Cycloalkane Stability Comparison

Cheatsheet Content

Cycloalkane Stability Overview The relative stability of cycloalkanes is determined by three main factors: Angle Strain: Deviation from ideal bond angles ($109.5^\circ$ for $sp^3$ carbons). Torsional Strain: Eclipsing interactions between adjacent C-H bonds. Ring Strain: The sum of angle and torsional strains. Individual Cycloalkane Analysis Cyclopropane Bond Angle: $60^\circ$ Angle Strain: High ($49.5^\circ$ deviation from $109.5^\circ$) Torsional Strain: High (all C-H bonds eclipsed) Ring Strain: Highest Stability: Least stable, highly reactive (ring-opening reactions). Cyclobutane Bond Angle: $90^\circ$ Angle Strain: Significant ($19.5^\circ$ deviation) Torsional Strain: Reduced by puckered conformation (staggered C-H bonds). Ring Strain: High, but less than cyclopropane. Stability: More stable than cyclopropane, less than cyclopentane/cyclohexane. Cyclopentane Bond Angle: $108^\circ$ Angle Strain: Minimal ($1.5^\circ$ deviation) Torsional Strain: Reduced by "envelope" conformation (staggered C-H bonds). Ring Strain: Low. Stability: More stable than cyclopropane and cyclobutane. Cyclohexane Bond Angle: $109.5^\circ$ (in chair conformation) Angle Strain: None (in chair conformation) Torsional Strain: None (all bonds staggered in chair conformation) Ring Strain: None (in chair conformation) Stability: Most stable cycloalkane. Summary of Stability Cycloalkane Bond Angle Angle Strain Torsional Strain Ring Strain Stability Cyclopropane $60^\circ$ High ($49.5^\circ$) High High Least Stable Cyclobutane $90^\circ$ Significant ($19.5^\circ$) Moderate Moderate Less Stable Cyclopentane $108^\circ$ Minimal ($1.5^\circ$) Low Low Stable Cyclohexane $109.5^\circ$ None None None Most Stable Theories Supporting Stability Baeyer's Strain Theory Premise: Cycloalkane stability depends on the deviation of bond angles from the ideal tetrahedral angle ($109.5^\circ$). Prediction: Small rings (cyclopropane, cyclobutane) are highly strained and less stable. Cyclopentane ($108^\circ$) and cyclohexane (if planar, $120^\circ$) would be increasingly stable up to cyclopentane, then decrease. Limitations: Assumes planar rings. Fails to explain the high stability of cyclohexane, which forms a non-planar chair conformation. Does not account for torsional strain. Sachse-Mohr Theory Premise: Cycloalkanes with more than three carbons can adopt non-planar, puckered conformations to relieve strain. Key Example: Cyclohexane adopts a "chair" conformation, which eliminates both angle strain (all bond angles are $109.5^\circ$) and torsional strain (all C-H bonds are staggered). This explains its exceptional stability. Coulson-Moffitt Model (Bent Bonds) Premise: Explains the stability of cyclopropane despite extreme angle strain. Mechanism: Cyclopropane forms "bent bonds" or "banana bonds" where the electron density is outside the direct internuclear axis, allowing for better overlap than a perfectly straight $60^\circ$ bond. Result: While it reduces angle strain, cyclopropane still has reduced orbital overlap and high torsional strain, making it less stable overall compared to larger rings. Essential Criteria for Aromaticity For a molecule to be considered aromatic, it must satisfy all of the following criteria: Cyclic Structure: The molecule must be cyclic (atoms arranged in a ring). Planarity: The ring must be planar or nearly planar for effective p-orbital overlap. Conjugation: Must have a continuous system of conjugated $\pi$-electrons (alternating single/double bonds, lone pairs, or empty p-orbitals) throughout the ring. Hückel’s Rule: The molecule must possess $(4n + 2)$ $\pi$-electrons, where $n$ is a non-negative integer ($0, 1, 2, ...$). This ensures electron delocalization and aromatic stability. Aromatic Nature: Cyclopentadienyl Anion vs. Cation Cyclopentadienyl Anion Structure: Five-membered ring with a negative charge (lone pair). Aromatic Criteria Check: Cyclic: Yes Planar: Yes Conjugation: Yes (continuous system from two double bonds and one lone pair). $\pi$-Electron Count: $4$ (from 2 double bonds) $+ 2$ (from lone pair) $= 6$ $\pi$-electrons. Hückel’s Rule: Yes, $6 = (4n + 2)$ where $n=1$. Conclusion: Aromatic and stable. Cyclopentadienyl Cation Structure: Five-membered ring with a positive charge (empty p-orbital). Aromatic Criteria Check: Cyclic: Yes Planar: Yes Conjugation: Yes (continuous system from two double bonds and one empty p-orbital). $\pi$-Electron Count: $4$ (from 2 double bonds) $+ 0$ (from empty p-orbital) $= 4$ $\pi$-electrons. Hückel’s Rule: No, $4 \neq (4n + 2)$. It fits $4n$ ($n=1$), indicating anti-aromaticity. Conclusion: Anti-aromatic and highly unstable. Comparison Table Property Cyclopentadienyl Anion Cyclopentadienyl Cation Structure Five-membered ring with a negative charge Five-membered ring with a positive charge $\pi$-Electron Count $6$ $\pi$-electrons $4$ $\pi$-electrons Hückel’s Rule Satisfies ($4n+2$, $n=1$) Does not satisfy ($4n$, $n=1$) Aromaticity Aromatic (stable) Anti-aromatic (unstable) Nitration of Chlorobenzene vs. Nitrobenzene The directing effects of substituents on electrophilic aromatic substitution (EAS) determine the product distribution during nitration. Nitration of Chlorobenzene Substituent: Chlorine (-Cl) Electronic Effects: -I Effect: Electron-withdrawing inductively, deactivating the ring. +M Effect: Electron-donating via resonance (lone pair delocalization), activating ortho and para positions. Directing Effect: Overall ortho / para director. The resonance effect dominates in directing the incoming electrophile, making ortho and para positions more electron-rich than meta . Products: Major products are ortho -nitrochlorobenzene and para -nitrochlorobenzene. The para isomer is typically favored due to less steric hindrance. Nitration of Nitrobenzene Substituent: Nitro group (-NO$_2$) Electronic Effects: -I Effect: Strong electron-withdrawing inductively. -M Effect: Strong electron-withdrawing via resonance (pulls electron density from ring into nitro group). Directing Effect: Strong meta director. The nitro group strongly deactivates the ortho and para positions, leaving the meta position as the "least deactivated" site for electrophilic attack. Products: Major product is meta -dinitrobenzene. Summary of Substituent Effects in Nitration Substituent Type of Group Directing Effect Major Products Chlorine (-Cl) Weak electron-withdrawing (-I), electron-donating (+M) Ortho / para o -nitrochlorobenzene, p -nitrochlorobenzene Nitro (-NO$_2$) Strong electron-withdrawing (-I and -M) Meta m -dinitrobenzene Cyclopropane Stability and Banana Bond Theory Cyclopropane, despite its high ring strain due to $60^\circ$ bond angles (deviating significantly from $109.5^\circ$), exhibits unique stability explained by the Banana Bond Theory (Coulson-Moffitt modification). Key Concepts of Banana Bond Theory Bond Angles and Strain: The $60^\circ$ internal bond angles in cyclopropane create substantial angle strain, forcing bonds to deviate from ideal geometry. Bent Bonds (Banana Bonds): To reduce this angle strain, the carbon-carbon bonds are "bent" or "banana-shaped". The $sp^3$ hybrid orbitals of the carbon atoms overlap in a curved manner. This bending redistributes electron density away from the internuclear axis, alleviating angle strain. Reduced Orbital Overlap: This bending results in less efficient overlap between $sp^3$ orbitals compared to normal sigma bonds, leading to weaker C-C bonds and contributing to cyclopropane's characteristic reactivity (e.g., ring-opening reactions). Delocalization of Electrons: Electron density is distributed outside the direct internuclear axis, including towards the center of the ring, which contributes to the molecule's relative stability. Stability of Cyclopropane Cyclopropane's relative stability, despite high ring strain, is attributed to: Bent Bonds: Effectively reduce angle strain by allowing electron density to be outside the direct bond path. Delocalized Electron Density: The unique electron distribution further stabilizes the molecule. Dynamic Nature: Slight puckering can occur to further minimize strain. Applications of Cyclopropane Anesthetic: Historically used as a general anesthetic (now largely replaced due to flammability). Organic Synthesis: Its high reactivity due to ring strain makes it a valuable precursor for ring-opening reactions, e.g., with halogens to form halogenated alkanes, and in the synthesis of pharmaceuticals and agrochemicals. Limitations of Friedel-Crafts Alkylation Friedel-Crafts alkylation is a powerful method but suffers from several key limitations: Carbocation Rearrangement: The reaction proceeds via a carbocation intermediate. If the initially formed carbocation is primary or secondary, it can rearrange (e.g., via hydride or alkyl shifts) to a more stable carbocation (secondary or tertiary). This leads to the formation of undesired, branched alkyl products. E.g., attempting to make n -propylbenzene from 1-chloropropane yields mostly isopropylbenzene. Polyalkylation: Alkyl groups are electron-donating and activate the benzene ring towards further electrophilic substitution. The product of alkylation is often more reactive than the starting material, leading to the addition of multiple alkyl groups and a mixture of products. Deactivation by Strong Electron-Withdrawing Groups: Benzene rings substituted with strong electron-withdrawing groups (e.g., $-\text{NO}_2$, $-\text{COOH}$, $-\text{SO}_3\text{H}$, carbonyl groups) are deactivated and generally do not undergo Friedel-Crafts alkylation. Reaction Conditions & Catalyst Sensitivity: Requires a Lewis acid catalyst (e.g., $\text{AlCl}_3$), which can be sensitive to moisture and lead to side reactions or catalyst deactivation. Can cause isomerization of alkyl halides. Synthesis of n -Propylbenzene: Alkylation vs. Acylation-Reduction Due to the carbocation rearrangement limitation, direct Friedel-Crafts alkylation is not suitable for synthesizing unbranched alkylbenzenes like n -propylbenzene. Preferred Method: Friedel-Crafts Acylation Followed by Reduction This two-step process avoids carbocation rearrangement and allows for the synthesis of unbranched alkylbenzenes. Step 1: Friedel-Crafts Acylation Benzene reacts with an acyl chloride (e.g., propanoyl chloride, $\text{CH}_3\text{CH}_2\text{COCl}$) in the presence of a Lewis acid ($\text{AlCl}_3$). Forms a ketone (e.g., propiophenone, $\text{C}_6\text{H}_5\text{COCH}_2\text{CH}_3$). $\text{C}_6\text{H}_6 + \text{CH}_3\text{CH}_2\text{COCl} \xrightarrow{\text{AlCl}_3} \text{C}_6\text{H}_5\text{COCH}_2\text{CH}_3 + \text{HCl}$ Why it works: The acylium ion ($\text{R-C=O}^+$) is resonance-stabilized and does not undergo rearrangement. Also, the resulting ketone is a deactivating group, preventing polyacylation. Step 2: Reduction of the Carbonyl Group The ketone is then reduced to the corresponding alkane using a suitable reduction method. Clemmensen Reduction: $\text{C}_6\text{H}_5\text{COCH}_2\text{CH}_3 \xrightarrow{\text{Zn(Hg), HCl}} \text{C}_6\text{H}_5\text{CH}_2\text{CH}_2\text{CH}_3$ Wolff-Kishner Reduction: $\text{C}_6\text{H}_5\text{COCH}_2\text{CH}_3 \xrightarrow{\text{NH}_2\text{NH}_2, \text{KOH, heat}} \text{C}_6\text{H}_5\text{CH}_2\text{CH}_2\text{CH}_3 + \text{N}_2 + \text{H}_2\text{O}$ Synthesis of m -Bromonitrobenzene from Benzene To synthesize m -bromonitrobenzene from benzene, the order of electrophilic aromatic substitution (EAS) reactions is crucial due to the directing effects of the substituents. Synthetic Route Step 1: Nitration of Benzene Reaction: Benzene is nitrated using concentrated nitric acid ($\text{HNO}_3$) and sulfuric acid ($\text{H}_2\text{SO}_4$). $\text{C}_6\text{H}_6 + \text{HNO}_3 \xrightarrow{\text{H}_2\text{SO}_4} \text{C}_6\text{H}_5\text{NO}_2 + \text{H}_2\text{O}$ Reasoning: The nitro group ($-\text{NO}_2$) is a strong electron-withdrawing group and a meta -director. Introducing it first ensures that the subsequent reaction will occur at the meta position relative to the nitro group. Step 2: Bromination of Nitrobenzene Reaction: Nitrobenzene is then brominated using bromine ($\text{Br}_2$) in the presence of a Lewis acid catalyst (e.g., $\text{FeBr}_3$). $\text{C}_6\text{H}_5\text{NO}_2 + \text{Br}_2 \xrightarrow{\text{FeBr}_3} \textit{m}\text{-BrC}_6\text{H}_4\text{NO}_2 + \text{HBr}$ Reasoning: The nitro group directs the incoming bromine to the meta position. While the nitro group deactivates the ring, the meta positions are the least deactivated, hence the preferred site for electrophilic attack. Why this Order is Preferred Directing Effects: The nitro group ($-\text{NO}_2$) is a strong electron-withdrawing group and a meta -director. A bromine atom ($-\text{Br}$) is a weak electron-withdrawing group (by induction) but an ortho / para director (by resonance). Order of Substitution: If bromination were performed first, the bromine would direct the subsequent nitration to the ortho and para positions, leading to a mixture of o -bromonitrobenzene and p -bromonitrobenzene. By nitrating first, the strong meta -directing effect of the nitro group ensures that the bromine substitutes exclusively at the meta position, yielding the desired m -bromonitrobenzene. Reactivity of Small Cycloalkanes (Cyclopropane, Cyclobutane) vs. Larger Rings (Cyclopentane, Cyclohexane) The Coulson-Moffitt theory (bent bond theory) helps explain the unique bonding and higher reactivity of small cycloalkanes compared to larger, more stable rings. Key Concepts Influencing Reactivity Bent Bonds (Banana Bonds): In cyclopropane and cyclobutane, bond angles ($60^\circ$, $90^\circ$ respectively) are much smaller than the ideal $109.5^\circ$. To accommodate this, C-C bonds are "bent" outwards, forming banana bonds. These bent bonds reduce angle strain but result in weaker orbital overlap, making the bonds less stable and more susceptible to ring-opening reactions. Angle Strain: Cyclopropane ($60^\circ$) & Cyclobutane ($90^\circ$): High angle strain due to significant deviation from $109.5^\circ$. Cyclopentane ($108^\circ$) & Cyclohexane ($109.5^\circ$ in chair): Minimal to no angle strain. Torsional Strain: Cyclopropane: High torsional strain due to eclipsed C-H bonds. Cyclobutane: Moderate torsional strain; puckered conformation helps reduce it but some eclipsing remains. Cyclopentane: Low torsional strain; "envelope" conformation minimizes it. Cyclohexane: No torsional strain; chair conformation ensures all bonds are staggered. Ring Strain: The sum of angle and torsional strains. Cyclopropane & Cyclobutane: High ring strain due to small size and significant angle/torsional strain. Cyclopentane: Moderate ring strain. Cyclohexane: No ring strain (in chair conformation). Why Cyclopropane and Cyclobutane are More Reactive High Ring Strain: The accumulated angle and torsional strains make the C-C bonds weaker and more prone to breaking, leading to higher reactivity (e.g., facile ring-opening reactions). Bent Bonds: The reduced orbital overlap in banana bonds further contributes to their instability and makes them more susceptible to attack by nucleophiles or electrophiles, facilitating ring-opening. Reactivity Comparison Summary Cycloalkane Bond Angle Angle Strain Torsional Strain Ring Strain Reactivity Cyclopropane $60^\circ$ High ($49.5^\circ$) High (eclipsed) Highest Most Reactive Cyclobutane $90^\circ$ Moderate ($19.5^\circ$) Moderate (puckered) High Reactive Cyclopentane $108^\circ$ Low ($1.5^\circ$) Low (puckered) Moderate Less Reactive Cyclohexane $109.5^\circ$ None None (staggered) None Least Reactive Relative Stability of Cyclopentane and Cyclohexane (Sachse-Mohr Theory) The Sachse-Mohr theory, or "Theory of Strainless Rings," explains how larger cycloalkanes achieve stability by adopting non-planar conformations to relieve strain. Cyclopentane Conformation & Stability Conformation: Adopts a puckered "envelope" conformation. Four carbons in a plane, one bent out. Reduces torsional strain by staggering some C-H bonds. Angle Strain: Minimal (bond angles $\approx 108^\circ$, deviation $1.5^\circ$ from $109.5^\circ$). Torsional Strain: Moderate; the puckering reduces it but does not eliminate it completely (some eclipsing interactions remain). Ring Strain: Moderate, primarily due to residual torsional strain. Stability: Relatively stable, but less stable than cyclohexane. Cyclohexane Conformation & Stability Conformation: Adopts a "chair" conformation. This is the most stable conformation. Allows all C-C bonds to have ideal tetrahedral angles ($109.5^\circ$). Ensures all C-H bonds are staggered. Angle Strain: None (bond angles are $109.5^\circ$). Torsional Strain: None (all C-H bonds are staggered). Ring Strain: None. Stability: Most stable cycloalkane. Why Cyclohexane is More Stable than Cyclopentane Angle Strain: Cyclohexane in its chair form completely eliminates angle strain, while cyclopentane has a slight residual angle strain. Torsional Strain: Cyclohexane's chair conformation eliminates torsional strain entirely, whereas cyclopentane's envelope conformation only reduces it, leaving some residual torsional strain. Overall Ring Strain: The complete absence of both angle and torsional strain in the chair conformation makes cyclohexane the most stable cycloalkane, surpassing cyclopentane. Sachse-Mohr Theory & Strain Avoidance Non-Planar Conformations: The theory emphasizes that rings larger than cyclopropane can achieve stability by existing in non-planar, flexible conformations. Relief of Strain: These puckered conformations allow: Bond angles to closely match the ideal tetrahedral angle (reducing angle strain). Bonds to adopt staggered arrangements (reducing torsional strain). Conversions 1. Aniline to Benzonitrile This conversion involves two main steps: diazotization and the Sandmeyer reaction. Step 1: Diazotization of Aniline Reaction: Aniline ($\text{C}_6\text{H}_5\text{NH}_2$) is treated with sodium nitrite ($\text{NaNO}_2$) and hydrochloric acid ($\text{HCl}$) at low temperatures ($0-5^\circ\text{C}$). Product: Benzenediazonium chloride ($\text{C}_6\text{H}_5\text{N}_2^+\text{Cl}^-$). $\text{C}_6\text{H}_5\text{NH}_2 + \text{NaNO}_2 + 2\text{HCl} \xrightarrow{0-5^\circ\text{C}} \text{C}_6\text{H}_5\text{N}_2^+\text{Cl}^- + 2\text{H}_2\text{O} + \text{NaCl}$ Step 2: Sandmeyer Reaction Reaction: Benzenediazonium chloride is treated with copper(I) cyanide ($\text{CuCN}$) in the presence of potassium cyanide ($\text{KCN}$). Product: The diazonium group ($-\text{N}_2^+$) is replaced by a cyano group ($-\text{CN}$), yielding benzonitrile ($\text{C}_6\text{H}_5\text{CN}$). $\text{C}_6\text{H}_5\text{N}_2^+\text{Cl}^- + \text{CuCN} \xrightarrow{\text{KCN}} \text{C}_6\text{H}_5\text{CN} + \text{N}_2 + \text{CuCl}$ Overall: $\text{C}_6\text{H}_5\text{NH}_2 \rightarrow \text{C}_6\text{H}_5\text{N}_2^+\text{Cl}^- \rightarrow \text{C}_6\text{H}_5\text{CN}$ 2. Aniline to 1,3,5-Tribromobenzene This conversion requires protecting the amino group and carefully controlling the bromination. Step 1: Acetylation of Aniline Reaction: Aniline ($\text{C}_6\text{H}_5\text{NH}_2$) reacts with acetic anhydride ($(\text{CH}_3\text{CO})_2\text{O}$) to form acetanilide ($\text{C}_6\text{H}_5\text{NHCOCH}_3$). Purpose: This step protects the highly activating amino group and moderates its activating effect. $\text{C}_6\text{H}_5\text{NH}_2 + (\text{CH}_3\text{CO})_2\text{O} \rightarrow \text{C}_6\text{H}_5\text{NHCOCH}_3 + \text{CH}_3\text{COOH}$ Step 2: Bromination of Acetanilide Reaction: Acetanilide is brominated using bromine ($\text{Br}_2$) in the presence of acetic acid. $\text{C}_6\text{H}_5\text{NHCOCH}_3 + 3\text{Br}_2 \rightarrow \text{C}_6\text{H}_2\text{Br}_3\text{NHCOCH}_3 + 3\text{HBr}$ Note: The provided text describes the acetyl group as electron-withdrawing and meta-directing, which is chemically inaccurate. The $-\text{NHCOCH}_3$ group is an ortho/para director. This step would typically lead to 2,4,6-tribromoacetanilide. Step 3: Hydrolysis of Tribromoacetanilide Reaction: The tribromoacetanilide is hydrolyzed using aqueous acid ($\text{HCl}$). The provided text states this forms 1,3,5-tribromobenzene directly. $\text{C}_6\text{H}_2\text{Br}_3\text{NHCOCH}_3 + \text{HCl} + \text{H}_2\text{O} \rightarrow \text{C}_6\text{H}_3\text{Br}_3 + \text{CH}_3\text{COOH} + \text{NH}_3$ Note: Hydrolysis of tribromoacetanilide yields tribromoaniline. To obtain 1,3,5-tribromobenzene, the amino group must then be removed via diazotization and subsequent reduction (e.g., with $\text{H}_3\text{PO}_2$). The reaction as written in the prompt is a simplification. Overall: $\text{C}_6\text{H}_5\text{NH}_2 \rightarrow \text{C}_6\text{H}_5\text{NHCOCH}_3 \rightarrow \text{C}_6\text{H}_2\text{Br}_3\text{NHCOCH}_3 \rightarrow \text{C}_6\text{H}_3\text{Br}_3$ Reaction Schemes for Conversions 1. Benzene to 4-Nitrophenol This conversion involves a series of electrophilic aromatic substitutions and a diazonium reaction. Step 1: Nitration of Benzene Reaction: Benzene is nitrated to nitrobenzene. Conditions: Conc. $\text{HNO}_3$, Conc. $\text{H}_2\text{SO}_4$, $50-60^\circ\text{C}$. $\text{C}_6\text{H}_6 + \text{HNO}_3 \xrightarrow{\text{H}_2\text{SO}_4} \text{C}_6\text{H}_5\text{NO}_2 + \text{H}_2\text{O}$ Step 2: Reduction of Nitrobenzene to Aniline Reaction: Nitrobenzene is reduced to aniline. Conditions: $\text{Sn/HCl}$ or $\text{H}_2/\text{Pd-C}$, room temperature. $\text{C}_6\text{H}_5\text{NO}_2 + 6[\text{H}] \rightarrow \text{C}_6\text{H}_5\text{NH}_2 + 2\text{H}_2\text{O}$ Step 3: Diazotization of Aniline Reaction: Aniline is converted to benzenediazonium chloride. Conditions: $\text{NaNO}_2$, $\text{HCl}$, $0-5^\circ\text{C}$. $\text{C}_6\text{H}_5\text{NH}_2 + \text{NaNO}_2 + 2\text{HCl} \rightarrow \text{C}_6\text{H}_5\text{N}_2^+\text{Cl}^- + 2\text{H}_2\text{O} + \text{NaCl}$ Step 4: Hydrolysis of Benzenediazonium Chloride Reaction: Benzenediazonium chloride is hydrolyzed to phenol. Conditions: $\text{H}_2\text{O}$, warm ($\sim 50^\circ\text{C}$). $\text{C}_6\text{H}_5\text{N}_2^+\text{Cl}^- + \text{H}_2\text{O} \rightarrow \text{C}_6\text{H}_5\text{OH} + \text{N}_2 + \text{HCl}$ Step 5: Nitration of Phenol Reaction: Phenol is nitrated to 4-nitrophenol. Conditions: Dilute $\text{HNO}_3$, room temperature. Reasoning: The hydroxyl ($-\text{OH}$) group is a strong activating and ortho / para directing group. Dilute $\text{HNO}_3$ is used to avoid oxidation. The para product is favored due to less steric hindrance. $\text{C}_6\text{H}_5\text{OH} + \text{HNO}_3 \rightarrow \text{C}_6\text{H}_4(\text{NO}_2)\text{OH} + \text{H}_2\text{O}$ Overall Scheme: $\text{C}_6\text{H}_6 \rightarrow \text{C}_6\text{H}_5\text{NO}_2 \rightarrow \text{C}_6\text{H}_5\text{NH}_2 \rightarrow \text{C}_6\text{H}_5\text{N}_2^+\text{Cl}^- \rightarrow \text{C}_6\text{H}_5\text{OH} \rightarrow 4\text{-Nitrophenol}$ 2. Toluene to m -Bromotoluene This conversion requires careful control of directing effects using a sequence of reactions. Step 1: Nitration of Toluene Reaction: Toluene is nitrated to o -/ p -nitrotoluene (with m -nitrotoluene as a minor product). Conditions: Conc. $\text{HNO}_3$, Conc. $\text{H}_2\text{SO}_4$, $50-60^\circ\text{C}$. Reasoning: The methyl group ($-\text{CH}_3$) is an ortho / para director. The prompt states "m-nitrotoluene as the major product", which is incorrect; ortho and para isomers are major. For m -bromotoluene, the nitration should ideally yield m -nitrotoluene selectively, which is challenging. A more common route involves oxidizing the methyl group to a carboxylic acid, then nitrating, then reducing, then removing the COOH. If the direct nitration yields mostly o - and p -nitrotoluene, separation would be necessary. Let's assume the goal is to use the m -nitrotoluene fraction. $\text{C}_6\text{H}_5\text{CH}_3 + \text{HNO}_3 \xrightarrow{\text{H}_2\text{SO}_4} \text{C}_6\text{H}_4(\text{NO}_2)\text{CH}_3 + \text{H}_2\text{O}$ Step 2: Reduction of m -Nitrotoluene to m -Toluidine Reaction: m -Nitrotoluene is reduced to m -toluidine. Conditions: $\text{Sn/HCl}$ or $\text{H}_2/\text{Pd-C}$, room temperature. $\text{C}_6\text{H}_4(\text{NO}_2)\text{CH}_3 + 6[\text{H}] \rightarrow \text{C}_6\text{H}_4(\text{NH}_2)\text{CH}_3 + 2\text{H}_2\text{O}$ Step 3: Diazotization of m -Toluidine Reaction: m -Toluidine is converted to m -tolyl diazonium chloride. Conditions: $\text{NaNO}_2$, $\text{HCl}$, $0-5^\circ\text{C}$. $\text{C}_6\text{H}_4(\text{NH}_2)\text{CH}_3 + \text{NaNO}_2 + 2\text{HCl} \rightarrow \text{C}_6\text{H}_4(\text{N}_2^+\text{Cl}^-)\text{CH}_3 + 2\text{H}_2\text{O} + \text{NaCl}$ Step 4: Substitution with Bromine (Sandmeyer Reaction) Reaction: The diazonium group is replaced by bromine. Conditions: $\text{CuBr}$. $\text{C}_6\text{H}_4(\text{N}_2^+\text{Cl}^-)\text{CH}_3 + \text{CuBr} \rightarrow \text{C}_6\text{H}_4\text{BrCH}_3 + \text{N}_2 + \text{CuCl}$ Overall Scheme: $\text{C}_6\text{H}_5\text{CH}_3 \rightarrow \text{C}_6\text{H}_4(\text{NO}_2)\text{CH}_3 \rightarrow \text{C}_6\text{H}_4(\text{NH}_2)\text{CH}_3 \rightarrow \text{C}_6\text{H}_4(\text{N}_2^+\text{Cl}^-)\text{CH}_3 \rightarrow \textit{m}\text{-Bromotoluene}$ Predicted Products of Given Reactions (a) Toluene + $\text{Br}_2/\text{FeBr}_3$ Reaction Type: Electrophilic Aromatic Substitution (Bromination). Substituent Effect: The methyl group ($-\text{CH}_3$) is an electron-donating group (+I and hyperconjugation), activating the ring and directing to ortho and para positions. Products: Major: p -Bromotoluene (steric hindrance favors para over ortho ). Minor: o -Bromotoluene. Conditions: $\text{Br}_2$, $\text{FeBr}_3$, room temperature. $\text{C}_6\text{H}_5\text{CH}_3 + \text{Br}_2 \rightarrow \text{C}_6\text{H}_4\text{BrCH}_3 (\textit{p}\text{-Bromotoluene}) + \text{C}_6\text{H}_4\text{BrCH}_3 (\textit{o}\text{-Bromotoluene}) + \text{HBr}$ (b) Nitrobenzene + $\text{HNO}_3/\text{H}_2\text{SO}_4$ Reaction Type: Electrophilic Aromatic Substitution (Nitration). Substituent Effect: The nitro group ($-\text{NO}_2$) is a strong electron-withdrawing group (-I and -M), deactivating the ring and strongly directing to the meta position. Product: m -Dinitrobenzene. Conditions: Conc. $\text{HNO}_3$, Conc. $\text{H}_2\text{SO}_4$, $50-60^\circ\text{C}$. $\text{C}_6\text{H}_5\text{NO}_2 + \text{HNO}_3 \rightarrow \text{C}_6\text{H}_4(\text{NO}_2)_2 (\textit{m}\text{-Dinitrobenzene}) + \text{H}_2\text{O}$ (c) Acetophenone + $\text{HNO}_3/\text{H}_2\text{SO}_4$ Reaction Type: Electrophilic Aromatic Substitution (Nitration). Substituent Effect: The acetyl group ($-\text{COCH}_3$) is a moderately electron-withdrawing group (-I and -M), deactivating the ring and directing to the meta position. Product: m -Nitroacetophenone. Conditions: Conc. $\text{HNO}_3$, Conc. $\text{H}_2\text{SO}_4$, $50-60^\circ\text{C}$. $\text{C}_6\text{H}_5\text{COCH}_3 + \text{HNO}_3 \rightarrow \text{C}_6\text{H}_4(\text{NO}_2)\text{COCH}_3 (\textit{m}\text{-Nitroacetophenone}) + \text{H}_2\text{O}$ (d) Anisole + $\text{CH}_3\text{Cl}/\text{AlCl}_3$ Reaction Type: Friedel-Crafts Alkylation. Substituent Effect: The methoxy group ($-\text{OCH}_3$) is a strong electron-donating group (+M effect), strongly activating the ring and directing to ortho and para positions. Products: Major: p -Methylanisole (steric hindrance favors para ). Minor: o -Methylanisole. Conditions: $\text{CH}_3\text{Cl}$, $\text{AlCl}_3$, room temperature. $\text{C}_6\text{H}_5\text{OCH}_3 + \text{CH}_3\text{Cl} \rightarrow \text{C}_6\text{H}_4(\text{CH}_3)\text{OCH}_3 (\textit{p}\text{-Methylanisole}) + \text{C}_6\text{H}_4(\text{CH}_3)\text{OCH}_3 (\textit{o}\text{-Methylanisole}) + \text{HCl}$ (e) Benzene + $\text{CH}_3\text{COCl}/\text{AlCl}_3$ Reaction Type: Friedel-Crafts Acylation. Substituent Effect: Benzene has no substituents, so the acyl group ($-\text{COCH}_3$) is introduced. Product: Acetophenone ($\text{C}_6\text{H}_5\text{COCH}_3$). Conditions: Acetyl chloride ($\text{CH}_3\text{COCl}$), $\text{AlCl}_3$, room temperature. $\text{C}_6\text{H}_6 + \text{CH}_3\text{COCl} \rightarrow \text{C}_6\text{H}_5\text{COCH}_3 (\text{Acetophenone}) + \text{HCl}$ Arrangement of Cyclic Compounds in Order of Increasing Strain The strain in cyclic compounds arises from angle strain, torsional strain, and ring strain. The order of increasing strain is: Order: Cyclohexane $ Explanation of Strain in Each Compound Cyclohexane: Bond Angle: $109.5^\circ$ (ideal tetrahedral angle in chair conformation). Angle Strain: None. Torsional Strain: None (all C-H bonds staggered in chair conformation). Ring Strain: None. It is the most stable cycloalkane. Cyclopentane: Bond Angle: $\approx 108^\circ$ (minimal deviation from $109.5^\circ$). Angle Strain: Minimal. Torsional Strain: Moderate (adopts puckered "envelope" conformation to reduce it, but some eclipsing remains). Ring Strain: Low, primarily due to residual torsional strain. Cyclobutane: Bond Angle: $\approx 90^\circ$ (significant deviation from $109.5^\circ$). Angle Strain: Moderate. Torsional Strain: Moderate (adopts puckered conformation to reduce it, but more eclipsing than cyclopentane). Ring Strain: High, due to both angle and torsional strain. Cyclopropane: Bond Angle: $60^\circ$ (very significant deviation from $109.5^\circ$). Angle Strain: Very high. Torsional Strain: High (all C-H bonds are eclipsed). Ring Strain: Highest among common cycloalkanes. Modern Understanding: Coulson-Moffitt Theory and Strain The Coulson-Moffitt theory (bent bond theory) provides a more detailed explanation for the unique bonding and strain in small rings: Cyclopropane & Cyclobutane: Form "bent bonds" (banana bonds) where orbital overlap is reduced and electron density is outside the internuclear axis. This bending helps accommodate the small bond angles, reducing angle strain to some extent, but results in weaker, more reactive bonds. Cyclopentane & Cyclohexane: Their ability to adopt puckered (cyclopentane) or chair (cyclohexane) conformations effectively minimizes angle and torsional strains, aligning well with classical understanding. The overall order of increasing strain remains consistent with both classical and modern theories: Cyclohexane $ Arrangement of Aniline, m -Nitroaniline, p -Nitroaniline, and o -Nitroaniline in Increasing Order of Basicity The basicity of aniline derivatives is determined by the electron density on the nitrogen atom, which influences the availability of its lone pair for protonation. Electron-withdrawing groups decrease basicity, while electron-donating groups increase it. Order of Increasing Basicity: p -Nitroaniline $ o -Nitroaniline $ m -Nitroaniline $ Justification of the Order Aniline ($\text{C}_6\text{H}_5\text{NH}_2$): Basicity: Most basic. Reason: No electron-withdrawing groups. The lone pair on nitrogen is readily available. Although the benzene ring slightly withdraws electron density via resonance, it's less significant than a nitro group. m -Nitroaniline ($\text{C}_6\text{H}_4(\text{NO}_2)\text{NH}_2$): Basicity: Less basic than aniline. Reason: The nitro group ($-\text{NO}_2$) is a strong electron-withdrawing group. At the meta position, it primarily exerts an inductive effect (-I), withdrawing electron density from the ring and, consequently, from the amino group's nitrogen. There is no direct resonance interaction between the meta -nitro group and the amino group's lone pair. p -Nitroaniline ($\text{C}_6\text{H}_4(\text{NO}_2)\text{NH}_2$): Basicity: Less basic than m -nitroaniline. Reason: The nitro group at the para position exerts both a strong inductive effect (-I) and a strong resonance effect (-M). The resonance effect withdraws electron density directly from the nitrogen atom's lone pair into the nitro group, making the lone pair significantly less available for protonation. This makes it less basic than meta -nitroaniline where only the inductive effect is prominent. o -Nitroaniline ($\text{C}_6\text{H}_4(\text{NO}_2)\text{NH}_2$): Basicity: Least basic. Reason: Similar to para -nitroaniline, the ortho -nitro group exerts strong inductive (-I) and resonance (-M) effects, significantly reducing electron density on the nitrogen. Additionally, the ortho position introduces a steric effect. The close proximity of the nitro group to the amino group can lead to intramolecular hydrogen bonding (between the amino hydrogen and nitro oxygen), which further reduces the availability of the lone pair and can hinder protonation. This combination of effects makes ortho -nitroaniline the least basic. Sandmeyer Reaction The Sandmeyer reaction is a versatile organic reaction used to synthesize aryl halides and aryl nitriles from aryl diazonium salts. It proceeds via a radical mechanism and is catalyzed by copper(I) salts. General Reaction $$ \text{ArN}_2^+\text{X}^- + \text{CuY} \rightarrow \text{ArY} + \text{N}_2 + \text{CuX} $$ Ar: Aryl group (e.g., phenyl, substituted phenyl). $\text{X}^-$: Counterion (usually $\text{Cl}^-$ or $\text{HSO}_4^-$). $\text{Y}$: Nucleophile (typically $\text{Cl}$, $\text{Br}$, or $\text{CN}$). Mechanism Overview Formation of Aryl Diazonium Salt (Diazotization): A primary aromatic amine ($\text{ArNH}_2$) is treated with sodium nitrite ($\text{NaNO}_2$) and a strong acid (like $\text{HCl}$ or $\text{HBr}$) at low temperatures ($0-5^\circ\text{C}$). $\text{ArNH}_2 + \text{NaNO}_2 + 2\text{HCl} \xrightarrow{0-5^\circ\text{C}} \text{ArN}_2^+\text{Cl}^- + 2\text{H}_2\text{O} + \text{NaCl}$ Aryl diazonium salts are highly reactive and unstable at higher temperatures. Reaction with Copper(I) Salt: The aryl diazonium salt solution is then treated with a copper(I) salt ($\text{CuCl}$, $\text{CuBr}$, or $\text{CuCN}$). The copper(I) ion acts as a catalyst, initiating a radical mechanism. $\text{ArN}_2^+\text{Cl}^- + \text{CuCl} \rightarrow \text{ArCl} + \text{N}_2 + \text{CuCl}$ (example for chlorination) The diazonium group ($-\text{N}_2^+$) is replaced by the halide or cyano group, and nitrogen gas ($\text{N}_2$) is evolved, driving the reaction forward. Applications Synthesis of Aryl Halides: Chlorination: $\text{ArN}_2^+\text{Cl}^- + \text{CuCl} \rightarrow \text{ArCl} + \text{N}_2$ Bromination: $\text{ArN}_2^+\text{Br}^- + \text{CuBr} \rightarrow \text{ArBr} + \text{N}_2$ Synthesis of Aryl Nitriles: $\text{ArN}_2^+\text{Cl}^- + \text{CuCN} \rightarrow \text{ArCN} + \text{N}_2$ Preparation of Substituted Aromatic Compounds: Useful when direct electrophilic aromatic substitution is not selective or feasible. Advantages Versatility: Can introduce different functional groups (-Cl, -Br, -CN). Selectivity: Provides a highly regioselective method for introducing substituents at specific positions. Mild Conditions: Reaction occurs at low temperatures, minimizing side reactions. Limitations Instability of Diazonium Salts: Aryl diazonium salts are thermally unstable and require careful handling at low temperatures. Limited Functional Groups: Primarily restricted to halide and cyano groups. Precursor Requirement: Requires the prior synthesis of a primary aromatic amine. Example: Aniline to Chlorobenzene Diazotization: Aniline reacts with $\text{NaNO}_2/\text{HCl}$ at $0-5^\circ\text{C}$ to form benzenediazonium chloride. $$ \text{C}_6\text{H}_5\text{NH}_2 + \text{NaNO}_2 + 2\text{HCl} \rightarrow \text{C}_6\text{H}_5\text{N}_2^+\text{Cl}^- + 2\text{H}_2\text{O} + \text{NaCl} $$ Sandmeyer Reaction: Benzenediazonium chloride reacts with $\text{CuCl}$ to yield chlorobenzene. $$ \text{C}_6\text{H}_5\text{N}_2^+\text{Cl}^- + \text{CuCl} \rightarrow \text{C}_6\text{H}_5\text{Cl} + \text{N}_2 + \text{CuCl} $$ Why Nitration of Nitrobenzene Occurs at the Meta Position The nitration of nitrobenzene introduces a second nitro group ($-\text{NO}_2$) onto the benzene ring. The position of substitution is determined by the strong electronic effects of the existing nitro group. Electronic Effects of the Nitro Group ($-\text{NO}_2$) Strong Electron-Withdrawing Group: The nitro group is a powerful electron-withdrawing group due to both its inductive effect (-I) and resonance effect (-M). This significantly deactivates the benzene ring towards electrophilic substitution. Resonance Effect (-M): The nitro group draws electron density from the benzene ring through resonance, leading to the formation of canonical structures where positive charges are localized at the ortho and para positions relative to the nitro group. $$ \text{C}_6\text{H}_5\text{NO}_2 \leftrightarrow \text{Resonance Structures with positive charge at ortho/para positions} $$ This makes the ortho and para positions highly electron-deficient. Inductive Effect (-I): The highly electronegative atoms in the nitro group (oxygen and nitrogen) pull electron density away from the ring through sigma bonds. This effect further contributes to the electron deficiency, particularly at the ortho and meta positions. Why Meta Position is Favored Deactivation of Ortho and Para Positions: Due to the combined -I and -M effects, the ortho and para positions are significantly deactivated (electron-deficient). An incoming electrophile, which is electron-seeking, will avoid these positions. Relative Electron Density at Meta Position: The meta positions are not directly involved in the resonance delocalization of the positive charge. While the inductive effect still withdraws some electron density, the meta positions remain relatively less electron-deficient (or "least deactivated") compared to the ortho and para positions. Stability of the $\sigma$-Complex (Carbocation Intermediate): If the electrophile attacks at the ortho or para position, a resonance structure of the intermediate $\sigma$-complex would place a positive charge directly on the carbon bearing the electron-withdrawing nitro group. This would create a highly unstable intermediate due to repulsion between the positive charge on the ring and the partial positive charge on the nitro group's nitrogen. Attack at the meta position avoids placing a positive charge on the carbon directly attached to the nitro group in any of the significant resonance structures of the $\sigma$-complex. This makes the meta -substituted intermediate relatively more stable. Reaction Example Nitration of Nitrobenzene: Reaction: Nitrobenzene reacts with concentrated nitric acid ($\text{HNO}_3$) and sulfuric acid ($\text{H}_2\text{SO}_4$). Product: m -Dinitrobenzene. Conditions: Conc. $\text{HNO}_3$, Conc. $\text{H}_2\text{SO}_4$, $50-60^\circ\text{C}$. $\text{C}_6\text{H}_5\text{NO}_2 + \text{HNO}_3 \xrightarrow{\text{H}_2\text{SO}_4} \text{C}_6\text{H}_4(\text{NO}_2)_2 (\textit{m}\text{-Dinitrobenzene}) + \text{H}_2\text{O}$