e o se CHAPTER 14 ORGANOMETALLIC COMPOUNDS O rganometallic compounds are compounds that have a carbon-metal bond; they lie at the place where organic and inorganic chemistry meet. You are already familiar with at least one organometallic compound, sodium acetylide NaC=CH), which has an ionic bond between carbon and sodium. But just because a compound contains both a metal and carbon isnt enough to classify it as organometal lic. Like sodium acetylide, sodium methoxide(NaOCH3) is an ionic compound. Unlike odium acetylide, however, the negative charge in sodium methoxide resides on oxygen, not carbol Na: OCH3 Sodium acetylide Sodium methoxide (has a carbon-to-metal bond)(does not have a carbon-to-metal bond) The properties of organometallic compounds are much different from those of the other classes we have studied to this point. Most important, many organometallic com- pounds are powerful sources of nucleophilic carbon, something that makes them espe- cially valuable to the synthetic organic chemist. For example, the preparation of alkynes by the reaction of sodium acetylide with alkyl halides(Section 9.6)depends on the pres ence of a negatively charged, nucleophilic carbon in acetylide ion Synthetic procedures that use organometallic reagents are among the most impor- tant methods for carbon-carbon bond formation in organic chemistry. In this chapter you will learn how to prepare organic derivatives of lithium, magnesium, copper, and zinc and see how their novel properties can be used in organic synthesis. We will also finish the tory of polyethylene and polypropylene begun in Chapter 6 and continued in Chapter 7 to see the unique way that organometallic compounds catalyze alkene polymerization. Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
CHAPTER 14 ORGANOMETALLIC COMPOUNDS Organometallic compounds are compounds that have a carbon–metal bond; they lie at the place where organic and inorganic chemistry meet. You are already familiar with at least one organometallic compound, sodium acetylide (NaCPCH), which has an ionic bond between carbon and sodium. But just because a compound contains both a metal and carbon isn’t enough to classify it as organometallic. Like sodium acetylide, sodium methoxide (NaOCH3) is an ionic compound. Unlike sodium acetylide, however, the negative charge in sodium methoxide resides on oxygen, not carbon. The properties of organometallic compounds are much different from those of the other classes we have studied to this point. Most important, many organometallic compounds are powerful sources of nucleophilic carbon, something that makes them especially valuable to the synthetic organic chemist. For example, the preparation of alkynes by the reaction of sodium acetylide with alkyl halides (Section 9.6) depends on the presence of a negatively charged, nucleophilic carbon in acetylide ion. Synthetic procedures that use organometallic reagents are among the most important methods for carbon–carbon bond formation in organic chemistry. In this chapter you will learn how to prepare organic derivatives of lithium, magnesium, copper, and zinc and see how their novel properties can be used in organic synthesis. We will also finish the story of polyethylene and polypropylene begun in Chapter 6 and continued in Chapter 7 to see the unique way that organometallic compounds catalyze alkene polymerization. Sodium acetylide (has a carbon-to-metal bond) Na CPCH Sodium methoxide (does not have a carbon-to-metal bond) Na OCH3 546 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
14.2 Carbon-Metal Bonds in Organometallic Compounds 14.1 ORGANOMETALLIC NOMENCLATURE Organometallic compounds are named as substituted derivatives of metals. The metal is the base name, and the attached alkyl groups are identified by the appropriate prefix. CHa=CHNa (CH;CH2)2Mg H Cyclopropyllithiur Im Dieth Magnesiun When the metal bears a substituent other than carbon. the substituent is treated as if it were an anion and named separately Igl (CH3CH,)2AICI hy magnesium iodide Diethylaluminum chloride PROBLEM 14.1 Both of the following organometallic reagents will be encoun- tered later in this chapter. Suggest a suitable name for eacl (a)(ch3)3CLi SAMPLE SOLUTION (a) The metal lithium provides the base name for(CH3)aCLi The alkyl group to which lithium is bonded is tert-butyl, and so the name of this organometallic compound is tert-butylithium. An alternative, equally correct name is 1, 1-dimethylethyllithium An exception to this type of nomenclature is NaC=CH, which is normally referred to as sodium acetylide. Both sodium acetylide and ethynylsodium are acceptable IUPAC names 14.2 CARBON-METAL BONDS IN ORGANOMETALLIC COMPOUNDS With an electronegativity of 2.5(Table 14.1), carbon is neither strongly electropositive nor strongly electronegative. When carbon is bonded to an element more electronegative han itself, such as oxygen or chlorine, the electron distribution in the bond is polarized TABLE 14.1 Electronegativities of Some Representative Elements Element Electronegativity odNcH 3.0 3.0 2. 19 mAM 1.6 1.0 Na 0.9 0.8 Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
14.1 ORGANOMETALLIC NOMENCLATURE Organometallic compounds are named as substituted derivatives of metals. The metal is the base name, and the attached alkyl groups are identified by the appropriate prefix. When the metal bears a substituent other than carbon, the substituent is treated as if it were an anion and named separately. PROBLEM 14.1 Both of the following organometallic reagents will be encountered later in this chapter. Suggest a suitable name for each. (a) (CH3)3CLi (b) SAMPLE SOLUTION (a) The metal lithium provides the base name for (CH3)3CLi. The alkyl group to which lithium is bonded is tert-butyl, and so the name of this organometallic compound is tert-butylithium. An alternative, equally correct name is 1,1-dimethylethyllithium. An exception to this type of nomenclature is NaCPCH, which is normally referred to as sodium acetylide. Both sodium acetylide and ethynylsodium are acceptable IUPAC names. 14.2 CARBON–METAL BONDS IN ORGANOMETALLIC COMPOUNDS With an electronegativity of 2.5 (Table 14.1), carbon is neither strongly electropositive nor strongly electronegative. When carbon is bonded to an element more electronegative than itself, such as oxygen or chlorine, the electron distribution in the bond is polarized H MgCl CH3MgI Methylmagnesium iodide (CH3CH2)2AlCl Diethylaluminum chloride Li H Cyclopropyllithium CH2 CHNa Vinylsodium (CH3CH2)2Mg Diethylmagnesium 14.2 Carbon–Metal Bonds in Organometallic Compounds 547 TABLE 14.1 Electronegativities of Some Representative Elements Element F O Cl N C H Cu Zn Al Mg Li Na K 4.0 3.5 3.0 3.0 2.5 2.1 1.9 1.6 1.5 1.2 1.0 0.9 0.8 Electronegativity Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER FOURTEEN Organometallic Compounds so that carbon is slightly positive and the more electronegative atom is slightly negative Conversely, when carbon is bonded to a less electronegative element, such as a metal he electrons in the bond are more strongly attracted toward carbon than carbon than carbon igure 14.1 uses electrostatic potential maps to show how different the electron distri- bution is between methyl fluoride(CH3F) and methyllithium(CH3Li) An anion that contains a negatively charged carbon is referred to as a carbanion Covalently bonded organometallic compounds are said to have carbanionic character As the metal becomes more electropositive, the ionic character of the carbon-metal bond becomes more pronounced Organosodium and organopotassium compounds have ionic carbon-metal bonds; organolithium and organomagnesium compounds tend to have covalent, but rather polar, carbon-metal bonds with significant carbanionic character. It is the carbanionic character of such compounds that is responsible for their usefulness as synthetic reagents (a)Methyl fluoride FIGURE 14.1 Elect static potential maps b)methyllithium. The elec tron distribution is reversed n the two compounds. Car bon is electron-poor(blue)in methyl fluoride, but electron rich(red)in methyllithium (b) Methyllithium Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
so that carbon is slightly positive and the more electronegative atom is slightly negative. Conversely, when carbon is bonded to a less electronegative element, such as a metal, the electrons in the bond are more strongly attracted toward carbon. Figure 14.1 uses electrostatic potential maps to show how different the electron distribution is between methyl fluoride (CH3F) and methyllithium (CH3Li). An anion that contains a negatively charged carbon is referred to as a carbanion. Covalently bonded organometallic compounds are said to have carbanionic character. As the metal becomes more electropositive, the ionic character of the carbon–metal bond becomes more pronounced. Organosodium and organopotassium compounds have ionic carbon–metal bonds; organolithium and organomagnesium compounds tend to have covalent, but rather polar, carbon–metal bonds with significant carbanionic character. It is the carbanionic character of such compounds that is responsible for their usefulness as synthetic reagents. C M M is less electronegative than carbon C X X is more electronegative than carbon 548 CHAPTER FOURTEEN Organometallic Compounds (a) Methyl fluoride (b) Methyllithium FIGURE 14.1 Electrostatic potential maps of (a) methyl fluoride and of (b) methyllithium. The electron distribution is reversed in the two compounds. Carbon is electron-poor (blue) in methyl fluoride, but electronrich (red) in methyllithium. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
14.3 Preparation of Organolithium Compounds 14.3 PREPARATION OF ORGANOLITHIUM COMPOUNDS Before we describe the applications of organometallic reagents to organic synthesis, let us examine their preparation. Organolithium compounds and other Group I organometal lic compounds are prepared by the reaction of an alkyl halide with the appropriate metal alide with lithium was cited RX 2M RM +mtX arlier(Section 2. 16) Group I reduction Group I metals a organometallic halide owerful reducing agents. CHacCI 2Li →(CH3)3CLi+LiCl tert-Butyl chloride Lithium terl-Butyllithium Lithium (75%) chloride The alkyl halide can be primary, secondary, or tertiary. Alkyl iodides are the most reac tive, followed by bromides, then chlorides. Fluorides are relatively unreactive Unlike elimination and nucleophilic substitution reactions, formation of organo- lithium compounds does not require that the halogen be bonded to sp-hybridized carbon Compounds such as vinyl halides and aryl halides, in which the halogen is bonded to hybridized carbon, react in the same way as alkyl halides, but at somewhat slower rates >Br+2Li→ Li+ liBr Bromobenzene Lith Phenyllithium Lithium 95-99%) Organolithium compounds are sometimes prepared in hydrocarbon solvents such as pentane and hexane, but normally diethyl ether is used. It is especially important that the solvent be anhydrous. Even trace amounts of water or alcohols react with lithium to form insoluble lithium hydroxide or lithium alkoxides that coat the surface of the metal and prevent it from reacting with the alkyl halide. Furthermore, organolithium reagent are strong bases and react rapidly with even weak proton sources to form hydrocarbons We shall discuss this property of organolithium reagents in Section 14.5 PROBLEM 14.2 Write an equation showing the formation of each of the fol owing from the appropriate bromide SAMPLE SOLUTION (a) In the preparation of organolithium compounds from organic halides, lithium becomes bonded to the carbon that bore the halogen Therefore, isopropenyllithium must arise from isopropenyl bromide ether CH2=CCH3 2Li CH=CC Br Isopropenyl bromide Lithium Reaction with an alkyl halide takes place at the metal surface. In the first step, ar electron is transferred from the metal to the alkyl halide. R:X:+ L IR.X Alkyl halide Lithium Anion radical Lithium cation Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
14.3 PREPARATION OF ORGANOLITHIUM COMPOUNDS Before we describe the applications of organometallic reagents to organic synthesis, let us examine their preparation. Organolithium compounds and other Group I organometallic compounds are prepared by the reaction of an alkyl halide with the appropriate metal. The alkyl halide can be primary, secondary, or tertiary. Alkyl iodides are the most reactive, followed by bromides, then chlorides. Fluorides are relatively unreactive. Unlike elimination and nucleophilic substitution reactions, formation of organolithium compounds does not require that the halogen be bonded to sp3 -hybridized carbon. Compounds such as vinyl halides and aryl halides, in which the halogen is bonded to sp2 - hybridized carbon, react in the same way as alkyl halides, but at somewhat slower rates. Organolithium compounds are sometimes prepared in hydrocarbon solvents such as pentane and hexane, but normally diethyl ether is used. It is especially important that the solvent be anhydrous. Even trace amounts of water or alcohols react with lithium to form insoluble lithium hydroxide or lithium alkoxides that coat the surface of the metal and prevent it from reacting with the alkyl halide. Furthermore, organolithium reagents are strong bases and react rapidly with even weak proton sources to form hydrocarbons. We shall discuss this property of organolithium reagents in Section 14.5. PROBLEM 14.2 Write an equation showing the formation of each of the following from the appropriate bromide: (a) Isopropenyllithium (b) sec-Butyllithium SAMPLE SOLUTION (a) In the preparation of organolithium compounds from organic halides, lithium becomes bonded to the carbon that bore the halogen. Therefore, isopropenyllithium must arise from isopropenyl bromide. Reaction with an alkyl halide takes place at the metal surface. In the first step, an electron is transferred from the metal to the alkyl halide. Li Lithium Lithium cation Li Alkyl halide R X Anion radical [R ] X CH2œCCH3 W Br Isopropenyl bromide 2Li Lithium W Li CH2œCCH3 Isopropenyllithium LiBr Lithium bromide diethyl ether diethyl ether 35°C Br Bromobenzene 2Li Lithium Li Phenyllithium (95–99%) LiBr Lithium bromide RX Alkyl halide 2M Group I metal MX Metal halide RM Group I organometallic compound (CH3)3CCl tert-Butyl chloride 2Li Lithium LiCl Lithium chloride (CH3)3CLi tert-Butyllithium (75%) diethyl ether 30°C 14.3 Preparation of Organolithium Compounds 549 The reaction of an alkyl halide with lithium was cited earlier (Section 2.16) as an example of an oxidation– reduction. Group I metals are powerful reducing agents. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER FOURTEEN Organometallic Compounds Having gained one electron, the alkyl halide is now negatively charged and has an odd number of electrons. It is an anion radical. The extra electron occupies an antibonding orbital. This anion radical fragments to an alkyl radical and a halide anion Anion radical Alkyl radical Halide anion Following fragmentation, the alkyl radical rapidly combines with a lithium atom to form the organometallic compound Alkyl radical Lithium Alkyllithium 14.4 PREPARATION OF ORGANOMAGNESIUM COMPOUNDS GRIGNARD REAGENTS The most important organometallic reagents in organic chemistry are organomagnesium compounds. They are called Grignard reagents after the French chemist Victor Grignard. Grignard developed efficient methods for the preparation of organic deriva- tives of magnesium and demonstrated their application in the synthesis of alcohols. For these achievements he was a corecipient of the 1912 Nobel Prize in chemistry who as Grignard reagents are prepared from organic halides by reaction with magnesium, a group ll metal ed to cat- RMgx alkenes Organic halide Magnesium Organomagnesium halide (R may be methyl or primary, secondary, or tertiary alkyl; it may also be a cycloalkyl alkenyl, or aryl group. ○xM=○ Cyclohexyl chloride Magnesium Cyclohexylmagnesium chloride(96%) Bromobenzene Magnesium Phenylmagnesium bromide(95% Anhydrous diethyl ether is the customary solvent used when preparing organo- magnesium compounds. Sometimes the reaction does not begin readily, but once started, it is exothermic and maintains the temperature of the reaction mixture at the boiling point of diethyl ether(35°C) The order of halide reactivity is I> Br >Cl>F, and alkyl halides are more reac- tive than aryl and vinyl halides. Indeed, aryl and vinyl chlorides do not form Grignard Recall the structure of reagents in diethyl ether. When more vigorous reaction conditions are required, tetrahy tetrahydrofuran from Sec. drofuran(THF) is used as the solvent. CH,=CHCI CH,-CHMgCI Vinyl chloride Viny magnesium chloride(92%) Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Having gained one electron, the alkyl halide is now negatively charged and has an odd number of electrons. It is an anion radical. The extra electron occupies an antibonding orbital. This anion radical fragments to an alkyl radical and a halide anion. Following fragmentation, the alkyl radical rapidly combines with a lithium atom to form the organometallic compound. 14.4 PREPARATION OF ORGANOMAGNESIUM COMPOUNDS: GRIGNARD REAGENTS The most important organometallic reagents in organic chemistry are organomagnesium compounds. They are called Grignard reagents after the French chemist Victor Grignard. Grignard developed efficient methods for the preparation of organic derivatives of magnesium and demonstrated their application in the synthesis of alcohols. For these achievements he was a corecipient of the 1912 Nobel Prize in chemistry. Grignard reagents are prepared from organic halides by reaction with magnesium, a Group II metal. (R may be methyl or primary, secondary, or tertiary alkyl; it may also be a cycloalkyl, alkenyl, or aryl group.) Anhydrous diethyl ether is the customary solvent used when preparing organomagnesium compounds. Sometimes the reaction does not begin readily, but once started, it is exothermic and maintains the temperature of the reaction mixture at the boiling point of diethyl ether (35°C). The order of halide reactivity is I Br Cl F, and alkyl halides are more reactive than aryl and vinyl halides. Indeed, aryl and vinyl chlorides do not form Grignard reagents in diethyl ether. When more vigorous reaction conditions are required, tetrahydrofuran (THF) is used as the solvent. Mg THF, 60°C Vinyl chloride CH2 CHCl Vinylmagnesium chloride (92%) CH2 CHMgCl diethyl ether 35°C Cl H Cyclohexyl chloride Mg Magnesium H MgCl Cyclohexylmagnesium chloride (96%) diethyl ether 35°C Br Bromobenzene Mg Magnesium MgBr Phenylmagnesium bromide (95%) Organic halide RX Magnesium Mg Organomagnesium halide RMgX Alkyl radical R Lithium Li Alkyllithium R Li Alkyl radical R Halide anion X Anion radical [R ] X 550 CHAPTER FOURTEEN Organometallic Compounds Grignard shared the prize with Paul Sabatier, who, as was mentioned in Chapter 6, showed that finely divided nickel could be used to catalyze the hydrogenation of alkenes. Recall the structure of tetrahydrofuran from Section 3.15: O Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
14.5 Organolithium and Organomagnesium Compounds as bronsted Bases PROBLEM 14.3 Write the structure of the grignard reagent formed from each of the following compounds on reaction with magnesium in diethyl ether (a)p-Bromofluorobenzene (c)lodocyclobutane (b) Allyl chloride ( d) 1-Bromocyclohexene SAMPLE SOLUTION (a)Of the two halogen substituents on the aromatic ring , bromine reacts much faster than fluorine with magnesium. Therefore, fluorine is left intact on the ring while the carbon-bromine bond is converted to a car- bon-magnesium bond m+=.(M The formation of a grignard reagent is analogous to that of organolithium reagents except that each magnesium atom can participate in two separate one-electron transfer steps R:X:+ M →R:X于+Mg Alkyl halide Magnesium Anion radical Anion radical Halide Alkylmagnesium halide Organolithium and organomagnesium compounds find their chief use in the prepara- tion of alcohols by reaction with aldehydes and ketones. Before discussing these reactions, let us first examine the reactions of these organometallic compounds with proton donors. 14.5 ORGANOLITHIUM AND ORGANOMAGNESIUM COMPOUNDS AS BRONSTED BASES Organolithium and organomagnesium compounds are stable species when prepared in suitable solvents such as diethyl ether. They are strongly basic, however, and react instantly with proton donors even as weakly acidic as water and alcohols. a proton is ransferred from the hydroxyl group to the negatively polarized carbon of the organometallic compound to form a hydrocarbon →R一H+R'O:M+ CH3CH,CH2 CH,Li+ H,0- CH, CH,CH3 LIOH Butyllithium Butane(100%) Lithium hydroxide lgBr+CH3OH— t Ch,OMg Br Phenylmagnesium Methanol Benzene Methoxymagnesi (100%) Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
PROBLEM 14.3 Write the structure of the Grignard reagent formed from each of the following compounds on reaction with magnesium in diethyl ether: (a) p-Bromofluorobenzene (c) Iodocyclobutane (b) Allyl chloride (d) 1-Bromocyclohexene SAMPLE SOLUTION (a) Of the two halogen substituents on the aromatic ring, bromine reacts much faster than fluorine with magnesium. Therefore, fluorine is left intact on the ring, while the carbon–bromine bond is converted to a carbon–magnesium bond. The formation of a Grignard reagent is analogous to that of organolithium reagents except that each magnesium atom can participate in two separate one-electron transfer steps: Organolithium and organomagnesium compounds find their chief use in the preparation of alcohols by reaction with aldehydes and ketones. Before discussing these reactions, let us first examine the reactions of these organometallic compounds with proton donors. 14.5 ORGANOLITHIUM AND ORGANOMAGNESIUM COMPOUNDS AS BRØNSTED BASES Organolithium and organomagnesium compounds are stable species when prepared in suitable solvents such as diethyl ether. They are strongly basic, however, and react instantly with proton donors even as weakly acidic as water and alcohols. A proton is transferred from the hydroxyl group to the negatively polarized carbon of the organometallic compound to form a hydrocarbon. H OR M R R H RO M CH3CH2CH2CH2Li Butyllithium H2O Water CH3CH2CH2CH3 Butane (100%) LiOH Lithium hydroxide MgBr Phenylmagnesium bromide CH3OH Methanol Benzene (100%) CH3OMgBr Methoxymagnesium bromide Magnesium Mg Mg Alkyl halide R X Anion radical [R ] X Alkyl radical R Halide ion X Anion radical [R ] X Alkylmagnesium halide Mg R X Mg F Br p-Bromofluorobenzene Mg Magnesium diethyl ether F MgBr p-Fluorophenylmagnesium bromide 14.5 Organolithium and Organomagnesium Compounds as Brønsted Bases 551 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER FOURTEEN Organometallic Compounds Because of their basicity organolithium compounds and grignard reagents can not be prepared or used in the presence of any material that bears a hydroxyl group Nor are these reagents compatible with -NH or-SH groups, which can also con vert an organolithium or organomagnesium compound to a hydrocarbon by proton transter The carbon-metal bonds of organolithium and organomagnesium compounds have appreciable carbanionic character. Carbanions rank among the strongest bases that we'l see in this text. Their conjugate acids are hydrocarbons-very weak acids indeed. The quilibrium constants Ka for ionization of hydrocarbons are much smaller than the kas for water and alcohols Table 14.2 presents some approximate data for the acid strengths of representative hydro- Acidity increases in progressing from the top of Table 14.2 to the bottom. An acid will transfer a proton to the conjugate base of any acid above it in the table. Organo- act like carbanions and will abstract from any substance more acidic than a hydrocarbon. Thus, N-H groups and terminal alkynes(RC=C-H) are converted to their conjugate bases by proton transfer to organolithium and organomagnesium compounds TABLE 14.2 Approximate Acidities of Some Hydrocarbons and Reference Materials pk Conjugate base 2-Methylpropane (CH3)3C-H (CH3)3C Ethane CH3CH2--H CH3CH2 Methane HaC CH2=CH一H10 Benzene H-H 10-43 H H2N一H 10-36 Acetylene 10-26 cHCH2O一H10-16 16 CH3CH2O HO-H 18×10 15.7Ho *The acidic proton in each compound is shaded in red Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Because of their basicity organolithium compounds and Grignard reagents cannot be prepared or used in the presence of any material that bears a hydroxyl group. Nor are these reagents compatible with ±NH or ±SH groups, which can also convert an organolithium or organomagnesium compound to a hydrocarbon by proton transfer. The carbon–metal bonds of organolithium and organomagnesium compounds have appreciable carbanionic character. Carbanions rank among the strongest bases that we’ll see in this text. Their conjugate acids are hydrocarbons—very weak acids indeed. The equilibrium constants Ka for ionization of hydrocarbons are much smaller than the Ka’s for water and alcohols. Table 14.2 presents some approximate data for the acid strengths of representative hydrocarbons. Acidity increases in progressing from the top of Table 14.2 to the bottom. An acid will transfer a proton to the conjugate base of any acid above it in the table. Organolithium compounds and Grignard reagents act like carbanions and will abstract a proton from any substance more acidic than a hydrocarbon. Thus, N±H groups and terminal alkynes (RCPC±H) are converted to their conjugate bases by proton transfer to organolithium and organomagnesium compounds. C H Hydrocarbon (very weak acid) Proton H C Carbanion (very strong base) 552 CHAPTER FOURTEEN Organometallic Compounds TABLE 14.2 Approximate Acidities of Some Hydrocarbons and Reference Materials Compound 2-Methylpropane Ethane Methane Ethylene Benzene Ammonia Acetylene Ethanol Water 1071 1062 1060 1045 1043 1036 1026 1016 1.8 1016 Ka 71 62 60 45 43 36 26 16 15.7 Formula* pKa (CH3)3C±H CH3CH2±H CH3±H CH2œCH±H H2N±H HCPC±H CH3CH2O±H HO±H H H H H H H Conjugate base H H H H H (CH3)3C H3C HCPC H2N CH3CH2O HO CH3CH2 CH2œCH *The acidic proton in each compound is shaded in red. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
14.6 Synthesis of Alcohols Using Grignard Reagents ChaLi+ CHa LiNH, Methyllithium Ammonia Methane Lithium amide (stronger base)(stronger acid (weaker acid:(weake Kn=10-3 Ka≈10 60 H2CH2MgBr+HC≡CH CH3 CH3 Ethylmagnesiu Acetylene Ethane Ethynylmagnesium bromide (stronger bas =( (weaker base PROBLEM 14.4 Butyllithium is commercially available and is frequently used by organic chemists as a strong base. Show how you could use butyllithium to pre pare solutions containing (a)Lithium diethylamide (CHa CH2)2NLi b) Lithium 1-hexanolate Cha(cH )4 CH oli (c) Lithium benzenethiolate, CsHsSLi SAMPLE SoLUTION When butyllithium is used as a base, it abstracts a proton, in this case a proton attached to nitrogen The source of lithium diethylamide must be diethylamine (CH3 CH2)2NH+ CH3 CH2 CH,Li ->(CH3 CH2) NLi CH3CH2 CH2 CH3 diethylamide (stronger acid (stronger base) (weaker base) (weaker acid) Although diethylamine is not specifically listed in Table 14.2, its strength as an acid (Ka ss 10)is, as might be expected, similar to that of ammonia It is sometimes necessary in a synthesis to reduce an alkyl halide to a hydrocar- bon. In such cases converting the halide to a grignard reagent and then adding water or an alcohol as a proton source is a satisfactory procedure. Adding DO to a grignard reagent is a commonly used method for introducing deuterium into a molecule at a spe- Deuterium is the mass 2 iso- cific location pe of hydrogen. Deute. CH3 CH=CHBr CHaCH=CHMgBr CHCHECHD times called"heavy water. Propenylmagnesium bromide I-Deuteriopropene(70%) 14.6 SYNTHESIS OF ALCOHOLS USING GRIGNARD REAGENTS The main synthetic application of Grignard reagents is their reaction with certain car bonyl-containing compounds to produce alcohols. Carbon-carbon bond formation is rapid and exothermic when a grignard reagent reacts with an aldehyde or ketone normally COMoX written as rMgX R—MgX A carbonyl group is quite polar, and its carbon atom is electrophilic. Grignard reagents are nucleophilic and add to carbonyl groups, forming a new carbon-carbon bond. This Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
PROBLEM 14.4 Butyllithium is commercially available and is frequently used by organic chemists as a strong base. Show how you could use butyllithium to prepare solutions containing (a) Lithium diethylamide, (CH3CH2)2NLi (b) Lithium 1-hexanolate, CH3(CH2)4CH2OLi (c) Lithium benzenethiolate, C6H5SLi SAMPLE SOLUTION When butyllithium is used as a base, it abstracts a proton, in this case a proton attached to nitrogen. The source of lithium diethylamide must be diethylamine. Although diethylamine is not specifically listed in Table 14.2, its strength as an acid (Ka 1036) is, as might be expected, similar to that of ammonia. It is sometimes necessary in a synthesis to reduce an alkyl halide to a hydrocarbon. In such cases converting the halide to a Grignard reagent and then adding water or an alcohol as a proton source is a satisfactory procedure. Adding D2O to a Grignard reagent is a commonly used method for introducing deuterium into a molecule at a specific location. 14.6 SYNTHESIS OF ALCOHOLS USING GRIGNARD REAGENTS The main synthetic application of Grignard reagents is their reaction with certain carbonyl-containing compounds to produce alcohols. Carbon–carbon bond formation is rapid and exothermic when a Grignard reagent reacts with an aldehyde or ketone. A carbonyl group is quite polar, and its carbon atom is electrophilic. Grignard reagents are nucleophilic and add to carbonyl groups, forming a new carbon–carbon bond. This normally written as COMgX R C R MgX O R MgX C O Mg THF D2O 1-Bromopropene CH3CH CHBr Propenylmagnesium bromide CH3CH CHMgBr 1-Deuteriopropene (70%) CH3CH CHD (CH3CH2)2NH Diethylamine (stronger acid) CH3CH2CH2CH2Li Butyllithium (stronger base) (CH3CH2)2NLi Lithium diethylamide (weaker base) CH3CH2CH2CH3 Butane (weaker acid) CH3Li Methyllithium (stronger base) NH3 Ammonia (stronger acid: Ka 1036) CH4 Methane (weaker acid: Ka 1060) LiNH2 Lithium amide (weaker base) CH3CH2MgBr Ethylmagnesium bromide (stronger base) HCPCH Acetylene (stronger acid: Ka 1026) CH3CH3 Ethane (weaker acid: Ka 1062) HCPCMgBr Ethynylmagnesium bromide (weaker base) 14.6 Synthesis of Alcohols Using Grignard Reagents 553 Deuterium is the mass 2 isotope of hydrogen. Deuterium oxide (D2O) is sometimes called “heavy water.” Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER FOURTEEN Organometallic Compounds addition step leads to an alkoxymagnesium halide, which in the second stage of the syn- thesis is converted to an alcohol by adding aqueous acid R-C-OMgX H,O+ -R-C-OH+ Mg2++X +H,0 Alkoxymagnes Acohol Magnesium Halide Water halide The type of alcohol produced depends on the carbonyl compound. Substituents pres ent on the carbonyl group of an aldehyde or ketone stay there-they become substituents on the carbon that bears the hydroxyl group in the product. Thus as shown in Table 14.3 secondary alcohols, and ketones yield tertiary alcohol e formaldehyde reacts with Grignard reagents to yield primary alcohols, aldehydes yield PROBLEM 14.5 Write the structure of the product of the reaction of propyl agnesium bromide with each of the following. Assume that the reactions are worked up by the addition of dilute aqueous acid none Formaldehyde, HCH benzaldehyde, CHs CH 2-Butanone, CH3CCH2 CH SAMPLE SOLUTION (a) Grignard reagents react with formaldehyde ri- ve or mary alcohols having one more carbon atom than the alkyl halide from which the Grignard reagent was prepared. The product is 1-butanol CHaCH2C CH3 CH2CH2 CH3CH2CH2CH2OH C=O Propylmagnesium bromide 1-Butanol formaldehyde An ability to form carbon-carbon bonds is fundamental to organic synthesis. The addition of Grignard reagents to aldehydes and ketones is one of the most frequently used reactions in synthetic organic chemistry. Not only does it permit the extension of carbon chains, but since the product is an alcohol, a wide variety of subsequent func tional group transformations is possible. 4.7 SYNTHESIS OF ALCOHOLS USING ORGANOLITHIUM REAGENTS Organolithium reagents react with carbonyl groups in the same way that Grignard reagents do. In their reactions with aldehydes and ketones, organolithium reagents are somewhat more reactive than grignard reagents Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
addition step leads to an alkoxymagnesium halide, which in the second stage of the synthesis is converted to an alcohol by adding aqueous acid. The type of alcohol produced depends on the carbonyl compound. Substituents present on the carbonyl group of an aldehyde or ketone stay there—they become substituents on the carbon that bears the hydroxyl group in the product. Thus as shown in Table 14.3, formaldehyde reacts with Grignard reagents to yield primary alcohols, aldehydes yield secondary alcohols, and ketones yield tertiary alcohols. PROBLEM 14.5 Write the structure of the product of the reaction of propylmagnesium bromide with each of the following. Assume that the reactions are worked up by the addition of dilute aqueous acid. (a) (c) (b) (d) SAMPLE SOLUTION (a) Grignard reagents react with formaldehyde to give primary alcohols having one more carbon atom than the alkyl halide from which the Grignard reagent was prepared. The product is 1-butanol. An ability to form carbon–carbon bonds is fundamental to organic synthesis. The addition of Grignard reagents to aldehydes and ketones is one of the most frequently used reactions in synthetic organic chemistry. Not only does it permit the extension of carbon chains, but since the product is an alcohol, a wide variety of subsequent functional group transformations is possible. 14.7 SYNTHESIS OF ALCOHOLS USING ORGANOLITHIUM REAGENTS Organolithium reagents react with carbonyl groups in the same way that Grignard reagents do. In their reactions with aldehydes and ketones, organolithium reagents are somewhat more reactive than Grignard reagents. diethyl ether H3O CH3CH2CH2 MgBr C H H O Propylmagnesium bromide formaldehyde CH3CH2CH2 H H C OMgBr CH3CH2CH2CH2OH 1-Butanol 2-Butanone, CH3CCH2CH3 O Benzaldehyde, C6H5CH O Cyclohexanone, O Formaldehyde, HCH O H3O Hydronium ion H2O Water Mg2 Magnesium ion X Halide ion Alkoxymagnesium halide R C OMgX Alcohol R C OH 554 CHAPTER FOURTEEN Organometallic Compounds Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
14.7 Synthesis of Alcohols Using Organolithium Reagents TABLE 14.3 Reactions of Grignard Reagents with Aldehydes and Ketones General equation and specific example Reaction with formaldehyde H Grignard reagents react with formal diethyl dehyde(CH2=o) to give primary alcohols having one more carbol than the Grignard reagent. Grignard Formaldehyde reagent HOH HCH diethyl ethe Cyclohexylmagnesium chloride (64-69% Reaction with aldehydes Grignard (RCH=O)to give secondary alcohols. RMgx Grignard Aldehyde Secondary Secondary alkoxymagnesium CH3 (CH 2)4CH2MgBr CH3 CH 1. diethyl ethe CH3(CH2)4CH2 CHCH3 HexyImagnesium Ethanal 2-Octanol (84%) Reaction with ketones Grignard diethyl RMgX R'CR OMaX reagents react with ketones(RCr) to give tertiary alcohols Grignard Ketone ertiary alkoxymagnesiun alcohol CHaMgCI 1. diethyl eth 2.H2O H3C Methylmagnesium Cyclopentanone 1-Methylcyclopentanol chloride Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
14.7 Synthesis of Alcohols Using Organolithium Reagents 555 TABLE 14.3 Reactions of Grignard Reagents with Aldehydes and Ketones Reaction Reaction with formaldehyde Grignard reagents react with formaldehyde (CH2œO) to give primary alcohols having one more carbon than the Grignard reagent. Reaction with aldehydes Grignard reagents react with aldehydes (RCHœO) to give secondary alcohols. Reaction with ketones Grignard reagents react with ketones (RCR) to give tertiary alcohols. O X General equation and specific example RMgX Grignard reagent Formaldehyde HCH O diethyl ether H3O OMgX H R C H Primary alkoxymagnesium halide OH H R C H Primary alcohol RMgX Grignard reagent Aldehyde RCH O diethyl ether H3O OMgX H R C R Secondary alkoxymagnesium halide OH H R C R Secondary alcohol RMgX Grignard reagent Ketone RCR O diethyl ether H3O R C OMgX R R Tertiary alkoxymagnesium halide R C OH R R Tertiary alcohol MgCl Cyclohexylmagnesium chloride CH2OH Cyclohexylmethanol (64–69%) Formaldehyde HCH O 1. diethyl ether 2. H3O CH3(CH2)4CH2MgBr Hexylmagnesium bromide Ethanal (acetaldehyde) CH3CH O 2-Octanol (84%) CH3(CH2)4CH2CHCH3 OH 1. diethyl ether 2. H3O CH3MgCl Methylmagnesium chloride O Cyclopentanone 1-Methylcyclopentanol (62%) H3C OH 1. diethyl ether 2. H3O Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
