Posts Tagged "organic"

Formation of Enols and Enolates

Posted on April 3rd, 2018

One question that comes up in organic chemistry often is “what is an enol or an enolate and how is it formed?”  These types of concepts are frequently covered quickly in class or not at all, but are very important for future reaction mechanisms.  We at Study Orgo have the combined experience of over 15 years of tutoring and teaching organic chemistry concepts to struggling students.  We have developed clear descriptions of reaction mechanisms and organic chemistry concepts to aid students in their studies.  Sign up today for access to over 180 reactions mechanisms and reviews!

The alpha carbon of a carbonyl, which is present in carboxylic acids, esters, ketones and aldehydes, are acidic which means the proton can be removed using a base.  In neutral or acidic conditions, this means the lone pairs on the C=O position can act as a weak nucleophile.

If the carbonyl oxygen can attack the alpha carbon C-H bond, it will abstract the hydrogen and perform a Keto-Enol tautomerization reaction that will lead to the resonance version of the carbonyl, which is the Enol (alkENE + alcohOL)

Enols – rearranging the pi bond and atoms of a carbonyl compound to an Enol

Catalyist: Acidic or Neutral Conditions to stabilize OH formation

Enols tautomers are generally unstable, preferring the “Keto” version 90-99% of the time versus the “Enol” version.  However, a catalytic amount of presence is sometimes enough to drive reactions forward if the mechanism requires the enol tautomer of the compound.

However, in some cases such as a beta diketone, shown below, the combined dipoles of two carbonyls makes the alpha carbon very acidic, meaning enol formation is very favorable.  In this case, it is 70-90% enol in solution.

 

Enolates – Deprotonating the alpha carbon and tautomerizing to the oxyanion

Catalyist: Strong Base to deprotonate the alpha carbon.

Like an Sn2 mechanism, a strong enough base will react with the acidic proton on the alpha carbon and deprotonate.  The electron density between the C-H bond will shift to make a new C=C bond, while the C=O electrons will be placed on the oxygen, creating and alkENE + alcohOL anion “ATE”) with a strong base to produce a stable carbanion.  The stability is due to the tautomerized structure that can be produced by placing the negative charge on the oxygen.

 

Enolates are generally forward reactions depending on the strength of the base.  How strong the base required depends on the pKa of the alpha C-H bond.  In the case of ketones, a strong base like LDA is required.  However, for beta dikeontes, a mild base like NaOH is enough to generate the enolate.

 

Formation of Enols and Enolates are an important source of carbon nucleophiles to make new C-C bonds in future reactions.

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How do you to tell when a hydrogen bond will occur?

Posted on March 7th, 2018

Hydrogen bonding is important for describing the driving force of reactions in organic chemistry and a very important concept for explaining the biochemistry of catalytic reactions that occur using protein as enzymes in biological systems.  In this post, we will discuss the rules and examples of hydrogen bond formation.  We at StudyOrgo have extensive experience instructing principles and reaction mechanisms frequently covered in Organic Chemistry. Sign up today for clear, detailed explanations of over 180 Orgo Chem reactions and reviews on conceptual topics!

Physical properties of molecules such as boiling and melting point, solubility and reactivity, are affected by the functional groups that make up the molecule. This can be explained by analyzing the type of intermolecular forces that are experienced between molecules.  Because these forces are not covalent, intermolecular forces are determined by the intensity of electrostatic forces which is what makes up each type of intermolecular force. As a review, the types of intermolecular forces are;

  • Van der Waals (London dispersion forces) – Weak, temporary dipole formed between hydrophobic C-H and C-C bonds.
  • Dipole-Dipole Interactions: – Strong, permanent dipole moments formed between atoms of functional groups containing bonds such as C=O, C=N, C-O, C-N, N-H and O-H bonds. The delta(-) side of one dipole is attracted to the delta(+) side of another molecule, forming a non-covalent electrostatic attraction.
  • Hydrogen Bonding: Sharing sharing of a hydrogen atom covalently attached to an electronegative element (typically O-H and N-H groups) between a lone pair of electrons on another electronegative element.

Two terms about hydrogen bonding that are key are;

  • The electronegative atom with the lone pair electrons is called the Hydrogen Bond Acceptor
  • The electronegative atom bonded to the hydrogen is called the Hydrogen Bond Donor
  • The Hydrogen Bond Donor must be aligned 180 degrees to the Hydrogen Bond Donor!

The more intermolecular forces the molecule has, the more energy will be required to disrupt these bonds when melting or boiling compounds, thus raising the observed temperatures from expected relative to their mass.  In addition, hydrogen bonds require polar bonds in the molecule and H-Bond Donor proton involved is protic (a donatable hydrogen atom). These are two terms that you will learn in the Sn1 mechanism.

Let’s look at ethanol as an example.  The hydrogen bonding occurs between the proton of one alcohol group and the oxygen lone pair electrons on another alcohol group.  This is a strong intermolecular force that holds the molecule in a complex 3D shape and makes it easier in reactions to attack the carbon connected to the O-H bond due to inductive effects, or the pulling of electrons away from the carbon.  Water is an extreme example, where all the atoms in the molecule participate in hydrogen bonding.  The oxygen lone pairs will accept a hydrogen from a neighboring molecule O-H.  Finally, acetic acid is another example.  Remember, that the H-Bond Acceptor can be any lone pairs, including those of C=O bonds.

 

These concepts are really important to understanding the more complex topics to come. With a membership to StudyOrgo, you will get even more tips and tricks on organic chemistry topics and detailed mechanisms with explanations.  Today’s blog is a preview of the detailed topics and materials available.

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Chirality and Assigning Stereochemistry to Molecules

Posted on August 11th, 2015

One of the most important skills to master in organic chemistry is the ability to assign stereochemistry.  We at StudyOrgo have devised clear cut explanations of these difficult concepts for students to maximize their time studying and learn difficult concepts quickly and easily. Sign up with StudyOrgo.com today for all of your organic chemistry studying needs!

Chirality is an important aspect of life.  This is so because many of the basic molecules used in living cells, in particular amino acids that form enzymes, are also chiral. Chirality imparts asymmetry on our molecules, allowing them the ability to recognize “handedness” and further add to the complexity and specificity of reactions. As organic chemists, we must pay constant attention to the chirality of molecules both before and after reactions, less the compounds lose their biological or chemical activity.

Chirality is defined as any object in which the mirror images are not superimposable. A good example is your hands; they are mirror images but not superimposable. Translating this to organic molecules, a stereocenter is a carbon center with 4 unique substituents that are arranged such that the mirror image is not superimposable. Thus, they “look” like to different molecules although they have the same substituents. If we alter the arrangement of the substituents, we can always come up with 2 arrangements for each substituent, R or S configuration.  Thus, each stereocenter must have 2 stereoisomers.

chiral 1

In order to determine whether the sterecenter is the the R or S configuration, there are a series of steps to follow.

  1. Identify the stereocenter as 4 unique substituents attached to the chiral center
  2. Assign priority based on atom atomic number, highest (1) to lowest (4) weight.
  3. If two atoms are same, move to next bond to find first point of difference
  4. Rotate the molecule so that Priority 4 atom is in the hashed wedge position.
  5. Determine the Priority sequence 1-2-3 rotates to the left (S) or the right (R).

chiral 2

Lastly, an important concept to keep in mind is that as molecules become more complex, they also can acquire more stereocenters.  Keeping in mind that each stereocenter can produce 2 stereoisomers, we describe possible stereoisomerism using the 2n rule. Let’s examine a molecule with 2 stereocenters, following the 2n rule that gives us 22=4 stereocenters.  The possible combinations are listed below.

Screen Shot 2014-12-18 at 1.00.28 PM

We now introduce the last concept to stereochemistry which is the difference between enantiomers and diastereomers.  Enantiomers are molecules with exactly opposite stereoisomers.  For example, the enantiomer of the molecule with stereochemistry R,R would be S,S.  The relationship between molecule R,R and R,S is what is described as diastereomers, which differ in some but not all stereocenters.

Let’s consider the biologically active form of testosterone, 5-DHT which is shown below.  We indicate that it has 7 stereocenters in the molecule.  Applying the 2n rule, we calculate 128 possible stereoisomer combinations.  That concludes that while testosterone has 1 enantiomer, it has 126 diastereomers and remember…only 5-DHT works on our bodies!

Screen Shot 2014-12-18 at 1.02.36 PM

 

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Organic Chemistry of Lipids

Posted on May 11th, 2015

Lipids are a fundamental part of biochemistry and draw many analogies to reactions with alkenes and alkanes.  In this article, we will review some basics of lipids and their organic chemistry implications.  Many of the reactions with lipids are simple hydrocarbon reaction mechanisms covered in Organic Chemistry 1.  With over 175 reaction mechanisms, StudyOrgo is devoted to making organic chemistry reaction mechanisms easy to learn and points out common places where errors are made.  Sign up with StudyOrgo.com today to get more in-depth coverage of common reactions for your next exam!

Lipids are any complex chain of hydrocarbons that may or may not contain additional functional groups. Some common classes of lipids are fatty acids and triglycerides, waxes, terpenes and steroids; examples of which are shown in Figure 1. 

Lipid Figure 1

Most lipids usually consist of a long hydrophilic tail coupled to a polar head group that undergoes reactions to elongate or shorted the hydrophobic tail.  We will cover some common organic chemistry reactions with each of these classes of lipids.

Complex Lipids – Fatty acids and Triglycerides

Complex lipids are capable of undergoing hydrolysis reactions.  The basic unit of a complex lipids are fatty acids, which are made up of a hydrophobic tail coupled to a carboxylic acid head group (Figure 2).  The length of the carbon chain denotes the lipid name.  In addition, the number of double bonds, or degree of unsaturation, also influences the name.  In biology, naturally occurring double bonds will always be found in the cis- configuration.

Lipid Figure 2

Hydrogenation of alkene groups to alkanes occurs at high temperatures, such as in deep fryers for cooking, and this side reaction leads to the isomerization of the double bond to the trans- conformation, hence trans-fatty acids.  These lipids are toxic in high quantities because they are unable to be metabolized by the cell, thus accumulating and undergoing oxidation reactions over time and theorized to promote inflammation and metabolic diseases.  Coupling of a fatty acids to the alcohol groups of glycerol forms the complex lipid, triglyceride (Figure 2).  This reaction occurs enzymatically in the cell but closely resembles the mechanism found in acid-catalyzed Fisher Esterification.

Lipid Figure 3

Simple Lipids – Sterols

Steroids are an integral part of cellular biology but are classified as simple lipids because they cannot be hydrolyzed (i.e. they do not have reactive carbonyl or carboxyl groups).  A lipid molecule having a tetracyclic shape in the arrangement similar to cholesterol is classified as a sterol.  Cholesterol serves as the building block of all steroids and substitution, addition and elimination of functional groups derives the variety of steroids found in the body. Cholesterol is synthesized from the 5 carbon lipid molecule isopentenyl phosphate.  Condensation of isopentenyl phosphate forms geranyl phosphate (10C) and farnesyl phosphate (15C) in a reaction mechanism that involves allylic carbocation and tertiary carbocation intermediates (Figure 3).  Condensation of two farnesyl phosphate molecules forms the 30 carbon intermediate squalene, which in several steps is converted to cholesterol.  Two important examples of steroids are the sex hormones found in humans, estradiol and testosterone, which regulate a wide range of biological functions.

Lipid Figure 4

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