Chapter 11 - Synthesis Flashcards
What are vitamins?
Essential nutrients required for proper body function
A deficiency in particular vitamins can lead to diseases, some of which can be fatal.
What is organic synthesis?
The laboratory synthesis of organic compounds, including vitamins
The synthesis of a particular vitamin marked a significant event in synthetic organic chemistry.
What factors must be considered when designing a synthesis?
Cost of reagents and ease of purification of products
A high-yield synthesis can be compromised by intractable side products.
What are one-step syntheses?
Synthesis problems that can be solved in just one step
Mastery of reagents from previous chapters is critical for solving these problems.
What are functional group transformations?
Reactions that change the identity or location of a functional group
Techniques for functional group transformations were developed in previous chapters.
What is a two-step strategy for changing a halogen substituent?
Performing an elimination reaction followed by an addition reaction
The regiochemical outcome must be carefully controlled.
What is the role of the base in the elimination step?
Determines whether the more substituted or less substituted alkene is formed
The choice of reagents impacts the outcome of the reaction.
What is the purpose of converting an OH group into a better leaving group?
To facilitate an E2 elimination process
This is necessary before employing elimination followed by addition.
What is radical halogenation?
A reaction used to convert an alkane into an alkyl bromide
This method is not suitable for making primary alkyl bromides.
What is retrosynthetic analysis?
Working backwards from the target molecule to determine starting materials
It helps in planning the synthesis step-by-step.
What is anti-Markovnikov addition?
Addition of HBr in the presence of peroxides leading to the less substituted product
This technique is useful in certain synthesis routes.
What are the two plausible routes to achieve a desired synthetic transformation?
1) HBr, ROOR
2) BH3 THF followed by TsCl, pyridine
Both methods can lead to the desired product but may differ in efficiency.
What happens to the carbon skeleton during synthesis?
It can change by increasing or decreasing the number of carbon atoms
The formation of C-C bonds is essential for increasing the carbon skeleton.
What is the result of treating an alkyl halide with cyanide?
Formation of a new C-C bond and generation of a nitrile product
Nitriles can be converted into various functional groups in later chapters.
What is the result of the reaction between cyanide and an alkyl halide?
The installation of one carbon atom on the carbon chain
This generates a nitrile product containing a C≡N group.
What anion can be used to lengthen the carbon chain by more than one carbon atom?
Alkynide anion
What reaction achieves bond cleavage at the location of the π bond?
Ozonolysis of an alkene (or alkyne)
What is the purpose of retrosynthetic analysis in organic synthesis?
To determine the starting materials required for the desired product
What are the two critical skills covered in Sections 11.2 and 11.3?
- Functional group transformations
- Changing the carbon skeleton
What is the significance of the sp hybridized carbon atom in a C–C bond-forming reaction?
It serves as the nucleophile
In the context of organic synthesis, what does an alkynide ion react with to install carbon atoms?
A primary alkyl halide
Fill in the blank: The reaction between an alkynide ion and an alkyl halide generally requires a _______ as the leaving group.
Br
What was discovered to reverse the effects of scurvy?
Eating oranges and lemons
What disease is caused by a deficiency of vitamin C?
Scurvy
Which vitamin is associated with the deficiency disease beriberi?
Thiamine (vitamin B1)
True or False: All vitamins contain an amino group.
False
What is the primary function of vitamins in the body?
Necessary for normal functioning
What type of reaction is used to make an alkene from an alkyl halide?
E2 elimination
What are the two questions to ask when approaching a synthesis problem?
- Is there a change in the carbon skeleton?
- Is there a change in the identity and/or location of the functional group?
What reaction is used to convert a triple bond into a double bond?
Hydrogenation
Identify a source of vitamin D2.
Fish, produced by the body when exposed to sunlight
What phenomenon was observed by Christiaan Eijkman related to rice consumption?
The fibrous husk of rice contained a vital growth factor.
What family do vitamins belong to based on their behavior?
Families designated with a letter
What is the primary role of the amino group in thiamine?
It classifies thiamine as an amine
Fill in the blank: The transformation of compound 1 to compound 2 in steroid synthesis requires _______ of two carbon atoms.
Installation
What are the key components of a synthetic toolbox in organic chemistry?
Reactions organized according to the functional group in the target molecule
What is the first step in the proposed synthesis to convert an alkyne into a trans alkene?
Alkylation of the alkyne
The alkylation of an alkyne involves introducing a new carbon chain to the alkyne structure.
What reagent is used to convert a triple bond into a double bond?
Dissolving metal reduction
This method is effective for transforming alkynes into trans alkenes.
Which starting material is preferred for synthesizing an alkene?
Alkyne
Alkynes are preferred because they enable further transformations through C–C bond disconnections.
What is required for the alkylation of an alkyne?
A terminal triple bond
Only terminal triple bonds can undergo alkylation, while terminal double bonds cannot.
What are the steps in the overall solution to the synthesis problem discussed?
1) Alkylation of the alkyne
2) Conversion of the triple bond into a double bond
What is the significance of the year 1947 in the context of vitamin B12?
Vitamin B12 was first isolated and purified
Ed Rickes at the Merck Chemical Company achieved this milestone.
Who determined the complete structure of vitamin B12?
Dorothy Crowfoot Hodgkin
She used X-ray crystallography to elucidate the structure of vitamin B12.
What type of ring system does vitamin B12 contain?
Corrin ring system
The corrin ring system is similar to the porphyrin ring system found in chlorophyll.
What were the two different approaches taken by Woodward and Eschenmoser in synthesizing vitamin B12?
A → B route and A → D route
These routes referred to the points of macrocyclization in the synthesis of the corrin ring system.
What challenge did Woodward and Eschenmoser face during the synthesis of vitamin B12?
Steric bulk of substituents
This issue complicated the coupling of heterocycles in the corrin system.
What innovative method did Eschenmoser develop to overcome the steric hindrance problem?
Temporary sulfur bridge
This method allowed the coupling process to occur intramolecularly.
What is retrosynthetic analysis?
A systematic approach to solving synthesis problems by working backward from the target molecule
E. J. Corey is credited with formalizing this method.
What is the role of an intermediate compound in multi-step synthesis?
Serves as a stepping stone for the transformation
Intermediate compounds help facilitate the conversion from starting materials to target molecules.
What type of elimination reaction can be used to prepare an alkyne from a vicinal dibromide?
E2 elimination
Two successive E2 eliminations can convert a vicinal dibromide into an alkyne.
Fill in the blank: The retrosynthetic arrow indicates a thought process working ______ from the target molecule.
backward
What must be converted to a tosylate before performing an E2 elimination?
Hydroxyl group
The tosylate is a better leaving group than the hydroxyl group.
What was a significant outcome of Woodward’s collaboration with Hoffmann?
Development of rules for pericyclic reactions
These rules help explain stereochemical outcomes in organic reactions.
True or False: The synthesis of vitamin B12 was completed in 1972.
True
What is the significance of the Woodward-Hoffmann rules?
They provide a framework for predicting stereochemical outcomes of pericyclic reactions
These rules were developed during the research on vitamin B12 synthesis.
What is the first step in proposing an efficient synthesis for a transformation?
Determine whether there is a change in the carbon skeleton.
How many carbon atoms does the starting compound have if the product has six?
Four carbon atoms.
What method is learned for installing two carbon atoms in a synthesis?
Alkylation of a terminal alkyne.
What functional group change occurs in the transformation from a starting compound to the product?
The functional group changes both its identity and location.
What is one way to produce an aldehyde from an alkyne?
Hydroboration-oxidation.
What type of bond disconnection is used in retrosynthetic analysis?
C–C bond disconnection.
What reagent is used to achieve anti-Markovnikov addition?
HBr in the presence of peroxides.
What is the role of a sterically hindered base in a synthesis?
To produce the Hofmann product (the less substituted alkene).
What is the strategy for bridging gaps in a multi-step synthesis?
Convert a double bond into a triple bond.
What is the purpose of retrosynthetic analysis in organic chemistry?
To break down complex synthesis problems into simpler parts.
Who developed the retrosynthetic methodology?
E. J. Corey.
What are some goals of the green chemistry movement?
- Prevent waste
- Use less hazardous reagents
- Use safer solvents
- Maximize atom economy
- Use catalysts instead of stoichiometric reagents
- Improve energy efficiency
- Use renewable feedstocks
What is a key principle of green chemistry related to waste?
Prevent waste by using reactions that produce little or no waste.
What is the difference in atom economy between oxymercuration-demercuration and acid-catalyzed hydration?
Oxymercuration-demercuration has poor atom economy, while acid-catalyzed hydration has good atom economy.
What is the importance of using catalysts in reactions?
They produce less waste and are more efficient/economical.
What should chemists consider regarding energy efficiency in reactions?
Use reactions that can be performed at room temperature.
What does it mean to maximize atom economy?
To use reactions where all or most atoms from the reagents are incorporated into the product.
What is one practical tip for increasing proficiency in synthesis?
Organize a synthetic ‘toolbox’ of reactions.
What should be included in the first list of a synthetic toolbox?
C–C bond-forming reactions and C–C bond-breaking reactions.
What can help in practicing synthesis strategies?
Creating your own synthesis problems.
What is a helpful method for practicing synthesis strategies?
Creating your own synthesis problems
This process uncovers patterns and new ways of thinking about reactions.
What is the first step in constructing your own synthesis problem?
Choose a starting compound
For example, starting with acetylene.
What type of reaction can be chosen for a triple bond during synthesis?
Alkylation
This can involve using NaNH2 and an alkyl group.
What is the purpose of creating your own synthesis problems?
Sharpen synthesis skills
It helps in understanding the synthesis process better.
True or False: There is always only one correct answer to a synthesis problem.
False
Many synthesis problems have multiple correct answers.
What is the goal of a synthesis problem?
Efficiency
A shorter synthesis with fewer steps is generally preferred.
What is Taxol also known as?
Paclitaxel
It is a powerful anticancer agent.
What does Taxol inhibit in cancer cells?
Mitosis
It can also induce apoptosis in some cancer cells.
What is a major challenge associated with Taxol?
Limited supply from the Pacific yew tree
The tree produces just over 0.5 g of Taxol on average.
What is 10-deacetylbacatin III?
A precursor to Taxol
It can be converted into Taxol and is sourced sustainably.
Which two research groups reported the synthesis of Taxol in 1994?
Robert Holton and Kyriacos Nicolaou
They worked independently and reported within days of each other.
What is a key advantage of using 10-deacetylbacatin III for Taxol production?
Sustainability
The harvesting of needles does not kill the plant.
What does retrosynthetic analysis involve?
Working backward from the product
Establishing the last step of the synthetic route first.
What does the term green chemistry refer to?
Minimizing negative impacts on the environment
It involves designing reactions with sustainability in mind.
What can be changed through elimination followed by addition?
Position of a halogen
This allows for rearrangement of functional groups.
What type of reaction is required when increasing the size of a carbon skeleton?
C-C bond-forming reaction
This is necessary to add more carbon atoms.
What type of reaction is needed for decreasing the size of a carbon skeleton?
C-C bond-breaking reaction
This is referred to as bond cleavage.
What are the two questions to ask for every synthesis problem?
- Is there any change in the carbon skeleton?
- Is there any change in the identity and/or location of the functional group?
What is the yield percentage for the Holton synthesis of Taxol?
Approximately 5%
This highlights the complexity and cost of the synthesis.
What is the significance of the synthesis of Taxol?
It exemplifies the development of new drugs through natural product discovery and synthetic chemistry
This combination is essential for producing effective treatments.
What is the role of an acetylide ion in organic reactions?
The acetylide ion functions as a nucleophile and can attack alkyl halides in an SN2 process.
What type of electrophiles can an acetylide ion attack?
Acetylide ions can attack various electrophiles, including epoxides and carbonyl compounds.
In the reaction between an acetylide ion and an epoxide, what does the acetylide ion generate?
The acetylide ion generates an alkoxide ion.
What is required after the acetylide ion reacts with an epoxide?
A proton source is used to protonate the alkoxide ion.
Fill in the blank: The acetylide ion will not survive in the presence of _______.
H2O
Starting with acetylene, how would you prepare CH3CHO?
Use acetylene as the only source of carbon atoms.
What is the synthesis challenge for 1,4-dioxane using acetylene?
Propose a plausible synthesis considering the use of NaH to deprotonate an alcohol.
What key compound was identified in the study of volatile components from cinnamon trees?
3-phenylpropyl acetate.
What synthesis is proposed for 1-penten-3-ol using acetylene?
Propose a synthesis starting from acetylene as the only source of carbon atoms.
What was the primary focus of the study on volatile components of cabernet sauvignon grapes?
To understand the relationship between grape development stages and volatile compound concentrations.
What two alcohols are needed to synthesize equimolar amounts of 3-methylbutanal and hexanal?
One 1° alcohol, one 2° alcohol, and one 3° alcohol, each with fewer than six carbons.
What compound was identified in the analysis of fried chicken volatiles?
Tetradecane.
What is the synthesis approach for (Z)-3-hexenyl acetate?
Use ethylene and acetic acid as the only carbon sources.
Fill in the blank: The conversion of compound 5 to compound 6 involves the removal of the _______ group.
THP
What conditions are required to remove the THP group in the synthesis of the sex pheromone?
Acidic conditions using tosic acid (TsOH).
What is the significance of volatile compounds in fish purchasing decisions?
Odor is a principal criterion for consumers.
What is a key step in synthesizing (E)-2-hexenal from 1,1-dibromopentane?
Use reactions that allow for the transformation of the starting compound.
What is the role of NaH in the synthesis of alcohols?
NaH acts as a strong base to deprotonate alcohols, forming alkoxide anions.
