{"id":563,"date":"2017-10-04T20:59:03","date_gmt":"2017-10-04T20:59:03","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/suny-mcc-organicchemistry\/?post_type=chapter&#038;p=563"},"modified":"2018-10-03T17:27:47","modified_gmt":"2018-10-03T17:27:47","slug":"introduction-to-cycloalkanes","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/suny-mcc-organicchemistry\/chapter\/introduction-to-cycloalkanes\/","title":{"raw":"Introduction to Cycloalkanes","rendered":"Introduction to Cycloalkanes"},"content":{"raw":"<div class=\"elm-header\"><\/div>\r\n<div id=\"elm-main-content\" class=\"elm-content-container\">\r\n<div>\r\n<div id=\"skills\">\r\n<div class=\"textbox learning-objectives\">\r\n<h3>Objectives<\/h3>\r\nAfter completing this section, you should be able to\r\n<ol>\r\n \t<li>determine whether or not a compound is chiral, given its Kelul\u00e9, condensed or shorthand structure, with or without the aid of molecular models.<\/li>\r\n \t<li>label the chiral centres (carbon atoms) in a given Kelul\u00e9, condensed or shorthand structure.<\/li>\r\n<\/ol>\r\n<\/div>\r\n<\/div>\r\n<div>\r\n<div class=\"textbox key-takeaways\">\r\n<h3>Key Terms<\/h3>\r\nMake certain that you can define, and use in context, the key terms below.\r\n<ul>\r\n \t<li>achiral<\/li>\r\n \t<li>chiral<\/li>\r\n \t<li>chiral (stereogenic) centre<\/li>\r\n \t<li>plane of symmetry<\/li>\r\n<\/ul>\r\n<\/div>\r\n<\/div>\r\nA consideration of the chirality of molecular configurations explains the curious stereoisomerism observed for <a title=\"Chirality\" rel=\"broken\">lactic acid, carvone<\/a> and a multitude of other organic compounds. Tetravalent carbons have a tetrahedral configuration. If all four substituent groups are the same, as in methane or tetrachloromethane, the configuration is that of a highly symmetric \"regular tetrahedron\". A regular tetrahedron several planes of symmetry and is achiral.\r\n\r\nA carbon atom that is bonded to four different atoms or groups loses all symmetry, and is often referred to as an asymmetric carbon. The configuration of such a molecular unit is chiral, and the structure may exist in either a right-handed configuration or a left-handed configuration (one the mirror image of the other). This type of configurational stereoisomerism is termed enantiomorphism, and the non-identical, mirror-image pair of stereoisomers that result are called enantiomers. In the general figure below, A and B are nonsuperposable mirror images of one another, and thus are a pair of enantiomers.\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205815\/image080.png\" alt=\"image080.png\" width=\"170px\" height=\"131px\" \/>\r\n\r\nThe structural formulas of lactic acid and carvone are drawn on the right with the asymmetric carbon colored red.\u00a0<img style=\"float: right;margin: 6px\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205817\/chirexp2.gif\" alt=\"image\" \/> Consequently, we find that these compounds exist as pairs of enantiomers. The presence of a single asymmetrically substituted carbon atom in a molecule is sufficient to render the whole configuration chiral, and modern terminology refers to such groupings as chiral centers. Most of the chiral centers we shall discuss are asymmetric carbon atoms, but it should be recognized that other tetrahedral or pyramidal atoms may become chiral centers if appropriately substituted. When more than one chiral center is present in a molecular structure, care must be taken to analyze their relationship before concluding that a specific molecular configuration is chiral or achiral. This aspect of stereoisomerism will be treated later.\r\n\r\nA useful first step in examining structural formulas to determine whether stereoisomers may exist is to identify all stereogenic elements. A stereogenic element is a center, axis or plane that is a focus of stereoisomerism, such that an interchange of two groups attached to this feature leads to a stereoisomer. Stereogenic elements may be chiral or achiral. An asymmetric carbon is often a chiral stereogenic center, since interchanging any two substituent groups converts one enantiomer to the other. Alkenes having two different groups on each double bond carbon constitute an achiral stereogenic element, since interchanging substituents at one of the carbons changes the cis\/trans configuration of the double bond.\r\n<p style=\"text-align: center\"><img id=\"prb1\" class=\"aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205819\/sterexp2.gif\" alt=\"image\" border=\"1\" \/><\/p>\r\nSome of the\u00a0 structures in the figure above are chiral and some are achiral. First, try to identify all chiral stereogenic centers. Formulas having no chiral centers are necessarily achiral. Formulas having one chiral center are always chiral; and if two or more chiral centers are present in a given structure it is likely to be chiral, but in special cases, to be discussed later, may be achiral.\r\n\r\nStructures F and G are achiral. The former has a plane of symmetry passing through the chlorine atom and bisecting the opposite carbon-carbon bond. The similar structure of compound E does not have such a symmetry plane, and the carbon bonded to the chlorine is a chiral center (the two ring segments connecting this carbon are not identical). Structure G is essentially flat. All the carbons except that of the methyl group are <em>sp<sup>2<\/sup><\/em> hybridized, and therefore trigonal-planar in configuration. Compounds C, D &amp; H have more than one chiral center, and are also chiral. Remember, all chiral structures may exist as a pair of enantiomers. Other configurational stereoisomers are possible if more than one stereogenic center is present in a structure.\r\n\r\nIn the 1960\u2019s, a drug called thalidomide was widely prescribed in the\u00a0Western Europe\u00a0to alleviate morning sickness in pregnant women.\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205821\/image074.png\" alt=\"image074.png\" width=\"219px\" height=\"152px\" \/>\r\n\r\nThalidomide had previously been used in other countries as an antidepressant, and was believed to be safe and effective for both purposes. The drug was not approved for use in the U.S.A. It was not long, however, before doctors realized that something had gone horribly wrong: many babies born to women who had taken thalidomide during pregnancy suffered from severe birth defects.\r\n\r\nResearchers later realized the that problem lay in the fact that thalidomide was being provided as a mixture of two different isomeric forms.\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205823\/image076.png\" alt=\"image076.png\" width=\"487px\" height=\"163px\" \/>\r\n\r\nOne of the isomers is an effective medication, the other caused the side effects. Both isomeric forms have the same molecular formula and the same atom-to-atom connectivity, so they are not constitutional isomers.\u00a0 Where they differ is in the arrangement in three-dimensional space about one tetrahedral, sp<sup>3<\/sup>-hybridized carbon.\u00a0 These two forms of thalidomide are <strong>stereoisomers<\/strong>.\r\n\r\nNote that the carbon in question has <em>four different substituents<\/em> (two of these just happen to be connected by a ring structure). Tetrahedral carbons with four different substituent groups are called <strong>stereocenters<\/strong>.\r\n<div>\r\n<div id=\"example\">\r\n<div class=\"textbox examples\">\r\n<h3>Example<\/h3>\r\n<div>Locate all of the carbon\u00a0stereocenters\u00a0in the molecules below.<\/div>\r\n<img class=\"internal default\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205825\/image078.png\" alt=\"image078.png\" width=\"602\" height=\"276\" \/>\r\n\r\n<a title=\"Organic Chemistry\/Organic Chemistry With a Biological Emphasis\/Solution Manual\/Chapter 3 Solutions\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry_Textbook_Maps\/Map%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)\/Solution_Manual\/Chapter_03_Solutions\" rel=\"internal\">Solution<\/a>\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<div>Looking at the structures of what we are referring to as the two isomers of thalidomide, you may not be entirely convinced that they are actually two different molecules.\u00a0 In order to convince ourselves that they are indeed different, let\u2019s create a generalized picture of a tetrahedral carbon stereocenter, with the four substituents designated R<sub>1<\/sub>-R<sub>4<\/sub>. The two stereoisomers of our simplified model look like this:<\/div>\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205828\/image080.png\" alt=\"image080.png\" width=\"243px\" height=\"187px\" \/>\r\n\r\nIf you look carefully at the figure above, you will notice that molecule A and molecule B are mirror images of each other (the line labeled 's' represents a mirror plane).\u00a0 Furthermore, <em>they are not superimposable<\/em>: if we pick up molecule A, flip it around, and place it next to molecule B, we see that the two structures cannot be superimposed on each other.\u00a0 They are different molecules!\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205830\/image082.png\" alt=\"image082.png\" width=\"217px\" height=\"127px\" \/>\r\n\r\nIf you make models of the two stereoisomers of thalidomide and do the same thing, you will see that they too are mirror images, and cannot be superimposed (it well help to look at a color version of the figure below).\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205833\/image084.png\" alt=\"image084.png\" width=\"479px\" height=\"287px\" \/>\r\n\r\nThalidomide is a <strong>chiral<\/strong> molecule.\u00a0 Something is considered to be chiral if it cannot be superimposed on its own mirror image \u2013 in other words, if it is <strong>asymmetric <\/strong>(lacking in symmetry). The term \u2018chiral\u2019 is derived from the Greek word for \u2018handedness\u2019 \u2013 ie. right-handedness or left-handedness.\u00a0 Your hands are chiral: your right hand is a mirror image of your left hand, but if you place one hand on top of the other, both palms down, you see that they are not superimposable.\r\n\r\nA pair of stereoisomers that are non-superimposable mirror images of one another are considered to have a specific type of stereoisomeric relationship \u2013 they are a pair of <strong>enantiomers<\/strong>. Thalidomide exists as a pair of enantiomers. On the macro level, your left and right hands are also a pair of enantiomers.\r\n\r\nHere are some more examples of chiral molecules that exist as pairs of enantiomers.\u00a0 In each of these examples, there is a single stereocenter, indicated with an arrow.\u00a0 (Many molecules have more than one stereocenter, but we will get to that that a little later!)\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205836\/image086.png\" alt=\"image086.png\" width=\"588\" height=\"264\" \/>\r\n\r\nHere are some examples of molecules that are <strong>achiral<\/strong> (<em>not<\/em> chiral). Notice that none of these molecules has a stereocenter.\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205839\/image088.png\" alt=\"image088.png\" width=\"471\" height=\"313\" \/>\r\n\r\nIt is difficult to illustrate on the\u00a0 two dimensional page, but you will see if you build models of these achiral molecules that, in each case, there is at least one <strong>plane of symmetry<\/strong>, where one side of the plane is the mirror image of the other.\u00a0 Chirality is tied conceptually to the idea of asymmetry, and <em>any molecule that has a plane of symmetry cannot be chiral<\/em>. When looking for a plane of symmetry, however, we must consider all possible conformations that a molecule could adopt.\u00a0 Even a very simple molecule like ethane, for example, is asymmetric in many of its countless potential conformations \u2013 but it has obvious symmetry in both the eclipsed and staggered conformations, and for this reason it is achiral.\r\n\r\nLooking for planes of symmetry in a molecule is useful, but often difficult in practice.\u00a0 In most cases, the easiest way to decide whether a molecule is chiral or achiral is to look for one or more stereocenters - with a few rare exceptions (see section 3.7B), the general rule is that molecules with at least one stereocenter are chiral, and molecules with no stereocenters are achiral.\u00a0 Carbon stereocenters are also referred to quite frequently as <strong>chiral carbons<\/strong>.\r\n\r\nWhen evaluating a molecule for chirality, it is important to recognize that the question of whether or not the dashed\/solid wedge drawing convention is used is irrelevant.\u00a0 Chiral molecules are sometimes drawn without using wedges (although obviously this means that stereochemical information is being omitted). Conversely, wedges may be used on carbons that are not stereocenters \u2013 look, for example, at the drawings of glycine and citrate in the figure above.\u00a0 Just because you see dashed and solid wedges in a structure, do not automatically assume that you are looking at a stereocenter.\r\n\r\nOther elements in addition to carbon can be stereocenters.\u00a0 The phosphorus center of phosphate ion and organic phosphate esters, for example, is tetrahedral, and thus is potentially a stereocenter.\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205841\/image090.png\" alt=\"image090.png\" width=\"520px\" height=\"125px\" \/>\r\n\r\nWe will see in chapter 10 how researchers, in order to investigate the stereochemistry of reactions at the phosphate center, incorporated sulfur and\/or <sup>17<\/sup>O and <sup>18<\/sup>O isotopes of oxygen (the \u2018normal\u2019 isotope is <sup>16<\/sup>O) to create chiral phosphate groups. Phosphate triesters are chiral if the three substituent groups are different.\r\n\r\nAsymmetric quaternary ammonium groups are also chiral.\u00a0 Amines, however, are not chiral, because they rapidly invert, or turn \u2018inside out\u2019, at room temperature.\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205844\/image092.png\" alt=\"image092.png\" width=\"470px\" height=\"194px\" \/>\r\n<div>\r\n<div class=\"textbox examples\">\r\n<h3>Example<\/h3>\r\n<div>Label the molecules below as\u00a0chiral\u00a0or\u00a0achiral, and locate all\u00a0stereocenters.<\/div>\r\n<img class=\"internal default\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205846\/image094.png\" alt=\"image094.png\" width=\"527\" height=\"309\" \/>\r\n\r\n<a title=\"Organic Chemistry\/Organic Chemistry With a Biological Emphasis\/Solution Manual\/Chapter 3 Solutions\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry_Textbook_Maps\/Map%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)\/Solution_Manual\/Chapter_03_Solutions\" rel=\"internal\">Solution<\/a>\r\n\r\n<\/div>\r\n<\/div>\r\n<div id=\"section_1\">\r\n<div class=\"textbox exercises\">\r\n<h3>Exercises<\/h3>\r\n<div id=\"s61692\">\r\n<div id=\"section_5\">\r\n<h3 id=\"Questions-61692\">Question<\/h3>\r\n<strong>1.<\/strong>\r\n\r\nIdentify the chiral centers in each of the following:\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205849\/5.2.png\" alt=\"\" width=\"392px\" height=\"154px\" \/>\r\n\r\n<\/div>\r\n<div id=\"section_6\">\r\n<h3 id=\"Solutions-61692\">Solution<\/h3>\r\n[reveal-answer q=\"312974\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"312974\"]\r\n\r\n<b>1.\u00a0<\/b>\r\n\r\n<a class=\"thumb\" title=\"\" href=\"https:\/\/chem.libretexts.org\/@api\/deki\/files\/108715\/5.2_ans.png?revision=1\" rel=\"internal\"><img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205851\/5.2_ans.png\" alt=\"\" width=\"388px\" height=\"152px\" \/><\/a>\r\n\r\n[\/hidden-answer]\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<div id=\"s61692\"><\/div>\r\n<\/div>\r\n<div id=\"section_2\">\r\n<h3 class=\"editable\">Contributors<\/h3>\r\n<ul>\r\n \t<li><a class=\"external\" title=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" href=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" target=\"_blank\" rel=\"external nofollow noopener\">Dr. Dietmar Kennepohl<\/a> FCIC (Professor of Chemistry, <a class=\"external\" title=\"http:\/\/www.athabascau.ca\/\" href=\"http:\/\/www.athabascau.ca\/\" target=\"_blank\" rel=\"external nofollow noopener\">Athabasca University<\/a>)<\/li>\r\n \t<li>Prof. Steven Farmer (<a class=\"external\" title=\"http:\/\/www.sonoma.edu\" href=\"http:\/\/www.sonoma.edu\" target=\"_blank\" rel=\"external nofollow noopener\">Sonoma State University<\/a>)<\/li>\r\n \t<li>William Reusch, Professor Emeritus (<a class=\"external\" title=\"http:\/\/www.msu.edu\/\" href=\"http:\/\/www.msu.edu\/\" target=\"_blank\" rel=\"external nofollow noopener\">Michigan State U.<\/a>), <a class=\"external\" title=\"http:\/\/www.cem.msu.edu\/~reusch\/VirtualText\/intro1.htm\" href=\"http:\/\/www.cem.msu.edu\/%7Ereusch\/VirtualText\/intro1.htm\" target=\"_blank\" rel=\"external nofollow noopener\">Virtual Textbook of\u00a0Organic\u00a0Chemistry<\/a><\/li>\r\n \t<li><a title=\"Organic_Chemistry_With_a_Biological_Emphasis\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry_Textbook_Maps\/Map%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)\" rel=\"internal\">Organic Chemistry With a Biological Emphasis <\/a>by\u00a0<a class=\"external\" title=\"http:\/\/facultypages.morris.umn.edu\/~soderbt\/\" href=\"http:\/\/facultypages.morris.umn.edu\/%7Esoderbt\/\" target=\"_blank\" rel=\"external nofollow noopener\">Tim Soderberg<\/a>\u00a0(University of Minnesota, Morris)<\/li>\r\n \t<li>Jim Clark (<a class=\"external\" title=\"http:\/\/www.chemguide.co.uk\" href=\"http:\/\/www.chemguide.co.uk\" target=\"_blank\" rel=\"external nofollow noopener\">Chemguide.co.uk<\/a>)<\/li>\r\n<\/ul>\r\n<\/div>\r\n<\/div>\r\n<\/div>","rendered":"<div class=\"elm-header\"><\/div>\n<div id=\"elm-main-content\" class=\"elm-content-container\">\n<div>\n<div id=\"skills\">\n<div class=\"textbox learning-objectives\">\n<h3>Objectives<\/h3>\n<p>After completing this section, you should be able to<\/p>\n<ol>\n<li>determine whether or not a compound is chiral, given its Kelul\u00e9, condensed or shorthand structure, with or without the aid of molecular models.<\/li>\n<li>label the chiral centres (carbon atoms) in a given Kelul\u00e9, condensed or shorthand structure.<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<div>\n<div class=\"textbox key-takeaways\">\n<h3>Key Terms<\/h3>\n<p>Make certain that you can define, and use in context, the key terms below.<\/p>\n<ul>\n<li>achiral<\/li>\n<li>chiral<\/li>\n<li>chiral (stereogenic) centre<\/li>\n<li>plane of symmetry<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<p>A consideration of the chirality of molecular configurations explains the curious stereoisomerism observed for <a title=\"Chirality\" rel=\"broken\">lactic acid, carvone<\/a> and a multitude of other organic compounds. Tetravalent carbons have a tetrahedral configuration. If all four substituent groups are the same, as in methane or tetrachloromethane, the configuration is that of a highly symmetric &#8220;regular tetrahedron&#8221;. A regular tetrahedron several planes of symmetry and is achiral.<\/p>\n<p>A carbon atom that is bonded to four different atoms or groups loses all symmetry, and is often referred to as an asymmetric carbon. The configuration of such a molecular unit is chiral, and the structure may exist in either a right-handed configuration or a left-handed configuration (one the mirror image of the other). This type of configurational stereoisomerism is termed enantiomorphism, and the non-identical, mirror-image pair of stereoisomers that result are called enantiomers. In the general figure below, A and B are nonsuperposable mirror images of one another, and thus are a pair of enantiomers.<\/p>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205815\/image080.png\" alt=\"image080.png\" width=\"170px\" height=\"131px\" \/><\/p>\n<p>The structural formulas of lactic acid and carvone are drawn on the right with the asymmetric carbon colored red.\u00a0<img decoding=\"async\" style=\"float: right;margin: 6px\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205817\/chirexp2.gif\" alt=\"image\" \/> Consequently, we find that these compounds exist as pairs of enantiomers. The presence of a single asymmetrically substituted carbon atom in a molecule is sufficient to render the whole configuration chiral, and modern terminology refers to such groupings as chiral centers. Most of the chiral centers we shall discuss are asymmetric carbon atoms, but it should be recognized that other tetrahedral or pyramidal atoms may become chiral centers if appropriately substituted. When more than one chiral center is present in a molecular structure, care must be taken to analyze their relationship before concluding that a specific molecular configuration is chiral or achiral. This aspect of stereoisomerism will be treated later.<\/p>\n<p>A useful first step in examining structural formulas to determine whether stereoisomers may exist is to identify all stereogenic elements. A stereogenic element is a center, axis or plane that is a focus of stereoisomerism, such that an interchange of two groups attached to this feature leads to a stereoisomer. Stereogenic elements may be chiral or achiral. An asymmetric carbon is often a chiral stereogenic center, since interchanging any two substituent groups converts one enantiomer to the other. Alkenes having two different groups on each double bond carbon constitute an achiral stereogenic element, since interchanging substituents at one of the carbons changes the cis\/trans configuration of the double bond.<\/p>\n<p style=\"text-align: center\"><img decoding=\"async\" id=\"prb1\" class=\"aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205819\/sterexp2.gif\" alt=\"image\" border=\"1\" \/><\/p>\n<p>Some of the\u00a0 structures in the figure above are chiral and some are achiral. First, try to identify all chiral stereogenic centers. Formulas having no chiral centers are necessarily achiral. Formulas having one chiral center are always chiral; and if two or more chiral centers are present in a given structure it is likely to be chiral, but in special cases, to be discussed later, may be achiral.<\/p>\n<p>Structures F and G are achiral. The former has a plane of symmetry passing through the chlorine atom and bisecting the opposite carbon-carbon bond. The similar structure of compound E does not have such a symmetry plane, and the carbon bonded to the chlorine is a chiral center (the two ring segments connecting this carbon are not identical). Structure G is essentially flat. All the carbons except that of the methyl group are <em>sp<sup>2<\/sup><\/em> hybridized, and therefore trigonal-planar in configuration. Compounds C, D &amp; H have more than one chiral center, and are also chiral. Remember, all chiral structures may exist as a pair of enantiomers. Other configurational stereoisomers are possible if more than one stereogenic center is present in a structure.<\/p>\n<p>In the 1960\u2019s, a drug called thalidomide was widely prescribed in the\u00a0Western Europe\u00a0to alleviate morning sickness in pregnant women.<\/p>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205821\/image074.png\" alt=\"image074.png\" width=\"219px\" height=\"152px\" \/><\/p>\n<p>Thalidomide had previously been used in other countries as an antidepressant, and was believed to be safe and effective for both purposes. The drug was not approved for use in the U.S.A. It was not long, however, before doctors realized that something had gone horribly wrong: many babies born to women who had taken thalidomide during pregnancy suffered from severe birth defects.<\/p>\n<p>Researchers later realized the that problem lay in the fact that thalidomide was being provided as a mixture of two different isomeric forms.<\/p>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205823\/image076.png\" alt=\"image076.png\" width=\"487px\" height=\"163px\" \/><\/p>\n<p>One of the isomers is an effective medication, the other caused the side effects. Both isomeric forms have the same molecular formula and the same atom-to-atom connectivity, so they are not constitutional isomers.\u00a0 Where they differ is in the arrangement in three-dimensional space about one tetrahedral, sp<sup>3<\/sup>-hybridized carbon.\u00a0 These two forms of thalidomide are <strong>stereoisomers<\/strong>.<\/p>\n<p>Note that the carbon in question has <em>four different substituents<\/em> (two of these just happen to be connected by a ring structure). Tetrahedral carbons with four different substituent groups are called <strong>stereocenters<\/strong>.<\/p>\n<div>\n<div id=\"example\">\n<div class=\"textbox examples\">\n<h3>Example<\/h3>\n<div>Locate all of the carbon\u00a0stereocenters\u00a0in the molecules below.<\/div>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205825\/image078.png\" alt=\"image078.png\" width=\"602\" height=\"276\" \/><\/p>\n<p><a title=\"Organic Chemistry\/Organic Chemistry With a Biological Emphasis\/Solution Manual\/Chapter 3 Solutions\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry_Textbook_Maps\/Map%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)\/Solution_Manual\/Chapter_03_Solutions\" rel=\"internal\">Solution<\/a><\/p>\n<\/div>\n<\/div>\n<\/div>\n<div>Looking at the structures of what we are referring to as the two isomers of thalidomide, you may not be entirely convinced that they are actually two different molecules.\u00a0 In order to convince ourselves that they are indeed different, let\u2019s create a generalized picture of a tetrahedral carbon stereocenter, with the four substituents designated R<sub>1<\/sub>-R<sub>4<\/sub>. The two stereoisomers of our simplified model look like this:<\/div>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205828\/image080.png\" alt=\"image080.png\" width=\"243px\" height=\"187px\" \/><\/p>\n<p>If you look carefully at the figure above, you will notice that molecule A and molecule B are mirror images of each other (the line labeled &#8216;s&#8217; represents a mirror plane).\u00a0 Furthermore, <em>they are not superimposable<\/em>: if we pick up molecule A, flip it around, and place it next to molecule B, we see that the two structures cannot be superimposed on each other.\u00a0 They are different molecules!<\/p>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205830\/image082.png\" alt=\"image082.png\" width=\"217px\" height=\"127px\" \/><\/p>\n<p>If you make models of the two stereoisomers of thalidomide and do the same thing, you will see that they too are mirror images, and cannot be superimposed (it well help to look at a color version of the figure below).<\/p>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205833\/image084.png\" alt=\"image084.png\" width=\"479px\" height=\"287px\" \/><\/p>\n<p>Thalidomide is a <strong>chiral<\/strong> molecule.\u00a0 Something is considered to be chiral if it cannot be superimposed on its own mirror image \u2013 in other words, if it is <strong>asymmetric <\/strong>(lacking in symmetry). The term \u2018chiral\u2019 is derived from the Greek word for \u2018handedness\u2019 \u2013 ie. right-handedness or left-handedness.\u00a0 Your hands are chiral: your right hand is a mirror image of your left hand, but if you place one hand on top of the other, both palms down, you see that they are not superimposable.<\/p>\n<p>A pair of stereoisomers that are non-superimposable mirror images of one another are considered to have a specific type of stereoisomeric relationship \u2013 they are a pair of <strong>enantiomers<\/strong>. Thalidomide exists as a pair of enantiomers. On the macro level, your left and right hands are also a pair of enantiomers.<\/p>\n<p>Here are some more examples of chiral molecules that exist as pairs of enantiomers.\u00a0 In each of these examples, there is a single stereocenter, indicated with an arrow.\u00a0 (Many molecules have more than one stereocenter, but we will get to that that a little later!)<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205836\/image086.png\" alt=\"image086.png\" width=\"588\" height=\"264\" \/><\/p>\n<p>Here are some examples of molecules that are <strong>achiral<\/strong> (<em>not<\/em> chiral). Notice that none of these molecules has a stereocenter.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205839\/image088.png\" alt=\"image088.png\" width=\"471\" height=\"313\" \/><\/p>\n<p>It is difficult to illustrate on the\u00a0 two dimensional page, but you will see if you build models of these achiral molecules that, in each case, there is at least one <strong>plane of symmetry<\/strong>, where one side of the plane is the mirror image of the other.\u00a0 Chirality is tied conceptually to the idea of asymmetry, and <em>any molecule that has a plane of symmetry cannot be chiral<\/em>. When looking for a plane of symmetry, however, we must consider all possible conformations that a molecule could adopt.\u00a0 Even a very simple molecule like ethane, for example, is asymmetric in many of its countless potential conformations \u2013 but it has obvious symmetry in both the eclipsed and staggered conformations, and for this reason it is achiral.<\/p>\n<p>Looking for planes of symmetry in a molecule is useful, but often difficult in practice.\u00a0 In most cases, the easiest way to decide whether a molecule is chiral or achiral is to look for one or more stereocenters &#8211; with a few rare exceptions (see section 3.7B), the general rule is that molecules with at least one stereocenter are chiral, and molecules with no stereocenters are achiral.\u00a0 Carbon stereocenters are also referred to quite frequently as <strong>chiral carbons<\/strong>.<\/p>\n<p>When evaluating a molecule for chirality, it is important to recognize that the question of whether or not the dashed\/solid wedge drawing convention is used is irrelevant.\u00a0 Chiral molecules are sometimes drawn without using wedges (although obviously this means that stereochemical information is being omitted). Conversely, wedges may be used on carbons that are not stereocenters \u2013 look, for example, at the drawings of glycine and citrate in the figure above.\u00a0 Just because you see dashed and solid wedges in a structure, do not automatically assume that you are looking at a stereocenter.<\/p>\n<p>Other elements in addition to carbon can be stereocenters.\u00a0 The phosphorus center of phosphate ion and organic phosphate esters, for example, is tetrahedral, and thus is potentially a stereocenter.<\/p>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205841\/image090.png\" alt=\"image090.png\" width=\"520px\" height=\"125px\" \/><\/p>\n<p>We will see in chapter 10 how researchers, in order to investigate the stereochemistry of reactions at the phosphate center, incorporated sulfur and\/or <sup>17<\/sup>O and <sup>18<\/sup>O isotopes of oxygen (the \u2018normal\u2019 isotope is <sup>16<\/sup>O) to create chiral phosphate groups. Phosphate triesters are chiral if the three substituent groups are different.<\/p>\n<p>Asymmetric quaternary ammonium groups are also chiral.\u00a0 Amines, however, are not chiral, because they rapidly invert, or turn \u2018inside out\u2019, at room temperature.<\/p>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205844\/image092.png\" alt=\"image092.png\" width=\"470px\" height=\"194px\" \/><\/p>\n<div>\n<div class=\"textbox examples\">\n<h3>Example<\/h3>\n<div>Label the molecules below as\u00a0chiral\u00a0or\u00a0achiral, and locate all\u00a0stereocenters.<\/div>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205846\/image094.png\" alt=\"image094.png\" width=\"527\" height=\"309\" \/><\/p>\n<p><a title=\"Organic Chemistry\/Organic Chemistry With a Biological Emphasis\/Solution Manual\/Chapter 3 Solutions\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry_Textbook_Maps\/Map%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)\/Solution_Manual\/Chapter_03_Solutions\" rel=\"internal\">Solution<\/a><\/p>\n<\/div>\n<\/div>\n<div id=\"section_1\">\n<div class=\"textbox exercises\">\n<h3>Exercises<\/h3>\n<div id=\"s61692\">\n<div id=\"section_5\">\n<h3 id=\"Questions-61692\">Question<\/h3>\n<p><strong>1.<\/strong><\/p>\n<p>Identify the chiral centers in each of the following:<\/p>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205849\/5.2.png\" alt=\"\" width=\"392px\" height=\"154px\" \/><\/p>\n<\/div>\n<div id=\"section_6\">\n<h3 id=\"Solutions-61692\">Solution<\/h3>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q312974\">Show Answer<\/span><\/p>\n<div id=\"q312974\" class=\"hidden-answer\" style=\"display: none\">\n<p><b>1.\u00a0<\/b><\/p>\n<p><a class=\"thumb\" title=\"\" href=\"https:\/\/chem.libretexts.org\/@api\/deki\/files\/108715\/5.2_ans.png?revision=1\" rel=\"internal\"><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1518\/2017\/10\/04205851\/5.2_ans.png\" alt=\"\" width=\"388px\" height=\"152px\" \/><\/a><\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"s61692\"><\/div>\n<\/div>\n<div id=\"section_2\">\n<h3 class=\"editable\">Contributors<\/h3>\n<ul>\n<li><a class=\"external\" title=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" href=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" target=\"_blank\" rel=\"external nofollow noopener\">Dr. Dietmar Kennepohl<\/a> FCIC (Professor of Chemistry, <a class=\"external\" title=\"http:\/\/www.athabascau.ca\/\" href=\"http:\/\/www.athabascau.ca\/\" target=\"_blank\" rel=\"external nofollow noopener\">Athabasca University<\/a>)<\/li>\n<li>Prof. Steven Farmer (<a class=\"external\" title=\"http:\/\/www.sonoma.edu\" href=\"http:\/\/www.sonoma.edu\" target=\"_blank\" rel=\"external nofollow noopener\">Sonoma State University<\/a>)<\/li>\n<li>William Reusch, Professor Emeritus (<a class=\"external\" title=\"http:\/\/www.msu.edu\/\" href=\"http:\/\/www.msu.edu\/\" target=\"_blank\" rel=\"external nofollow noopener\">Michigan State U.<\/a>), <a class=\"external\" title=\"http:\/\/www.cem.msu.edu\/~reusch\/VirtualText\/intro1.htm\" href=\"http:\/\/www.cem.msu.edu\/%7Ereusch\/VirtualText\/intro1.htm\" target=\"_blank\" rel=\"external nofollow noopener\">Virtual Textbook of\u00a0Organic\u00a0Chemistry<\/a><\/li>\n<li><a title=\"Organic_Chemistry_With_a_Biological_Emphasis\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry_Textbook_Maps\/Map%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)\" rel=\"internal\">Organic Chemistry With a Biological Emphasis <\/a>by\u00a0<a class=\"external\" title=\"http:\/\/facultypages.morris.umn.edu\/~soderbt\/\" href=\"http:\/\/facultypages.morris.umn.edu\/%7Esoderbt\/\" target=\"_blank\" rel=\"external nofollow noopener\">Tim Soderberg<\/a>\u00a0(University of Minnesota, Morris)<\/li>\n<li>Jim Clark (<a class=\"external\" title=\"http:\/\/www.chemguide.co.uk\" href=\"http:\/\/www.chemguide.co.uk\" target=\"_blank\" rel=\"external nofollow noopener\">Chemguide.co.uk<\/a>)<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"author":311,"menu_order":10,"template":"","meta":{"_candela_citation":"[]","CANDELA_OUTCOMES_GUID":"","pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":[],"pb_section_license":""},"chapter-type":[],"contributor":[],"license":[],"class_list":["post-563","chapter","type-chapter","status-publish","hentry"],"part":21,"_links":{"self":[{"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-organicchemistry\/wp-json\/pressbooks\/v2\/chapters\/563","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-organicchemistry\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-organicchemistry\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-organicchemistry\/wp-json\/wp\/v2\/users\/311"}],"version-history":[{"count":5,"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-organicchemistry\/wp-json\/pressbooks\/v2\/chapters\/563\/revisions"}],"predecessor-version":[{"id":2247,"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-organicchemistry\/wp-json\/pressbooks\/v2\/chapters\/563\/revisions\/2247"}],"part":[{"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-organicchemistry\/wp-json\/pressbooks\/v2\/parts\/21"}],"metadata":[{"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-organicchemistry\/wp-json\/pressbooks\/v2\/chapters\/563\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-organicchemistry\/wp-json\/wp\/v2\/media?parent=563"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-organicchemistry\/wp-json\/pressbooks\/v2\/chapter-type?post=563"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-organicchemistry\/wp-json\/wp\/v2\/contributor?post=563"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-organicchemistry\/wp-json\/wp\/v2\/license?post=563"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}