formed from aromatic primary amines like aniline) are comparatively much more stable at low temperature (0-5°C), due to resonance stabilisation involving the adjacent aromatic ring — these stable aromatic diazonium salts can be isolated (in solution) and subsequently used in a wide variety of further synthetically useful reactions.

While the inductive (+I) effect alone would predict basicity increasing steadily with more alkyl substitution (tertiary > secondary > primary), in aqueous solution, an additional factor — solvation of the resulting ammonium cation — becomes significant.

Bulkier, more heavily alkyl-substituted ammonium ions (like trimethylammonium) have fewer available N-H bonds and greater steric bulk, both of which reduce their ability to be effectively stabilised by hydrogen bonding with surrounding water molecules (poorer solvation) — this reduced solvation stabilisation partially or fully offsets the inductive effect's influence, resulting in an experimentally observed aqueous basicity order that doesn't simply match the naive inductive-effect-only prediction (typically observed as secondary > primary > tertiary > ammonia for methylamines in water, though exact orders can vary).

In Gabriel synthesis, potassium phthalimide (formed by treating phthalimide with KOH) is reacted with an alkyl halide via SN2 substitution, forming N-alkylphthalimide. This intermediate is then hydrolysed (typically with aqueous acid or hydrazine) to release the free primary amine and regenerate phthalic acid (or its hydrazide derivative).

This method reliably produces exclusively pure primary amines because the nitrogen atom is "protected" within the rigid phthalimide ring structure throughout the alkylation step — since there is no free N-H available on the nitrogen during this alkylation stage (it's fully incorporated within the ring), no possibility exists for over-alkylation to form secondary or tertiary amine byproducts, unlike the direct alkylation of ammonia (which readily suffers from this over-alkylation problem).

The nitrogen atom's lone pair of electrons can be donated via resonance into the aromatic ring, significantly increasing electron density specifically at the ortho and para ring positions (relative to the amino substituent) — this occurs through additional resonance structures showing negative charge specifically localised at these ortho/para carbon positions.

Since electrophiles are attracted to and preferentially attack positions of highest electron density, and this resonance donation specifically increases electron density at the ortho and para positions (not meta), the amino group directs incoming electrophiles predominantly to these ortho/para positions — additionally, since overall ring electron density is substantially increased compared to unsubstituted benzene, the amino group is also strongly activating, significantly increasing the overall rate of electrophilic aromatic substitution reactions.

Hofmann bromamide degradation starts from an amide ($RCONH_2$), treating it with bromine and concentrated sodium hydroxide, ultimately converting it into a primary amine ($RNH_2$) with one fewer carbon atom than the original amide (the carbonyl carbon is lost as $CO_2$/carbonate during the mechanism).

Gabriel synthesis starts from potassium phthalimide, which is alkylated with an alkyl halide, then hydrolysed to release the primary amine — in this case, the amine produced has the same number of carbon atoms as the alkyl group originally present in the alkyl halide reagent used (no carbon is lost or gained from the phthalimide portion itself, which is simply removed as a byproduct during the final hydrolysis step).

Step 1: Bromine reacts with the amide's N-H in basic conditions, forming an N-bromoamide intermediate: $CH_3CONH_2 + Br_2 + NaOH \rightarrow CH_3CONHBr + NaBr + H_2O$

Step 2: Further treatment with base removes the remaining N-H proton, and the resulting anion undergoes rearrangement — the alkyl group migrates from carbon to nitrogen as bromide simultaneously leaves, forming a reactive isocyanate intermediate: $CH_3-N=C=O$

Step 3: The isocyanate is rapidly hydrolysed by the aqueous basic medium, first to an unstable carbamic acid, which spontaneously decarboxylates (loses $CO_2$, as carbonate under basic conditions), releasing the final amine product.

Final product: Methylamine ($CH_3NH_2$) — with one fewer carbon than the starting acetamide, since the carbonyl carbon is lost as carbonate/$CO_2$.

Step 1 (diazotisation): Aniline is treated with sodium nitrite and hydrochloric acid at 0-5°C: $C_6H_5NH_2 + NaNO_2 + 2HCl \xrightarrow{0-5°C} C_6H_5N_2^+Cl^- + NaCl + 2H_2O$

Step 2 (hydrolysis): The diazonium salt solution is then warmed with water (or dilute acid), causing it to decompose, releasing nitrogen gas and forming phenol: $C_6H_5N_2^+Cl^- + H_2O \xrightarrow{\text{warm}} C_6H_5OH + N_2 + HCl$

This two-step sequence (diazotisation followed by controlled hydrolysis) provides a valuable, reliable synthetic method for converting an aromatic amine specifically into the corresponding phenol at the exact same ring position.

The diazonium ion ($C_6H_5N_2^+$) acts as a weak electrophile, attacking the strongly activated (electron-rich) para position of phenol (or the ortho position, if para is blocked), in a typical electrophilic aromatic substitution mechanism — this reaction is carried out in mildly alkaline conditions (to ensure phenol is sufficiently activated, while the diazonium salt still remains stable).

Product: 4-hydroxyazobenzene ($HO-C_6H_4-N=N-C_6H_5$), an "azo compound" containing the characteristic $-N=N-$ linkage connecting the two aromatic rings.

Typical use: Azo compounds like this are typically intensely and vividly coloured (due to extensive conjugation across the two connected aromatic rings and the azo linkage), making this coupling reaction a widely used, important method for synthesising azo dyes, extensively used commercially in the textile and other colouring industries.

Step 1: Ammonia acts as a nucleophile, attacking ethyl bromide via SN2, displacing bromide and forming ethylammonium bromide, which is deprotonated by excess ammonia to release free ethylamine ($CH_3CH_2NH_2$).

Step 2 (over-alkylation problem): The newly formed ethylamine is itself a nucleophile (in fact, typically a somewhat stronger nucleophile than ammonia, due to the electron-donating ethyl group) — it readily competes with the remaining ammonia for reaction with any unreacted ethyl bromide, forming diethylamine.

Step 3 (continued over-alkylation): This process continues, with diethylamine reacting further to form triethylamine, and triethylamine potentially reacting even further to form the quaternary ammonium salt (tetraethylammonium bromide) — since each successive amine product remains nucleophilic and can continue competing for the alkylating agent, a statistical mixture of all these possible products (mono-, di-, tri-substituted amine, plus quaternary salt) is typically obtained, rather than a single, pure primary amine product — this is precisely why this direct method is generally considered impractical for the clean, selective synthesis of pure primary amines (Gabriel synthesis is preferred instead).

Basicity order: Aniline < Ammonia < Methylamine

Aniline is the weakest base of the three, since its nitrogen lone pair is significantly delocalised into the aromatic ring via resonance, making it substantially less available for accepting a proton.

Methylamine is more basic than ammonia, since the electron-donating methyl group increases electron density on nitrogen (via the +I inductive effect), making its lone pair more available/reactive for protonation.

Ammonia falls in between — it has no aromatic ring to delocalise its lone pair (unlike aniline, making it more basic than aniline), but also lacks any electron-donating alkyl group (unlike methylamine, making it less basic than methylamine).

LiAlH₄ is a powerful hydride-donating reducing agent. It delivers a hydride ion ($H^-$) to the electrophilic carbon of the nitrile's carbon-nitrogen triple bond, forming an imine anion intermediate (with the nitrogen now bearing a negative charge, and one C=N double bond remaining).

A second hydride delivery to this same carbon further reduces the imine to a fully saturated amine anion (a dianion intermediate, in effect, though this simplifies the overall electron bookkeeping) — upon aqueous acidic workup, this is protonated to give the final primary amine.

Overall reaction: $R-C\equiv N + 4[H] \xrightarrow{LiAlH_4} R-CH_2-NH_2$ — this reduction adds a full 4 hydrogen atoms overall (2 hydride equivalents plus 2 protons upon workup), converting the nitrile fully into the corresponding primary amine, with the same number of carbon atoms as the starting nitrile (since the nitrile carbon becomes the new $CH_2$ group directly attached to the amine nitrogen).

Moles of aniline $= \dfrac{4.5}{93} \approx 0.0484\text{ mol}$

Since diazotisation proceeds 1:1 (one mole of aniline gives one mole of diazonium salt): moles of diazonium salt $= 0.0484\text{ mol}$

Mass of benzenediazonium chloride $= 0.0484\times140.5 \approx \mathbf{6.80\text{ g}}$

The nitro group is a strongly electron-withdrawing substituent, both through the inductive effect and, importantly, through resonance — when positioned at the para position (directly conjugated through the ring with the amino group), the nitro group can withdraw electron density directly from the amino nitrogen's lone pair via an extended resonance pathway through the entire conjugated ring system.

This resonance-based electron withdrawal significantly reduces the electron density/availability of the amino nitrogen's lone pair (which is now partially delocalised even further away from nitrogen, towards the electron-withdrawing nitro group), making this lone pair considerably less available for accepting/bonding with an incoming proton.

This substantial reduction in lone pair availability is precisely why para-nitroaniline is considerably less basic (weaker as a base) than unsubstituted aniline — the strongly electron-withdrawing, resonance-conjugated nitro group dramatically decreases the amine's inherent basicity.

Complete reduction of a nitrile ($R-C\equiv N$) to a primary amine ($R-CH_2-NH_2$) adds 4 hydrogen atoms overall (as established by the balanced reduction equation, $R-CN + 4[H] \rightarrow R-CH_2NH_2$), without any change in carbon or nitrogen count.

Starting nitrile: $C_3H_5N$. Adding 4 hydrogen atoms: $C_3H_5N + 4H \rightarrow C_3H_9N$

Molecular formula of the amine product: $\mathbf{C_3H_9N}$ (consistent, for example, with n-propylamine, $CH_3CH_2CH_2NH_2$, if the starting nitrile was propanenitrile/propionitrile, $CH_3CH_2CN$)

(a) Chlorobenzene: Treatment with cuprous chloride ($Cu_2Cl_2$ or $CuCl$) — the Sandmeyer reaction: $C_6H_5N_2^+Cl^- \xrightarrow{CuCl} C_6H_5Cl + N_2$

(b) Benzonitrile: Treatment with cuprous cyanide ($CuCN$) — also a Sandmeyer-type reaction: $C_6H_5N_2^+Cl^- \xrightarrow{CuCN} C_6H_5CN + N_2$

(c) Benzene: Treatment with a reducing agent such as hypophosphorous acid ($H_3PO_2$) or ethanol — this simply replaces the diazonium group with a hydrogen atom (reductive deamination): $C_6H_5N_2^+Cl^- \xrightarrow{H_3PO_2} C_6H_6 + N_2 + H_3PO_3 + HCl$

These varied transformations highlight the remarkable synthetic versatility of the diazonium salt functional group, allowing it to be converted into a wide range of otherwise difficult-to-access substituted (or unsubstituted) benzene derivatives.