Saturday, 25 June 2011

Organic Chemistry An Introduction

Organic Chemistry

An Introduction

by Anthony Carpi, Ph.D.

To understand life as we know it, we must first understand a little bit of organic chemistry. Organic molecules contain both carbon and hydrogen. Though many organic chemicals also contain other elements, it is the carbon-hydrogen bond that defines them as organic. Organic chemistry defines life. Just as there are millions of different types of living organisms on this planet, there are millions of different organic molecules, each with different chemical and physical properties. There are organic chemicals that make up your hair, your skin, your fingernails, and so on. The diversity of organic chemicals is due to the versatility of the carbon atom. Why is carbon such a special element? Let's look at its chemistry in a little more detail.
Carbon (C) appears in the second row of the periodic table and has four bonding electrons in its valence shell (see our Periodic Table module for more information). Similar to other non-metals, carbon needs eight electrons to satisfy its valence shell. Carbon therefore forms four bonds with other atoms (each bond consisting of one of carbon's electrons and one of the bonding atom's electrons). Every valence electron participates in bonding, thus a carbon atom's bonds will be distributed evenly over the atom's surface. These bonds form a tetrahedron (a pyramid with a spike at the top), as illustrated below:

Carbon forms 4 bonds

Organic chemicals get their diversity from the many different ways carbon can bond to other atoms. The simplest organic chemicals, called hydrocarbons, contain only carbon and hydrogen atoms; the simplest hydrocarbon (called methane) contains a single carbon atom bonded to four hydrogen atoms:

Methane - a carbon atom bonded to 4 hydrogen atoms

But carbon can bond to other carbon atoms in addition to hydrogen, as illustrated in the molecule ethane below:

Ethane - a carbon-carbon bond

In fact, the uniqueness of carbon comes from the fact that it can bond to itself in many different ways. Carbon atoms can form long chains:

Hexane - a 6-carbon chain

branched chains:

Isohexane - a branched-carbon chain

rings:

Cyclohexane - a ringed hydrocarbon

There appears to be almost no limit to the number of different structures that carbon can form. To add to the complexity of organic chemistry, neighboring carbon atoms can form double and triple bonds in addition to single carbon-carbon bonds:


Single bonding	Double bonding	Triple bonding

Keep in mind that each carbon atom forms four bonds. As the number of bonds between any two carbon atoms increases, the number of hydrogen atoms in the molecule decreases (as can be seen in the figures above).

Simple hydrocarbons

The simplest hydrocarbons are those that contain only carbon and hydrogen. These simple hydrocarbons come in three varieties depending on the type of carbon-carbon bonds that occur in the molecule. Alkanes are the first class of simple hydrocarbons and contain only carbon-carbon single bonds. The alkanes are named by combining a prefix that describes the number of carbon atoms in the molecule with the root ending "ane". The names and prefixes for the first ten alkanes are given in the following table.

Carbon Atoms	Prefix	Alkane Name	Chemical Formula	Structural Formula
1	Meth	Methane	CH₄	CH₄
2	Eth	Ethane	C₂H₆	CH₃CH₃
3	Prop	Propane	C₃H₈	CH₃CH₂CH₃
4	But	Butane	C₄H₁₀	CH₃CH₂CH₂CH₃
5	Pent	Pentane	C₅H₁₂	CH₃CH₂CH₂CH₂CH₃
6	Hex	Hexane	C₆H₁₄	...
7	Hept	Heptane	C₇H₁₆
8	Oct	Octane	C₈H₁₈
9	Non	Nonane	C₉H₂₀
10	Dec	Decane	C₁₀H₂₂

Oxidation and Reduction

Kiyotomi Kaneda of Osaka University devised (Angew. Chem. Int. Ed. 2010, 49, 5545. DOI: 10.1002/anie.201001055) gold nanoparticles that efficiently deoxygenated an epoxide 1 to the alkene 2. Robert G. Bergman of the University of California, Berkeley and Jonathan A. Ellman, now of Yale University, reported (J. Am. Chem. Soc. 2010, 132, 11408. DOI: 10.1021/ja103436v) a related protocol for deoxygenating 1,2-diols. Dennis A. Dougherty of Caltech established (Org. Lett. 2010, 12, 3990. DOI: 10.1021/ol1015493) that an acid chloride 3 could be reduced to the phosphonate 4.

Pei-Qiang Huang of Xiamen University effected (Synlett 2010, 1829. DOI: 10.1055/s-0030-1258111) reduction of an amide 5 by activation with Tf₂O followed by reduction with NaBH₄. André B. Charette of the Université de Montreal described (J. Am. Chem. Soc. 2010, 132, 12817. DOI: 10.1021/ja105194s) parallel results with Tf₂O/Et₃SiH. David Milstein of the Weizmann Institute of Science devised (J. Am. Chem. Soc. 2010, 132, 16756. DOI: 10.1021/ja1080019) a Ru catalyst for the alternative reduction of an amide 7 to the amine 8 and the alcohol 9.
Shi-Kai Tian of the University of Science and Technology of China effected (Chem. Commun. 2010, 46, 6180. DOI: 10.1039/C0CC00765J) reduction of a benzylic sulfonamide 10 to the hydrocarbon 11. Thirty years ago, S. Yamamura of Nagoya University reported (Chem. Commun. 1967, 1049. DOI: 10.1039/C19670001049) the efficient reduction of a ketone to the corresponding methylene with Zn/HCl. Hirokazu Arimoto of Tohoku University established (Tetrahedron Lett. 2010, 51, 4534. DOI: 10.1016/j.tetlet.2010.06.102) that a modified Zn/TMSCl protocol could be used following ozonolysis to effect conversion of an alkene 12 to the methylene 13.

José Barluenga and Carlos Valdés of the Universidad de Oviedo effected (Angew. Chem. Int. Ed. 2010, 49, 4993. DOI: 10.1002/anie.201001704) reduction of a ketone to the ether 16 by way of the tosylhydrazone 14. Kyoko Nozaki and Makoto Yamashita of the University of Tokyo and Dennis P. Curran of the University of Pittsburgh found (J. Am. Chem. Soc. 2010, 132, 11449. DOI: 10.1021/ja105277u) that the hydride 18 (actually a complex dimer) could effect the direct reduction of a halide 17, and also function as the hydrogen atom donor for free radical reduction, and as the hydride donor for the Pd-mediated reduction of an aryl halide.

Masayuki Inoue, also of the University of Tokyo used (Org. Lett. 2010, 12, 4195. DOI: 10.1021/ol1018079) Cl₃CCN to promote MCPBA oxidation of an ether 20 to the ketone 21. Kandikere Ramaiah Prabhu of the Indian Institute of Technology, Bangalore oxidized (Angew. Chem. Int. Ed. 2010, 49, 6622. DOI: 10.1002/anie.201002635) a primary azide 22 to the nitrile 23 using commercial aqueous t-BuOOH. Debashis Chakraborty of the Indian Institute of Technology, Madras found (Tetrahedron Lett. 2010, 51, 3521. DOI: 10.1016/j.tetlet.2010.04.101) that commercial aqueous t-BuOOH could also be used to oxidize an aldehyde 24 to the acid 25. Masahito Ochiai of the University of Tokushima and Waro Nakanishi of Wakayama University devised (J. Am. Chem. Soc. 2010, 132, 9236. DOI: 10.1021/ja104330g) the reagent 26 to effect oxidation of the aldehyde 24 to the Baeyer-Villiger product 27.

Jonathan M. J. Williams of the University of Bath used (Org. Lett. 2010, 12, 5096. DOI: 10.1021/ol101978h) hydroxylamine to oxidize an aldehyde 28 to the amide 30. Jörg Sedelmeier, Steven V. Ley and Marcus Baumann of the University of Cambridge established (Org. Lett. 2010, 12, 3618. DOI: 10.1021/ol101345z) that flow conditions could be used to oxidize a nitro derivative 31 to the aldehyde 32, or (not illustrated) to the corresponding carboxylic acid or (from a secondary nitro) the ketone.

Neighbouring group participation

The stereochemical outcome of a glycosylation reaction may in certain cases be affected by the type of protecting group employed at position 2 of the glycosyl donor. A participating group, typically one with a carboxyl group present, will predominantly result in the formation of a β-glycoside. Whereas a non-particiapting group, a group usually without a carboxyl group, will often result in an α-glycoside.
Below it can be seen that having an acetyl protecting group at position 2 allows for the formation for an acetoxonium ion intermediate that blocks attack to the bottom face of the ring therefore allowing for the formation of the β-glycoside predominantly.

Alternatively, the absence of a participating group at position 2, allows for either attack from the bottom or top face. Since the α-glycoside product will be favoured by the anomeric effect, the α-glycoside usually predominates.

Building blocks

[edit] Building blocks

Common donors in oligosaccharide synthesis are glycosyl halides, glycosyl acetates, thioglycosides, trichloroacetimidates, pentenyl glycosides, and glycals. Of all these donors, glycosyl halides are classic donors, which played a historical role in the development of glycosylation reactions. Thioglycoside and trichloroacetimidate donors are used more than others in contemporary glycosylation methods. When it comes to the trichloroacetimidate method, one of the advantages is that there is no need to introduce heavy metal reagents in the activation process. Moreover, using different bases can selectively lead to different anomeric configurations. (Scheme 2) As to the thioglycosides, the greatest strength is that they can offer a temporary protection to the anomeric centre because they can survive after most of the activation processes.^[3] Additionally, a variety of activation methods can be employed, such as NIS/ AgOTf, NIS/ TfOH, IDCP (Iodine dicollidine perchlorate), iodine, and Ph₂SO/ Tf₂O. Furthermore, in the preparation of 1, 2-trans glycosidic linkage, using thioglycosides and imidates can promote the rearrangement of the orthoester byproducts, since the reaction mixtures are acidic enough.

Oligosaccharide synthesis

Oligosaccharides have diverse structures. The number of monosaccharides, ring size, the different anomeric stereochemistry, and the existence of the branched-chain sugars all contribute to the amazing complexity of the oligosaccharide structures. The essence of the reducing oligosaccharide synthesis is connecting the anomeric hydroxyl of the glycosyl donors to the alcoholic hydroxyl groups of the glycosyl acceptors. Protection of the hydroxyl groups of the acceptor with the target alcoholic hydroxyl group unprotected can assure the regiochemical control. Additionally, factors such as the different protecting groups, the solvent, and the glycosylation methods can influence the anomeric configurations. This concept is illustrated by an oligosaccharide synthesis in Scheme 1. Oligosaccharide synthesis normally consists of four parts: preparation of the glycosyl donors, preparation of the glycosyl acceptors with a single unprotected hydroxyl group, the coupling of them, and the deprotection process.

Classification of organic compounds

[edit] Functional groups

Main article: Functional group

The family of carboxylic acids contains a carboxyl (-COOH) functional group. Acetic acid is an example.

The concept of functional groups is central in organic chemistry, both as a means to classify structures and for predicting properties. A functional group is a molecular module, and the reactivity of that functional group is assumed, within limits, to be the same in a variety of molecules. Functional groups can have decisive influence on the chemical and physical properties of organic compounds. Molecules are classified on the basis of their functional groups. Alcohols, for example, all have the subunit C-O-H. All alcohols tend to be somewhat hydrophilic, usually form esters, and usually can be converted to the corresponding halides. Most functional groups feature heteroatoms (atoms other than C and H). Organic compounds are classified according to functional groups, alcohols, carboxylic acids, amines, etc.

[edit] Aliphatic compounds

Main article: Aliphatic compound

The aliphatic hydrocarbons are subdivided into three groups of homologous series according to their state of saturation:

paraffins, which are alkanes without any double or triple bonds,
olefins or alkenes which contain one or more double bonds, i.e. di-olefins (dienes) or poly-olefins.
alkynes, which have one or more triple bonds.

The rest of the group is classed according to the functional groups present. Such compounds can be "straight-chain," branched-chain or cyclic. The degree of branching affects characteristics, such as the octane number or cetane number in petroleum chemistry.
Both saturated (alicyclic) compounds and unsaturated compounds exist as cyclic derivatives. The most stable rings contain five or six carbon atoms, but large rings (macrocycles) and smaller rings are common. The smallest cycloalkane family is the three-membered cyclopropane ((CH₂)₃). Saturated cyclic compounds contain single bonds only, whereas aromatic rings have an alternating (or conjugated) double bond. Cycloalkanes do not contain multiple bonds, whereas the cycloalkenes and the cycloalkynes do.

Organic Chemistry

Saturday, 25 June 2011