Different systems in a thermodynamics

Thermodynamics: Types of Systems and Entropy

Three different thermodynamic systems are under study. Their analysis is given below:

(a) Type of system in Case 1

Case 1: Water is boiling in an open container with continuous supply of heat.

Type of system: Open system

Reason: An open system allows exchange of both matter and energy with surroundings. Heat enters the system continuously and water vapour escapes from the container.

(b) Case in which entropy increases continuously

Answer: Case 1

During boiling, liquid water changes into vapour. Continuous heat supply and phase change increase molecular randomness, hence entropy increases continuously.

(c) Expression for internal energy change in Case 1

For an open system, internal energy change is given by:

dU = δQ − δW + Σh_indm_in − Σh_outdm_out

Where δQ is heat supplied, δW is work done, h is enthalpy and dm represents mass flow.

(d) System in which entropy decreases with time

Answer: Case 3

In freezing, liquid changes into solid. Molecular motion decreases and order increases, therefore entropy decreases with time.

Summary Table

Case	Type of System	Entropy Change
Case 1 (Boiling, open)	Open system	Increases continuously
Case 2 (Boiled water, closed)	Closed system	Nearly constant
Case 3 (Freezing, closed)	Closed system	Decreases

Suzuki and Negishi reaction

SN

Suzuki & Negishi Coupling Reactions — Clear Guide for Students

Simple explanations, examples, mechanism highlights, and a comparison table — ready for Blogger.

Summary: Suzuki and Negishi reactions are powerful palladium-catalyzed cross-coupling methods that form new carbon–carbon bonds. The Suzuki reaction uses boronic acids/esters, while the Negishi reaction employs organozinc reagents. Both are widely used in pharmaceuticals, material science, and advanced organic synthesis because of their reliability and functional-group tolerance.

Suzuki Reaction (Suzuki–Miyaura Coupling)

What it does: Couples an aryl or vinyl halide with an aryl or vinyl boronic acid/ester to form a new C–C bond.

Typical reagents & conditions: Pd(0) or Pd(II) catalyst (e.g., Pd(PPh3)4), base (K2CO3, NaOH), solvent (ethanol, toluene, DMF, water mixtures), room temperature to 80 °C.

Ar–X + Ar'–B(OH)2  —(Pd catalyst, base)—>  Ar–Ar'  (X = Br, Cl, I)

Mechanistic highlights: oxidative addition of Ar–X to Pd(0), transmetallation with boron species (assisted by base), and reductive elimination giving the biaryl product while regenerating Pd(0).

Why Suzuki is popular:

• Boronic acids/esters are stable and easy to handle.
• Reaction tolerates many functional groups (alcohols, ethers, esters).
• Works well for sp2–sp2 couplings (biaryls, styrenes).

Negishi Reaction

What it does: Couples an organozinc reagent with an aryl, vinyl, or alkyl halide under Pd or Ni catalysis to form a C–C bond.

Typical reagents & conditions: R–ZnX (prepared from R–Li or R–MgBr and ZnCl2), Pd or Ni catalyst, mild temperatures (often 0–50 °C), solvents like THF or toluene.

R–ZnX + R'–X  —(Pd or Ni catalyst)—>  R–R'  

Mechanistic highlights: oxidative addition of R'–X to Pd(0), transmetallation from the organozinc to Pd, then reductive elimination to form R–R'. Organozinc reagents are more nucleophilic than boronic acids and often react faster.

Strengths of Negishi:

• Organozinc reagents are reactive and enable sp3–sp2 and sp3–sp3 couplings that can be challenging by other methods.
• High chemoselectivity in many cases.

Practical comparison (quick table)

Suzuki (at a glance)
Organometallic partner	Boronic acids/esters
Moisture sensitivity	Low — tolerant to water
Functional group tolerance	Very good
Typical use	Biaryl formation, pharmaceuticals

Negishi (at a glance)
Organometallic partner	Organozinc (R–ZnX)
Moisture sensitivity	Higher — requires dry conditions
Functional group tolerance	Good, but preformed R–Zn may require precautions
Typical use	sp3–sp2 and sp3–sp3 couplings, complex molecule building

Examples

Suzuki example: Synthesis of biphenyl from bromobenzene and phenylboronic acid.

Ph–Br + Ph–B(OH)2 —(Pd(0), K2CO3)—> Ph–Ph (biphenyl)

Negishi example: Coupling of ethylzinc bromide with 1-bromobenzene to form ethylbenzene.

Et–ZnBr + Ph–Br —(Pd or Ni)—> Ph–Et (ethylbenzene)

Teaching tips & exam points

• Draw and label the three key steps: oxidative addition, transmetallation, reductive elimination.
• Ask students to list why Suzuki is preferred in industry (stable reagents, green solvent options, scalability).
• Pose a problem: plan a synthesis of 4-phenylbenzaldehyde using Suzuki coupling — what protecting groups (if any) are needed?

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Corey–House Reaction

Corey–House Reaction (Corey–Posner–Whitesides–House)

Introduction: The Corey–House reaction is a reliable method for making carbon–carbon single bonds by coupling alkyl fragments using organocuprate reagents (Gilman reagents). The reaction is useful for forming higher alkanes.

General Reaction

2 R–Li + CuI  →  R2CuLi  (Gilman reagent)

R2CuLi + R'–X → R–R' + R–Cu + LiX

(X = Br, Cl, I)

Mechanism (Short)

The reaction follows an SN2-type nucleophilic substitution on an alkyl halide. One alkyl group of the Gilman reagent couples with the electrophilic carbon, forming a new C–C bond.

• Formation of R2CuLi from organolithium and CuI
• Nucleophilic substitution on R'–X
• New C–C bond formed

Scope

• Best with primary alkyl halides
• Secondary moderate
• Tertiary not suitable (elimination)
• Aryl/vinyl halides usually unreactive

Example:

C2H5Li + CuI → (C2H5)2CuLi

(C2H5)2CuLi + C3H7Br → C5H12

Advantages

• Forms C–C bonds under mild conditions
• Good for making larger alkanes

Limitations

• Organolithiums are moisture sensitive
• Poor functional group tolerance
• Modern Pd-couplings have broader scope

Teaching Question

• Compare Corey–House vs Suzuki/Negishi for different substrates.

SN1 and SN2 reaction comparision

Comparison Between SN1 and SN2 Reactions

1. Basic Definition

SN1 Reaction (Unimolecular Nucleophilic Substitution)

SN1 is a two-step nucleophilic substitution reaction where the rate depends only on the concentration of the substrate.

SN2 Reaction (Bimolecular Nucleophilic Substitution)

SN2 is a one-step nucleophilic substitution reaction where the rate depends on both the nucleophile and the substrate.

2. Mechanism

SN1 Mechanism

• Step 1: Formation of a carbocation (rate-determining step)
• Step 2: Nucleophile attacks carbocation
• Intermediate: Carbocation forms

SN2 Mechanism

• Single-step mechanism
• Nucleophile attacks from the backside of the leaving group
• No intermediate, only transition state

3. Kinetics

SN1: First-order kinetics → Rate = k[substrate]

SN2: Second-order kinetics → Rate = k[substrate][nucleophile]

4. Substrate Preference

• SN1: 3° > 2° > 1° (stable carbocation)
• SN2: 1° > 2° > 3° (less steric hindrance)

5. Stereochemistry

• SN1: Racemization occurs due to planar carbocation
• SN2: Inversion of configuration (Walden inversion)

6. Nucleophile Requirement

• SN1: Weak nucleophile is sufficient
• SN2: Strong nucleophile required

7. Solvent Effect

• SN1: Favors polar protic solvents
• SN2: Favors polar aprotic solvents

8. Leaving Group Ability

Both SN1 and SN2 require a good leaving group, but SN1 is more sensitive to leaving group stability because carbocation formation is key.

9. Summary Table

Feature	SN1	SN2
Reaction Order	First-order	Second-order
Mechanism	Two-step (carbocation)	One-step (backside attack)
Substrate	3° > 2° > 1°	1° > 2° > 3°
Stereochemistry	Racemization	Inversion
Nucleophile	Weak	Strong
Solvent	Polar Protic	Polar Aprotic

Conclusion

SN1 and SN2 reactions differ in mechanism, kinetics, stereochemistry, and substrate preference. SN1 involves carbocation formation and racemization, while SN2 proceeds in one step with inversion of configuration. Understanding these differences helps in predicting reaction outcomes in organic chemistry.

Substitution vs elimination reaction

Substitution vs Elimination Reactions — Comparison

This page gives a concise, exam-friendly comparison between substitution and elimination reactions, covering definitions, types, mechanisms, factors affecting each, examples, and a summary table.

1. Basic Definitions

Substitution Reaction

In a substitution reaction, one atom or group in a molecule is replaced by another atom or group.

General example: R–X + Nu- → R–Nu + X-

Elimination Reaction

In an elimination reaction, two atoms or groups are removed from adjacent carbon atoms to form a double bond (an alkene).

General example: R–CH2–CH2–X → Alkene + HX

2. Types

• Substitution: SN1 (unimolecular), SN2 (bimolecular)
• Elimination: E1 (unimolecular), E2 (bimolecular)

3. Reaction Mechanisms

SN1 (Substitution, Unimolecular)

Two-step: (1) leaving group leaves forming a carbocation, (2) nucleophile attacks carbocation. Rate depends on substrate concentration.

SN2 (Substitution, Bimolecular)

One-step concerted attack by nucleophile from the back-side → inversion of configuration. Rate depends on both substrate and nucleophile.

E1 (Elimination, Unimolecular)

Two-step: formation of carbocation (same intermediate as SN1), then base removes a proton to give an alkene. Competes with SN1.

E2 (Elimination, Bimolecular)

One-step concerted removal of β-hydrogen by a base while leaving group leaves. Requires anti-periplanar geometry for the eliminated hydrogen and leaving group.

4. Nature of Substrate

Substrate vs Favored Pathway

Substrate	Substitution	Elimination
Primary	SN2 favored	E2 if strong base
Secondary	SN1/SN2 mixture	E2 strongly favored (with strong base)
Tertiary	SN1 favored	E1/E2 both possible (E2 with strong base)

5. Role of Nucleophile / Base

Substitution reactions require a nucleophile (Nu^-) such as OH-, CN-, I-. Strong nucleophiles favor SN2.

Elimination reactions require a base (B^-) such as OH-, OR-, t-BuO-. Strong, especially bulky, bases favor E2 and can lead to Hoffmann product.

6. Temperature Effect

Low temperature generally favors substitution, while high temperature favors elimination because elimination often produces more molecules (increased entropy).

7. Major Products

Substitution: new substituted compound; stereochemical consequences: SN2 → inversion, SN1 → racemization.

Elimination: alkene formed. Zaitsev's rule: the more substituted alkene is generally the major product; bulky bases give Hofmann product.

8. Solvents

• Polar protic solvents (e.g., water, alcohols) favor SN1 and E1 (stabilize carbocations).
• Polar aprotic solvents (e.g., DMSO, acetone) favor SN2 (they do not strongly solvate nucleophiles).

9. Competition Between Substitution and Elimination

Often the same substrate and reagent mixture can undergo both substitution and elimination. General trends:

• Strong base + high temperature → elimination dominates.
• Strong nucleophile + low temperature → substitution dominates.
• Bulky base (e.g., t-BuO^-) → elimination (Hofmann product).

Quick Summary Table

Feature	Substitution	Elimination
What happens?	Group replaced	Groups removed to form double bond
Typical product	Substituted compound	Alkene
Requires	Nucleophile	Strong base
Favored by	Low temp	High temp
Mechanisms	SN1 / SN2	E1 / E2
Stereochemistry	Inversion (SN2), racemization (SN1)	Anti-periplanar requirement (E2); product stereochemistry depends on alkene geometry

10. Simple Examples

SN2 example: CH3CH2Br + CN- → CH3CH2CN + Br-

E2 example: CH3CH2CH2Br + KOH (alc.) → CH3CH=CH2 + KBr + H2O

Study Tips

1. Practice mechanism arrows for SN1, SN2, E1, and E2 to understand intermediates and transition states.
2. Memorize how substrate structure (primary/secondary/tertiary) biases the pathway.
3. Use temperature and base/nucleophile strength to predict the major outcome when routes compete.

Conclusion

Substitution and elimination are often competing reactions. By examining substrate structure, nucleophile/base strength, solvent, and temperature, you can predict which pathway will dominate. Understanding the detailed mechanisms (SN1 vs SN2 and E1 vs E2) helps in predicting stereochemistry and products.

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Peptide Bond

Short definition: A peptide bond is the covalent bond formed between the carboxyl group (−COOH) of one amino acid and the amino group (−NH₂) of another amino acid, producing −CONH− and releasing a molecule of water (condensation reaction).

Overview

Peptide bonds link amino acids together to form peptides and proteins. A chain of two amino acids joined by a single peptide bond is called a dipeptide, three is a tripeptide, and many (tens to thousands) form a polypeptide or protein.

Formation of a Peptide Bond (Condensation Reaction)

When the carboxyl group of one amino acid reacts with the amino group of another, a molecule of water is removed and a peptide bond forms:

Amino acid 1:   H₂N–CH(R¹)–COOH

Amino acid 2:   H₂N–CH(R²)–COOH

Condensation:

H₂N–CH(R¹)–COOH  +  H₂N–CH(R²)–COOH

         ↓ (loss of H₂O)

H₂N–CH(R¹)–CONH–CH(R²)–COOH  +  H₂O

        

Biologically, peptide bond formation is catalyzed by the ribosome during translation. In cells, the activated amino acid is attached to tRNA and peptide bond formation occurs in the ribosomal active center (peptidyl transferase). This enzymatic process is energetically driven and not a simple spontaneous dehydration.

Structure and Resonance

The peptide bond (–CO–NH–) has a partial double-bond character due to resonance between the carbonyl group and the amide nitrogen:

• Resonance form A: O=C–N– (canonical)
• Resonance form B: O⁻–C═N⁺– (contribution gives partial C=N character)

Because of this resonance:

1. The C–N bond length is shorter than a typical single bond and longer than a double bond.
2. Rotation about the C–N peptide bond is restricted — the peptide bond is effectively planar.
3. Peptide bonds have a dipole moment (carbonyl oxygen is partially negative, amide nitrogen partially positive), important for hydrogen bonding in protein secondary structure.

Planarity and Geometry

The six atoms forming the peptide plane — O, C (carbonyl), Cα, N, H, and the next Cα — lie roughly in one plane. Two important dihedral angles describe the backbone conformation:

• Φ (phi) — rotation about N–Cα
• Ψ (psi) — rotation about Cα–C (carbonyl)

The restricted rotation around the peptide C–N bond and allowed rotations about Φ and Ψ determine secondary structures like α-helices and β-sheets.

Chemical Properties

Key properties of peptide bonds

Property	Explanation
Stability	Relatively stable under neutral conditions; enzymatic hydrolysis is required for rapid cleavage in biological systems.
Planarity	Partial double-bond character causes planarity and limited rotation.
Polarity	Polar bond capable of participating in hydrogen bonds (NH donor, C=O acceptor).
Acid/base behavior	Amide nitrogen is not basic like free amine; it does not protonate easily due to resonance.

Hydrolysis of Peptide Bonds

Peptide bonds can be hydrolysed (broken) to yield free amino acids. Hydrolysis can occur:

• Enzymatically — proteases and peptidases (e.g., trypsin, chymotrypsin, pepsin, carboxypeptidase) catalyze peptide bond cleavage under physiological conditions.
• Chemically — strong acids (e.g., 6 M HCl, heat) or strong bases can hydrolyze peptide bonds, but these conditions are harsh and not biologically relevant.

Typical hydrolysis reaction:

R¹–CO–NH–R²  +  H₂O  →  R¹–COOH  +  H₂N–R²

        

Role in Proteins and Function

Peptide bonds form the protein backbone. The order (sequence) of amino acids linked by peptide bonds — the primary structure — determines how the chain folds into secondary, tertiary, and quaternary structures, which in turn determine protein function.

Hydrogen bonds between backbone C=O and N–H groups stabilize secondary structures:

• α-helix: hydrogen bond between C=O of residue i and N–H of residue i+4.
• β-sheet: hydrogen bonding between C=O and N–H of neighboring strands.

Special Notes and Exceptions

• Proline: When proline is involved, the N–Cα bond is part of a ring; the peptide bond preceding proline has restricted geometry and can exist in both cis and trans forms more readily than other residues. Proline often introduces kinks.
• Disulfide bonds: These are not peptide bonds — they form between cysteine side chains (–SH) to stabilize tertiary structure.

Biological Synthesis (Ribosomal vs Non-ribosomal)

Most peptide bonds in cells are formed by ribosomes translating mRNA into polypeptide chains. There are also non-ribosomal peptide synthetases (NRPS) in some microorganisms that assemble peptides (often with unusual amino acids) using enzyme complexes.

Tests & Methods of Detection

Some methods used to detect peptide bonds and proteins include:

• Biuret test: Peptide bonds form a violet complex with copper(II) in alkaline solution; used to detect proteins/peptides (positive for two or more peptide bonds).
• UV absorption: Peptides/proteins absorb at 190–230 nm (peptide bond absorption) and aromatic residues absorb at 280 nm.
• Proteolytic digestion + mass spectrometry: Identify peptide sequences by fragmenting proteins and analyzing masses.

Summary

Peptide bonds are the fundamental linkages that connect amino acids into peptides and proteins. They are formed by condensation between an amino group and a carboxyl group, are planar due to resonance (partial double-bond character), participate in hydrogen bonding that stabilizes secondary structure, and are cleaved by specific enzymes during protein turnover. Understanding peptide-bond chemistry is essential for grasping how proteins are made, folded, and degraded.

Further Reading & Study Tips

1. Study the ribosomal mechanism of peptide bond formation (peptidyl transferase center) to link chemistry with biology.
2. Practice drawing peptide linkages and short peptides — visualize φ and ψ rotations and where hydrogen bonds form in helices and sheets.
3. Compare amide chemistry to ester chemistry to appreciate resonance and stability differences.

Ring expansion

Ring Expansion and Related Reactions in Organic Chemistry

Audience: Class 11–12 students, undergraduate organic chemistry learners, and teachers.

Introduction

Ring expansion is a class of organic reactions in which the size of a cyclic molecule increases by one or more atoms. These reactions are important in synthesis because changing ring size alters ring strain, conformational preference, and reactivity. Ring expansion commonly occurs via carbocation rearrangements, migration of atoms or groups, and insertion reactions involving oxygen, nitrogen, carbenes or nitrenes.

Why Rings Expand

• Relief of ring strain: Small rings (3- and 4-membered) are strained and often rearrange to larger, more stable rings.
• Carbocation stability: A less-stable carbocation can rearrange by a 1,2-shift to give a more-stable carbocation; when this occurs inside a ring, expansion may result.
• Formation of stable functional groups: Insertion of heteroatoms (oxygen or nitrogen) can convert ketones to lactones or oximes to lactams, increasing ring size.
• Synthetic strategy: Access to medium-sized rings (7–12 members) is often achieved by ring expansion tactics.

Important Named Reactions that Cause Ring Expansion

1. Baeyer–Villiger Oxidation

Conversion: Ketone → Ester (open chain) or Lactone (cyclic ketone).

Reagents: Peracids (e.g., mCPBA), peroxides.

Mechanism: The peracid forms a Criegee intermediate followed by migration of the group adjacent to the carbonyl to oxygen. In cyclic ketones this migration inserts O and gives a larger-ring lactone. Migration aptitude: tertiary > secondary > phenyl > primary > methyl.

Example: Cyclohexanone + mCPBA → ε-caprolactone (a seven-membered lactone used in polymer chemistry).

2. Beckmann Rearrangement

Conversion: Oxime → Amide (or Lactam for cyclic oximes).

Reagents/Conditions: Strong acid (H₂SO₄), PCl₅, or other dehydrating agents.

Mechanism: Protonation of the oxime, followed by migration of the group anti to the OH to nitrogen and cleavage of the N–O bond. In cyclic oximes, this leads to ring expansion producing lactams (e.g., cyclohexanone oxime → caprolactam, precursor to Nylon-6).

3. Wagner–Meerwein Rearrangement

Type: Carbocation rearrangement (1,2-alkyl or hydride shift).

When a carbocation is formed on a ring, a neighboring bond may migrate to stabilize the cation. A 1,2-shift in a cyclic system can lead to a larger ring if the migrating group opens or relocates the ring connectivity.

Applications: Common in terpene and steroid rearrangements where complex ring skeletons are built.

4. Pinacol–Pinacolone Rearrangement

Conversion: Vicinal diol → Ketone (with group migration).

Mechanism: Protonation of one hydroxyl, loss of water to give a carbocation, then 1,2-shift of an alkyl group resulting in a new carbonyl. In cyclic diols, this shift can expand the ring.

5. Favorskii Rearrangement

Conversion: α-Haloketone → Carboxylic acid derivative after rearrangement.

Notes: Usually gives ring contraction for cyclopropanones, but certain substituted systems and pathways can effectively lead to ring-size changes; the mechanism involves carbanion/enolate intermediates and ring opening followed by reclosure.

6. Carbene and Carbenoid Insertions

Carbenes (e.g., generated from diazomethane) or carbenoids (Simmons–Smith) can insert into C–C bonds or add across double bonds to form new rings or enlarge existing ones. For example, addition of a CH₂ unit to a cyclic alkene can give a larger ring after subsequent transformations.

7. Nitrene Insertions and Rearrangements

Nitrenes can insert into C–H or C–C bonds and can be trapped to form azacycles or lactams, leading to ring expansion in appropriate systems.

8. Photochemical Ring Expansion

Under UV light, certain strained rings undergo rearrangement to larger rings via excited-state processes. Examples include cyclobutane rearrangements to cyclohexenes or ring expansions connected to pericyclic photochemical pathways.

Typical Mechanistic Pattern

Although mechanisms differ, common steps include:

1. Activation (protonation, oxidation, photochemical excitation, or formation of carbene/nitrene).
2. Migration or insertion (1,2-shift, oxygen insertion, nitrene/carbenoid insertion).
3. Rearrangement and reclosure to form the expanded ring (or formation of a lactone/lactam).

ICE-style analysis and careful electron-pushing (arrow-pushing) help predict which group migrates and the stereochemical outcome where relevant.

Examples and Synthetic Applications

Polymer pre-cursors: Caprolactone (from Baeyer–Villiger of cyclohexanone) and caprolactam (from Beckmann of cyclohexanone oxime) are industrially important for producing polyesters and nylon.

Steroid/terpene synthesis: Wagner–Meerwein rearrangements are used to rearrange and build complex multi-ring skeletons in natural product synthesis.

Medicinal chemistry: Changing ring size alters biological activity and pharmacokinetic properties; ring expansion techniques enable medicinal chemists to explore structure–activity space.

Common Exam Tips & Mistakes

• Always identify which atoms or groups are migrating and whether migration is favored (migration aptitude differs by reaction).
• When dealing with cyclic substrates, verify whether the product will be a lactone, lactam, or expanded carbocycle.
• For Baeyer–Villiger, remember the order of migratory aptitude (tertiary > secondary > phenyl > primary > methyl).
• Check stereochemistry: migrations generally retain configuration at the migrating center (concerted or stereospecific pathways may apply).

Summary

Ring expansion encompasses a diverse set of reactions—oxidative insertions (Baeyer–Villiger), rearrangements of oximes (Beckmann), carbocation shifts (Wagner–Meerwein), diol rearrangements (Pinacol), and insertion reactions (carbenes, nitrenes). These transformations are powerful tools in organic synthesis for accessing rings of sizes that may be otherwise difficult to construct directly. Understanding the mechanism and migration preferences is key to predicting and designing ring-expansion pathways.

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