74058-71-2

Basic information

• Product Name: HexadecanaMide, N-(phenylMethyl)-
• Synonyms: HexadecanaMide, N-(phenylMethyl)-;N-benzylpalMitaMide;Macamide 1;N-Benzylhexadecanamide;Hexadecanamide, N-benzyl-;Macamide B
• CAS NO: 74058-71-2
• Molecular Formula: C₂₃H₃₉NO
• Molecular Weight: 345.56186
• Mol File: 74058-71-2.mol
• Article Data: 13

Chemical Properties

• Melting Point: 95-96℃
• Boiling Point: 501.9±29.0 °C(Predicted)
• Appearance: /
• Density: 0.919±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: ≤2mg/ml in organic solvent ethanol
• PKA: 16.39±0.46(Predicted)
• CAS DataBase Reference: HexadecanaMide, N-(phenylMethyl)-(CAS DataBase Reference)
• NIST Chemistry Reference: HexadecanaMide, N-(phenylMethyl)-(74058-71-2)
• EPA Substance Registry System: HexadecanaMide, N-(phenylMethyl)-(74058-71-2)

Safety Data

• Hazardous Substances Data: 74058-71-2(Hazardous Substances Data)

Usage

Uses

N-Benzyl Hexadecanamide is a non-?polar, long-?chain fatty acid N-?benzylamide part of a group of macamides tested as potential inhibitors of the human enzyme, fatty acid amide hydrolase (FAAH)?.

Biological Activity

n-benzylpalmitamide is an inhibitor of fatty acid amide hydrolase (faah) [1].the fatty acid amide hydrolase (faah) is a mammalian integral membrane enzyme responsible for the hydrolysis of anandamide, an endocannabinoid. the faah is involved in degrading the fatty acid amide family of endogenous signaling lipids, including the endogenous cannabinoid anandamide and the sleep-inducing substance oleamide. faah belongs to is a member of amidase signature (as) family. the faah integrates into cell membranes and terminates fatty acid amide signaling in vivo [2]. genetic mutations in faah may constitute important risk factors for problem drug use and support a potential link between functional abnormalities in the endogenous cannabinoid system and drug abuse and dependence [3].n-benzylpalmitamide was a long-chain fatty acid amide isolated from the maca (l. meyenii) plant and was structurally related to cannabinoids. n-benzylpalmitamide was a moderate inhibitor of faah and inhibited 44% activity of faah at 500 μm [1].

references

[1] wu h, kelley c j, pino-figueroa a, et al. macamides and their synthetic analogs: evaluation of in vitro faah inhibition[j]. bioorganic & medicinal chemistry, 2013, 21(17): 5188-5197.[2] deutsch d g, ueda n, yamamoto s. the fatty acid amide hydrolase (faah)[j]. prostaglandins, leukotrienes and essential fatty acids (plefa), 2002, 66(2): 201-210.[3] sipe j c, chiang k, gerber a l, et al. a missense mutation in human fatty acid amide hydrolase associated with problem drug use[j]. proceedings of the national academy of sciences, 2002, 99(12): 8394-8399.

Synthetic route

C28H40N2O2 (100663-86-3) + benzylamine (100-46-9) → hexadecanoic acid benzylamide (74058-71-2) + (E)-2-pyridylphenyl ketoxime (14178-31-5)

Conditions	Yield
In dichloromethane for 24h; Ambient temperature;	A 99% B 100%

1-(2-Thioxo-thiazolidin-3-yl)-hexadecan-1-one (74058-64-3)

Conditions	Yield
In dichloromethane for 0.0333333h; Ambient temperature;	96%

+ benzylamine → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
at 50 - 60℃; for 16h;	94%

1-hexadecylcarboxylic acid (57-10-3) + benzylamine (100-46-9) → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
With mesoporous silica MCM-41 In toluene for 12h; Reflux;	92%
Stage #1: 1-hexadecylcarboxylic acid With Bromotrichloromethane; triphenylphosphine In dichloromethane for 0.75h; Reflux; Stage #2: benzylamine In dichloromethane for 14h; Reflux;	89%
Stage #1: 1-hexadecylcarboxylic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 2h; Stage #2: benzylamine With dmap In dichloromethane at 20℃; for 18h;	86%

hexadecanoic acid ethyl ester (628-97-7) + benzylamine (100-46-9) → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
With indium (III) iodide at 110 - 120℃; for 8.5h;	91%
at 150℃;

n-tetradecanoic acid (544-63-8) + benzylamine (100-46-9) → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
Stage #1: n-tetradecanoic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 2h; Stage #2: benzylamine With dmap In dichloromethane at 20℃; for 18h;	89%

diphenylmethylsilanecarboxylic acid (18414-58-9) + pentadecylzinc(II) bromide + benzylamine (100-46-9) → hexadecanoic acid benzylamide (74058-71-2)

Conditions

Yield

Stage #1: pentadecylzinc(II) bromide With (2-morpholino-N-(quinolin-8-yl)acetamido)nickel(II) chloride In tetrahydrofuran; N,N-dimethyl acetamide at 20℃; for 0.5h; Inert atmosphere; Glovebox; Stage #2: diphenylmethylsilanecarboxylic acid; benzylamine With potassium fluoride; 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere; Sealed tube; Glovebox;

46%

benzylamine (100-46-9) + n-hexadecanoyl chloride (112-67-4) → hexadecanoic acid benzylamide (74058-71-2)

1-hexadecylcarboxylic acid (57-10-3) + thorium oxide → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: DCC-DMAP 2: 99 percent / CH2Cl2 / 24 h / Ambient temperature View Scheme

n-hexadecanoyl chloride (112-67-4) + ent-17-methyl-morphinan-3-ol → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N 2: 99 percent / CH2Cl2 / 24 h / Ambient temperature View Scheme

1-hexadecylcarboxylic acid (57-10-3) → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: dicyclohexylcarbodiimide 2: 96 percent / CH2Cl2 / 0.03 h / Ambient temperature View Scheme

pentadecyl bromide (629-72-1) → hexadecanoic acid benzylamide (74058-71-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: iodine / N,N-dimethyl acetamide / 20 °C / Inert atmosphere; Glovebox 1.2: 70 °C / Inert atmosphere; Glovebox 2.1: (2-morpholino-N-(quinolin-8-yl)acetamido)nickel(II) chloride / tetrahydrofuran; N,N-dimethyl acetamide / 0.5 h / 20 °C / Inert atmosphere; Glovebox 2.2: 2 h / 20 °C / Inert atmosphere; Sealed tube; Glovebox View Scheme

Upstream product

• 57-10-3 1-hexadecylcarboxylic acid 
• 100-46-9 benzylamine 
• 628-97-7 hexadecanoic acid ethyl ester 
• 112-67-4 n-hexadecanoyl chloride 
• 74058-64-3 1-(2-Thioxo-thiazolidin-3-yl)-hexadecan-1-one 
• 100663-86-3 C₂₈H₄₀N₂O₂ 
• 555-44-2 glyceroltripalmitate 
• 544-63-8 n-tetradecanoic acid 
• 629-72-1 pentadecyl bromide 
• 18414-58-9 diphenylmethylsilanecarboxylic acid 

Relevant articles and documents

Synthesis and biological screening of a library of macamides as TNF-α inhibitors

Thirty-five macamide analogues were synthesised by modifying the initial molecular structure. The resulting structures were confirmed using NMR and MS. Cytotoxicity and the anti-inflammatory activity of these synthetic macamides were evaluated in the THP-1 cell line. Preliminary biological evaluation indicated that most of these synthetic macamides did not present cytotoxicity (MTT assay) in the tested cell line with respect to the control (actinomycin D). Regarding the anti-inflammatory activity, several analogues had a greater potential for inhibition of TNF-α than natural macamides. Synthetic macamide 4a was the most active (IC50 = 0.009 ± 0.001 μM) compared to the C87 (control). Through looking at the link between the chemical structure and the activity, our study proves that changes made to natural macamides at the level of the alkyl chain, the benzyl position, the amide bond, and the addition of two methyl groups to the aromatic ring (meta position) lead us to obtaining new macamides with greater anti-inflammatory activity. This journal is

Maca amide synthesis method and use thereof

The invention relates to a synthetic method of MACAmide. The method includes following steps: with a fatty acid and benzylamine or m-methoxybenzylamine as reaction raw materials, mixing the raw materials in a dichloromethane solution in which HOAt, EDC.HCl and DIPEA are dissolved; performing a reaction with stirring; washing a reaction product with water; and drying a substance being undissolved in water to obtain the MACAmide. The method is simple in processes and the raw materials are easy to obtain. Operation conditions of the method are easy to control. The reaction product can reach a purity of 95% without purification. The invention provides basis for industrialized synthesis of the MACAmide. In addition, the MACAmide has effects of enhancing male reproductive ability and treating male sexual dysfunction. The invention provides market prospects to application of the MACAmide.

Antiproliferative activity of synthetic fatty acid amides from renewable resources

In the work, the in vitro antiproliferative activity of a series of synthetic fatty acid amides were investigated in seven cancer cell lines. The study revealed that most of the compounds showed antiproliferative activity against tested tumor cell lines, mainly on human glioma cells (U251) and human ovarian cancer cells with a multiple drug-resistant phenotype (NCI-ADR/RES). In addition, the fatty methyl benzylamide derived from ricinoleic acid (with the fatty acid obtained from castor oil, a renewable resource) showed a high selectivity with potent growth inhibition and cell death for the glioma cell line - the most aggressive CNS cancer.