Draw the products formed from LiAlH4 reduction of each compound. a. OH O b. NH2 O c. C

a. What orbitals are used to form the indicated bonds in -sinensal? b. In what type of orbitals do the lone pairs on O reside?O H [3] -sinensal [2] [

Which compounds undergo nucleophilic addition and which undergo substitution? a. (CH3)2C O b. CH3CH2CH2COCl c. CH3COOCH3 d. C6H5CHO

Which carbonyl groups in the anticancer drug taxol (Section 5.5) will undergo nucleophilic addition and which will undergo nucleophilic substitution? N O O taxol O O O O O O O O H O OH HO H OH

Which compound in each pair is more reactive towards nucleophilic attack? a. CH3CH2CH2CHO or CH3CH2CH2COCH3 c. CH3CH2COCl or CH3COOCH3 b. CH3CH2COCH3 or CH3CH(CH3)COCH2CH3 d. CH3COOCH3 or CH3CONHCH3

What alcohol is formed when each compound is treated with NaBH4 in CH3OH? a. O C CH3CH2CH2 H b. O c. O

What aldehyde or ketone is needed to prepare each alcohol by metal hydride reduction? a. OH b. OH c. OH

Why cant 1-methylcyclohexanol be prepared from a carbonyl compound by reduction?

Draw the products formed when CH3COCH2CH2CH CH2 is treated with each reagent: (a) LiAlH4, then H2O; (b) NaBH4 in CH3OH; (c) H2 (1 equiv), Pd-C; (d) H2 (excess), Pd-C; (e) NaBH4 (excess) in CH3OH; (f) NaBD4 in CH3OH.

Draw the products formed (including stereoisomers) when each compound is reduced with NaBH4 in CH3OH. a. O b. CHO c. (CH3)3C O

Draw a stepwise mechanism for the following reaction. CH3COCl CH3CH2OH [1] LiAlH4 [2] H2O

Draw the structure of both an acid chloride and an ester that can be used to prepare each compound by reduction. a. CH2OH b. OH c. CH2OH CH3O

Draw the products formed from LiAlH4 reduction of each compound. a. OH O b. NH2 O c. C N(CH3)2 O d. NH O

What amide(s) will form each of the following amines on treatment with LiAlH4? a. CH2NH2 b. N CH2CH3 CH2CH3 c. CH3CH2NHC(CH3)3

What product is formed when each compound is treated with either LiAlH4 (followed by H2O), or NaBH4 in CH3OH? a. COOCH3 O b. OH O CH3O O c. CH3O O

What product is formed when (CH3)2C CHCH2COCH2CH2CO2CH2CH3 is treated with each reagent: (a) H2 (1 equiv), Pd-C; (b) H2 (2 equiv), Pd-C; (c) LiAlH4, followed by H2O; (d) NaBH4, CH3OH?

What product is formed when each compound is treated with either Ag2O, NH4OH or Na2Cr2O7, H2SO4, H2O: (a) C6H5CH2OH; (b) CH3CH(OH)CH2CH2CH2CHO?

Review the oxidation reactions using Cr6+ reagents in Section 12.12. Then, draw the product formed when compound B is treated with each reagent. HO CHO OH B a. NaBH4, CH3OH d. Ag2O, NH4OH b. [1] LiAlH4; [2] H2O e. CrO3, H2SO4, H2O c. PCC

Write the step(s) needed to convert CH3CH2Br to each reagent: (a) CH3CH2Li; (b) CH3CH2MgBr; (c) (CH3CH2)2CuLi.

Draw the product formed when each organometallic reagent is treated with H2O. a. Li b. (CH3)3CMgBr c. MgBr d. CH3CH2C C Li

Draw the product formed when each carbonyl compound is treated with C6H5MgBr, followed by protonation with H2O. a. O C HH b. O C CH3CH2 CH2CH3 c. O C CH3CH2 H d. O

Draw the product of each reaction. a. O [1] CH3CH2CH2Li [2] H2O c. [2] H2O O [1] C6H5Li b. [2] H2O O C HH [1] Li d. [2] H2O C Na+ C [1] CH2 O

Draw the products (including stereochemistry) of the following reactions. a. O C H [1] CH3CH2MgBr CH [2] H2O 3 b. [1] CH3CH2Li CH3 O [2] H2O

What Grignard reagent and carbonyl compound are needed to prepare each alcohol? As shown in part (d), 3 alcohols with three different R groups on the carbon bonded to the OH group can be prepared by three different Grignard reactions. a. CH3 C OH CH3 H b. CH2OH c. OH H CH2CH3 (two methods) C d. OH (three methods)

Linalool and lavandulol are two of the major components of lavender oil. (a) What organolithium reagent and carbonyl compound can be used to make each alcohol? (b) How might lavandulol be formed by reduction of a carbonyl compound? (c) Why cant linalool be prepared by a similar pathway? OH OH linalool (three methods) lavandulol

What Grignard reagent and carbonyl compound can be used to prepare the antidepressant venlafaxine (trade name Effexor)? N(CH3) 2 OH venlafaxine OCH3

Using protecting groups, show how estrone can be converted to ethynylestradiol, a widely used oral contraceptive. HO O estrone C CH HO OH ethynylestradiol

Draw the product formed when each compound is treated with two equivalents of CH3CH2CH2CH2MgBr followed by H2O. a. CH3CH2 Cl C O b. C OCH3 O c. OCH2CH3 O

What organocuprate reagent is needed to convert CH3CH2COCl to each ketone? a. CH3CH2 CH3 C O b. O c. Ph O

What reagent is needed to convert (CH3)2CHCH2COCl into each compound? a. (CH3)2CHCH2CHO b. HO c. O d. (CH3)2CHCH2CH2OH

Draw two different ways to prepare each ketone from an acid chloride and an organocuprate reagent: (a) C6H5COCH3; (b) (CH3)2CHCOC(CH3)3.

What carboxylic acid is formed from each alkyl halide on treatment with [1] Mg; [2] CO2; [3] H3O+ ? a. Br b. Cl c. CH CH2Br 3O

What epoxide is needed to convert CH3CH2MgBr to each of the following alcohols, after quenching with water? a. OH (+ enantiomer) b. OH c. OH d. OH

Draw the product when each compound is treated with either (CH3)2CuLi, followed by H2O, or HC CLi, followed by H2O. a. O CH3 CH3 b. O c. O

How can (CH3)2C CHCOCH3 (mesityl oxide) be converted to each compound? a. O b. OH c. OH

Synthesize each compound from cyclohexanol, ethanol, and any other needed reagents. a. OH b. Br c. d. O e. OH

Draw the product formed when pentanal (CH3CH2CH2CH2CHO) is treated with each reagent. With some reagents, no reaction occurs. a. NaBH4, CH3OH g. [1] CH3MgBr; [2] H2O b. [1] LiAlH4; [2] H2O h. [1] C6H5Li; [2] H2O c. H2, Pd-C i. [1] (CH3)2CuLi; [2] H2O d. PCC j. [1] HC CNa; [2] H2O e. Na2Cr2O7, H2SO4, H2O k. [1] CH3C CLi; [2] H2O f. Ag2O, NH4OH l. The product in (a), then TBDMS Cl, imidazole

Draw the product formed when 1-bromobutane is treated with each reagent. a. Li (2 equiv) d. The answer in (a), then H2O b. Mg in (CH3CH2)2O solvent e. The answer in (b), then D2O c. Li (2 equiv), then CuI (0.5 equiv) f. The answer in (a), then CH3C CH

Draw the product formed when CH3CH2CH2MgBr is treated with each compound. a. CH2 O, then H2O e. H2O i. CO2, then H3O+ b. O, then H2O f. CH3CH2OH j. CH3, then H2O CH3 O c. CH3CH2COCl, then H2O g. CH3COOH k. D2O d. CH3CH2COOCH3, then H2O h. CHHC l. O, then H2O

Draw the product formed when (CH3CH2CH2CH2)2CuLi is treated with each compound. In some cases, no reaction occurs. a. C O Cl b. C O OCH3 c. , then H2O CH3 O d. CH3, then H2O CH3 O

The stereochemistry of the products of reduction depends on the reagent used, as you learned in Sections 20.5 and 20.6. With this in mind, how would you convert 3,3-dimethyl-2-butanone [CH3COC(CH3)3] to: (a) racemic 3,3-dimethyl-2-butanol [CH3CH(OH)C(CH3)3]; (b) only (2R)-3,3-dimethyl-2-butanol; (c) only (2S)-3,3-dimethyl-2-butanol?

Draw the product formed when the ,-unsaturated ketone A is treated with each reagent. C A O CH3 a. NaBH4, CH3OH d. [1] CH3Li; [2] H2O b. H2 (1 equiv), Pd-C e. [1] CH3CH2MgBr; [2] H2O c. H2 (excess), Pd-C f. [1] (CH2 CH)2CuLi; [2] H2O

What reagent is needed to convert (CH3)2CHCH2CH2COCl to each compound? a. (CH3)2CHCH2CH2CHO c. (CH3)2CHCH2CH2C(OH)(C6H5)2 b. (CH3)2CHCH2CH2COCH CH2 d. (CH3)2CHCH2CH2CH2OH

What reagent is needed to convert CH3CH2COOCH2CH2CH3 to each compound? a. CH3CH2CH2OH b. CH3CH2C(OH)(CH2CH2CH3)2 c. CH3CH2CHO

As discussed in Sections 12.12 and 20.8, some oxidizing agents selectively oxidize a particular functional group, whereas others oxidize many different functional groups. Draw the product formed when HOCH2CH2CH2CH2CHO is treated with each reagent: (a) CrO3, H2SO4, H2O; (b) PCC; (c) Ag2O, NH4OH; (d) Na2Cr2O7, H2SO4, H2O.

Draw the products of each reduction reaction. a. NaBH4 CH3OH O COOCH3 c. [1] LiAlH4 [2] H2O O O OH (CH3) 2N b. [1] LiAlH4 [2] H2O O COOCH3 d. [1] LiAlH[OC(CH3)3]3 [2] H2O O O OH

Draw all stereoisomers formed in each reaction. a. [1] C6H5MgBr [2] H2O O e. [1] Mg [2] CO2 [3] H3O+ Br H b. (CH3)3C [1] CH3Li [2] H2O O f. [1] (S)-CBS reagent [2] H2O O c. [1] CH3CH2MgBr [2] H2O O g. [1] (R)-CBS reagent [2] H2O O d. O [2] H2O [1] (CH2 CH)2CuLi h. [1] LiAlH4 [2] H2O O OCH2CH3 H

Explain why metal hydride reduction gives an endo alcohol as the major product in one reaction and an exo alcohol as the major product in the other reaction. O endo OH group OH H [1] LiAlH4 [2] H2O O exo OH group H OH [1] LiAlH4 [2] H2O

A student tried to carry out the following reaction sequence, but none of diol A was formed. Explain what was wrong with this plan, and design a successful stepwise synthesis of A. OH Br Mg OH BrMg OH A [1] O [2] H2O OH

Identify the lettered compounds in the following reaction scheme. Compounds F, G, and K are isomers of molecular formula C13H18O. How could 1 H NMR spectroscopy distinguish these three compounds from each other? [1] C6H5MgBr H2SO4 O A PBr3 I Mg H J B E D C [2] H2O [1] C6H5CHO [2] H2O [1] LiAlH4 [2] H2O [1] (CH3)2CuLi [2] H2O [1] Mg F K G [3] H2O [1] O3 HCl mCPBA [2] CH3SCH3 [2] CH2 O

Fill in the lettered products (AG) in the synthesis of the three biologically active compounds drawn below. a. O [1] (R)-CBS reagent NaI [2] H2O (CH3CH2)3SiCl imidazole (R)-isoproterenol trade name: Isuprel KF HO OH HO A B C (CH3)2CHNH2 D Si O O R R Cl N H b. H2SO4 E F (Z and E isomers) The Z isomer is tamoxifen. (used in treatment of breast cancer) [1] C6H5MgBr [2] H2O O O N(CH3)2 c. PGE1 (a prostaglandin) G [2] H2O several steps COOCH3 O RO COOH O OH HO [1] LiCu(CH CH OR' CHC5H11)2

Draw a stepwise mechanism for each reaction. a. O O [1] CH3MgBr (excess) [2] H2O OH OH b. O O [1] BrMgCH2CH2CH2CH2MgBr [2] H2O OH OH

Draw a stepwise mechanism for the following reaction. Account for the formation of all of the products. O O O OCH3 [1] CH3MgBr (excess) [2] H2O OH OH + + CH3OH (CH3)3COH

Tertiary alcohols can be formed by the reaction of dimethyl carbonate [(CH3O)2C O] with excess Grignard reagent. Draw a stepwise mechanism for the following transformation. C6H5MgBr + + (excess) dimethyl carbonate CH3O OCH3 H2O O C C6H5 C6H5 CH3OH + HOMgBr C6H5 C OH

What Grignard reagent and aldehyde (or ketone) are needed to prepare each alcohol? Show all possible routes. a. CH2OH b. OH c. (C6H5)3COH d. HO e. OH

What organolithium reagent and carbonyl compound can be used to prepare each of the following compounds? You may use aldehydes, ketones, or esters as carbonyl starting materials. a. OH (two ways) b. (three ways) C OH c. (three ways) C CH2CH3 OH

What epoxide and organometallic reagent are needed to synthesize each alcohol? a. OH b. OH C6H5 c. H H HO

Propose at least three methods to convert C6H5CH2CH2Br to C6H5CH2CH3.

Devise a synthesis of each alcohol from organic alcohols having one or two carbons and any required reagents: (a) CH3CH2CH(OH)CH3; (b) (CH3)3COH; (c) (CH3)2CHCH2OH; (d) CH3CH2CH2CH2OH.

Propose two different methods to synthesize 1-octen-3-ol [CH3(CH2)4CH(OH)CH CH2] using a Grignard reagent and a carbonyl compound. 1-Octen-3-ol is commonly called matsutake alcohol because it was fi rst isolated from the Japanese matsutake mushroom.

Synthesize each compound from cyclohexanol using any other organic or inorganic compounds. a. CH2OH c. O e. g. O (Each cyclohexane ring must come from cyclohexanol.) b. COOH d. O C6H5 f. CHO O h. (Each cyclohexane ring must come from cyclohexanol.)

Convert 2-propanol [(CH3)2CHOH] into each compound. You may use any other organic or inorganic compounds. a. (CH3)2CHCl b. (CH3)2C O h. OH j. O c. (CH3)2CHCH(OH)CH3 d. (CH3)2CHCH2CH2OH e. (CH3)2CHCOOH i. OH f. (CH3)2CHCHO g. (CH3)2CHD

Devise a synthesis of mestranol, a synthetic estrogen used in oral contraceptives, from the female sex hormone estradiol. You may use any needed organic compounds or inorganic reagents. CH3O OH C CH H H H mestranol HO OH H H H H estradiol

Devise three different methods to prepare each compound from benzene: (a) C6H5CH2CH2OH (2-phenylethanol); (b) C6H5COCH3 (acetophenone). You may also use organic compounds that have one or two carbons, and any required inorganic reagents. At least two of the three methods must use a reaction of the organometallic reagents described in this chapter.

Convert benzene into each compound. You may also use any inorganic reagents and organic alcohols having three carbons or fewer. One step of the synthesis must use a Grignard reagent. a. COOH b. CHO c. O d. HO e. O B

Design a synthesis of each compound from alcohols having four carbons or fewer as the only organic starting materials. You may use any other inorganic reagents you choose. a. O b. OH c. O d. CO2H e

Synthesize each compound from the given starting material. You may use any other required inorganic reagents. a. O + organic halides c. Br C6H5CO2CH3 + organic halides O b. CN OH (the only organic starting material) d. C6H5CH2CH(OH)CH2CH3 hydrocarbons having 6 C's e. CH3CH(OH)C CCH2CH2OH HC CH + compounds having 2 Cs

An unknown compound A (molecular formula C7H14O) was treated with NaBH4 in CH3OH to form compound B (molecular formula C7H16O). Compound A has a strong absorption in its IR spectrum at 1716 cm1. Compound B has a strong absorption in its IR spectrum at 36003200 cm1. The 1 H NMR spectra of A and B are given. What are the structures of A and B? 0 ppm 8 7654 3 2 1 1H NMR of A 0 ppm 8 7654 3 2 1

Treatment of compound C (molecular formula C4H8O) with C6H5MgBr, followed by H2O, affords compound D (molecular formula C10H14O). Compound D has a strong peak in its IR spectrum at 36003200 cm1. The 1 H NMR spectral data of C and D are given. What are the structures of C and D? Compound C signals at 1.3 (singlet, 6 H) and 2.4 (singlet, 2 H) ppm Compound D signals at 1.2 (singlet, 6 H), 1.6 (singlet, 1 H), 2.7 (singlet, 2 H), and 7.2 (multiplet, 5 H) ppm

Treatment of compound E (molecular formula C4H8O2) with excess CH3CH2MgBr yields compound F (molecular formula C6H14O) after protonation with H2O. E shows a strong absorption in its IR spectrum at 1743 cm1. F shows a strong IR absorption at 3600 3200 cm1. The 1 H NMR spectral data of E and F are given. What are the structures of E and F? Compound E signals at 1.2 (triplet, 3 H), 2.0 (singlet, 3 H), and 4.1 (quartet, 2 H) ppm Compound F signals at 0.9 (triplet, 6 H), 1.1 (singlet, 3 H), 1.5 (quartet, 4 H), and 1.55 (singlet, 1 H) ppm

Reaction of butanenitrile (CH3CH2CH2CN) with methylmagnesium bromide (CH3MgBr), followed by treatment with aqueous acid, forms compound G. G has a molecular ion in its mass spectrum at m/z = 86 and a base peak at m/z = 43. G exhibits a strong absorption in its IR spectrum at 1721 cm1 and has the 1 H NMR spectrum given below. What is the structure of G? We will learn about the details of this reaction in Chapter 22. 0 ppm 8 7654 3 2 24 25 17 17 1

Treatment of isobutene [(CH3)2C CH2] with (CH3)3CLi forms a carbanion that reacts with CH2 O to form H after water is added to the reaction mixture. H has a molecular ion in its mass spectrum at m/z = 86, and shows fragments at 71 and 68. H exhibits absorptions in its IR spectrum at 36003200 and 1651 cm1, and has the 1 H NMR spectrum given below. What is the structure of H? 0 ppm 8 7654 3 3 H 2 H 1 H 2 H 1 H 1 H 2 1

Reaction of oxetane with CH3MgBr followed by H2O forms a compound that shows a strong absorption in its IR spectrum at 36003200 cm1 and the following 1 H NMR data: 0.94 (triplet, 3 H), 1.39 (multiplet, 2 H), 1.53 (multiplet, 2 H), 2.24 (singlet, 1 H), and 3.63 (triplet, 2 H) ppm. Draw the structure of the product and write a mechanism that illustrates its formation.

Lithium tri-sec-butylborohydride, also known as L-selectride, is a metal hydride reagent that contains three sec-butyl groups bonded to boron. When this reagent is used to reduce cyclic ketones, one stereoisomer often predominates as product. Explain why the reduction of 4-tert-butylcyclohexanone with L-selectride forms the cis alcohol as the major product. LiBH[CH(CH3)CH2CH3]3 (CH3)3C O OH lithium tri-sec-butylborohydride L-selectride 4-tert-butylcyclohexanone cis-4-tert-butylcyclohexanol (CH3)3C [1] L-selectride [2] H2O

Explain why the carbon of an ,-unsaturated carbonyl compound absorbs farther downfi eld in the 13C NMR spectrum than the carbon, even though the carbon is closer to the electron-withdrawing carbonyl group. For example, the carbon of mesityl oxide absorbs at 150.5 ppm, while the carbon absorbs at 122.5 ppm. O 122.5 ppm 150.5 ppm mesityl oxide

Identify X and Y, two of the intermediates in a synthesis of the antidepressant venlafaxine (trade name Effexor), in the following reaction scheme. Write a mechanism for the formation of X from W. OCH3 OCH3 CH2CN C15H19NO2 H2O OH W venlafaxine [1] Li+ [2] [3] [1] LiAlH4 [2] H2O one step O X Y N[CH(CH3)2]2 N(CH3)2