MCAT-3200184 book October 30, 2015 10:18 MHID: 1-25-958837-8 ISBN: 1-25-958837-2 CHAPTER 9 Structure, Function, and Reactivity of Biologically Relevant Molecules Read This Chapter to Learn About ➤ Nomenclature of Organic Compounds ➤ Fundamental Reaction Mechanisms ➤ Chemistry of Biologically Important Compound Classes NOMENCLATURE OF ORGANIC COMPOUNDS If organic chemistry is a language, then organic compounds constitute its basic vocabulary. Thus, the mastery of basic nomenclature is essential for understanding and communicating organic phenomena. IUPAC Nomenclature The entrée into organic nomenclature is typically the class of compounds known as the simple alkanes, straight-chain hydrocarbons that are named according to the number of carbons in the chain (see the following table). The first four alkanes bear nonintu- itive, historically-derived names; however, from pentane onward they are constructed 263 MCAT-3200184 book October 30, 2015 10:18 MHID: 1-25-958837-8 ISBN: 1-25-958837-2 264 UNIT II: from the Latin roots. If used as a substituent, the names are modified by changing the Chemical suffix -ane to -yl; thus a two-carbon alkane is ethane, but a two carbon substituent is Foundations of ethyl. Biological Systems TABLE 9-1 Simple Alkanes Name Number of Carbons Formula methane 1 CH4 ethane 2 CH3CH3 propane 3 CH3CH2CH3 ) butane 4 CH3(CH2 2CH3 ) pentane 5 CH3(CH2 3CH3 ) hexane 6 CH3(CH2 4CH3 ) heptane 7 CH3(CH2 5CH3 ) octane 8 CH3(CH2 6CH3 ) nonane 9 CH3(CH2 7CH3 ) decane 10 CH3(CH2 8CH3 ) undecane 11 CH3(CH2 9CH3 ) dodecane 12 CH3(CH2 10CH3 In the case of branched alkanes, International Union of Pure and Applied Chemistry (IUPAC) rules dictate that the longest possible chain be used as the main chain, and all remaining carbons constitute substituents. If two different chains of equal length can be identified, then the one giving the fewest number of substituents should be chosen. For example, in Figure 9-1 two 7-membered chains are possible (highlighted in blue). However, the left-hand choice is preferred, since it gives two substituents—as opposed to the right-hand option, which gives only one substituent. This rule may seem arbitrary, but more substituents means less complex substituents, so naming is easier. better than 2 substituents 1 substituents FIGURE 9-1 Maximizing substituents. The key to understanding IUPAC nomenclature is realizing that it follows syntac- tical rules just like any other language. A basic premise of this syntax is that there can be only one main chain in a compound, which is grammatically analogous to a noun. Once identified, this main chain may be appended with as many substituents as nec- essary, but they are always auxiliaries, much like adjectives and adverbs. The follow- ing table illustrates this concept with the use of sentence diagrams. Thus in the name, “5-propyldecane,” propyl is an adjective and decane is the noun it modifies. MCAT-3200184 book October 30, 2015 10:18 MHID: 1-25-958837-8 ISBN: 1-25-958837-2 265 TABLE 9-2 The Syntax of Nomenclature CHAPTER 9: Structure, Function, Expression Diagram and Reactivity embellishment embellishment of Biologically Relevant Molecules woodwork embellished woodwork embellished 2 3 1 propane propane 2 3 1 decane propyl 9 7 5 3 1 10 8 6 4 2 5-propyldecane Generally, compounds contain functional groups, which are atomic assemblies associated with certain properties or reactivities, such as the hydroxy group ( OH) or = the carbonyl group (R2C O). For the purposes of nomenclature, IUPAC has assigned priorities to these functional groups, as illustrated in the following table. TABLE 9-3 IUPAC Priorities of the Functional Groups Functional Group Formula As a Parent Compound As a Modifier O carboxylic ester R alkyl -oate — O O carboxylic acid -oic acid carboxy- OH O acyl halide X 5 Br, Cl, F -oyl halide — X O carboxamide -amide — NH2 nitrile CN -nitrile cyano- O aldehyde -al oxo- H O ketone -one oxo- alcohol OH -ol hydroxy- amine NH2 -amine amino- ether OR (only as modifier) alkoxy- nitro NO2 (only as modifier) nitro- halide X X 5 F, Cl, Br, I (only as modifier) halo- (e.g., chloro-) MCAT-3200184 book October 30, 2015 10:18 MHID: 1-25-958837-8 ISBN: 1-25-958837-2 266 UNIT II: When molecules contain functional groups, then the parent chain is defined as the Chemical longest possible carbon chain that contains the highest order functional group. Once Foundations of that parent chain is identified, then all other functionalities become substituents Biological Systems (modifiers). For example, consider the two compounds in the following table. Both contain the hydroxy ( OH) functional group, but in the top it defines the parent chain. Therefore, the -ol form is used, and the compound is named propan-2-ol. However, the lower compound has both the hydroxy and the carbonyl functional groups. Since the car- bonyl has the higher IUPAC priority, it defines the parent chain; the hydroxy group thus serves only as a modifier, and the -ol suffix is not used. TABLE 9-4 Functional Groups in the Main Chain and as Substituent Name Diagram OH propan-2-ol 2 31 propan-2-ol OH decan-3,6-dione 2 O propyl 3 1 6 9 7 5 3 1 hydroxy 10 8 4 2 O 5-(2-hydroxypropyl)decan-3,6-dione Double bonds add an interesting wrinkle in the process. While they do not carry much priority alone, the parent chain should contain the highest order functional group and as many double bonds as possible, even if this means that a shorter par- ent chain will be obtained or if other functionality will be excluded. For example, the compound in Figure 9-2 contains four functional groups: the carboxylic acid, carbonyl, hydroxy, and alkenyl functionalities. Of these, the carboxylic acid has highest priority, so the parent chain must include it. It is tempting to also include the carbonyl group to make a 13-carbon chain; however, IUPAC dictates that both double bonds be included (as highlighted), even though this results in a shorter 9-carbon chain that does not encompass the carbonyl functionality. As the previous examples illustrate, a parent chain may contain multiple functional groups of the same type, or a functional group with one or more double bonds. Using the grammatical analogy, this is like having a compound noun (e.g., boxcar). In the former case, appropriate prefixes are used (i.e., di-, tri-, etc.); in the latter, the en- prefix is used, as shown in the following table. However, aside from the alkene, two different MCAT-3200184 book October 30, 2015 10:18 MHID: 1-25-958837-8 ISBN: 1-25-958837-2 267 COOH CHAPTER 9: Structure, Function, O and Reactivity of Biologically OH Relevant Molecules 4-(4-hydroxybutyl)-7-(3-oxohexyl)-nona-2,8-dienoic acid FIGURE 9-2 Naming a multifunctional acyclic compound. functional groups may not be included in the same parent chain. For example, if an alcohol and a ketone are present in the same molecule, it must be named as a ketone with a hydroxy substituent. TABLE 9-5 Examples of Multiple Functionalities in the Parent Chain Multiple Functionalities in the Multiple Functionalities in the Parent Chain That Are Consistent Parent Chain That Are Not with IUPAC Consistent with IUPAC OH O O O HO OH HO OH IUPAC: 4-hydroxypentan-2-one Propanedioic acid Propan-1,3-diol (NOT pent-2-on-4-ol) O O O OH OH IUPAC: 3-oxobutanoic acid But-3-en-1-ol Pent-4-en-2-one (NOT butan-4-on-1-oic acid) In summary, the parent chain should be established using the following guidelines (in order of priority): 1. Include the highest order functional group. 2. Include as many double bonds as possible. 3. Select the longest carbon chain (with the maximum number of substituents). Compounds containing cyclic arrays of carbon atoms are known as carbocycles. The presence of a ring does not change any of the considerations discussed so far; how- ever, it does force a choice. Either the ring becomes the parent chain or it is part of some substituent. Being cyclic does not confer any special consideration—if it happens to represent the longest chain with the highest-order functional group, then it is the par- ent chain; otherwise, it is a substituent. Figure 9-3 shows two examples of compounds in which the ring is the parent and two in which the ring is a substituent. MCAT-3200184 book October 30, 2015 10:18 MHID: 1-25-958837-8 ISBN: 1-25-958837-2 268 UNIT II: O OH Chemical Foundations of Biological Systems OH O 1,2,3-trimethyl- 2-cyclopropyl- 2-(2-hydroxypropyl)- 1-(2-hydroxycyclohexyl)- cyclopropane pentane cyclohexanone propan-2-one FIGURE 9-3 Examples of carbocyclic compounds. Common Nomenclature With a pretty good understanding of nomenclature rules in hand, consider some mis- cellaneous vocabulary used by organic chemists to describe carbon centers (Fig- ure 9-4). One set of terms arises from considering how many other carbons are attached to a given center. If a carbon has only one other carbon attached to it, then it ◦ is designated a primary (1 ) center; if two other carbons are attached, it is a secondary center, and so on. This terminology is also used for substituents, so if a chloro sub- stituent is attached to a carbon that is attached to two other carbons, it is said to be a secondary chloride. The other way to describe carbon centers is by examining how many hydrogens are attached. Carbons with three hydrogens are called methyl groups; those with two are methylene groups; and those with only one are known as methines.