Nuggets of Knowledge for Chapter 9 Reactions of Alkyl Halides Chem Aryl halides have a halogen connected directly to a benzene ring.

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1 I. Intrductin t Alkyl Halides Types f Organic Halides Nuggets f Knwledge fr Chapter 9 Reactins f Alkyl Halides Chem 2310 Organic halides can be rganized int fur majr categries. These cmpunds underg very different kinds f reactins. Aryl halides have a halgen cnnected directly t a benzene ring. Vinyl halides have a halgen cnnected directly t a C=C. Acid chlrides have a chlride cnnected directly t a C=O. Alkyl halides have a halgen cnnected t an sp 3 carbn. These are the cmpunds that will be discussed in this chapter. Alkyl halides can be further classified as methyl, primary 1, secndary 2, r tertiary 3. methyl a halgen attached t a methyl grup primary (1 ) halgen attached t an sp 3 carbn with 1 ther carbn n it secndary (2 ) halgen attached t an sp 3 carbn with 2 ther carbns n it tertiary (3 ) halgen attached t an sp 3 carbn with 3 ther carbns n it Alkyl halides can als be labeled as benzyl r allyl. allyl halide halgen attached t an sp 3 carbn next t a C=C benzyl halide halgen attached t an sp 3 carbn next t a benzene ring If there are tw halgens in the right psitins, alkyl halides can be labeled as geminal r vicinal. geminal dihalide tw halgens n the same carbn vicinal dihalide tw halgens n carbns that are next t each ther All alkyl halides underg the same reactins, but they are affected by whether they are 3, 2, 1, methyl, allyl, r benzyl.

2 Where rganic halides are fund Organic cmpunds cntaining halgens are rarely fund in nature. An imprtant exceptin is thyrid hrmne. Idine is necessary in ur diet in rder t synthesize thyrid hrmne. It is usually btained frm idized salt. Peple wh d nt get enugh idine in their diet suffer frm giter, an enlarged thyrid gland. Alkyl halides are ften used in medical, industrial, and cmmercial applicatins: 1,1,1-trichlrethane (CH 3 CCl 3 ) is used as a dry cleaning slutin. Chlrfrm (CHCl 3 ) was ne f the first anesthetics, but it isn t used nw n humans because f the small windw between an effective dse and death. Fren-12 (CF 2 Cl 2 ) was a widely used refrigerant, but it has been replaced because f damage t the zne layer. Dichlrmethane (CH 2 Cl 2 ) is used as a slvent. Halthane is an anesthetic currently in use. Chlrdane is a pesticide. Preparatin f Alkyl Halides One way t prepare alkyl halides is the halgenatin reactin discussed in chapter 4. In the presence f light r heat, alkanes react with Cl 2 r Br 2 t prduce alkyl halides. Multiple prducts are usually bserved; these can be separated by fractinal distillatin, which is nly practical n an industrial scale. F 2 is nt used because it is s energetic the reactin becmes explsive; I 2 is nt used because the reactin is t slw. This reactin fllws a radical mechanism, and is the example used in chapter 7. Initiatin step: hmlytic cleavage f Cl 2 r Br 2 Prpagatin steps: 1) attack f the halide radical n the alkane, taking a H and creating a carbn radical; 2) attack f the carbn radical n a chlrine r brmine mlecule Terminatin steps: cmbinatin f halide radicals and carbn radicals.

3 Radicals are stabilized by hypercnjugatin and resnance. hypercnjugatin makes radicals mre stable: 3 > 2 > 1 > methyl radicals with resnance structures are mre stable than thse withut A reagent called N-brmsuccinimde (NBS) is ften used in place f Br 2. It prduces small amunts f Br 2 because f an unfavrable equilibrium. The Br 2 reacts, causing mre t be created. NBS is much easier t wrk with than Br 2 because it is slid and desn't cause dangerus fumes. We will encunter ther (better) ways t frm alkyl halides in future chapters. Spectrscpy f Alkyl Halides Alkyl halides have the fllwing IR bands: C-H cm -1 CH 2 bending 1460, 1380 cm -1 C-X cm -1 (ften hard t find) Alkyl halides have the fllwing characteristic NMR chemical shift values: Chemical shift f H s n carbns next t halgens: 3-4 ppm Reactivity f Alkyl Halides The carbn-halgen bnd is a plar cvalent bnd. The halgens higher n the Peridic Table are mre electrnegative, making the bnd mre plar. All are mre electrnegative than carbn. The halgens lwer n the Peridic Table are larger, making the bnd weaker. When these tw factrs are cmbined, the result is that carbn-idine bnds are weakest, carbn-brmine bnds are next, carbn-chlrine bnds are als reactive, but carbn-flurine bnds are t strng t react easily. Because f the plarity and weakness f the carbn-chlrine, carbn-brmine, and carbn-idine bnds, they can react in three ways:

4 They can dissciate t frm a carbcatin and a halide in. The carbcatin will react further, either as an electrphile r acid. They participate in displacement reactins with a nuclephile, frming a new bnd t the nuclephile and frming a halide in. They can participate in acid/base reactins with a base by giving up a hydrgen next t the carbn with the halgen. A carbn-carbn duble bnd is frmed, and a halide in is frmed. In each f these reactins, the carbn-halgen bnd is brken, and a halide in is frmed. Nmenclature f alkyl halides Sme functinal grups have tw ways t name them: IUPAC names, smetimes called substitutive names, and cmmn names. IUPAC names fllw the rules we discussed in the chapter n alkanes. Cmmn names are much simpler, but nly wrk fr a few f the cmpunds. Cmmn names fr alkyl halides are frmed by using the substituent name fr the alkyl grup attached t the halide. Fr example, CH 3 Br is called methyl brmide. The fllwing are substituents we learned in Ch 4; review their structures if yu dn t remember them: methyl, ethyl, prpyl, isprpyl, cyclprpyl, butyl, isbutyl, sec-butyl, and tert-butyl and s n. Substituent names fr alkyl grups that cntain a C=C are vinyl (directly attached t the C=C) and allyl (ne carbn away frm the C=C). The name fr alkyl grups that cntain a benzene ring are phenyl (directly attached t the benzene ring) and benzyl (ne carbn away frm the benzene ring). Hwever, nly benzyl is used in cmmn names fr alkyl halides. Aryl halides are named differently. Cmmn names are nt used if there is nt a simple name fr the alkyl substituent. IUPAC, r substitutive names, fllw the same rules we learned fr naming alkanes. Refer t the nuggets fr Ch 4 fr full details; here is an abbreviated frm. 1) Chse the principle chain r ring, name it. 1 st pririty: lngest cntinuus chain 2 nd pririty: mst substituents 2) Number the principle chain.

5 1 st pririty: give the lwest number t the first substituent, then the secnd, etc. 2 nd pririty: if all numbers are the same, use the alphabet 3) Name and rder the substituents. Halgen substituents are treated just like alkyl substituents; use flur, chlr, brm, and id t name them. 4) Give the sterechemistry, if needed. Use the rules fr R and S that we learned in Ch 6. II. Substitutin Reactins f Alkyl Halides Intrductin The tw basic types f reactins that alkyl halides can underg are substitutin and eliminatin reactins. In a substitutin reactin, a nuclephile takes the place f the halide. We will study substitutins in this chapter. In an eliminatin reactin, hwever, the halide and a hydrgen are remved frm the mlecule, leaving a C=C behind. We will study eliminatins in the next chapter. Mechanisms The actual steps by which the reactin ccurs is called the mechanism f the reactin. There are tw ways in which substitutin can ccur. The S N 2 reactin takes place in a single displacement step. We will call this attack-push ff. The S N 1 reactin takes place in three steps: dissciatin, assciatin, and an acid/base reactin. We will call this fall ff, attack, deprtnate. Which Substitutin Reactin? Bth S N 2 and S N 1 reactins invlve the attack f a nuclephile, which ends up being substituted fr the halide. The difference is hw the reactin ccurs. The difference in the mechanisms is caused by the strength f the nuclephile.

6 In the S N 2 reactin, the nuclephile is strng enugh t attack the alkyl halide. The alkyl halide is a weaker electrphile than a carbcatin, since it is a stable mlecule, s it needs a strng nuclephile t attach it. In the S N 1 reactin, the nuclephile is nt strng enugh t attack the alkyl halide. The alkyl halide must first dissciate, frming a mre reactive carbcatin, a gd electrphile. The carbcatin can react with the weak nuclephile. Nuclephiles in Substitutin Reactins Nuclephiles require a pair f electrns with which t attack a carbn atm. As we have seen, we can determine whether a substitutin will be r S N 1 by lking at the strength f its nuclephile. Nuclephiles which will react in S N 2 reactins include: acetylide ins, cyanide ins, thilates, hydrxide ins, alkxide ins, and halide ins. exceptin: tert-butxide ins wn't attack at all because they are t sterically hindered Nuclephiles which will react in S N 1 reactins include: water and alchls exceptin: tert-butyl alchl wn't attack at all Prducts Many different prducts may be frmed using substitutin reactins. Whatever the nuclephile is will end up attached t the carbn chain where the halide was. The fllwing types f prducts can be frmed using substitutin reactins: nuclephile acetylide ins cyanide ins hydrxide ins r water alkxide ins r alchls thilate ins halide ins prduct alkynes nitriles alchls ethers sulfides alkyl halides Sterechemistry A substitutin reactin cannt create a new sterecenter, but it can invlve a carbn that is already a sterecenter. When a sterecenter is invlved in a substitutin reactin, we need t knw what will happen t it. If the cmpund underges an S N 2 reactin, the sterecenter will be inverted.

7 This ccurs because the nuclephile must apprach the carbn frm behind the halide in rder t push it ff. The carbn is turned inside ut like an umbrella, ging frm tetrahedral t trignal bipyramid t tetrahedral again. If the cmpund underges an S N 1 reactin, the sterecenter will be racemized. This ccurs because nce the halide leaves, the carbcatin is trignal planar, and is n lnger a sterecenter. The nuclephile may apprach frm either side, s bth stereismers are frmed. The tw stereismers are nt actually frmed in equal amunts. The departing halgen in partly blcks ne side, s that there is slightly mre inverted prduct than cnserved. Rate Laws In the S N 2 reactin, there is nly ne step, and the transitin state invlves bth the alkyl halide and the nuclephile. The bnd t the nuclephile is being frmed, and the bnd t the halide is being brken. Since bth reagents are part f the transitin state f the rate limiting step, bth are included in the rate law: rate = k r [RX] [Nu] Changing the cncentratin f the alkyl halide r the nuclephile will change the rate f the reactin by the same amunt. The reactin is first rder in the alkyl halide and first rder in the nuclephile, making it secnd rder verall. S N 2 stands fr substitutin, nuclephilic, 2 nd rder. The rates f S N 2 reactins are strngly affected by the structure f the alkyl halide. The less hindered the alkyl halide is, the mre easily the nuclephile can attack. This makes the activatin energy lw, and the rate f the reactin fast. Carbn grups attached t the carbn with the halgen make it mre difficult fr the nuclephile t attack. This increases the activatin energy, and slws dwn the reactin. The rates f S N 2 reactins with different alkyl halides is methyl > 1 > 2 >> 3. Methyl and primary alkyl halides react quickly. Secndary alkyl halides react mre slwly. Tertiary reactins are s slw that n prduct is frmed. The rates f S N 2 reactins are als affected by the structure f the nuclephile. The mre hindered the nuclephile is, the slwer the reactin rate. Tert-butyl nuclephiles are s hindered that substitutin reactins cannt ccur.

8 In S N 1 reactins, there are multiple steps. Hwever, the first step, in which the carbcatin is frmed, is the ne with the highest activatin energy, and therefre cntrls the rate f the reactin this is said t be the rate-limiting step. The bnd between the carbn and the halide is being brken. Since nly the alkyl halide is part f the transitin state fr the rate limiting step, it is the nly thing in the rate law: rate = k r [RX] Changing the cncentratin f the alkyl halide will change the rate f the reactin, but the cncentratin f the nuclephile will nt change the reactin rate. The reactins are first rder in the alkyl halide and zerth rder in nuclephile, making them first rder verall. S N 1 stands fr substitutin, nuclephilic, 1 st rder. The rates f S N 1 reactins are als strngly affected by the structure f the alkyl halide, but in a different way. The rate limiting step is nt the attack f the nuclephile, but the frmatin f the carbcatin. The mre stable the carbcatin is, the lwer the activatin energy will be, and the faster the reactin will g. The mre carbn grups that are attached t the carbn with the halgen, the mre stable the carbcatin will be, lwering the activatin energy and making the reactin g faster. Since the carbcatin is trignal planar, steric hindrance is nt an issue nuclephiles can apprach 3 carbcatins just as easily as less substituted nes. The rates f S N 1 reactins with different alkyl halides is 3 > 2 >> 1 > methyl. Primary and methyl carbcatins are s slw that n prducts are bserved. Carbcatins can als be stabilized by resnance a 1 carbcatin can frm if it is benzyl r allyl. In bth S N 2 and S N 1 reactins, the halgen-carbn bnd is brken in the rate-limiting step. Therefre, the lnger, weaker bnds will decrease the activatin energy and increase the rate f reactin. The rate f reactin fr bth types f substitutin is R-I > R-Br > R-Cl >> R-F. Alkyl flurides are t strng t be remved by substitutin, and dn't participate in substitin reactins.

9 Rearrangements Carbcatins are frmed nly in S N 1 reactins, nt S N 2 reactins. Once frmed, the carbcatin can rearrange t give a mre stable carbcatin. Whenever reactin ccurs in which a carbcatin is frmed, yu shuld draw ut the carbcatins t see if they will rearrange. If rearrangements can ccur, bth prducts will be frmed, thse with the riginal carbcatin, and thse with the rearranged ne. The carbcatin may cllide with the nuclephile befre r after it rearranges. Only 2 carbcatins cmmnly underg rearrangements. Primary carbcatins rarely underg rearrangements because they are t unstable t frm in the first place, while tertiary carbcatins are already as stable as they can be, s they d nt usually underg rearrangements. Secndary carbcatins are stable enugh t frm, but if there is a way fr them t rearrange and becme tertiary, this can ccur. There are tw ways fr a 2 carbcatin t becme tertiary by underging a rearrangement. Bth f them invlve electrns n a neighbring bnd shifting t ccupy the empty p rbital, leaving anther, mre stable ne behind. They are called hydride shifts and alkyl shifts. In a hydride shift, a hydrgen mves with its pair f electrns frm a tertiary carbn t the carbcatin, leaving the psitive charge n the tertiary carbn. In an alkyl shift, a carbn grup mves with its pair f electrns frm a quaternary carbn t the carbcatin, leaving the psitive charge n the nw tertiary carbn. Slvents In many cases, a slvent is needed in rder t disslve the reagents s that they have the chance t cllide. The slvent can als affect the rate f the reactin, s it is imprtant t cnsider this factr as well. The main things t cnsider are the plarity f the slvent, and whether r nt it can frm hydrgen bnds. Plarity is determined by the strength f the intermlecular frces. Mlecules with nly van der Waals frces are nnplar slvents. Mlecules with diple frces may be mderately plar r highly plar depending n the strength f the diple. Mlecules with hydrgen bnding are highly plar. Plar slvents with n hydrgen bnding are called aprtic slvents, while plar

10 slvents that d have hydrgen bnding are called prtic slvents. Plarity f the slvent can be imprtant because it is imprtant that the reagents will disslve in the slvent. S N 2 reactins require a plar slvent in rder t disslve the strng nuclephile, because it usually has a charge. S N 1 reactins emply weak nuclephiles which are usually nt charged, s there are n particular requirements fr the slvent t disslve the reagents. Hydrgen bnding is imprtant because it can affect the rate f the reactin in different ways depending n the reagents and the mechanism. In S N 2 reactins, hydrgen bnding slws dwn the reactin by surrunding the nuclephile and making it difficult fr them t react. Therefre, aprtic slvents are best. In S N 1 reactins, hydrgen bnding speeds up the reactin by stabilizing the carbcatin, making it easier t frm. Therefre, prtic slvents are best. Examples f suitable and unsuitable slvents are as fllws: Nnplar slvents include hexanes, tluene, and petrleum ether. These are unsuitable fr substitutin reactins because they will nt disslve charged reagents r stabilize a carbcatin. Mildly plar slvents include dichlrmethane, ethyl acetate, and diethyl ether. Althugh they are better than nnplar slvents, they are nt plar enugh t disslve charged reagents very well, and cannt stabilize a carbcatin. Highly plar, aprtic slvents include acetne, N,N-dimethylfrmamide, and acetnitrile. They are very gd at disslving charged reagents, but they d nt have any hydrgen bnding. This makes them ideal fr S N 2 reactins. Highly plar, prtic slvents include water and alchl slvents such as methanl r ethanl. They have hydrgen bnding, s they are ideal fr S N 1 reactins. In mst cases the nuclephile is used as the slvent. Exclusin f aryl halides, vinyl halides, and acid chlrides frm substitutin reactins Aryl halides, vinyl halides, and acid chlrides dn't participate in S N 2 reactins because the pi bnds prevent the nuclephile frm attacking frm behind, as the mechanism requires. Aryl halides, vinyl halides, and acid chlrides dn't participate in S N 1 reactins because the carbcatin that wuld be frmed is t unstable (high in energy).

11 III. Synthesis Using Substitutin Reactins One f the principle uses f rganic chemistry is t synthesize cmpunds in ther wrds, t make cmpunds we want frm thse we have. Each reactin we learn is a tl we can use t make a specific change t a mlecule. Substitutin reactins are ways t make alkyl halides int ther functinal grups. When designing a synthesis, yu start with the mlecule that yu want t make. Then: First, cnsider what starting materials and reagents culd be reacted t give this mlecule. Secnd, examine yur reactin t see if it will be gd way t make the mlecule. Will the reactin be favrable? Will any ther prducts be frmed? When using substitutin reactins, first determine what nuclephiles culd be used. Then cnsider what alkyl halides wuld be used. In sme cases, there is nly ne ptin fr the nuclephile, but in thers there is a chice f either a weak r a strng nuclephile. When there is nly ne ptin, cnsider the alkyl halide and decide whether it will be favrable with the mechanism that will result. When there are tw ptins, again cnsider the alkyl halide but nw decide if either ptin will be favrable. In sme cases, nly ne alkyl halide is pssible as the starting material, but in thers there is mre than ne ptin. When there is nly ne ptin, cnsider whether the resulting reactin will be favrable. When there are tw ptins, cnsider bth t see if ne wuld be a mre favrable reactin than the ther.