acyl halides - SUMMARY General Information Synthesis ofAcyl...

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Unformatted text preview: SUMMARY General Information Synthesis ofAcyl Hafides 0 From Carboxylic Acids Reactions of Acyl Halides ' Preparation of Carboxylic Acids ' Preparation of Esters ' Preparation of Amides ' Preparation of Acid Anhydrides ° Preparation of Ketones 0 Friedel-Crafts Acylation Reaction Acyi Halides 1 (see Carboxylz'c Acids 5) Acyl Halides 2 Acyl Halides 3 Acyl Halides 4 (see Acid Anhydrides 2A) Acyl Halides 5 (see Benzenes 6) Acyl Halides REACTIONS OF ACYL HALIDES Acyl Halides 1 Acyl Halides 0 || FIG—X Introduction: Acyl halides, commonly known as acid halides, are acyl derivatives in which the Y group of the acyl deriva- tive is a halogen atom (X). Ac-yl chlorides are the most common acyl halides. Chemical Properties: 0 Like other acyl derivatives, the carbonyl carbon is sp2 hybridized and has a planar configuration. The bond angle of the R—C'"‘=O is about 120° (where C* represents the carbonyl carbon). | X 0 Acyl halides are one of the most reactive classes of compounds among the acyl derivatives. Reason: The strongly electronegative halide atom withdraws electrons from the carbonyl carbon and therefore increases its electrophilicity, rendering the carbonyl atom more susceptible to nucleophilic attack. Nomenclature: Acyl halides are named by first replacing the -ic ending of the parent carboxylic acids with -yl and then replacing the word acid with the name of the halide, for example, if i’ . cascnzcim enacnzc—on Propanoyl chloride Propnnoic acid . g Spectroscopy: C NMR: Characteristic peak at 5 = 170 ppm. IR: The C=O bond has an absorption around 1800 cm‘l. REACTIONS OF ACYL HALIDES Acyl Halides 2 PREPARATION OF CARBOXYLIC ACIDS ii i enacnzcm + H20 ——> CHQCHQCOH ' + Hci Propanoyl chloride Water Propanoic acid Hydrogen chloride (acyl halide) (carboxylic acid) (acid) 1231: 1. This is a nucleophilic acyl substitution reaction in which the —X is replaced by wOH. 2. This reaction proceeds through two stages: a. Conversion of the starting acyl halide to the tetrahedral intermediate. This is the rate-limiting step of the overall reaction. b. Breakdown of the intermediate to form the carboxylic acid and the by-product hydrogen chloride. Note: Addition of base speeds the hydrolysis reaction. Mechanism: Stage I 1. Nucleophilic attack on the carbonyl carbon by water forms a tetrahedral intermediate. This is the rate- ljmiting step. CO: 26:9 u '_ 3) Slow I FI—C —CI -0H2 t— \\\\\\i\ Acyl halide Water R EEO Cl / \ H H Tetrahedral intermediate Stage II 2.. The oxygen anion donates a pair of electrons and restores the double bond between oxygen and carbon atom. The leaving group Cl— is expelled. 3. The chloride ion abstacts a proton, forming the carboxylic acid and HCl. .. “Q o m (\QJ: 0 Q (g) u 69/” n \\\i\q —> R—C —0\ H—C—OH + HCI \ 3* CI H /g\ Protonated Chloride Carboxylie H H carboxylic acid ion acid Tetrahedrul intermediate REACTIONS OF ACYL HALIDES Acyl Halides 3 PREPARATION OF ESTERS E? l CH36H2—CCI + casoa fl» CHacHchCHg + HCI Propanoy] chloride Methanol Methyl propanoate Acid (acyl halide) (1" alcohol) (ester) Keys: 1. This is a nucleophilic acyl substitution reaction between acyl halides and alcohols to produce esters. 2. Like many other nucleophilic acyl substitution reactions; this reaction proceeds through two stages: a. The starting acyl halide reacts with the nucleophilic alcohol to form the tetrahedral intermediate. Steric hindrance slows the rate of this step. Although all alcohols can be converted to esters this way, 1° alcohols are more reactive because they are less bulky than 2" and 3° alcohols. b. Breakdown of the intermediate to form the ester and the by—product hydrogen chloride. 3. In this reaction, none of the bonds attached to the stereogenic carbon in the alcohol is broken (See Mechanism). Thus, the stereoconfiguration of the alcohol is retained. CH3 (H) CH3 (“3 enscn2 + OH + 02" [email protected] cc: m» CHJCH2+ oc [email protected] N02 H H (R)-2-Butanol peNitrobenzoyl ehioride (RJ-l-Methyl—l-propyl (alcohol) (acyl halide) p-nitrobenzoate ' (ester) Notes: a 1. Pyridine or sodium hydroxide (NaOH) is often added to react with the by—productdiydrochloric acid. 2. The reaction works well with 1°, 2°, and 3° alcohols and phenols. Mechanism: Stage I 1. The nucleophilic alcohol attacks the carbonyl carbon to form a tetrahedral intermediate. Stage II 2. The oxygen anion donates a pair of electrons to restore the carbonyl double bond, and the Cl group is expelled. 3. The chloride anion abstracts a proton and forms the ester and HCl. Pyridine in the reaction is used to neutralize the HCl by-product. Cl) 3) Ci” ll e/cHa to l R—c—CI —> \‘c\ T R—c—o T~> R—C—OCH3 K—deHCHa “*1 {3| cle 0H a HCI Eater Acyl halide o Protnnaled be]? ' AR ‘ .. CH:l CMEI' Tetrahedral intermediate REACTIONS OF ACYL HALIDES Acyl Halides 4 PREPARATION OF AMIDES 0 0 ll ll 33 CHJCHziCiCI + 2 HN — (CH3)2 —p CH3€H20N(CH3)2 + NH2(CH3)ZCI Propanoyl chloride N.N-Dimelhylamine N.N—Diethylpropanamide N,NADiethylammonium (acyl halide) (amine) (amide) chloride ( ammonium salt) Keys: 1. This is a nucleophilic acyl substitution reaction between acyl halides and amines (or ammonia) to form amides. 2. Similar to other nucleophilic acyl substitution reactions, this reaction proceeds through two stages: a. The starting acyl halide reacts with nucleophilic amines or ammonia to form the tetrahedral intermediate. Only ammonia and 1° and 2° amines are used for this reaction; 3" amines cannot be used because they have no hydrogen attached to the N atom. b. Breakdown of the intermediate to form the amide and the lay-product hydrogen chloride. 3. Two molar equivalents of amines or ammonia are needed for the reaction: The first mole converts the acyl halide to an amide, and the second mole is needed to neutralize the by-product hydrochloric acid (HCl). If a base, such as pyridine or sodium hydroxide, is used to neutralize the acid formed, only one equivalent of amine is required. Note: Although carboxylic acids are less reactive than acyl halides, amines can react with carboxylic acids to form amides in two steps (see Amides 2). o 0 Heat 0 ii Step I II 9 a) Step 2 ll CH30H2’C-OH + HN —(CH3)2 —> CHJCHZCO + NH2(C:H;.)2 —> H20 + CH36H2CN(CH3)2 Propanoic acid N.N-Dimethy]amine Propanoate ion N_N-Dimethylamine ion N,N—Dimethyi [carboxylic acid] (carboxylale ion) propanamidc (amide) Mechanism: 1. A nucleophiiic amine attacks the carbonyl carbon of the acyl halide to form the tetrahedral intermediate. 2. The oxygen anion donates a pair of electrons to form the carbonyl double bond, and the Cl group is expelled, giving an amide protonated on the nitrogen. 3. A base [e.g., the second molar equivalent of the amine (or added pyridine)] neutralizes the HCI to form the amide and an ammonium salt. CO I O I'l”—‘_\:Base 3 ii Cl .\—‘ ® R Fl ii: I CH “mm H ‘93 ©I a [pyn‘dinel Acy] halide ‘ CHg—N—CHa 6 CH3 =NVCH3 l Amide ‘ H CH? Telrahedra] é) Ammi intermediate k '0 GE 9 ll RzNchl + R—C— N(CH:.)2 Ammonium Amide salt REACTIONS OF ACYL HALIDES Acyl Halides 5 PREPARATION OF KETONES if ‘n’ CH3CHZC—Cl + (CHalgcueLi© fig. CHacch—Cflg Propanoyl chlunde Lithium Z—Butanone dimethy] copper Keys: 1. This is a useful reaction between acyl halides and organocuprate compounds for generating ketones (for details on RZCuLi, see Alley! Halide: 5). 2. The ketone product of this reaction does not react with the organocopper reagent. 3. Only one of the two R groups of RzCuLi is used; the by-product, RCu, is inactive. Note: The reaction between (1) acyl halides and Grignard reagents or (2) acyl halides and organolithium compounds does not form ketones. Reason: These reagents are too reactive, so the ketone intermediates react further to form 3" alcohols. Hence, the ketones cannot be isolated. RMgBr + Acyl chlorides —) [Ketone intermediates] —> 3° Alcohols RLi + Acyl chlorides —> [Ketone intermediates] —> 3° Alcohols ...
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This note was uploaded on 09/13/2009 for the course CHEM 12-636 taught by Professor Hubbard during the Spring '09 term at University of Georgia Athens.

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acyl halides - SUMMARY General Information Synthesis ofAcyl...

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