Current Polymer and Organic Chemistry

24 May 2016
Instructor: Prof. Susumu Saito

Letitia Sarah 061302856

Lecture date:

1. In conventional methods for N-alkylation, salt wastes production is inevitable or

mandatory. What are the best two textbook reactions for N-alkylation? Compare the
two methods and answer advantages and disadvantages for each.
The most common reactions for N-alkylation are
1. Nucleophilic aliphatic substitution (of the halide)
This reaction is widely used for synthesis of alkylated amines in the laboratory,
but it is of less importance industrially. This reaction is difficult to control
because the reaction products (secondary amine in this example) are often
more nucleophilic than the reactants and will thus preferentially react with
alkylating reagent through another nucleophilic substitution. This secondary
reaction will compete for bromobenzene and produce tertiary ammonium salt,
and eventually quartenary ammonium salt. Furthermore, the salt can donate
proton to either of the other two nitrogen bases present, furnishing
alkanamines. Finally, the final product is a mixture of alkyl-ammonium salts and
alkanamines.
2. Synthesis of amines by reductive amination
This is the more general method of amine alkylation. Reductive amination of
aldehydes and ketones allow construction of primary, secondary, and tertiary
amines. The carbonyl compound is exposed to an amine containing at least one
N-H bond (NH3, secondary, tertiary and tertiary amine respectively). This new CN bond is formed to the carbonyl carbon of the aldehyde and/ or ketones.
Compared to nucleophilic substitution, synthesis of amines by reductive
amination produces more targeted products in shorter time. Reducing agents,
either hydrogen gas in the presence of catalyst or sodium cyanoborohydride
react with imine double bond. With Na+ BH3CN-, the conditions are relatively
acidic (pH 2-3), activating the imine double bond by protonation on nitrogen and
thus facilitating hydride attack at carbon. Finally, product can be obtained in
high percentage (>78%) unlike the product of nucleophilic substitution which
also contains salts.

2. What are the best methods or reagents to reduce amides and carboxylic acids?
With the methods, what is the major product? Are there any differences from the
hydrogenation?
One of the most common and practical reagents used for amides and carboxylic
acids reduction is LiAlH4. Other than LiAlH4, similar metal hydride agents can also
be used. Some of them are DIBAL, Red-Al, AlH3, BH3 and LiEt3BH.

However, there are few disadvantages of this reduction of carboxylic acid and
amide using lithium alumunium hydride. First, this reaction also synthesizes waste
metal salts as byproducts even though amine and alcohol compounds are still the
major product. Second, this reaction needs complicated workup and has poor atom
efficiency. Lastly, this reaction also has low chemoselectivity. Other functional
groups such as ketones, nitro groups, and some alkynes will be reduced as well. This
would be a problem, especially at the end stage of synthesis.

Another reaction pathway that is targeted to reduce amide is silane reduction. This
reduction reaction only works for tertiary amides and ketone, nitrile, nitro group,
olefin, ester and diimide are tolerated.

Even though the above reactions are more commonly used, catalytic hydrogenation
can reduce amide and carboxylic acid more efficiently. In this process, water is the
only waste which makes purification process easier. Also, it is possible to control the
chemoselectivity by modifying catalysts.

3. Fill the dotted and bold blanks to complete the synthesis of Aricept from the
starting ester. Are salt wastes produced?
Donepezil is the most widely prescribed of the cholinesterase inhibitors. It improves
cognitive performance and stabilizes functional abilities in people with mild-tomoderate Alzheimer disease by increasing the amount of the ACh in the brain. The
synthesis of donepezil (Aricept) involves the condensation of 5,6-dimethoxy-1indanone and 1-benzyl-4-piperidinecarbox-aldehyde in the presence of n-Buli, at
-78oC in THF/HMPTA mixture. The resulting compound is hydrogenated over
palladium carbon to produce the desired donepezil. In some cases, catalytic
hydrogenation with Pd on charcoal also produces an undesired side product (not
salt) along with the main product due to over reduction. However, removal process
can be done by crystallization or column chromatography.

4. What is the significant difference between the following two reactions, although
both can synthesize the aldehyde as well. Clue: argue energy change before and
after the reaction.
According to Prof. Ryoji Noyori, Prof. Masao Aoki and Prof. Kazuhiko Sato in Green
oxidation with aqueous hydrogen peroxide, addition of several catalysts and
hydrogen peroxide will enhance the yield of alcohol oxidation. The catalysts used
are combination of sodium tungstate (Na2WO4) and methyltrioctylammonium
hydrogensulfate [CH3(n-C8H17)3N+HSO4-(Q+ HSO4-)] as a PTC. This combined catalyst
catalyzes efficiently the dehydrogenation of alcohols with 30% H 2O2 to give the
corresponding carbonyl compounds in high yields.

Addition of hydrogen peroxide can accelerate the oxidation reaction because

hydrogen peroxide decomposition is exothermic with a standard reaction enthalpy
of -983 kJ/mol. Due to the nature of the additional exothermic reaction brought by
hydrogen peroxide, the potential energy level of product would decrease. Also, less
energy would be needed to initiate the reaction. This means that reaction with
hydrogen peroxide added would proceed significantly easier hence faster.
5. In 2011, world-production of propylene was 4.93 million tons. What is the most
popular way to produce propylene currently on such an enormous scale?
Currently, propylene is mainly produced a by-product of ethylene plants and
gasoline machine/fluid catalytic cracking (FCC) units. Propylene production can be
optimized by running the steam cracker at low severity or by transforming an FCC
unit into a petrochemical FCC after a major revamp. However, the gasoline surplus
will result in a gradual slowdown in FCC production. Therefore, secondary propylene
production is sought after.
How the shale gas revolution changed the game?
Propylene has traditionally been produced as a by-product during naphta steam
cracking, one of the major processes of ethylene production. However, in 2010, the
US shale gas revolution has sparked an increase in ethane cracking. Ethane
cracking is a cost-advantage technology which produces minimal propylene yield.
This has caused propylene production loss by 3.5 million tons.
Despite the current supply shortage, it is forecasted that the worlds propylene
capacity will increase from around 109 million tons today to 165 million tons by
2030. This is due to new on-purpose propylene synthesis from propane called
propane dehydrogenation (PDH). PDH removes two hydrogen atoms from propane
(C3H8), converting it to propylene (C3H6).
How can H2 be produced on an enormous scale?

Answer the current state-of-the art and your future perspectives.

Currently, majority of hydrogen (95%) is produced from fossil fuels by steam
reforming of methane or natural gas. This type of production is the cheapest way to
produce hydrogen. In this process, gas is heated in the presence of steam and
nickel catalyst. The resulting exothermic reaction breaks up the methane molecule
and forms carbon monoxide CO and hydrogen H 2. The carbon monoxide then can be
passed with steam over iron oxide or other oxides and undergo a water gas shift
reaction.
However, hydrogen production via steam reforming causes buildup of CO, CO 2 and
other greenhouse gases as by-products. Depending on the quality of the starting
material, one ton of hydrogen produced will also produce 9 to 12 tons of CO 2.

http://large.stanford.edu/

Steam reforming reaction of methane

Other than steam reforming, hydrogen can also be obtained from electrolysis of
water. Even though this process has been around for quite a while, simultaneous
hydrogen and oxygen production is a problem because these gas mix can pass
through and degrade expensive Nafion polymer membranes meant to separate
tehem in electrolysers, with potentially explosive consequences. Regarding this
problem, Lee Cronin and Mark Symes from University of Glasgow used a
phosphomolybdate anion buffer ot store protons and electrons generated when
oxidising water to oxygen. The reason for this buffer to be chosen is due to the
electron-coupled-proton buffer (ECPB) properties that might lie within the transition
metal and oxygen containing networks of polyoxometalate anions. Next, this buffer
lets the scientist chooses where and when they want to release hydrogen.

In my opinion, green chemistry process would be great consideration in determining

hydrogen production methods. As fossil fuels and shale gas amount decrease,
renewable source of hydrogen is highly sought. There is great possibility that water
electrolysis could be a major method to obtain hydrogen. However, it is known that
current water electrolysis needs to be improved in order to be chemically and
economically efficient. Another interesting method of hydrogen production is by
production of bio-hydrogen using waste as starting material. Bio-hydrogen
production is usually achieved by bio-photolysis of water by algae, dark and photofermentation of organic materials, usually carbohydrates by bacteria. Nevertheless,
one of the major problems in dark and photo-fermentation process is the high cost
of starting materials. Due to this problem, scientists tried to utilize carbohydrate
rich, nitrogen deficient solid wastes such as cellulose and starch containing
agricultural and food industry wastes and some food industry wastewaters such as
cheese whey, olive mill and bakers yeast industry wastewaters for hydrogen
production.

Reference
How will US shale gas alter the global propylene market? Retrieved from
http://www.woodmac.com/analysis/12524872
Kapdan, Ilgi Karapinar, and Fikret Kargi. "Bio-hydrogen Production from Waste
Materials." Enzyme and Microbial Technology 38.5 (2006): 569-82. Web.
Noyori, Ryoji, Masao Aoki, and Kazuhiko Sato. "Green Oxidation with Aqueous
Hydrogen Peroxide." Chemical Communications Chem. Commun. 16 (2003):
1977. Web.
Split
water
splitting
raises
green
hydrogen
hopes.
Retrieved
from
http://www.rsc.org/chemistryworld/2013/04/green-energy-cheaper-hydrogenseparate-water-splitting
Vardanyan, Ruben. Synthesis of Best-seller Drugs. Amsterdam: Academic, 2016.
Print.