Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms within molecules. An important branch of stereochemistry is the study of chiral molecules
Stereochemistry is also known as 3D chemistry because the prefix "stereo-" means "three-dimensionality".
The study of stereochemical problems spans the entire range of organic, inorganic, biological, physical and supramolecular chemistries. Stereochemistry includes methods for determining and describing these relationships; the effect on the physical or biological properties these relationships impart upon the molecules in question, and the manner in which these relationships influence the reactivity of the molecules in question (dynamic stereochemistry).

Stereochemistry

• chemistry in three dimensions
• includes both structure and reactivity effects

Enantiomers

• mirror-image stereoisomers
• like left and right hands
  (see page 172 in your text)
• observed when a carbon atom has four different groups attached to it
  CHXYZ or CX1X2X3X4

Enantiomer Examples






Chirality

• property of having "handedness"
  (different from its mirror image)
• a molecule with any element of symmetry (e.g., a mirror plane) must be achiral

Stereogenic Centers

• chiral centers or stereocenters
• a molecule with a stereogenic center (e.g., CX1X2X3X4) will be chiral
• a stereogenic center cannot be:
  sp- or sp2-hybridized (must be sp3)
  an atom with 2 identical substituents (e.g., any -CH2- group)

Identifying Chiral Molecules

• achiral
  
  
  
• chiral
  

Properties of Enantiomers

• enantiomers have identical physical and chemical properties,
  EXCEPT they
• interact with another chiral molecule differently
  (like trying on left- or right-handed gloves - left and right hands react differently)
• rotate the plane of plane-polarized light by equal amounts but in opposite directions

Optical Activity

• chiral compounds rotate the plane of plane-polarized light
• rotation measured in degrees
  clockwise (dextrorotatory or +) or
  counterclockwise (levorotatory or -)
• polarimeter - instrument for measuring optical activity

Specific Rotation

• standard amount of optical rotation by 1 g/mL of compound
  in a standard 1 decimeter (10 cm) cell
• [a] = a / l C
• where [a] is specific rotation
  a = observed rotation in degrees
  l = path length in dm
  C = concentration in g/mL

Absolute Configuration

• nomenclature method for designating the specific arrangement of groups about a stereogenic center
• differentiates between enantiomers
• uses the same sequence rules for establishing priority of groups as was used for E and Z

R and S Designations

• assign priorities 1-4 (or a-d) to the four different groups on the stereogenic center
• align the lowest priority group (4 or d) behind the stereogenic carbon
• if the direction of a-b-c is clockwise, it is R
• if a-b-c is counterclockwise, it is S

Right- and Left-Hand Views

• textbook analogy - steering wheel
• alternative analogy - your hands
  assign priorities to your fingers in order of height
  a = middle finger, b = pointer finger, c = thumb, d = wrist
  R - this works for your right hand
  S - this works for your left hand
  

Drawing 3-D Structures

• practice with models
• dotted-line & wedge
• Fischer projections
  

Fischer Projections

• a method for depicting stereochemistry at a series of chiral centers
• arrange the chiral center so that:
  • horizontal groups are forward
  • vertical groups are oriented backward

• Note that there are numerous ways to show a given chiral center
  • 12 different Fischer projections represent (R)
  • 12 different Fischer projections represent (S)

Multiple Stereogenic Centers

• compounds with more than 2 stereocenters have more than 2 stereoisomers
  e.g., 2-bromo-3-chlorobutane
  (2R,3R) and (2S,3S) are enantiomers
  (2R,3S) and (2S,3R) are enantiomers
• in general, n stereocenters give 2^n stereoisomers

Diastereomers

• stereoisomers that are not enantiomers
  e.g., (2R,3R) and (2R,3S)
  (not mirror images, but not the same either)
• diastereomers may have different chemical and physical properties

Meso Compounds

• compounds with stereogenic centers but which are not chiral
  e.g., (2R,3S)-2,3-dibromobutane
  (same as its mirror image)
  

Identifying Meso Compounds

• mirror plane of symmetry
• one stereocenter is the mirror image of the other
• cis-1,2-disubstituted cycloalkanes are meso if the two substituents are identical
  

Cyclohexane Derivatives

• chair interconversions affect conformation, but not configuration
• trans-1,2-dichlorocyclohexane is (R,R) or (S,S)
• cis-1,2-dichlorocyclohexane is (R,S)
  • one chair has the R stereocenter with axial Cl and S with equatorial
  • the other chair has R equatorial and S axial
  • the two chair forms are enantiomers but not isolatable

Configurations and Conformations of Disubstituted Cyclohexanes

substitution	cis	trans
1,2-X2	eq,ax <==> ax,eq (R,S) interconverting enantiomers	eq,eq <==> ax,ax (R,R) & (S,S) isolable enantiomers two conformations each
1,2-XY	eq,ax <==> ax,eq isolable enantiomers two conformations each	eq,eq <==> ax,ax isolable enantiomers two conformations each
1,3-X2	eq,eq <==> ax,ax (R,S) - meso compound two conformations	eq,ax <==> ax,eq isolable enantiomers two conformations each
1,3-XY	eq,eq <==> ax,ax isolable enantiomers two conformations each	eq,ax <==> ax,eq isolable enantiomers two conformations each
1,4-X2 no stereocenters	eq,ax <==> ax,eq equivalent conformations	eq,eq <==> ax,ax two conformations
1,4-XY no stereocenters	eq,ax <==> ax,eq two conformations	eq,eq <==> ax,ax two conformations

Racemic Mixtures

• an equal mix of both enantiomers (also called a racemate)
• a common form in the laboratory (but not in nature)
• optical resolution - separating enantiomers from a mix (typically difficult)

Optical Purity / Enantiomeric Excess

• unequal mixtures of enantiomers may occur
• optical purity - compare actual rotation with what a pure enantiomer would give (in %)
• enantiomeric excess - % excess of one pure enantiomer over the other
• % optical purity = % enantiomeric excess
• example - consider a mix of 75% (R) + 25% (S)
  • optical rotation would be 50% (50% inactive racemic + 50% R)
  • enantiomeric excess is also 50% (75% - 25%)

Optical Resolution

• for acids or bases - formation of diastereomeric salts from a naturally ocurring acid or base
• enzymatic resolution - preferential binding or reaction of just one enantiomer

Isomerism - Summary

• isomers - same molecular formula (same collection of atoms used)
• constitutional isomers -differ in the connections between atoms
  different carbon skeletons
  different functional groups
  different locations of a functional group

Stereoisomers - Summary

• stereoisomers - same connections but in different 3D arrangement
• enantiomers - mirror-image stereoisomers
• diastereomers - non-mirror-image stereoisomers:
  cis-trans diastereomers
  other diastereomers

lactone, any of a class of cyclic organic esters, usually formed by reaction of a carboxylic acid group with a hydroxyl group or halogen atom present in the same molecule. Commercially important lactones include diketene and β-propanolactone used in the synthesis of acetoacetic acid derivatives and β-substituted propanoic (propionic) acids, respectively; the perfume ingredients pentadecanolide and ambrettolide; vitamin C; and the antibiotics methymycin, erythromycin, and carbomycin.

The γ- and δ-lactones, containing five- and six-membered rings, respectively, are the most common. They are formed by loss of water from the corresponding hydroxy acids, a process that often occurs spontaneously even in aqueous solution. Diketene and β-propanolactone are made by the reaction of ketene with itself or with formaldehyde, respectively. Lactones with 7 to 24 atoms in the ring are prepared by slow distillation of the appropriate hydroxy acids under greatly reduced pressure.

Sesquiterpene lactones are a class of chemical compounds; they are sesquiterpenoids (built from three isoprene units) and contain a lactone ring, hence the name. They are found in many plants and can cause allergic reactions and toxicity if overdosed, particularly in grazing livestock.^[1]

Types

Structures of some sesquiterpene lactones:
A: Germacranolides, B: Heliangolides, C+D: Guaianolides, E: Pseudoguaianolides, F: Hypocretenolides, G: Eudesmanolides.

Sesquiterpene lactones can be divided into several main classes including germacranolides, heliangolides, guaianolides, pseudoguaianolides, hypocretenolides, and eudesmanolides.

Examples

Artemisinin, a new, highly-effective anti-malarial compound, is a sesquiterpene lactone found in Chinese wormwood. Lactucin, desoxylactucin, lactucopicrin, lactucin-15-oxalate, lactucopicrin-15-oxalate are some of the most prominent found in lettuce and spinach, giving most of the bitter taste to these crops.

One eudesmanolide, 3-oxo-5αH,8βH-eudesma-1,4(15),7(11)-trien-8,12-olide, can work with vernolic acid and other compounds in plants to reduce inflammation.^[2]

N-Acyl homoserine lactone

From Wikipedia, the free encyclopedia

General chemical structure of an N-acyl homoserine lactone

N-Acyl homoserine lactones (AHLs or N-AHLs) are a class of signaling molecules involved in bacterial quorum sensing. Quorum sensing is a method of communication between bacteria that enables the coordination of group-based behavior based on population density. They signal changes in gene expression, such as switching between the flagella gene and the gene for pili for the development of a biofilm.

Mechanism

Signaling molecules are produced within the cell and are released into the environment. The resulting concentration of signaling molecules in the environment is dependent upon population density. Once the population density has reached a particular threshold, gene expression can begin. This allows bacteria to coordinate group-based behavior. N-AHLs produced by different bacteria differ in the length of the R-group side-chain. Chain lengths vary from 4 to 18 carbon atoms and in the substitution of a carbonyl at the third carbon.  It has also been suggested that N-AHLs alter local surface tension enough to create Marangoni flows which facilitate swarming and colony motility.

Example

One example of the involvement of AHLs in quorum sensing is in the regulation of the bioluminescent protein luciferase in the luminescent bacteria Vibrio fischeri. Similar pathways occur in other luminescent bacteria. In Vibrio fischeri, AHL binds to the protein product of the LuxR gene and activates it. The C-terminal domain of activated LuxR relieves the repression exerted by H-NS nucleoid proteins that bind to the promoters of LuxR, LuxI and the LuxCDABEG operon, as well as to A-T-rich stretches within that operon and other genomic regions. The product of LuxI catalyses the synthesis of AHL. Thus, AHL acts as an autoinducer. Transcription of the LuxCDABEG operon results in luminescence due to the expression of LuxA and LuxB, which form a protein known as a luciferase and the expression of LuxC, D, E, and G, which are involved in the synthesis of the luciferase's substrate, tetradecanal. This is an important feature of quorum sensing, as it makes little sense for one cell to waste the energy producing light, as the resulting light will be so faint that it will be more or less undetectable. Instead, once the bacterial population has reached a specific size, only then does light production commence.

Edman degradation

Homoserine lactone is also a product of the proteolytic reaction of cyanogen bromide (CNBR) with a methionine residue in a protein. This reaction is important for chemical sequencing of proteins, as the Edman degradation process is unable to sequence more than 70 consecutive residues.

PROBLEM
Can we not in the synthesis of lactone using catalyst?
Lactone is a cyclic ester is a condensation product of the alcohol-OH and-COOH carboxylic acid in the same compound. Characteristic of the lactone ring that is a cover consisting of two or more who has the carbonyl carbon and oxygen atoms are adjacent. This condensation reaction can also be referred to as the esterification reaction.
Transesterification reaction is an equilibrium reaction, therefore the presence of a catalyst to accelerate the achievement of a state of equilibrium of the reaction. Meanwhile, to obtain a greater abundance of the product ester compound, one of the reagents used must be in excess amount. The catalyst used can be either strong acid or strong base.
so, if the problem can only be or not, I think it can, but the reaction is slower

HYDROLYSIS OF NITRILES     Reaction type:  Nucleophilic Addition

Overview

• Nitriles typically undergo nucleophilic addition to give products that often undergo a further reaction.
• The chemistry of the nitrile functional group, CºN, is very similar to that of the carbonyl, C=O of aldehydes and ketones. Compare the two schemes:

        versus 

• However, it is convenient to describe nitriles as carboxylic acid derivatives because:
• the oxidation state of the C is the same as that of the carboxylic acid derivatives.
• hydrolysis produces the carboxylic acid
• Like the carbonyl containing compounds, nitriles react with nucleophiles via two scenarios:

• Strong nucleophiles (anionic) add directly to the CºN to form an intermediate imine salt that protonates (and often reacts further) on work-up with dilute acid.

            Examples of such nucleophilic systems are :  RMgX, RLi, RCºCM, LiAlH₄
 
• Weaker nucleophiles (neutral) require that the CºN be activated prior to attack of the Nu.

     This can be done using a acid catalyst which protonates on the Lewis basic N and makes the system more electrophilic.

 

            Examples of such nucleophilic systems are :  H₂O, ROH
 


The protonation of a nitrile gives a structure that can be redrawn in another resonance form that reveals the electrophilic character of  the C since it is a carbocation.

Hydrolysis of Nitriles

Reaction type:  Nucleophilic Addition then Nucleophilic Acyl Substitution

Summary

• Nitriles, RCºN, can be hydrolyzed to carboxylic acids, RCO₂H via the amide, RCONH₂.
• Reagents : Strong acid (e.g. H₂SO₄) or strong base (e.g. NaOH) / heat.

Related Reactions

• Hydrolysis of Esters and Amides

 

MECHANISM OF THE ACID catalyzed HYDROLYSIS OF NITRILES
Step 1: An acid/base reaction. Since we only have a weak nucleophile so activate the nitrile, protonation makes it more electrophilic.
Step 2: The water O functions as the nucleophile attacking the electrophilic C in the CºN, with the electrons moving towards the positive center.
Step 3: An acid/base reaction. Deprotonate the oxygen that came from the water molecule. The remaining task is a tautomerization at N and O centers.
Step 4: An acid/base reaction. Protonate the N gives us the -NH2 we need....
Step 5: Use the electrons of an adjacent O to neutralise the positive at the N and form the p bond in the C=O.
Step 6: An acid/base reaction. Deprotonation of the oxonium ion reveals the carbonyl in the amide intermediate....halfway to the acid.....

 

Reactions usually in Et₂O or THF followed by H₃O⁺ work-up Reaction type: Nucleophilic Addition

Summary

• The nitrile, RCºN, gives the 1^o amine by conversion of the CºN to -CH₂-NH₂
• Nitriles can be reduced by LiAlH₄ but NOT the less reactive  NaBH₄
• Typical reagents :  LiAlH₄  / ether solvent followed by aqueous work-up.
• Catalytic hydrogenation (H₂ / catalyst) can also be used giving the same products.
• R may be either alkyl or aryl substituents

Reactions of RLi or RMgX with Nitriles

Reaction usually in Et₂O or  THF Reaction type:  Nucleophilic Acyl Substitution then Nucleophilic Addition

Summary:

• Nitriles, RCºN, react with Grignard reagents or organolithium reagents to give ketones.
• The strongly nucleophilic organometallic reagents add to the CºN bond in a similar fashion to that seen for aldehydes and ketones.
• The reaction proceeds via an imine salt intermediate that is then hydrolyzed to give the ketone product.

• Since the ketone is not formed until after the addition of water, the organometallic reagent does not get the opportunity to react with the ketone product.
• Nitriles are less reactive than aldehydes and ketones.
• The mechanism is an example of the reactive system type.

REACTION OF RMgX WITH AN NITRILE

Step 1: The nucleophilic C in the organometallic reagent adds to the electrophilic C in the polar nitrile group. Electrons from the CºN move to the electronegative N creating an intermediate imine salt complex.

Step 2: An acid/base reaction. On addition of aqueous acid, the intermediate salt protonates giving the imine.

Step 3: An acid/base reaction. Imines undergo nucleophilic addition, but require activation by protonation (i.e. acid catalysis)

Step 4: Now the nucleophilic O of a water molecule attacks the electrophilic C with the p bond breaking to neutralize the change on the N.

Step 5: An acid/base reaction. Deprotonate the O from the water molecule to neutralize the positive charge.

Step 6: An acid/base reaction. Before the N system leaves, it needs to be made into a better leaving group by protonation.

Step 7: Use the electrons on the O in order to push out the N leaving group, a neutral molecule of ammonia.

Step 8: An acid/base reaction. Deprotonation reveals the carbonyl group of the ketone product. PROBLEM The chemistry of the nitrile functional group, CºN, is very similar to that of the carbonyl, C=O of aldehydes and ketones. but why nitrile is less reactive than aldehydes or ketones?         versus   as nitrile containing a triple bond to be decided by a nucleophile while aldehyde or ketone containing only double bonds. obviously a little difficult for nucleophiles react with nitri compared with aldehyde or ketone. so that the nitrile is less reactive than the aldehyde or ketone group, although both have similar chemical properties.

Nitriles

Suffix:    -nitrile or -onitrile

Prefix:    cyano-

Nitriles contain a carbon - nitrogen triple bond (R-CºN or R-CN). They are indirectly related to amides (by the loss of H₂O from a primary amide), and react chemically similar to carboxylic acids and their derivatives.  It should be noted that H-CºN is not truly a nitrile and is named hydrogen cyanide.

When a nitrile group is the highest priority functional group present in the molecule, it is named as an alkanenitrile (alkenenitrile, alkynenitrile, ...). Since the -CºN must occur at the end of a chain of carbon atoms, the carbon of the nitrile will be carbon 1 in the numbering scheme. Other functional groups are located by this numbering scheme. Since the nitrile group is always at carbon number 1, there is no need to indicate its' location.

Examples naming simple nitriles:

Compound Name	Line Drawing	3D Model
ethanenitrile
propanenitrile
butanenitrile
2-methylpropanenitrile
cyclobutyronitrile *
pentanedinitrile **

* note: the -yl is changed to a -yro.
** note: numbers are not needed as the nitriles must be at the ends of the chain.

---

Examples naming more complex nitriles:

Compound Name	Line Drawing
4,4-dimethylpentanenitrile
2,4-pentadienenitrile
4-amino-3-hydroxy-2-methylhexanenitrile
4-chloro-2-cyclohexenenitrile
2-mercapto-4-oxo-6-heptynenitrile

Physical properties Boiling points The small nitriles are liquids at room temperature. nitrile boiling point (°C) CH3CN 82 CH3CH2CN 97 CH3CH2CH2CN 116 - 118
These boiling points are very high for the size of the molecules - similar to what you would expect if they were capable of forming hydrogen bonds. However, they don't form hydrogen bonds - they don't have a hydrogen atom directly attached to an electronegative element. They are just very polar molecules. The nitrogen is very electronegative and the electrons in the triple bond are very easily pulled towards the nitrogen end of the bond. Nitriles therefore have strong permanent dipole-dipole attractions as well as van der Waals dispersion forces between their molecules.
Solubility in water Ethanenitrile is completely soluble in water, and the solubility then falls as chain length increases. nitrile solubility at 20°C CH3CN miscible CH3CH2CN 10 g per 100 cm3 of water CH3CH2CH2CN 3 g per 100 cm3 of water The reason for the solubility is that although nitriles can't hydrogen bond with themselves, they can hydrogen bond with water molecules. One of the slightly positive hydrogen atoms in a water molecule is attracted to the lone pair on the nitrogen atom in a nitrile and a hydrogen bond is formed. There will also, of course, be dispersion forces and dipole-dipole attractions between the nitrile and water molecules. Forming these attractions releases energy. This helps to supply the energy needed to separate water molecule from water molecule and nitrile molecule from nitrile molecule before they can mix together. As chain lengths increase, the hydrocarbon parts of the nitrile molecules start to get in the way. By forcing themselves between water molecules, they break the relatively strong hydrogen bonds between water molecules without replacing them by anything as good. This makes the process energetically less profitable, and so solubility decreases.

Lactam

From Wikipedia, the free encyclopedia

From left to right, general structures of a β-lactam, a γ-lactam, a δ-lactam and a ε-lactam.

A lactam (the noun is a portmanteau of the words lactone + amide) is a cyclic amide. Prefixes indicate how many carbon atoms (apart from the carbonyl moiety) are present in the ring: β-lactam (2 carbon atoms outside the carbonyl, 4 ring atoms in total), γ-lactam (3 and 5 total), δ-lactam (4 and 6 total). Beta β, gamma γ and delta δ are the second, third and fourth letters in the alphabetical order of the Greek alphabet, respectively.

Synthesis

General synthetic methods exist for the organic synthesis of lactams.

• Lactams form by the acid-catalyzed rearrangement of oximes in the Beckmann rearrangement.
• Lactams form from cyclic ketones and hydrazoic acid in the Schmidt reaction.
• Lactams form from cyclisation of amino acids.
• Lactams form from intramolecular attack of linear acyl derivatives from the nucleophilic abstraction reaction.
• In iodolactamization an iminium ion reacts with an halonium ion formed in situ by reaction of an alkene with iodine.

• Lactams form by copper catalyzed 1,3-dipolar cycloaddition of alkynes and nitrones in the Kinugasa reaction
• Diels-Alder reaction between cyclopentadiene and chlorosulfonyl isocyanate (CSI) can be utilized to obtain both β- as well as γ-lactam. At lower temp (−78 °C) β-lactam is the preferred product. At optimum temperatures, a highly useful γ-lactam known as Vince Lactam is obtained.

Tautomerization to Lactim

Lactim is a cyclic carboximidic acid compound characterized by an endocyclic carbon-nitrogen double bond. It is formed when lactam undergoes tautomerization.

Reactions

• Lactams can polymerize to polyamides.

See also

• β-lactam with a four-membered ring found in beta-lactam antibiotics. Penicillin, considered the most famous antibiotic, is a β-lactam antibiotic.
• Lactone, a cyclic ester.
• Caprolactam

 problem

How the formation of lactams in the Schmidt reaction?

The Schmidt reaction is an organic reaction involving alkyl migration over the carbon-nitrogen chemical bond in an azide with expulsion of nitrogen A key reagent introducing this azide group is hydrazoic acid and the reaction product depends on the type of reactant: Carboxylic acids form amines through an isocyanate intermediate (1) and ketones form amides (2):

A catalyst that can be a protic acid - usually sulfuric acid or a Lewis acid - is required. The reaction was discovered in 1924 by Karl Friedrich Schmidt (1887–1971) who successfully converted benzophenone and hydrazoic acid to benzanilide. It is a tool regularly used in organic chemistry for the synthesis of new organic compounds, for example, in that of the unusual 2-quinuclidone.

Reaction mechanism

The carboxylic acid Schmidt reaction starts with acylium ion 1 obtained from protonation and loss of water. Reaction with hydrazoic acid forms the protonated azido ketone 2, which goes through a rearrangement reaction with the alkyl group R, migrating over the C-N bond with expulsion of nitrogen. The protonated isocyanate is attacked by water forming carbamate 4, which after deprotonation loses carbon dioxide to the amine.

The reaction is related to the Curtius rearrangement except that in this reaction the azide is protonated and hence with different intermediates.

In the reaction mechanism for the ketone Schmidt reaction, the carbonyl group is activated by protonation for nucleophilic addition by the azide, forming intermediate 3, which loses water in a elimination reaction to temporary imine 4, over which one of the alkyl groups migrates from carbon to nitrogen with loss of nitrogen. A similar migration is found in the Beckmann rearrangement. Attack by water and proton loss converts 5 to 7, which is a tautomer of the final amide.

Reactions involving alkyl azides

The scope of this reaction has been extended to reactions of carbonyls with alkyl azides R-N₃. This extension was first reported by J.H. Boyer in 1955 (hence the name Boyer reaction), for example, the reaction of m-nitrobenzaldehyde with β-azido-ethanol:

Variations involving intramolecular Schmidt reactions have been known since 1991. An intramolecular reaction has been applied to the synthesis of novel bicyclic lactams