8. CA and derivatives

Question 1

What are dicarboxylic acids? What are beta-dicarboxylic acids? What is a beta keto acid?

Answer 1

CA at each end of molec; they spont become cyclic anhydrides when heated. CA’s at beta C’s. Ketone at beta C

Question 2

How to make CAs?

Answer 2

[O] of primary alc

Question 3

For nuc acyl subst’n, after a nuc attacks, you could have multiple leaving groups. What makes a good leaving group? Trend on periodic table? Under which slns does nuc acyl subst’n occur?

Answer 3

lower pKa/weak bases (weak bases are most stable, low energy; it must accept e-), have to be stable once they leave molec; bigger = better b/c basicity dec as radius inc, more electroneg = better b/c LG will take e- and leave, forming resonance structures after leaving = better b/c resonance dec basicity. Inc down and right. Occurs in acidic or basic slns

Question 4

What are cyclic amides called? beta vs gamma vs delta etc. How are they formed?

Answer 4

lactams. number of sides (beta = 4 sides, there is no alpha and there is no 3 sides). Formed by intramolec rxns of amino acids (ie. CA with amino group)

Question 5

How does CA become amide?

Answer 5

when CA reacts w/ ammonia or amine in either acidic or basic solns
CONDENSATION RXN

Question 6

How does CA become ester?

Answer 6

when CA reacts w/ alc + acid => Fischer esterification, best w/ primary alc

1) =OH takes H+
2) alc attacks carbonyl C –> -OH at top
3) methyl OH takes H from bonded alc –> becomes water
4) -OH at top goes back to carbonyl C and water = leaving group —> CONDENSATION RXN
5) =OH = deprotonated —> ester

Question 7

How does CA become anhydride?

Answer 7

when CA reacts w/ another CA via condensation

Question 8

Saponification

Answer 8

when long chain CA (ie. fatty acids) mix with a strong base and form a salt called soap

Ester hydrolysis of triacylglycerols using a strong base

Question 9

Anhydrides are cleaved by a nuc. How does anhydride become amide + CA? ester + CA? 2 CA?

Answer 9

ammonia or amine = nuc; ether or alc = nuc; water = nuc

Question 10

How does ester become alc + CA?

Answer 10

Hydrolysis: water attacks carbonyl and adjacent O grabs bonded water’s H, another water grabs doubled bonded OH and makes CA

Question 11

Esters can be reduced to primary alcs by what?

Answer 11

LAH

Question 12

Descending reactivity of CA derivatives towards nuc SUBSTITUTION (not nuc addn) attack

Answer 12

Acyl halides > anhydrides > CAs and esters > amides

They can react spont going down but need a catalyst going up

Question 13

How do you know if a reagent will [O] -OH to ald/ket or CA intentionally?

Answer 13

If they really only want ald/ket, they will use a reagent specific for [O] to ald/ket. Otherwise, it’ll go straight to CA

Question 14

Which substituents can cause e- w/drawing (and thus inc acidity) vs e- donating (and this dec acidity) on carboxyl group?

Answer 14

NO2 and halides vs NH2 and OCH3 b/c these destablize neg charge

Question 15

Acyl derivatives

Answer 15

Cmpds that retain C=O from CA (ex: esters, amides, anhydrides, other CAs)

Question 16

Beta dicarboxylic acids and beta keto acids spont undergo what rxn? What about gamma or delta dicarboxylic acids?

Answer 16

Decarboxylation. Gamma and delta = more difficult to decarboxylate

Question 17

How can CAs become alkenes?

Answer 17

Reduce to alcs, then do elimination to become alkene (takes 2 steps)

Question 18

Can NaBH4 reduce CAs?

Answer 18

Nope, not even to ald

Question 19

What are cyclic esters called? Alpha vs beta vs gamma vs delta etc. How are they formed?

Answer 19

Lactones. Alpha = 3 sides, beta = 4 sides, gamma = 5 sides, etc. formed by intramolec rxns with hydroxycarboxylic acids ie. CA with alc)

Question 20

Ways to make esters

Answer 20

1) CA + alc under acidic conditions aka Fischer esterification
2) anhydride + alc
3) transesterifcation

Question 21

Induction

Answer 21

Refers to distribution of charge across sigma bonds. Electronegative atoms like more e- around them —> more neg (this less electronegative atoms = more pos)

Question 22

Conjugated system

Answer 22

Alternating single bonds and multiple bonds; this allows pi e- to delocalized throughout unhybridized p orbitals OR heteroatoms with lone pairs of e-

Question 23

Transesterification

Answer 23

When ester + alc reacts to make a diff ester + alc

Question 24

Amides can be hydrolyzed under STRONG acidic or basic conditions into what? Describe mechanism

Answer 24

CA + amine

1) Carbonyl O = protonated —> =OH at top
2) water attacks carbonyl C of amide —> -OH at top, water at bottom
3) amino group steals H from water
4) -OH at top doubles bonds with C —> kicks out amino group, =OH at top again
5) =OH = deprotonated —> CA + amino group

Question 25

How to name esters?

Answer 25

“R”yl “parent”oate

“R”yl = ester part
“Parent”oate = CA part

Question 26

How to convert CA and esters into alc with LAH

Answer 26

1) LAH attacks carbonyl C –> single bonds around carbonyl C
2) single carbonyl O becomes a double bond again with carbonyl C and kicks out -OR –> ald
3) more LAH attacks like BH4 –> alc product