Synthesis of Aldehydes and Ketones from Acid Chlorides

Because aldehydes are easily oxidized to acids, one might wonder whether adds are easily reduced back to aldehydes. Aldehydes tend to be more reactive than acids, however, and redudng agents that are strong enough to reduce adds also reduce aldehydes even faster. 

18-11 Synthesis of Aldehydes and Ketones from Acid Chlorides 

Acids can be reduced to aldehydes by first converting them to a functional group that is easier to reduce than an aldehyde the acid chloride. Acid chlorides (acyl chlorides) are reactive derivatives of carboxylic acids in which the acidic hydroxyl group is replaced by a chlorine atom. Acid chlorides are often synthesized by treatment of carboxylic acids with thionyl chloride, SOCI2- 

To stop at the ketone stage, a weaker organometallic reagent is needed one that reacts faster with acid chlorides than with ketones. A lithium dialkylcuprate (Gilman reagent) is such a reagent. 

The lithium dialkylcuprate is formed by the reaction of two equivalents of the corresponding organolithium reagent (Section 10-8B) with cuprous iodide. 

---

Hydrolytic reactions can also be applied in the synthesis of aldehydes or ketones via the corresponding 1,3-oxazine derivatives. The anion formed from 3-methyl-2-(4-pyridyl)tetrahydro-l,3-oxazine 155 on treatment with BuLi proved to react with various electrophiles (alkyl halides, carboxylic esters, acid chlorides, or aldehydes) exclusively at position 2 of the 1,3-oxazine ring and not at the pyridine nitrogen atom. The readily formed 2,2-disubstituted-l,3-oxazine... 

It is not always necessary to start with gem-dihalides for the synthesis of aldehydes or ketones. There is a process by which carbonyl compounds can be obtained from monohalides, sometimes in excellent yield for instance, when 3-chlorocyclopentene is stirred vigorously with aqueous sodium dichromate solution at 0°, a chromium complex of 2-cyclopenten-l-one is formed, and this is decomposed to give a 60-68% yield of the ketone if 50% sulfuric acid is dropped in carefully with cooling 513 and 1,2-cyclopentanedione can be obtained in 80% yield by dropwise addition of aqueous iron(m) chloride solution to 2-chlorocyclopentanone in water with rapid stirring at 100°.539... 

The photochemical addition of 2H-azirines to the carbonyl group of aldehydes, ketones and esters is completely regiospecific (77H143). Besides the formation of the isomeric oxazolines 18 from 3 and ethyl cyanoformate, there is also formed the imidazole 19 from addition to the C = N in the expected regioselective manner. Thioesters lead to thiazolines 20, while isocyanates and ketenes produce heterocycles 21 (Scheme 4). The photocycloaddition of arylazirines with a variety of multiple bonds proceeds in high yield and provides a convenient route for the synthesis of five-membered heterocyclic rings. Some of the dipolarophiles include azodicarboxylates, acid chlorides, vinylphospho-nium salts and p-quinones. 

Synthesis of ketones and aldehydes from acid chlorides (or esters) via reaction of N-methoxy-N-methylamides with a Grignard or organolithium reagent (see 1 edition). 

Ketone synthesis. 5-Keto-a-amino acid derivatives and 2-oxathianyl ketones are accessible from the functionalized organocoppers and relatively simple acid chlorides. Thioesters can be used instead of acid chlorides for ketone synthesis. Addition to the carbonyl group. Reaction at the aldehyde function of jS-formyl esters is under chelation control. The entering group becomes trans to the original chain in the y-lactones thus generated. More readily understood is the diastereoselec-tivity in the reactions of protected a-amino aldehydes. ... 

Alexander Mikhaylovich Saytzev (Saytzeff) (Kazan 20 June 1841 (O.S.)-2 September 1910) studied with Kolbe in Marburg and Leipzig, and was professor in the University of Kazan. He discovered the synthesis of primary and secondary alcohols from esters, ketones, and aldehydes by the action of zinc and alkyl iodides (see Reformatsky, p. 858). He also discovered aliphatic sulphoxides. His brother Mikhayl Mikhaylovich (b. Kazan, 30 August 1845), at first his assistant and later manager of a chemical works in Kazan, discovered the reduction of acid chlorides to aldehydes by hydrogen gas in presence of palladium. ... 

Louis Bouveault (Nevers, ii February 1864-Paris, 6 September 1909), assistant professor in the Paris Faculty of Sciences, worked out methods for the conversion of nitriles or amides to acids, the synthesis of aromatic aldehydes and acids by the use of aluminium chloride, the synthesis of aldehydes from nitro-olefins, and the reduction of aldehydes, ketones, and esters to alcohols by boiling with alcohol and sodium. ... 

Iminium salts, generated in situ from the amides and lactams, react with 1 to produce the corresponding thioamides and thio-lactams, respectively, in good yields (eq T)P- The advantages of this methodology are the easy work-up and chemoselectively amides are thionated in the presence of ketones, aldehydes, and esters (eq 8). ra-Halo acid chlorides react with 1 and the corresponding thiolactones are obtained in moderate yields under mild reaction conditions (eq 9). This reaction works well for the synthesis of small and medium ring thiolactones, but is not useful for the synthesis of macrocyclic thiolactones. ... 

The allylation of a carbonyl compound, or equivalent thereof (aldehydes, ketones, acetals, ketals, enones, acid chlorides, epoxides, etc.), performed with an allylsilane 39 promoted by a Lewis acid (TiCl, SnCl, BF3-OEt2, AICI3, EtjAlCl, etc.) is known as Hosomi-Sakurai reaction (Scheme 12.11, Eq. 1) [68, 69]. This reaction was first described in 1976, allowing the synthesis of homoallylic alcohols 43 from aldehydes and ketones 40 [70]. A year later, the authors extended the method to ketals 41, which provide homoallylic ethers 44 (Scheme 12.11, Eq. 2) [71], and to a,p-unsaturated ketones 42 (Scheme 12.11, Eq. 3) [72]. 

---