University of Santo Tomas Faculty of Pharmacy Scholia Tutorial Club Chemistry Review Group INTRODUCTORY GUIDE ORGANIC CHEMISTRY (CHEM 200) LECTURE Prepared by: Ser Loisse R. Mortel Chemistry Review Group INTRODUCTION Chemistry ~ the scientific study of properties of and changes in matter. Organic Chemistry — branch of Chemistry that deals with properties and changes in organic compounds. Organic Compound - historically defined as a compound that originates from living creatures. = now more correctly and conveniently defined as any ‘compound that contains carbon (proven by synthesis of organic compound Urea from inorganic sources by Friedrich Wohler|, Given that organic compounds are not just existent in living systems, it would be present in practically every place here in the biosphere. Living creatures like you and plants and bacteria, plastic, wood, fabric, paper, most drugs, and many more are organic compounds. Learning Organic Chemistry Organic Chemistry discussion will be divided through using groups of similar compounds. General chemistry essentials of interest in organic chemistry are discussed first, followed by reactions specific for those similar ‘compounds. Functional group ~ a small identifiable chemical entity that should always be seen in a family of organic compounds. Functional Groups “Most atoms that comprise the functional groups are non: metals and mast of the time are connected by covalent bonds. Because of this, we give a name for that small functional group as well as a distinct collective name for the family of organic compounds bearing the functional group (For example, organic compounds with an amino (~ NH.) group are called “amines”). ‘Alkyithiocarbony! Thioesters Halocarbonyl ‘Acid halides ‘Aminocarbonyi/ ‘Amides Carbamoyl cyano Nitriles Formyl Aldehydes Carbonyl Ketones, Hydroxyl ‘Alcohols Mercaptan/Thiol Thiol ‘Amino ‘Amines Alkoxy Ethers Alkylthio Sulfides Carbon-carbon triple bond ‘Alkynes Carbon-carbon double Alkenes bond Carbon-carbon single bond alkanes Halogen (Organic halides Functional Group Family of Organic ‘Compounds Carbonyl Carboxylic acids ‘Acyloxycarbonyl ‘Acid anhydrides ‘Alkoxycarbonyl Esters Structural Formula Formats Table Pt. Table depicting some names of functional groups, and corresponding name (or family) of arganic compounds with the functional group. PART 2. STRUCTURAL FORMULAS Before the structure, function and reactivity of organic ‘compounds can even be discussed, erative for fone to be trained as much as possible in identifying the structure and giving the name of a presented organic ‘compound. In this, the formula and nomenclature (system of naming) of organic compounds is a good starting topic to kick off Organic Chemistry. Chemical Formula - is a written depiction of a chemical ‘compound by using the letter symbols of the elements as written in the periodic table of elements (Organic compounds’ function and reactivity are so much better explained through depicting them as atoms connected together by specific bonds with specific shapes rather than using letters alone, so we use structural chemical formulas instead. In a structural (chemical) formula, atoms are written as they are bonded to each other in space. There are several ways of writing chemical formula. They will be listed down from basic to advanced (not necessarily becoming more complicated along the way). As a note, in case the reader is still confused on how many hydrogens to attach to another atom (lke carbon or oxygen), it would depend on the atom itself (and we will know why later on) carbon should always have 4 bonds, oxygen 2 bonds, nitrogen 3 bonds and halogens (F, Ci Br |) 1 bond. JRBM/SLRM2015 | 1‘Name of Structural Definition ‘Example (Compound used: 1-butanol) Formula {A Straight-line/ Kekule | Encountered in general chemistry. Here, a H H Srucute chemical Sond deplced ora STEN Ine, wat (Recall: Lewis structures still depict a and lone electrons are depicted 2s dots | y_(— B. Condensed Structure | The only difference with the kekule sameeren’ | CL CL CUCHOH triple bonds are drawn (sometimes not at | 7! 2 z all; people have different preferences) C. 3D (Dash-Wedge- ‘Takes into consideration the three- H Line) Seucture dimensional. perspective of the atoms Wedged ~ the substituent faces the reader. | Dashes ~ the substituent fs far fom the reader C ther“sesataueestihenbne orbs | MCHC H LEN paper. ACH iC a YOu . Skeletal Formula/ | This formula treats any end point in a Line Angle Formula | written structural formula as a carbon atom with all other C-H bonds implied. OH Table P2. The different structural formulas used in organic chemistry NOMENCLATURE Like people with real names and nicknames \Whether people call you by complete name, nickname ora combination ofboth, those names pertain only to you. This is teu to organtc compounds, They to have real names and nicknames. + Systematicname real name of compounds based on specialized nang rules t ams to describe the number, lection and precise structure ofthe compound in question + Trivial name nick name of compounds based solely on tradition and famiaization by people. does not depict the precise structure of the compound in question, + Semsystematic~names of compounds describe only partly the structure of the compound in question because a st of rules were not employed O \ thCOCNoy Figure P1. Ethanoic acid is a systematic name, depicting the number of carbon atoms (“eth” means two according to rules), ‘acetic acid is semi-systematic (“acet” means two, but does not follow current naming rules) and its diluted form has the trivial nome vinegar. ‘Systematic Names: Prefixes, Parents, and Suffixes The International Union of Pure and Applied Chemistry (IUPAC) governs most of the rules in naming organic compounds. By their rules, the systematic name must contain three essential parts: the parent, prefix, and suffix PREFIX-PARENT-SUFFIX ‘The parent is the part of the compound that represents it. In the name, its between the prefix and suffix. The prefix is written before the parent name, and means all other parts of the compound branching out from the parent (called substituents). Substituents may be further named clearer in the prefix by using focants, descriptors, and multipliers. a, Locant~ may be any number or italicized letter (ex. N) that designates on which part of the parent chain 2 particular substituent is placed. Locants are also used in suffixes. b. Descriptor ~a necessary prefix that describes a certain structural aspect of a compound, usually stereochemistry (ex. cis-trans, €2, $-R) & Multiplier ~ a prefix that indicates a number of identical substituents. ‘The suffixis written after the parent name, and means either carbon-carbon multiple bonds or the highest priority functional group. SLRM2013 | 2GENERAL RULES IN NOMENCLATURE Chemistry Review Group Portion of Systematic Name Rule/s Chere isa rule “2", “b* onwards, the first rule overrules ‘others next to it. Example: Rule 8 overtules C, but A Demonstration Parent ‘La. On assigning the parent chain: The parent is the carbon chain that bears the most funetional groups. Note: If there are two candidates for this rule, choose the one with a higher total priority of substituents accordance to hierarchy of functional groups). Demonstration: Some people may think that rule 1b longest chain rule) will apply here, but 10 overrules it 1b. The parent isthe longest carbon chain. Demonstration: Since the 5-carbon and 7-carbon chain both have the some number of substituents (1), pick the longer chain, 1c. Cyclic chains take precedence over linear chains. Demonstration: Since both chains can either have 1 substituent and are of equal length, the cyclic chain becomes the parent. 2. On weiting the parent in the name: ‘The parent shall be named according to the carbon chain length. The first few prefixes are listed below. ‘Warbons | Carbon length prefix 1 Meth Eth Prop: ‘But Pent Hex: Hept (Oct 9 Non: and soon Dee and soon Table P3. Carbon length prefixes. Prefix ‘La, On assigning locants: Locants will be assigned starting from the carbon of a terminal functional group (WHICH ARE carboxyl, carboxyl derived group, formyl, nitrile) Demonstration: The functional group at the right is 0 carboxy! group. It fs terminal, and 50 the carbon there willbe the number 1 carbon. NOTE: Systematic naming only allows numbers as locants (1, 2, 3, etc). Trivial names allow locant assignment as greek letters (alpha, beta, gamma) and will also follow this rule about terminal functional groups. Demonstration: On the compound at the right, the NH, group is placed on the 4” carbon, “gamma” in greek. NOTE: If you don't need locants, DO NOT use them. ~ net, Br oO Nn oO e ° AA Qo Left: Butyric acid (trivial) Right: gamma-aminobutyric acid (trivial) SLRMChemistry Review Group 1b, Lowest sum rule: Locants will be assigned in a way that they add up to the lowest possible sum in the final name. 1c. First point of difference rule: If you can start on two different functional groups interchangeably Without violating the lowest sum rule, locants shall start from the higher priority group, © Demonstration: The cyclopropyl has 3 carbons while the methyl has 2, and like how we decide parents, we prioritize the longer chain. EXCEPTION: If you can start on a double bond and triple bond can be named interchangeably without Violating rule of first difference, locants shall start from the double bond. 2-cyclepropy-4-methylpentane 4 Cututa, C= bu Hex-d-en-5-yne 2. On writing the prefixes (punctuations): Upon writing the compound name, the punctuations ‘© Hyphen (-)- between a letter and a number and between a letter/number and parenthesis. © Comma (,) between two numbers Nothing is placed between two letters. Spaces are used when a specific nomenclature calls for them. 0 AY 2,4-dimethythexanoic acid 3. On writing the prefixes (precedence): The prefixes shall be listed alphabetically, with the locant always immediately before the substituent it locates. Prefixes cyclo. alphabetization. ‘+ Multiplier prefixes, listed below, and all descriptors (cis, trans, etc.) ate NOT part of the alphabetization ‘© NOTE: A multiplier prefix is written IMMEDIATELY BESIDE THE substituent it describes. Iso, and neo: are PART of © Similar ‘+ Multiplier prefix substituents 2 or 3 Te 4 Terra: 5 Penta Gand soon Hexa- and so on Table Pa. Multiplier prefixes. DE 2.cyclopropyl-4-methyloentane CH AN CHy (2-Hydroxy-2,4-diMethylbutane- 4. On writing the prefixes (complex substituents): If there are substituents on a substituent, enclose that “secondary” substituent in a parenthesis. In alphabetiztion, the first letter of the complex substituent is considered, Demonstration: The 4C chain holds the higher priority keto group, overruling the 5C chain with hydroxyl. The choin with the hydroxyl is treated as substituent. 2.(2-hydroxypropy!)-3-oxobutanoic acid Suffix 1. Highest priority rule: The highest priority functional group will occupy the suffix portion, with the appropriate locant. (The hierarchy that determines which group is of the highest priority is in the next part). If the functional group is terminal, no locant should be placed because it’s given that the terminal carbon is assigned 1. Demonstration: Hydroxy and keto groups are of lower priority than the corboxyl group. Thus, the carboxyl group will occupy the suffix of this compound's name. 6 oO How %. a) > 3) ey ow 2-(2-hydroxypropyl)-3-oxobutanoie acie SLRM2013 | 4Chemistry Review Group 2. Multiple suffixes due to double/triple bonds: Double and triple bonds, whether highest priority or not, are named with suffixes. Between the two, the {rile bond is the priority group. cata cu ty, C= 0H Hex: 3. On elision (removal of letters) No two vowels or two consonants may be beside each other. For vowels, one of the two is removed. For consonants, a vowel may be placed in between, Propan-2-0l, not propane-2-0l NOMENCLATURE HIERARCHY: SUBSTITUENTS AND SUFFIXES, ‘As said in suffix rule 1, there is a hierarchy being followed for functional groups. This arose from the case wherein a parent ‘compound contains more than one functional group (a polyfunctional compound). In the current rules, the highest priority {functional group determines the suffix of the compound, and the lower functional groups will be treated as substituents of the compound. Thus, given the fact that only one functional group is present, their suffix will be used. ‘The table below lists the according suffix and substituent names of compounds with that functional group. Functional Group Prefix Suffix Carboxyl Carboxy: vic acid/-carboxylic acd ‘cyloxycarbonyl - ‘ic anhydride/ carboxylic anhydride ‘Alkoxycarbonyl ‘Alkoxycarbony Sate) carboxylate Alkylthiocarbonyl Alkyithiocarbonyi- -thioate/ -carbothioate Halocarbonyl Halocarbonyi- oy! halide/ -carbonyl halide ‘Aminocarbonyi/ Carbamoyl Carbamoyi- -amide/ “carboxamide cyano. Cyano- nitrile) -carbonitrile Formyl (0x0: -alf -carbaldehyde Carbonyl (Oxo: ‘one’ Hydroxy! Hydroxy ol Thiol ‘Mercapto: thiol ‘Amino ‘Amino “amine Alkony ® Alkony Ether ‘Alkyithio™ ‘Alkyithio= Sulfide Carbon-carbon triple bond - “ye Carbon-carbon double bond - ene ‘Carbon-carbon single bond = “ane ‘As long as hydrocarbon ‘Aly: 2 Halogen * Halo Halide Table PS. List of functional groups olong with their prefixes and suffixes in naming. * the sufficis used only in the trivial name of a organic compound, and thus, the systematic name uses purely the prefix of the compound even ifthe functional group is the highest priority. Do not worry about the tables and asterisks, as the next part wll be a walkthrough of how to actually use the table above. PART 5. IUPAC NOMENCLATURE DIVIDED BY ORGANIC CLASS ‘A. NOMENCLATURE OF ALKANES AND ALKYL HALIDES Alkanes, agreeably the simplest of all organic compounds are those which contain purely only carbon and hydrogen atoms, all connected through single bonds. NAMING ALKANES 1. The substituent alkanes use the prefix corresponding to the carbon chain length plus the suffixyl, written with their corresponding locant. 2. The parent is written after substituents are chronologically arranged, by use of the prefix gto the carbon chain length plus the 3. For cyclic alkanes as well as alkenes and alkynes, the prefix cyclo- will simply be added. Figure P2. Methane aa Figure P3. 3-methylpentane 's Figure Pa. Methyleyclohexane SLRM2013 | 5Aly! Halides are alkanes with halides as substituents. The only additional naming rule is that the halides use the following substituent names: C. NOMENCLATURE OF AMINES Amines are organic compounds which contain an a group (-NH,) attached to the parent. Table P6. Prefixes for halides substituents. “Ns er Figure P5. 1-bromopropane & r HC —GH F Figure P6. 1,1-difluoroethane B. NOMENCLATURE OF ALKENES AND ALKYNES Alkenes differ only from alkanes in that there is at least fone carbon-carbon double bond, the functional group corresponding to this class of organic compounds. NAMING ALKENES 1. Follow asin alkanes. 2. Replace-ane with suffix, preceded by the locant for the double bond. 3. If there isa triple bond, the suffix for the triple bond is the ultimate suffix of the parent chain, with the ~ene suffix being trimmed to -8f-. “N\ CHC=CHCHCH, Figure P8. Penta-1,2-diene & ‘Alkynes only differ from alkanes in that there is at least ‘one carbon-carbon triple bond, the functional group corresponding to this class of organic compounds. NAMING ALKYNES 1. Follow asin alkanes. 2. The sufi ofthe parent chain must use the sufix~ ‘ne, preceded by the locant forthe triple bond 3. there is a double bond, the Bi wil preva asthe ultimate suffix ofthe parent chain W.CC=CHCACH, aCCR=ChC=Ccn, Figure P10. Hex-2-en-4-yne 1. If there are any carbon chains attached to the nitrogen other than the parent, label them as substituent with the locant designated the letter Ne. In this, Mis treated as a number. 2. Write the parent chain, changing the suffix from ~ ane to’ Halide Substituent Name NAMING AMINES F Fluoro- a Chloro- Br Bromo- i odo. N \ Figure P11. N-ethyl-N-methylbutan-1-amine D. NOMENCLATURE OF ALCOHOLS, THIOLS AND. PHENOLS Alcohols are organic compounds which contain at least fone hydroxyl group (-OH) attached to an aliphatic chain (aliphatic and aromatic compounds discussed more on Proper 5). Phenols are organic compounds with at least fone hydroxy! group attached to an aliphatic chain and ‘may also refer to the compound hydroxybenzene. Thiols are actually the sulfur analogs (or version) of alcohols, and instead of a hydroxyl group, the thiol or mercapto (- SH) group is attached. NAMING ALCOHOLS AND THIOLS 1) Follow as in alkanes. 2a) The suffic must be changed from ane to Hl with the corresponding loca. JN on Figure P12. Butan-1-o! 2b) The suc must be changed from -ane to ER, with the corresponding locant. oH Figure P13. Butone-2-thiol ‘Naming substituent hydroxyls and thiols 1) Follow asin alkanes 2a) Use the substituent name FOR tached tothe parent name. 6 i He Cyoy Ou Figure P24. 2-hydroxyethancc acid 2b) Use the substituent name MGB. attached to the parent name. SLRM2013 | 6Figure P15. 2-mercoptoethanoic acid NAMING PHENOLS 1) Name the substituents outside the hydroxy! group of the aromatic rng. 2). Use phenolexclusively as the suffix oF x Ch, Figure P16, 3-methylpheno! oF E, NOMENCLATURE OF ETHERS AND SULFIDES Ethers are organic compounds with an alkoxy functional group (-OR), one where an oxygen is attached to a carbon chain other than the parent. Sulfides are organic compounds with the alkylthio functional group, the sulfur analogs of ethers. mM th nd_alkylthio groups alw: turn out as prefixes in the name (and are never suffixed NAMING ETHERS AND SULFIDES 1) Follow as in alkanes. 2a) Indicate the presence ofthe alkoxy group by using the carbon length istiefeiowed by EB 2b) Indicate the presence of the alkylthio group by using the carbon length prfifollowed by Sti. 2} Indicate the parent chain ve 0. ~ CH Figure P18. 2-methoxybutane Sxcu, Figure P19. 2-methylthiobutane “ S™ On Figure P20. 3-ethylthio-2-methylthioheptane Chemistry Review Group F, NOMENCLATURE OF KETONES AND ALDEHYDES Ketones are organic compounds with the carbonyl ( functional group, 9 carbon double bonded to an oxygen. Aldehydes are organic compounds with the formyl (CHO) functional group, a carbonyl group attached to @ hydrogen. Note that the formyl group requires three bonds other than the parent, and wl always be terminal ) IMPORTANT NOTE: In terminal groups, the suffix used is different when they are used in linear/acyclic parents and when they are used in cyclic parents. NAMING KETONES 1. Follow as in alkanes 2. Change the suc rom ane to BG, with the corresponding locant O Figure P21, Pentan-2-one Naming carbonyl as substituent 1. Follow asin alkanes 2. Indicate presence of carbonyl group by using the prefix 3. Indicate parent chain ok NAMING ALDEHYDES 1) Because the formyl group is terminal, assign the formyl caroon the locant number 2) indicate all substituents 3} Change the sufi from ane tol without nyore the locant. 9° \ + ow Figure P23. 2-hydroxyheptanal 4). Cyclicaldehydes use the sux BeaSaIgGhae instead, without removal of the ~ane. ° . 4 oh Figure P24, 2-hydroxycyclohexanecarbaldehyde Naming formyl a5 substituent 1. Follow ain akanes 2. indicate presence of formyl group by using the prefix Bx: 3. Indicate parent chai, SLRM2013 | 7o Oo AA H On Figure P25. Hoxopropancic acid G. NOMENCLATURE OF CARBOXYLIC ACIDS AND ITS DERIVATIVES Carboxylic acids are organic compounds with the carboxyl functional group (-COOH|), a earbonyi-hydroxy! functional group. The carboxylic acid derivatives are those which can be produced with the carboxylic acid as starting material, and may not necessarily always show a functional group similar to a carboxy © Amides are carboxylic acid derivatives with the ‘carbamoyl (CONH,) functional group. © Acid halides are carboxylic acid derivatives with the halocarbonyl (COX) functional group. © Esters and thioesters are carboxylic acid derivatives with the alkoxycarbonyl (COOR) and alkylthiocarbonyl (COSR) group, respectively. ‘= Acid anhydrides are carboxylic acid derivatives wherein two carboxylic acids are bonded to ‘each other through an oxygen atom. ‘© Nitriles are carboxylic acid derivatives with a cyano or carbonitrle group (CN). Because carboxylic acids or their derivatives are usually the highest priority group in a compound, their nomenclature as substituents will not anymore be discussed. NAMING CARBOXYLIC ACIDS 1. Follow asin alkanes. 2. Change the suffi from -ane to GiGi, without any more using the locant 0 \ OW ow Figure P26. 2-hydroxyheptanoic acid 3. Cyclic carboxylic acids use the suffix carboxylic acid instead, ° on ‘On Figure P27. 2-hydroxycyclohexanecarboxylic acid NAMING AMIDES 1. If there are any carbon chains attached to N, name as ifnaming amines. 2, Follow asin alkanes for the parent chai 3. Change the suffix from —ane to chemist Review cup @) 0 W HC Cy | Figure P28. N-methylethanamide 4. Gycic amides use the suff HERBGHAREnstead without removal of the -ane. NCH, Figure P29. N-methylcyclobutanecarboxamide NAMING ACID HALIDES 1. Follows in alkanes. 2. Change the suffix from -ane to BOGS 0 Figure P30. Butanoy! chloride Cycle acd halides use the suffix RRBSRVNAS instead, ° 1’ Figure P31. 4-hydroxycyclohexanecarbonyl bromide NAMING ESTERS AND THIOESTERS 1. Teeat the carbon chain connected to the single bonded oxygen as the substituent. 2. Treat the carbon chain connected to the carbonyl carbon as the parent. 3. ae the suffix of the parent from ~ane to Hat or respectively. oO Figure P32. Ethyl propanoate A 3 Figure P33. Ethyl proponethioate 4. Cyclic esters and thioesters use suffixes SPESR/aRS and EESPDGRRGHRSnsteod without removal of — o AX Figure P34, Ethyl cyclopropanecarborylate SLRM2013 | 8° ° Oo or 0A>N iS Figure P35. Ethycyclopropanecorbotholate Figure P38. Glohexonyl butyl carboxyle anhydride NAMING ACID ANHYDRIDES: NAMING NITRILES 1. Ifthe two chains are of same identity, ust identify 1, Follow asin alkanes. one and change the suffix from -ane to=ole 2. Change the suffix from ane to C=N o Oo AA pH. Y Figure P39, 2-hydroxybutanenitrle Figure P36. Propanoic anhydride vero ; 3. Cyclic nities use the sufi ERSSTAATRsteod ifthe two chains are of cifferent identity, identify eee both, change their suffixes from —ane to Sigand fitout a end with the word anivdid, on Oo Oo Paw oy CEN Figure P40, 2-bydroxycyclobutanecarbonitile Figure P37. Ethanoic methanoic anhydride 3. Cyclic anhydrides use the sufi SER stead. SLRM2013 | 9istry Review Group PROPERTIES OF ORGANIC COMPOUNDS ARISING FROM STRUCTURE ‘Organic Chemistry is not without properties specific for its discussion. The following are terms that describe an organic compound based on their structure alone (and not their function or innate chemical properties). Property Classification of the property Example Ring closure/ being cyclic | Linear compounds — no rin Carbocyclic compounds are those whose ring consists entirely of carbon. Tieterocyli compounds are those whose _~ rring consists of at least one atom other N than carbon (aka heteroatom). 0 Saturation refers tothe | Saturated —no wasted double or tiple q saturation ofcontent of | bond (wasted instea of being used to p hhydrogen atoms in the | bond to hydrogen) y—C —C-# compound ro4 How Unsaturated = double or tiple bond = exists and wastes maximum bonding with H-C =C-# more hydrogens. “Multiple double bond | Conjugated - theres exactly one single pattern — how many bond in between two or more double ZN J" single bonds separate | bonds. ‘two double bonds? Isolated there is more than one single bond between the two double bonds. ‘Cumulated — there is no single bond inbetween the two double bonds Zw References 1) Campbell, M., Farell, S.(2012). Biochemistry 7” Edition. Belmont, CA: Thomson Brooks/Cole. 2) McMurry J. 2011). Fundamentals of Organic Chemistry 7” Ealtion. Belmont, CA: Brooks/Cole. 3) Brown, W., Poon, T. (2011). Introduction to Organic Chemistry 4” Edition, New York: John Wiley & Sons. 4) Whitten et al. (2010). Chemistry 8” Edition. Belmont, CA: Brooks/Cole. 5) Boyer, R. (2006). Concepts in Biochemistry 3” Edition. New York: John Wiley & Sons. 6) Brown, T.L., LeMay, H.E,, Bursten, B.E. (2004). Chemistry: The Central Science Ninth Edition. San Francisco: Pearson Education, Inc. 7) Ouelette, RJ. (1994). Organic Chemistry: A Brief Introduction. New York: Macmillan, Inc. SLRM2013 | 10