Sodium borohydride-carboxylic acid systems. Useful reagents for the alkylation of amines

Marchini, Paolo; Liso, Gaetano; Reho, A.; Liberatore, Felice; Moracci, Franco Micheletti

doi:10.1021/jo00911a038

Cited by 126 publications

(53 citation statements)

References 4 publications

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“…Hence, it was suggested that the amines to be alkylated by NaBH(OAc) 3 with carboxylic acid should have some basicity. Next, we found that the acetyl group on the aromatic ring in the substrate remained after N-alkylation by NaBH(OAc) 3 , but was reductively removed by the previously reported reagents 8) (entries 4,5). This selectivity that N-alkylation was faster than reductive elimination of carbonyl moiety was confirmed by the reactions of 4-aminobenzophenone (13) and p-aminopropiophenone (15) (entries 6, 7).…”

Section: Resultssupporting

confidence: 56%

“…Saturated aqueous NaHCO 3 was dropped into the reaction mixture, and then the mixture was stirred until the foaming stopped. After extracting with EtOAc, the organic layer was dried over MgSO 4 . Removal of solvent from EtOAc extract under reduced pressure by a rotary evaporator gave crude products that were purified by column chromatography.…”

Section: Methodsmentioning

confidence: 99%

“…Previous reviews 2,3) of reductive amination methods using carbonyl compounds have briefly mentioned such phenomena as side reactions, and similar reactions using carboxylic acids with amines in the presence of sodium borohydride have already been reported. [4][5][6][7] In addition, other recent studies achieved an improvement of N-alkylation using carboxylic acids as the alkyl source by a single step reaction under a reductive condition. [8][9][10] Considering the various disadvantages of the traditional reductive amination by carbonyl derivatives-such as the instability of aldehydes, low reactivity of ketone carbonyl and necessity of a stepwise protocol-carboxylic acids should be a useful material, because they are normally more stable in air than aldehydes, and because various carboxylic acids are readily available.…”

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confidence: 99%

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<i>N</i>-Alkylation Using Sodium Triacetoxyborohydride with Carboxylic Acids as Alkyl Sources

Tamura

Sato

Kawano

2018

CHEMICAL & PHARMACEUTICAL BULLETIN

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A versatile N-alkylation was performed using sodium triacetoxyborohydride and carboxylic acid as an alkyl source. The combination of these reagents furnished products different from those given previously by a similar reaction. Moreover, the mild conditions of our method allowed some functional groups to remain through the reaction, whereas they would react and be converted into other moieties in the similar reductive N-alkylation reported previously. Herein, we provide a new procedure for the preparation of various compounds containing nitrogen atoms.

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Section: Resultssupporting

confidence: 56%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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<i>N</i>-Alkylation Using Sodium Triacetoxyborohydride with Carboxylic Acids as Alkyl Sources

Tamura

Sato

Kawano

2018

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Optical resolution of the racemate 82 brought about a dramatic change in the pharmacological profile with the (R)-enantiomer exhibiting a strong affinity for both the dopamine D 2 and the 5-HT 3 receptors, while the corresponding (S)-enantiomer had a potent and selective serotonin 5-HT 3 receptor binding affinity. Introduction of the butyl, 2,2,2-trifluoroethyl, 2,2-difluoroethyl, and 2-methoxyethyl groups at the nitrogen atom in the hexahydro-1,4-diazepine ring was performed by reductive alkylation according to the method of Marchini et al 24) Treatment of 6-acetylamino-1-ethylhexahydro-1,4-diazepine (12) and 6-benzoylamino-1-methylhexahydro-1,4-diazepine (15) prepared by debenzylation of the 6-(protected amino)-hexahydro-1,4-diazepines 11 20) and 14 22) with the corresponding carboxylic acids and NaBH 4 directly gave the 6-(protected amino)hexahydro-1,4-diazepines 13 and 16i-k in moderate to good yield. Deprotection of 13 and 16i-k with aqueous HCl produced the desired amines 8h-k.…”

mentioning

confidence: 99%

Synthesis and Structure-Activity Relationships of 4-Amino-5-chloro-N-(1,4-dialkylhexahydro-1,4-diazepin-6-yl)-2-methoxybenzamide Derivatives, Novel and Potent Serotonin 5-HT3 and Dopamine D2 Receptors Dual Antagonist.

Hirokawa

Harada

Yoshikawa

et al. 2002

CHEMICAL & PHARMACEUTICAL BULLETIN

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A number of the 2-alkoxy-4-amino-5-chlorobenzamide family possessing a potent serotoninergic or dopaminergic activity has been reported.1) The potency and selectivity of the benzamides are dependent upon the structure of their basic moiety. The classic and parent benzamide of this family is metoclopramide, which is used clinically as a stimulant of upper gastrointestinal motility and an antiemetic agent. 2,3) Effects of metoclopramide are believed to be due to a combination of a relatively weak serotonin (5-hydroxytryptamine) 5-HT 3 (5-HT 3 ) and dopamine D 2 receptors antagonism and a serotonin 5-HT 4 receptor agonism. The weak affinity and lack of selectivity of metoclopramide for these receptors can be explained by the large number of permissible conformers due to the flexibility of the 2-(diethylamino)ethyl chain. To date, several benzamide derivatives with potent and selective activity for the dopamine D 2 , and the serotonin 5-HT 4 , and 5-HT 3 receptors have been reported. Thus, zacopride, 4) BRL 24682, 5) renzapride, 6) SC 53116, 7) and mosapride 8,9) with a rigid folded framework as the amine moiety showed good affinity for the 5-HT 3 and/or serotonin 5-HT 4 receptors. On the other hand, clebopride, a compound 1, and BRL 25594 having a benzyl group on the nitrogen atom in the amine moiety had high affinity for the dopamine D 2 and D 3 receptors. 10)Several potent and selective 5-HT 3 receptor antagonists such as ondansetron and granisetron have been used clinically to prevent nausea and emesis induced by cancer chemotherapeutic agents such as cisplatin and radiation treatment. [11][12][13][14] The nausea and emesis are common side effects that can cause patients to refuse subsequent chemotherapeutic sessions.15) On the other hand, dopamine D 2 receptor antagonists such as phenothiazines and butyrophenones are known to be effective in the treatment of emesis and vomiting induced by centrally acting emetic stimuli such as antiparkinsonian drugs, loperamide, apomorphine, and morphine. 16) In addition, the traditional antiemetic agent domperidone, a peripheral dopamine D 2 receptor antagonist, has been shown to be effective for the treatment of chronic upper gastrointestinal distress and the prevention of nausea and vomiting resulting from variety of causes. 17,18) However, dopamine D 2 receptor antagonists including domperidone are only minimally effective against chemotherapy-or radiationinduced nausea and vomiting.19) Previously, we reported that the structurally novel 4-amino-N-(1-benzyl-4-methylhexahydro-1,4-diazepin-6-yl)-5-chloro-2-methoxybenzamide (2x) and the corresponding 4-amino-5-chloro-2-ethoxybenzamide (2y) are potent and selective 5-HT 3 receptor antagonists. 20) In the course of our studies on the structure-activity relationships (SARs) of 2x, y, we found that replacement of the benzyl group in the hexahydro-1,4-diazepine ring by an alkyl group results in a significant increase in the dopamine D 2 receptor binding affinity along with a potent 5-HT 3 receptor antagonistic activity. 21) Thu...

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“…3 Although the reaction of β-enamino ketones 1 with NaBH 4 in glacial acetic acid for 3 hours at room temperature leads to products from total reduction (γ-amino alcohols 2), 1 under the same conditions, using NaBH(OAc) 3 as a reducing agent we have the Mannich base 3 as a product (Scheme 1, Table 1). These results are obtained when we add comercial NaBH(OAc) 3 to a solution of β-enamino ketone 1 in glacial acetic acid or when firstly we add NaBH 4 to glacial acetic acid and then add the β-enamino ketones 1, 4,5 and shows that in the reduction of the β-enamino ketones 1 to γ-amino alcohols 2, the reducing agent is not the NaBH(OAc) 3 as it is normally interpreted in this type of reaction. 7 These data imply that sodium borohydride added directly to acetic acid, as it is used in the total reduction of β-enamino ketones 1 to γ-amino alcohols 2, does not quantitatively give sodium triacetoxyborohydride.…”

Section: Resultsmentioning

confidence: 94%

Studies on the reduction of beta-enamino ketones

Machado¹,

Harris²,

Braga³

2006

J. Braz. Chem. Soc.

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A redução de β-enamino cetonas 1 com NaBH(OAc) 3 em ácido acético glacial produziu β-amino cetonas 3 em 65% a 67% de rendimento. Esses resultados, juntamente com outros, obtidos nas reduções de β-enamino cetonas 1 a γ-amino álcoois 2, preferencialmente syn, com NaBH 4 /HOAc, sugerem que o curso reacional desta última reação passa inicialmente pela redução de β-enamino cetonas 1 a β-amino cetonas 3 e estas são reduzidas posteriormente a γ-amino álcoois 2. Com esses resultados podemos dizer que a diastereosseletividade da redução de β-enamino cetonas 1, a γ-amino álcoois 2 dando preferencialmente produtos syn pode ser analisada como o resultado de uma competição entre um estado de transição tipo bote e um estado de transição tipo cadeira, obtidos a partir das β-amino cetonas 3.Reduction of β-enamino ketones 1 with NaBH(OAc) 3 in glacial acetic acid gave β-amino ketones 3 in 65% to 67% yield. These data and others observed in the reduction of β-enamino ketones 1 to preferentially syn γ-amino alcohols 2 with NaBH 4 /HOAc suggest that in this last reaction we have firstly the reduction of the β-enamino ketones 1 to produce the β-amino ketones 3, and then this compound is reduced to the γ-amino alcohols 2. We can say from this results that the diastereosselectivity of the reduction of β-enamino ketones 1 to mainly syn γ-amino álcohols 2, can be analysed as a competition between a chair-like transition state and a boat-like transition state, obtained from the β-amino ketones 3.

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Sodium borohydride-carboxylic acid systems. Useful reagents for the alkylation of amines

Cited by 126 publications

References 4 publications

<i>N</i>-Alkylation Using Sodium Triacetoxyborohydride with Carboxylic Acids as Alkyl Sources

<i>N</i>-Alkylation Using Sodium Triacetoxyborohydride with Carboxylic Acids as Alkyl Sources

Synthesis and Structure-Activity Relationships of 4-Amino-5-chloro-N-(1,4-dialkylhexahydro-1,4-diazepin-6-yl)-2-methoxybenzamide Derivatives, Novel and Potent Serotonin 5-HT3 and Dopamine D2 Receptors Dual Antagonist.

Studies on the reduction of beta-enamino ketones

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