Stereochemistry

Stereochemistry Stereochemistry is important as they are found many deformed babies because, during pregnancy the baby's mother was taking Thalidomide. One stereoisomer stereoisomer serves as a sedative while the other is the cause of the disability. The fact also shows a lot of drug molecules that have similarity with the properties of thalidomide, a helpful dangerous.

Stereochemistry

Stereochemistry Stereochemistry is important as they are found many deformed babies because, during pregnancy the baby's mother was taking Thalidomide. One stereoisomer stereoisomer serves as a sedative while the other is the cause of the disability. The fact also shows a lot of drug molecules that have similarity with the properties of thalidomide, a helpful dangerous.

summary

Summary StereoisomersStereoisomers:isomers that have same formula and connectivity butdiffer in the position of the atoms in space. They possess one or more stereocenters. StereocenterStereocenter: a carbon atom bearing 4 different atoms or group of atoms. ChiralChiral:any molecule that is nonsuperposable with its mirror image. EnantiomersEnantiomers: stereoisomers that are non superposable mirror images. Racemic mixtureRacemic mixture: a 1:1 (equimolar) mixture of two enantiomers. Optically ActiveOptically Active:the ability of some compounds to rotate plane polarized light.

Stereochemistry

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).

History and significance

Louis Pasteur could rightly be described as the first stereochemist, having observed in 1849 that salts of tartaric acid collected from wine production vessels could rotate plane polarized light, but that salts from other sources did not. This property, the only physical property in which the two types of tartrate salts differed, is due to optical isomerism. In 1874, Jacobus Henricus van 't Hoff and Joseph Le Bel explained optical activity in terms of the tetrahedral arrangement of the atoms bound to carbon.
Cahn-Ingold-Prelog priority rules are part of a system for describing a molecule's stereochemistry. They rank the atoms around a stereocenter in a standard way, allowing the relative position of these atoms in the molecule to be described unambiguously. A Fischer projection is a simplified way to depict the stereochemistry around a stereocenter

1.    What are we talking about?

The bottom line of this whole chapter is learning the difference between isomers.  There are two types of isomers, constitutional and stereoisomers.  Constitutional isomers are two compounds that have the same atoms present, but differ in their connectivity. 
ie:   

These compounds contain the same number of atoms, but the oxygen has been moved to form an ether instead of an alcohol.  Therefore, these compounds are constitutional isomers. 

Stereoisomers also have the same atoms present, however the connectivity is the same.  This means the same number of hydrogens will be attached to each carbon and the same number of carbons will be attached to each carbon.  Picture this:

Now, these structures both appear to be the same, but careful observation will reveal that the amine groups attached are in the cis conformation on the left and the trans conformation on the right.  Therefore, the same atoms are present, but just in a different spatial arrangement. 

Not to beat this idea into your head, but here is another example of a stereoisomer, but this time we will use a hydrocarbon chain.

Notice that the chain on the left is in the cis conformation at the double bond and the chain on the right is trans.  This makes them stereoisomers.

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2.    I understand that chiral compounds are mirror images of each other that are not superposable, but how do I tell they are superposable?

The easiest way to tell if the mirror image is superimposable or not and superposable is to find the stereochemistry at the stereocenter. This entails you to find the stereocenter first and then label the groups attached to it in order of their priority. This means the atom with the highest atomic number will be labeled A and the next highest B. The next step is to rotate the molecule so the D group is facing away from you.
ie.

If the groups go from A to C clockwise, it is in the R configuration. If the groups are arranged counterclockwise, it is in the S configuration.

Practice a few

A                                                           B                                      C

 A has two stereocenters.  The top stereocenter is an R configuration and the bottom stereocenter is an S configuration.  For B the stereocenter is an S.  C does not have to be considered because there are two of the same groups attached, and is not chiral.

If the two compounds you are looking at are mirror images of each other, but the configuration at the stereocenter differs, they are not superposable.  Therefore they are chiral compounds.  If they are superposable, then they are achiral.   

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3.    How do I tell the difference between an Enantiomer and Diastereomer?

The easiest way to tell apart an enantiomer and a diastereomer is to look at whether or not the compounds are mirror images of each other. The best way to learn this is through practice. Here are a few examples, see if you can determine whether or not the compounds are enantiomers, the same, or diastereomers.

Hint: first determine if the compounds are mirror images of each other, and then find the individual stereochemistry around each chiral carbon.  Remember the hand rule or the clockwise/counterclockwise arrangement discussed in the previous section.

D

If you are having problems determining the configuration at each stereocenter, I suggest building a model. 

A is a pair of diastereomers, because the configuration is S, S in the first compound and R,S in the second compound.

B is a tricky one.  They are both in the trans configuration and there is a plane of symmetry.  Also, notice there is no carbon with four different groups.  Therefore, they are not enantiomers and there is no stereochemistry. 

C does not have a carbon with four different groups, so it does not have a stereocenter either. 

D is a pair of enatiomers. Notice they are mirror images of each other.

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4.    There is an R and there is an S, but I don’t know what to do with them.  Help!

If you have read the past few sections you know what the S and R designations are.    They tell what type of stereochemistry is found at the stereocenter.  Finding the stereochemistry at the stereocenters can help determine whether two compounds are enantiomers or diastereomers.  Also, R and S versions of the same compound will have different optical activity values. 

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5.    Quick Review of optical activity

Optical activity is the only physical property that differs from one enantiomer to the next.  Optical activity is measured when plane polarized light is passed through a compound.  When the light passes through the compound, it is bent either with positive rotation (dextrorotary) or with negative rotation (levorotary).  There is no correlation between positive or negative rotation with the S or R configuration.  S can be either dextrorotary or levorotary and the R enantiomer will be the opposite of the S.  The value given to optical activity is specific rotation.  The equation to figure out specific rotation can be found page 203 in your textbook. 

 

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6.    Okay, I’m getting this stereocenter thing, but somebody had to go and screw everything up and stick two stereocenters together.

When dealing with two or more stereocenters on the same compound, there are a lot of possibilities.  The first possibility is that the compounds are enantiomers of each other, the second that they are diastereomers, and finally that they can be meso compounds.  Diastereomers occur when the compounds have the same chemical formula, but are not mirror images of each other.
ie. 

 

Now look at these same atoms arranged differently to form an enatiomer.  These compounds are mirror images of each other.  However, they do have different stereochemistries, which makes them enantiomers. 

 

You should also look at these next compounds and discover what makes them different from the above. 

These compounds appear to be enatiomers, because they are mirror images of each other. They really are not. The middle two compounds are the meso compound, since they are the same. The outside two compounds are enatiomers of each other. Therefore, a meso compound is observed with stereoisomers where you would expect four different possible structures (two pairs of enantiomers), but there are only three stereoisomers.
 

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7.    Fischer Projections doesn’t mean a weekend out on the lake.  How do I interpret them?

Fischer projections are a quick way to show three dimensions without the hassle of having to draw 3-D.  They are very effective for those of us who lack artistic skills.  When you look at the diagram the horizontal lines represent atoms that are coming out at you.  The vertical lines mean they are going away from you.  Fischer projections can be rotated 180 degrees and still be the same compound.  However, if you flip it vertically or horizontally, it becomes the enantiomer. 

This Fischer projection has been flipped horizontally.  These two are enatiomers of each other.  The first projection has an S, R configuration.  The second projection has an R, S configuration.  

Now lets look at a vertically flipped diagram. 

These compounds are enatiomers of each other.  

Finally, notice what happens when the diagrams are rotated 180 degrees in the plane of the paper.

 

The configuration at each stereocenter remains the same.

 

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8.    Cyclic Compounds

 

If you are anything like me, it is very hard for you to determine the stereochemistry in cyclic compounds the best way is just practice.   Hopefully, this area will help.  Do your best to determine the stereochemistry.

 

Analysis:

 

Problem Sianida (nitril)

How to Changing Cyanide Being Raw Drugs ?


Most would be surprised, how could compound poisons such as cyanide (nitrile) can be utilized as raw material for medicine. Cyanide in small amounts if accidentally consumed is very dangerous. Let alone use it for drugs.
The use of cyanide can be implemented through biotransformation technology with the help of biochemical enzymatic reactions. The role of nitrilase enzymes are very important because it could change the substrate cyanide into carboxylic acid and ammonia compounds are relatively non-toxic to the body. Nitrilase enzymes belonging to the hydrolase enzyme able to hydrolyze the cyanide compounds with the aid of water. Nitrilase enzymes are produced in nature by several microorganisms such as bacteria of the strain Rhodococcus rhodochrus, Pseudomonas putida, Rhodococcus erytropolis, Bacillus licheniformis,Alcaligenes faecalis and so on. In addition to the harness track the performance of the enzyme nitrilase, the use of cyanide can be done also through a amidase enzyme nitrile hidratase and gradually. Hidratase enzyme nitrile group will convert the nitrile compound (R-CN) into a compound with a group Amide (R-CONH2). Meanwhile amidase enzyme will convert the amide compound (R-CONH2) a carboxylic acid compound bergugus (R-COOH) and form a compound of ammonia (NH4).
One application of the use of cyanide compounds, the raw material can be found in drug biotransformation process mandelonitril compound into a compound R-and S-amino acid mandelat mandelat. Compound (S)-acid utilized for the synthesis of alternative mandelat cyclopentenon and commercial drug compounds that are widely used as nonsteroidal antiinflammatory drugs on (anti-inflammatory). Meanwhile, the compound (R)-acid as a precursor mandelat useful semisynthetic penicillins, cephalosporins, and drug antiobesitas. Utilization of cyanide compounds into industrial raw materials can be found in theacetonitrile biotransformation, laktonitril, and with the help of the enzyme nitrilase benzonitril a compound of acetic acid, lactic acid, and benzoic acid. Acetic acid is a raw material for acetic acid in the food industry; lactic acid as raw material for the manufacture of yoghurt (sour milk), and benzoic acid is used as a food preservative.
The results of biotransformation enzymes nitrilase other is for the manufacture of adipic acid compound of the substrate adiponitril. Adipic acid is the main ingredient used to synthesize nylon as a very important ingredient in industrial polyamide. Nylon are used as raw material for making fabric, paint, tires, films, resins, and monofilament. Addition of adipic acid is also used as one component in the manufacture of agar-agar, electronic materials such as cables, and carpet cleaning agents.
Utilization of cyanide compounds biotransformation process is also performed in the production of acrylonitrile compound akrilamide of the substrate. Akrilamide is a chemical compound widely used in molecular biology, particularly for the identification and analysis of protein molecular weight compounds by the technique of SDS-PAGE (Sodium Sulfate-Poly Dedosil Acrilamide Gel electrophoresis).
In the last decade, most of the processes in the fields of pharmaceuticals (drugs) and the industry is more geared to the biotransformation process rather than chemical synthesis. As for some of the advantages to be gained by utilizing the biotransformation process, among others, can produce specific chemicals with a high degree of purity, the condition is easily managed, and safe for the environment. Respect that, in the Field of Microbiology any research activities being carried out is the identification and characterization of bacteria that have the ability to produce enzymesthem.

NITRILES

A nitrile is any organic compound that has a -C≡N functional group. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, including methyl cyanoacrylate, used in super glue, and nitrile butadiene rubber, a nitrile-containing polymer used in latex-free laboratory and medical gloves. Organic compounds containing multiple nitrile groups are known as cyanocarbons.
Inorganic compounds containing the -C≡N group are not called nitriles, but cyanides instead.Though both nitriles and cyanides can be derived from cyanide salts, most nitriles are not nearly as toxic.



HYDROLYSING NITRILES This page looks at the hydrolysis of nitriles under either acidic or alkaline conditions to make carboxylic acids or their salts.

The hydrolysis of nitriles Introduction
When nitriles are hydrolysed you can think of them reacting with water in two stages - first to produce an amide, and then the ammonium salt of a carboxylic acid.
For example, ethanenitrile would end up as ammonium ethanoate going via ethanamide.



In practice, the reaction between nitriles and water would be so slow as to be completely negligible. The nitrile is instead heated with either a dilute acid such as dilute hydrochloric acid, or with an alkali such as sodium hydroxide solution.
The end result is similar in all the cases, but the exact nature of the final product varies depending on the conditions you use for the reaction.

Acidic hydrolysis of nitriles
The nitrile is heated under reflux with dilute hydrochloric acid. Instead of getting an ammonium salt as you would do if the reaction only involved water, you produce the free carboxylic acid.
For example, with ethanenitrile and hydrochloric acid you would get ethanoic acid and ammonium chloride.



Why is the free acid formed rather than the ammonium salt? The ethanoate ions in the ammonium ethanoate react with hydrogen ions from the hydrochloric acid to produce ethanoic acid. Ethanoic acid is only a weak acid and so once it has got the hydrogen ion, it tends to hang on to it.

Alkaline hydrolysis of nitriles
The nitrile is heated under reflux with sodium hydroxide solution. This time, instead of getting an ammonium salt as you would do if the reaction only involved water, you get the sodium salt. Ammonia gas is given off as well.
For example, with ethanenitrile and sodium hydroxide solution you would get sodium ethanoate and ammonia.



The ammonia is formed from reaction between ammonium ions and hydroxide ions.
If you wanted the free carboxylic acid in this case, you would have to acidify the final solution with a strong acid such as dilute hydrochloric acid or dilute sulphuric acid. The ethanoate ion in the sodium ethanoate will react with hydrogen ions as mentioned above.

Nitrile oxides

Nitrile oxides have the general structure R-CNO.

NITRILES

A nitrile is any organic compound that has a -C≡N functional group. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, including methyl cyanoacrylate, used in super glue, and nitrile butadiene rubber, a nitrile-containing polymer used in latex-free laboratory and medical gloves. Organic compounds containing multiple nitrile groups are known as cyanocarbons.

Inorganic compounds containing the -C≡N group are not called nitriles, but cyanides instead. Though both nitriles and cyanides can be derived from cyanide salts, most nitriles are not nearly as toxic.

Nitrile oxides

Nitrile oxides have the general structure R-CNO.

 

Problem

i read from one source about lactam
how to decrease carbonil in lactam for CH2 ?
and what for that decrease ?

please give your opinion, i still confuse

Lactams

Lactams - Cyclic Amides
With some modification, a reaction may be carried out that generates a ring structure containing a similar linkage. Consider the result if two functional groups are a distance apart on the same molecule and react together. Consider, for instance, 4-aminobutyric acid, H₂N-CH₂CH₂CH₂-COOH. If reacted utilizing the proper conditions,²
H₂N-CH₂CH₂CH₂-COOH → 5-member ring + HOH (see associated image).
The amino group at one end reacts with the carboxylic acid group at the other, closing the molecule to form the ring. The ring structure is called a lactam. The type of lactam is designated by using a Greek letter prefix that indicating the number of carbons in the ring, not counting the carbonyl group. For instance, if there are two such carbons, the prefix is beta (the 2nd letter of the alphabet)-if there are four, the prefix is delta, and so on. The ring formed in the above reaction is a gamma-lactam. It's name is based on the number of carbon atoms in the skeleton-in this instance, butyrolactam. There are other ways of naming the structure, one of which is 2-pyrollidinone.

Lactam

Lactams 

Internal cyclic amides of amino carboxylic acids that contain a —CO—NH— group in the ring (I). The tautomeric, enol form of lactam is known as lactim (II):

 

Lactams are classified as β-, γ-, δ-, ε-, and so forth according to the type of amino carboxylic acids included in their composition, for example, β-propiolactam (III; melting point, 73°-74°C), γ-butyrolactam (IV; melting point, 24.6°C), and ε-caprolactam (V; melting point, 68°-69°C):

Lactams are primarily obtained by the cyclization of amino carboxylic acids or their derivatives [Y—(CH₂)_nNH₂, where Y = COOH, COOR, CONH₂, CN], as well as by the cyclization of amides of halogen carboxylic or hydroxycarboxylic acid [X—(CH₂)_nCONHR, where X = OH or a halogen]. An important method of obtaining lactam is the Beckmann rearrangement of cyclic ketoximes, which is used in the industrial preparation of ε-caprolactam.

Lactams readily undergo alkylation, acylation, and halogena-tion with retention of the ring. The lactam ring, however, is opened at the —CO—NH—bond during hydrolysis, ammonolysis, hydrogenolysis, and polymerization. For example, ε-caprolactam polymerization yields polycaproamide, from which nylon 6 fiber is made. Many lactams are biologically active substances (for example, a molecule of penicillin contains a β-propiolactam residue).

Problem

why amides are less soluble in comparison with amine and carboxylic acid are comparable ?
answer : because these compounds can both donate and accept a hydrogen bond

please guys give your opinoin