Lecture 15 Carbonyl Chemistry - A C B A C + B March 6, 2018
Some loose ends
Substitution Reactions Aryl halides do not undergo nucleophilic substitution by either S N 1 or S N 2 pathways! But..
But.this is fact When heated under pressure with aqueous Na, chlorobenzene is converted to sodium phenoxide Cl - Na + Chlorobenzene + 2 Na 2 pressure, 300 o C + Sodium phenoxide NaCl + 2 neutralization with Cl gives phenol????? What is this??
Also fact. The same reaction with 2-chlorotoluene gives a mixture of ortho- and meta-cresol???? rtho and meta.huh???? C3 C3 C3 Cl 1. Na, heat, pressure + 2. Cl, 2 2-Methylphenol 3-Methylphenol (o-cresol) (m-cresol)
Also true The same type of reaction can be brought about by the use of sodium amide in liquid ammonia! C 3 C 3 C 3 + NaN 2 N 3 (l) (-33 o C) + + NaCl Cl N 2 N 2
Proposed Benzyne Intermediate -elimination of X gives a benzyne intermediate, that then adds the nucleophile to give products C 3 C 3 Cl NaN 2 -elimination A benzyne intermediate
Proposed Benzyne Intermediate C 3 C 3 C 3 + N 2 - C 3 N 2 - C 3 N 2 - N 2 N 2 C 3 C 3 N 2 Cl + N 2 - N 2 N 2 - N 2 N 2
Proposed Benzyne Intermediate Another Mystery?? CF 3 Cl N 3 (l) CF 3 NaN 2 N 2 More than 95% of the product is the meta isomer??
Nucleophilic Addition-Elimination When an aryl halide contains strongly electronwithdrawing -N 2 groups ortho and/or para to X, nucleophilic aromatic sub. takes place readily Cl N 2 Na 2 C 3, 2 100 o C - Na + N 2 N 2 N 2 1-Chloro-2,4- dinitrobenzene Sodium 2,4-dinitro phenoxide
Meisenheimer Complex - + N Cl N 2 + Nu - slow, ratelimiting (1) - - + N Cl Nu N 2 fast (2) - + N Nu N 2 + Cl - A Meisenheimer complex
Addition Elimination F N 2 C 3 - C 3 C 3 N 2
A word of caution regarding acylation reactions C Cl Does not exist!! = C + Cl
Gatterman-Koch Reaction C Cl = Cl + C C, Cl AlCl 3, CuCl C
Vilsmeier Reaction + C N C 3 P C l 3 C C 3 2 P d / C C 3
Diazonium Salts - quick review The -N 2+ group of an arenediazonium salt can be replaced in a regioselective manner by these groups 2 Ar- Ar-N 2 + (-N 2 ) BF 4 Cl, CuCl Br, CuBr KCN, CuCN KI Ar-F Ar-Cl Ar-Br Ar-CN Ar-I Schiemann reaction Sandmeyer reaction 3 P 2 Ar-
Reactions of Diazonium Salts
Fill in the blanks C 3 Cl C 3 N 2 C 3 C 3 C N C 2 N 2 C 3 N 2 C 3 Cl Cl Cl Cl
r l Practice work backwards B????? C
Synthesis Strategy The if only approach??
Resonance Description of Carbonyl Group C C + nucleophiles attack carbon; electrophiles attack oxygen
Nomenclature-Aldehydes IUPAC names: select as the parent alkane the longest chain of carbon atoms that contains the carbonyl group..subtract e and add al because the carbonyl group of the aldehyde must be on carbon 1, there is no need to give it a number For unsaturated aldehydes, show the presence of the C=C by changing -an- to -en- the location of the suffix determines the numbering pattern
Nomenclature-Aldehydes Methane Methanal C 5 4 3 C 3 C 2 C 2 C 2 C Pentane Pentanal 2 1 4 3 C 3 2 1 C 3 CC 2 C 3-Methylbutanal 3 2 1 C 2 =CC 2-Propenal (Acrolein) 8 7 6 5 4 (2E)-3,7-Dimethyl-2,6-octadienal (Geranial) 3 2 1
Formaldehyde Formalin is an aqueous solution of a mixture of formaledyde derived species Used for emblaming and preservation of tissue samples, bugs, etc. Widely used in melamine resins for plywood, flooring, etc Naturally occuring at 0.1mm in blood derived from metbolism of amino acids Toxicity is an issue and level set at 0.016ppm in air.
Nomenclature-Ketones IUPAC names: select as the parent alkane the longest chain that contains the carbonyl group, number to give C= the smaller number and then subtract e and add one C 3 CC 3 C3 C 2 CC 2 CC 3 Propanone 5-Methyl-3-hexanone (Acetone) C 3 1 2 3 4 5 6
IUPAC Nomenclature of Ketones C 3 C 2 CC 2 C 2 C 2 C 3 3-heptanone C 3 CC 2 CC 3 C 3 4-methyl-2-pentanone 3 C 4-methylcyclohexanone
IUPAC Nomenclature of Ketones C 3 C 2 CC 2 C 2 C 3 3-hexanone C 3 C 2 CC 2 C 2 C 3 ethyl propyl ketone (trivial) C 3 CC 2 CC 3 C 3 4-methyl-2-pentanone 4-oxohexanal
Trivial Nomenclature of Ketones C 3 CC 2 C 3 Methyl ethyl ketone C 2 CC 2 C 3 benzyl ethyl ketone 2 C CCC C 2 divinyl ketone
Precedene rder of Precedence (Pecking order) For compounds that contain more than one functional group indicated by a suffix Functional Group Suffix if igher in Precedence Prefix if Lower in Precedence -C 2 -C -oic acid -al oxo- C= -one oxo- - -N 2 -S -ol -amine -thiol hydroxy- amino- mercapto-
Many aldehydes and ketones occur naturally 2-heptanone (component of alarm pheromone of bees) trans-2-hexenal (alarm pheromone of myrmicine ant) Testosterone
Synthesis of Aldehydes and Ketones A number of reactions already studied provide efficient synthetic routes to aldehydes and ketones. from alkenes by ozonolysis (p271-273) from alkynes by hydration (via enol) from arenes via Friedel-Crafts acylation
Reaction Theme The most common reaction of a carbonyl group is addition of a nucleophile to form a tetrahedral addition compound Nu - R + C R ere it is an acid or electrophile - Nu C R R Tetrahedral carbonyl addition compound
Reaction Theme A second common reaction is with a proton or Lewis acid to form a resonance-stabilized cation R R C + -B R fast + C R + B - ere it is a base or Nucleophile! protonation increases the electron deficiency of the carbonyl carbon and makes it more reactive toward nucleophiles
Carbon Nucleophiles Addition of carbon nucleophiles is one of the most important types of nucleophilic additions to a C= group; a new carbon-carbon bond is formed in the process!!!! RMgX A Grignard reagent RLi An organolithium reagent RC C - An anion of a terminal alkyne - C N Cyanide ion We will study the addition of these carbon nucleophiles
Victor Grignard Shared Nobel Prize with Sabatier in 1912 student of Philippe Barbier
Grignard Reagents Given the difference in electronegativity between carbon and magnesium, the C-Mg bond is polar covalent, with C - and Mg + Grignard reagents behave like a carbanions Carbanion: an anion in which carbon has an unshared pair of electrons and bears a negative charge a carbanions are good nucleophiles and add efficiently to the carbonyl group of aldehydes and ketones
Grignard Reagents Addition of a Grignard reagent to formaldehyde followed by 3 + gives a 1 alcohol C 3 C 2 - MgBr + C 3 + C 3 C 2 C - MgBr + C 3 C 2 C TF dil. + Mg +2 This sequence (mechanism) is general and important!
Grignard Reagents Addition to any other RC gives a 2 alcohol C 3 C 2 - MgBr + C 3 + C 3 C 2 C - MgBr + C 3 C 2 C + TF dil. Mg +2 You may change decorations at will read pages 567-573 but, be careful of acidic functions like -
Grignard Reagents Addition to a ketone gives a 3 alcohol C 3 C 2 C 3 C 2 C 3 C 2 C 2 C 2 - + 3 + C 3 C 2 MgBr C C 3 C 2 C - MgBr + TF C C dil. 3 3 C 2 C 3 C 2 C C 3 + Mg +2 Please try this with other Grignard reagents and other ketones
Grignard Reactions C 3 C 2 - MgBr + C 3 + C 3 C 2 C - MgBr + C 3 C 2 C TF dil. + Mg +2 C 3 C 2 - MgBr + C 3 + C 3 C 2 C - MgBr + C 3 C 2 C + TF dil. Mg +2 C 3 C 2 C 3 C 2 C 3 C 2 C 2 C 2 - + 3 + C 3 C 2 MgBr C C 3 C 2 C - MgBr + TF C C dil. 3 3 C 2 C 3 C 2 C C 3 + Mg +2