CSIR NET Chemical Sciences Organic Chemistry Syllabus

What is umpolung (polarity reversal) in synthesis? Give a classic example.

Umpolung is the reversal of the normal electronic character of a functional group. The classic example is converting an aldehyde (electrophilic carbonyl carbon) into a nucleophilic acyl anion equivalent via a dithiane (1,3-dithiane formation, then deprotonation).

What is a convergent synthesis and why is it preferred over a linear synthesis?

A convergent synthesis builds large fragments separately and joins them near the end, whereas a linear synthesis adds one step at a time. Convergent routes give higher overall yield and efficiency because losses are not multiplied across every step of the whole sequence.

Name a common protecting group for alcohols and how it is installed/removed.

TBS (tert-butyldimethylsilyl) ether: installed with TBSCl/imidazole, removed with fluoride (TBAF). Other examples: acetate (Ac2O; removed by base hydrolysis) and benzyl ether (BnBr/base; removed by H2/Pd hydrogenolysis).

How are aldehydes/ketones and 1,2-diols protected?

Carbonyls are protected as acetals/ketals (e.g., reaction with ethylene glycol/acid to give a 1,3-dioxolane), removed by aqueous acid. 1,2-diols are protected as acetonides (cyclic ketals with acetone), also removed by aqueous acid.

What protecting groups are commonly used for amines in peptide synthesis, and how are they removed?

Boc (tert-butoxycarbonyl): removed by TFA (acid). Fmoc (9-fluorenylmethoxycarbonyl): removed by base (piperidine). Cbz/Z (benzyloxycarbonyl): removed by H2/Pd hydrogenolysis.

State the Woodward-Hoffmann rule for the Diels-Alder [4+2] cycloaddition.

The Diels-Alder is a thermally allowed, suprafacial-suprafacial [4pi + 2pi] cycloaddition (4n+2 = 6 pi electrons). It is concerted, stereospecific (cis principle), and follows the endo rule under kinetic control.

Summarize the selection rules for cycloadditions: thermal vs photochemical.

Thermal cycloadditions are allowed (supra-supra) when the total number of pi electrons is 4n+2; photochemical when 4n. Thus [4+2] (6 e) is thermal-allowed and [2+2] (4 e) is photochemical-allowed.

What is the endo rule in the Diels-Alder reaction?

Under kinetic control, the endo adduct predominates because secondary orbital overlap between the diene and the dienophile's substituent stabilizes the endo transition state, even though the exo product is usually thermodynamically more stable.

Define a sigmatropic rearrangement and state the order notation.

A sigmatropic rearrangement is a pericyclic reaction in which a sigma bond migrates across a pi system to a new position with reorganization of pi bonds. The [i,j] order counts atoms over which each end of the breaking sigma bond migrates (numbering from the bond).

What are the Cope and Claisen rearrangements, and what type of sigmatropic shift are they?

Both are thermally allowed suprafacial-suprafacial [3,3]-sigmatropic rearrangements. The Cope is the rearrangement of a 1,5-diene; the Claisen is of an allyl vinyl ether (e.g., allyl aryl ether to o-allyl phenol).

State the selection rule for [1,j]-hydrogen sigmatropic shifts (thermal).

Thermal [1,j]-H shifts are suprafacial for j = 4n+3 (e.g., [1,5]) and antarafacial for j = 4n+1 (e.g., [1,3], which is therefore geometrically difficult). Photochemical rules are reversed.

State the Woodward-Hoffmann rules for electrocyclic reactions.

For 4n pi electrons: thermal = conrotatory, photochemical = disrotatory. For 4n+2 pi electrons: thermal = disrotatory, photochemical = conrotatory. (e.g., thermal ring closure of a triene, 6 e, is disrotatory.)

Define conrotatory and disrotatory ring closure.

In an electrocyclic reaction, the two terminal p-orbitals rotate to form the new sigma bond. Conrotatory = both ends rotate in the same direction; disrotatory = they rotate in opposite directions. The mode determines the stereochemistry of substituents.

Rank pyrrole, furan, and thiophene by aromaticity and explain the trend.

Aromaticity order: thiophene > pyrrole > furan. Greater aromaticity correlates with the heteroatom's lower electronegativity and better lone-pair donation into the ring; oxygen holds its lone pair most tightly, making furan least aromatic and most diene-like.

Where does electrophilic aromatic substitution occur on pyrrole/furan/thiophene, and on pyridine?

For five-membered heterocycles (pyrrole, furan, thiophene), EAS occurs preferentially at the alpha (C-2) position. Pyridine is deactivated toward EAS and reacts at C-3 (beta); it instead favors nucleophilic substitution at C-2/C-4.

Why is pyridine a stronger base than pyrrole?

In pyridine the nitrogen lone pair is in an sp2 orbital in the ring plane, not part of the aromatic sextet, so it is available for protonation. In pyrrole the lone pair is delocalized into the aromatic ring; protonating it would destroy aromaticity, so pyrrole is a very weak base.

Name the heterocycle synthesis: the Paal-Knorr and the Fischer indole syntheses.

Paal-Knorr: 1,4-dicarbonyl compounds cyclize to furans (acid), pyrroles (with amines/NH3), or thiophenes (with P2S5/Lawesson's). Fischer indole synthesis: an arylhydrazine plus an aldehyde/ketone under acid gives an indole via a [3,3]-sigmatropic step.

Classify carbohydrates as aldoses/ketoses and by ring size (furanose/pyranose).

Aldoses contain an aldehyde group; ketoses contain a ketone group. A five-membered cyclic hemiacetal ring is a furanose; a six-membered ring is a pyranose (e.g., glucose exists mainly as glucopyranose).

What is the anomeric effect and what are alpha/beta anomers?

Anomers are cyclic sugar stereoisomers differing in configuration at the new anomeric carbon (C-1 in aldoses): alpha has the OH trans to the CH2OH reference (axial in glucopyranose), beta is cis (equatorial). The anomeric effect is the tendency of an electronegative C-1 substituent to prefer the axial position.

Distinguish reducing and non-reducing sugars; classify glucose, maltose, and sucrose.

Reducing sugars have a free anomeric (hemiacetal) carbon that can open to an aldehyde and reduce Tollens'/Fehling's reagent. Glucose and maltose are reducing; sucrose is non-reducing because both anomeric carbons are joined in the glycosidic bond.

Describe the four levels of protein structure.

Primary: the amino acid sequence (peptide bonds). Secondary: local folding into alpha-helices and beta-sheets stabilized by H-bonds. Tertiary: overall 3D fold of one chain (disulfides, hydrophobic, ionic, H-bonds). Quaternary: assembly of multiple polypeptide subunits.

What is the zwitterionic form and isoelectric point (pI) of an amino acid?

A zwitterion has both a protonated amino group (-NH3+) and a deprotonated carboxyl group (-COO-), so it is dipolar but net neutral. The isoelectric point (pI) is the pH at which the amino acid has zero net charge; for a neutral amino acid pI = (pKa1 + pKa2)/2.

What forces define the geometry of the peptide bond?

The peptide (amide) bond has partial double-bond character due to resonance, making it planar and restricting rotation; it is usually in the trans configuration. This planarity defines the phi/psi backbone torsion angles described by the Ramachandran plot.

Describe the Watson-Crick base pairing in DNA and the helix dimensions.

Adenine pairs with thymine via 2 hydrogen bonds; guanine pairs with cytosine via 3 hydrogen bonds. DNA is an antiparallel right-handed double helix (B-form) with ~10 base pairs per turn and the two strands running 5'->3' opposite each other.

List the structural differences between DNA and RNA.

DNA: deoxyribose sugar, thymine base, usually double-stranded. RNA: ribose sugar (2'-OH), uracil instead of thymine, usually single-stranded. The 2'-OH makes RNA more reactive/less stable than DNA.

Classify lipids and define a triglyceride.

Lipids include fatty acids, triglycerides (fats/oils), phospholipids, glycolipids, steroids, and waxes. A triglyceride is a triester of glycerol with three fatty acids; saturated fats (no C=C) are solids, unsaturated (with C=C) are oils.

What is saponification and what is the iodine value of a fat?

Saponification is base-catalyzed hydrolysis of a triglyceride into glycerol and fatty acid salts (soaps). The iodine value is the grams of iodine absorbed per 100 g of fat, measuring the degree of unsaturation (higher value = more C=C double bonds).

State the Beer-Lambert law used in UV-visible spectroscopy.

A = epsilon x c x l, where A is absorbance, epsilon is the molar absorptivity (L mol-1 cm-1), c is concentration (mol/L), and l is path length (cm). Absorbance is linearly proportional to concentration.

Define chromophore, auxochrome, and bathochromic shift in UV-Vis.

A chromophore is the unsaturated group responsible for absorption (e.g., C=C, C=O). An auxochrome is a saturated group with lone pairs (-OH, -NH2) that intensifies/shifts absorption when attached to a chromophore. A bathochromic (red) shift moves lambda_max to longer wavelength; hypsochromic (blue) shifts it shorter.

Give characteristic IR stretching frequencies for O-H, C=O, C≡N, and C≡C.

Broad O-H: ~3200-3600 cm-1; C=O (carbonyl): ~1700-1750 cm-1; nitrile C≡N: ~2200-2260 cm-1; alkyne C≡C: ~2100-2260 cm-1. (N-H ~3300-3500; sp3 C-H ~2850-2960 cm-1.)

What molecular property must change for a vibration to be IR active?

A vibrational mode is IR active only if it produces a change in the molecule's dipole moment. Symmetric vibrations in symmetric molecules (e.g., N2, the symmetric stretch of CO2) give no dipole change and are IR inactive.

In 1H NMR, what do chemical shift, integration, and the n+1 rule tell you?

Chemical shift (ppm, relative to TMS) reflects the electronic environment/deshielding. Integration gives the relative number of protons. The n+1 multiplicity rule: a proton with n equivalent neighboring protons is split into n+1 peaks (e.g., 3 neighbors give a quartet).

Give approximate 1H NMR chemical shifts for TMS, aliphatic CH, vinyl/aromatic H, and aldehyde/COOH protons.

TMS = 0 ppm (reference); aliphatic C-H ~0.8-2 ppm; allylic/adjacent to C=O ~2-3 ppm; vinylic ~4.5-6.5 ppm; aromatic ~6.5-8 ppm; aldehyde ~9-10 ppm; carboxylic acid ~10-12 ppm.

In mass spectrometry, what are the molecular ion peak and the base peak?

The molecular ion (M+) peak corresponds to the intact molecule minus one electron and gives the molecular mass. The base peak is the most intense peak in the spectrum (assigned 100% relative abundance), representing the most stable/abundant fragment ion.

What does the nitrogen rule and the M+2 isotope pattern indicate in mass spectrometry?

Nitrogen rule: an odd molecular ion mass implies an odd number of nitrogen atoms. M+2 peaks indicate halogens: chlorine gives an M:M+2 ratio of ~3:1, bromine gives ~1:1, due to the natural abundances of their isotopes.